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2013 ANNUAL HIGHLIGHTS

ISSUE HIGHLIGHTS:

7 Cancer care challenges in developing countries 10 Cancer statistics, 2013 14 Active surveillance for prostate cancer compared with immediate treatment: An economic analysis

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14 American Cancer Society lung cancer screening guidelines 31 NOW AVAILABLE: Free CME & CNE Credits from CA 33 Download the ACS Family of Journals App

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American Cancer Society Journals‌ Support Your Important Work in the Battle against Cancer Cancer Cytopathogy | Cancer | CA: A Cancer Journal for Clinicians The American Cancer Society estimates a total of 1,660,290 new cancer cases and 580,350 cancer deaths will occur in the United States in 2013. Despite a reduction in overall cancer death rates since the early 1990s, further progress can be accelerated by applying existing cancer control knowledge across all segments of the population. Whether you are in research, clinical practice, or public health, you can depend on ACS journals to support and advance your own work. Take a look for yourself: this selection of ground-breaking articles published in ACS journals presents some of the latest emerging therapeutic strategies, evidence-based care practices, screening and prevention tools, and trends and risk factors in cancer. In short, you’ll find the information you need to do your best work in the battle against cancer.

Did You Know That...? > ACS has issued official guidelines for lung cancer screening. > Although lung cancer is the third most common cancer diagnosed among men and women, the annual burden of disease is larger than that of any other cancer, accounting for approximately 28% of all deaths from cancer in the United States. > Higher levels of physical activity significantly increase survival in women with colorectal cancer. > African Americans bear a disproportionate share of the cancer burden in the United States, having the highest death rate and shortest survival of any racial or ethnic group for most cancers. > Ultimate outcomes of adult acute lymphoblastic leukemia treatments may be independent of the specific regimen chosen. > Physicians are less likely to have ever told high school-educated versus collegeeducated individuals that they were at risk for skin cancer.

Read On to Discover More News and Breakthroughs in Cancer Research and Care! > > >

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Contents Volume 120/Issue 2 April 25, 2012 Pages 71–142

ancer C Cytopathology

Cancer

Bioethics and Legal Oncology Ethical aspects of participation in the Database of Genotypes and Phenotypes of the National Center for Biotechnology Information: The Cancer and Leukemia Group B Experience ................................................................................................................................................ 5 Breast Pregnancy after a diagnosis of estrogen receptor-positive breast cancer does not affect prognosis .................................................................. 5 Added cancer yield of breast magnetic resonance imaging screening in women with a prior history of chest radiation therapy ........................ 5 Clinical Trials Phase 3, randomized, placebo-controlled study of zibotentan (ZD4054) in patients with castration-resistant prostate cancer metastatic to bone ............................................................................................................................................................................................ 6 A phase II study of the survivin suppressant YM155 in patients with refractory diffuse large B-cell lymphoma ................................................. 6 Colorectal Higher levels of physical activity significantly increase survival in women with colorectal cancer ...................................................................... 6 Complementary Medicine Use of complementary medications among older adults with cancer ................................................................................................................. 7 Disparities Survival disparities by Medicaid status: An analysis of 8 cancers ...................................................................................................................... 7 Cancer care challenges in developing countries ................................................................................................................................................ 7 Surveillance after resection for colorectal cancer .............................................................................................................................................. 8 Epidemiology Cancer burden in Africa and opportunities for prevention ................................................................................................................................. 8 Completion of the human papillomavirus vaccine series among insured females between 2006 and 2009 ...................................................... 9 Annual number of lung cancer deaths potentially avertable by screening in the United States ......................................................................... 9 Decreasing incidence of late-stage breast cancer after the introduction of organized mammography screening in Italy ................................... 9 Cancer statistics for Hispanics/Latinos, 2012 ................................................................................................................................................10 Cancer statistics, 2013 ..................................................................................................................................................................................10 Cancer statistics for African Americans, 2013 ..............................................................................................................................................11 Fine-Needle Aspiration Role of BRAFV600E mutation analysis and second cytologic review of fine-needle aspiration for evaluating thyroid nodule............................11 Clinical and pathologic features and clinical impact of false negative thyroid fine-needle aspirations .............................................................12 Prospective analysis of atypical epithelial cells as a high-risk cytologic feature for malignancy in pancreatic cysts ........................................12 The atypical thyroid fine-needle aspiration: Past, present, and future .............................................................................................................12 Cytomorphological and molecular genetic findings in pediatric thyroid fine-needle aspiration ........................................................................13 Genitourinary Disease Deletions of chromosomes 3p and 14q molecularly subclassify clear cell renal cell carcinoma ......................................................................13 Active surveillance for prostate cancer compared with immediate treatment: An economic analysis .............................................................14 Guideline American Cancer Society lung cancer screening guidelines ............................................................................................................................14 Gynecologic Cytopathology Should LSIL-H be a distinct cytology category? A study on the frequency and distribution of 40 human papillomavirus genotypes in 808 women .................................................................................................................................................................................15 Adherence to practice guidelines for atypical glandular cells on cervical cytology .........................................................................................15 The role of human papillomavirus type 16/18 genotyping in predicting high-grade cervical/vaginal intraepithelial neoplasm in women with mildly abnormal Papanicolaou results .....................................................................................................................................15 Pericardial fluid cytology: An analysis of 128 specimens over a 6-year period ...............................................................................................16 Peritoneal washing cytologic analysis of ovarian serous tumors of low malignant potential to detect peritoneal implants and predict clinical outcome .........................................................................................................................................................................16 Head and Neck Recent developments in esophageal adenocarcinoma ....................................................................................................................................16 Early detection of nasopharyngeal carcinoma by plasma Epstein-Barr virus DNA analysis in a surveillance program .....................................17 Hematologic Malignancies Treatment of adults with acute lymphoblastic leukemia: Do the specifics of the regimen matter? Results from a prospective randomized trial ............................................................................................................................................................................17 Pooled analysis of AIDS malignancy consortium trials evaluating rituximab plus CHOP or infusional EPOCH chemotherapy in HIV-associated non-Hodgkin lymphoma ......................................................................................................................................................17 Comparative effectiveness and cost of adding rituximab to first-line chemotherapy for elderly patients diagnosed with diffuse large B-cell lymphoma ..................................................................................................................................................................18 American Cancer Society Family of Journals

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Contents, con’t.

Histopathology Harmony at LAST .............................................................................................................................................................................................18 Immunocytochemistry p16INK4a—Is the future of cervical cancer screening rosy? ................................................................................................................................18 Endobronchial ultrasound fine-needle aspiration biopsy of pulmonary non–small cell carcinoma with subclassification by immunohistochemistry panel ......................................................................................................................................................................19 Lung Rapid-onset hypogonadism secondary to crizotinib use in men with metastatic nonsmall cell lung cancer......................................................19 Melanoma Behavioral determinants of successful early melanoma detection: Role of self and physician skin examination .............................................20 Examining the pathways linking lower socioeconomic status and advanced melanoma .................................................................................20 Patterns of onset and resolution of immune-related adverse events of special interest with ipilimumab: Detailed safety analysis from a phase 3 trial in patients with advanced melanoma .................................................................................................................20 Molecular Diagnostics and Cytogenetics Cytologic and molecular diagnosis of thyroid cancers: Is it time for routine reflex testing? ..............................................................................21 Identification of tissue of origin in body fluid specimens using a gene expression microarray assay ................................................................21 Immunoglobulin heavy-chain fluorescence in situ hybridization-chromogenic in situ hybridization DNA probe split signal in the clonality assessment of lymphoproliferative processes on cytological samples ...................................................................22 Targeting tyrosine kinases in cancer: The converging roles of cytopathology and molecular pathology in the era of genomic medicine .................................................................................................................................................................................22 Non-Gynecologic Cytopathology The diagnostic value of cell block as an adjunct to liquid-based cytology of bronchial washing specimens in the diagnosis and subclassification of pulmonary neoplasms ................................................................................................................................22 A review of reporting systems and terminology for urine cytology ...................................................................................................................23 Subclassification of lymphoproliferative disorders in serous effusions: A 10-year experience .........................................................................23 Outcomes and Treatment/Therapies Lack of benefit of central nervous system prophylaxis for diffuse large B-cell lymphoma in the rituximab era: Findings from a large national database ..........................................................................................................................................................23 Electronic patient-reported outcome systems in oncology clinical practice .....................................................................................................24 Hypnosis for cancer care: Over 200 years young ...........................................................................................................................................24 Understanding, recognizing, and managing toxicities of targeted anticancer therapies .................................................................................24 Impairment-driven cancer rehabilitation: An essential component of quality care and survivorship ..............................................................25 Palliative Care Early integration of palliative care services with standard oncology care for patients with advanced cancer ..................................................25 Pancreas Recent progress in pancreatic cancer .............................................................................................................................................................26 Prostate Clinical development of novel therapeutics for castration-resistant prostate cancer .......................................................................................26 Low rate of bone density testing in men receiving androgen deprivation therapy ..........................................................................................26 Psychosocial Oncology Patient–physician communication about code status preferences: A randomized controlled trial....................................................................27 Radiology Advances in oncologic imaging: Update on 5 common cancers ......................................................................................................................27 Screening/Early Detection Cancer screening in the United States, 2013: A review of current American Cancer Society guidelines, current issues in cancer screening, and new guidance on cervical cancer screening and lung cancer screening ............................................27 Surgical Oncology The current status of robotic oncologic surgery .............................................................................................................................................. 28 Symptom Control and Palliative Care Attrition rates, reasons, and predictive factors in supportive care and palliative oncology clinical trials .........................................................28 Meet the Editors .............................................................................................................................................................................................29

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Bioethics and Legal Oncology Cancer | Volume 118, Issue 20, pages 5060-5068, 15 October 2012

Ethical aspects of participation in the Database of Genotypes and Phenotypes of the National Center for Biotechnology Information: The Cancer and Leukemia Group B experience Jeffrey Peppercorn, Iuliana Shapira, Teressa Deshields, Deanna Kroetz, Paula Friedman, Patricia Spears, Deborah E. Collyar, Lawrence N. Shulman, Lynn Dressler, and Monica M. Bertagnolli

Read this article to explore the complex issues surrounding informed consent for future use of tissue samples and data from completed clinical trials. Ideally, participants in any study would provide informed consent both to the principle of future use of their tissue and to specific planned research, understanding potential risks and benefits. However, not all future research, risks, or benefits can be anticipated at the time samples are obtained. Faced with an ethical dilemma regarding sharing genetic data from a completed genome-wide association study, the Cancer and Leukemia Group B (CALGB) Oncology Cooperative Group Ethics Committee conducted a series of meetings with patient advocates, bioethicists, clinical researchers, and clinical oncologists to evaluate the ethical issues raised by this case and identify lessons for improving informed consent for future genetics research in oncology trials. The authors make an urgent call for a national consensus on the appropriate use of archival tissues and standardized informed consent for future research.

Breast CA: A Cancer Journal for Clinicians | Volume 63, Issue 3, pages 143-144, May/June 2013

Pregnancy after a diagnosis of estrogen receptor-positive breast cancer does not affect prognosis Mary Kay Barton

Read this article for details on the relationship between pregnancy and the recurrence of ER-positive breast cancer. A previous meta-analysis suggested a lower risk of recurrence in patients who subsequently became pregnant, but this was believed to be possibly due to selection bias: patients who become pregnant are usually recurrence-free. This new study suggests that a pregnancy after treatment for early-stage, ER-positive breast cancer does not affect the recurrence rate. The project addressed previous data limitations with a study to correct for selection bias as much as possible. Investigators conducted a multicenter, retrospective cohort study, matching patients with known ER status who became

pregnant post-diagnosis at a ratio of 1:3 with those who did not become pregnant, based on ER status, lymph node status, adjuvant therapy, age, and year of diagnosis.

The study does not eliminate the possibility of pregnancy having some positive effect. It does establish that pregnancy neither prevents nor encourages recurrence of ER-positive breast cancer.

Cancer | Volume 119, Issue 3, pages 495-503, 1 February 2013

Added cancer yield of breast magnetic resonance imaging screening in women with a prior history of chest radiation therapy Vivianne Freitas, Anabel Scaranelo, Ravi Menezes, Supriya Kulkarni, David Hodgson, and Pavel Crystal

Magnetic resonance imaging (MRI) is a useful adjunct modality to screen high-risk women with a previous history of chest radiation therapy, resulting in a 4.1% (4 of 98 women) added cancer detection rate. The results of this

study support American Cancer Society recommendations that advise annual breast MRI screening in patients with a prior history of chest radiation therapy. American Cancer Society Family of Journals

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Clinical Trials Cancer | Volume 118, Issue 22, pages 5709–5718, 15 November 2012

Phase 3, randomized, placebo-controlled study of zibotentan (ZD4054) in patients with castration-resistant prostate cancer metastatic to bone Joel B. Nelson, Karim Fizazi, Kurt Miller, Celestia Higano, Judd W. Moul, Hideyuki Akaza, Thomas Morris, Stuart McIntosh, Kristine Pemberton, and Martin Gleave

Prostate cancer is the second most frequently diagnosed cancer worldwide and accounts for almost 10% of all male cancer deaths in the developed world. Although early detection and treatment options have helped decrease death rates for patients with prostate cancer in developed countries, patients with castration-resistant prostate cancer (CRPC) have a poor prognosis with limited therapeutic options. The disease state is defined by evidence of prostate cancer progression, despite serum testosterone being controlled below a castrate level.

Endothelin-1 and the endothelin A (ETA) receptor have been implicated in prostate cancer progression in bone. This study aimed to determine whether the specific ETA receptor antagonist, zibotentan, prolonged overall survival (OS) in patients with castration-resistant prostate cancer and bone metastases who were pain-free or mildly symptomatic for pain. In this large, randomized, placebo-controlled phase 3 trial, treatment with zibotentan 10 mg/day did not lead to a statistically significant improvement in OS in this patient population. Zibotentan had an acceptable safety profile.

Cancer | Volume 118, Issue 12, pages 3128-3134, 15 June 2012

A phase II study of the survivin suppressant YM155 in patients with refractory diffuse large B-cell lymphoma Bruce D. Cheson, Nancy L. Bartlett, Julie M. Vose, Andres Lopez-Hernandez, Amanda L. Seiz, Anne T. Keating, and Setareh Shamsili

Patients with refractory diffuse large B-cell lymphoma (DLBCL) have few effective treatment options. A prior correlation demonstrated a correlation between survivin levels and outcome in such patients. YM155, a small molecule survivin suppressant, inhibits in vitro growth of lymphoma cell lines. In an earlier phase I study, YM155

demonstrated activity against DLBCL. Whereas limited activity was observed in this phase II trial, an interaction between YM155 and rituximab has been demonstrated and will be exploited in an ongoing clinical trial to hopefully provide an active regimen for these patients.

Colorectal CA: A Cancer Journal for Clinicians | Volume 63, Issue 2, pages 83-84, March/April 2013

Higher levels of physical activity significantly increase survival in women with colorectal cancer Mary Kay Barton

This review focuses on a study that gives women yet another very good reason to stay physically active. Using data from the Women’s Health Initiative (WHI) study, researchers investigated the relationship between body mass index (BMI), recreational activity both pre- and post-diagnosis, and survival in postmenopausal women with colorectal cancer. The study found a statistically significant association between increasing levels of activity and lower cancerspecific and all-cause mortality. Women with a physical activity level of 18 or more metabolic equivalent hours/week had a 71% lower risk of colorectal cancer-specific mortality, and a 59% lower risk of all-cause mortality compared with inactive patients. Similar to the prediagnostic results, BMI was not associated with mortality. The lack of an association between BMI and mortality is at least partially due to the fact that BMI measurements were taken at baseline when the participants entered the WHI, with a median time between baseline BMI measurement and colorectal cancer diagnosis of 5.8 years.

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Complementary Medicine Cancer | Volume 118, Issue 19, pages 4815–4823, 1 October 2012

Use of complementary medications among older adults with cancer Ronald J. Maggiore, Cary P. Gross, Kayo Togawa, William P. Tew, Supriya G. Mohile, Cynthia Owusu, Heidi D. Klepin, Stuart M. Lichtman, Ajeet Gajra, Rupal Ramani, Vani Katheria, Shira M. Klapper, Kurt Hansen, and Arti Hurria, on behalf of the Cancer and Aging Research Group

The use of herbal/complementary medications is observed in up to 17% of older adults with cancer who are receiving chemotherapy. The types of these agents used in this population may be distinct from those encountered among older adults in general.

Disparities Cancer | Volume 118, Issue 17, pages 4271–4279, 1 September 2012

Survival disparities by Medicaid status: An analysis of 8 cancers Siran M. Koroukian, Paul M. Bakaki, and Derek Raghavan

This study documents important disparities in survival outcomes for 8 cancers by Medicaid status. These disparities persist after adjusting for patient demographics, marital status, and county of residence.

Cancer | Volume 118, Issue 14, pages 3627-3635, 15 July 2012

Cancer care challenges in developing countries Adi J. Price, Paul Ndom, Etienne Atenguena, Jean Pierre Mambou Nouemssi, and Robert W. Ryder

The inability of Sub-Saharan Africa’s health systems to cope with projected rising cancer rates over the next decades can be understood, in part, by examining the region’s current state of cancer care. This article focuses on Yaounde General Hospital (YGH), the only site in Cameroon (population: 18.8 million) where adults can receive chemotherapy from the country’s two trained medical oncologists. The experiences of YGH patients represent a useful paradigm for describing cancer care in this region.

Researchers interviewed 79 consecutive patients already diagnosed with breast cancer, Kaposi sarcoma, or lymphoma. A third of patients reported waiting more than six months for their first consultation. Nearly half had waited an additional three months for a diagnosis. One fourth had traveled more than seven hours to reach YGH. This article sounds an alarm bell for regional governments, international health organizations, NGOs, cancer centers, and specialists worldwide. As cancer increases in Africa, an already unacceptable situation could become an ongoing international disaster.

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Disparities, con’t. Cancer | Volume 119, Issue 6, pages 1235-1242, 15 March 2013

Surveillance after resection for colorectal cancer Phyllis Brawarsky, Bridget A. Neville, Garrett M. Fitzmaurice, Craig Earle, and Jennifer S. Haas

Colorectal cancer (CRC) is the third most common type of cancer in the United States and the third leading cause of cancer death. CRC survivors are at risk for local recurrences and second primary cancers even if the first cancer is completely removed. Routine follow-up is recommended to detect new precancerous lesions in the colon or recurrent cancer when potentially curative surgical resection is possible. This article describes the use of surveillance over time, focusing on racial/ethnic disparities and area characteristics, such as capacity for CRC screening. SEER-Medicare data

were used to identify individuals aged 66 to 85 years who were diagnosed with CRC from 1993 to 2005 and treated with surgery. The study examined factors associated with subsequent receipt of a colonoscopy, carcinoembryonic antigen (CEA) testing, primary care visits, and a composite measure of overall surveillance. Findings reveal that many CRC survivors do not get recommended surveillance, and black/white disparities in rates of surveillance have not improved.

Epidemiology Cancer | Volume 118, Issue 18, pages 4372–4384, 15 September 2012

Cancer burden in Africa and opportunities for prevention Ahmedin Jemal, Freddie Bray, David Forman, Meg O’Brien, Jacques Ferlay, Melissa Center, and D. Maxwell Parkin

Cancer is an emerging public health problem in Africa. About 715,000 new cancer cases and 542,000 cancer deaths occurred in 2008 on the continent, with these numbers expected to double in the next 20 years simply because of the aging and growth of the population. Furthermore, cancers such as lung, female breast, and prostate cancers are diagnosed at much higher frequencies than in the past because of changes in lifestyle factors and detection practices associated with urbanization and economic development. Breast cancer in women and prostate cancer in men have now become the most commonly diagnosed cancers in many Sub-Saharan African countries, replacing cervical and liver cancers. In most African countries, cancer control programs and the provision of early detection and treatment services are limited despite this increasing burden. This paper reviews the current patterns of cancer in Africa and the opportunities for reducing the burden through the application of resource level interventions, including implementation of vaccinations for liver and cervical cancers, tobacco control policies for smoking-related cancers, and low-tech early detection methods for cervical cancer, as well as pain relief at the palliative stage of cancer.

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Epidemiology, con’t. Cancer | Volume 118, Issue 22, pages 5623–5629, 15 November 2012

Completion of the human papillomavirus vaccine series among insured females between 2006 and 2009 Jacqueline M. Hirth, Alai Tan, Gregg S. Wilkinson, and Abbey B. Berenson

The percentage of insured females who complete the human papillomavirus (HPV) vaccine series is declining, particularly among females aged 9 years to 12 years and 13 years to 18 years. Physicians should increase their efforts to encourage their patients to complete the HPV vaccine series.

Cancer | Volume 119, Issue 7, pages 1381–1385, 1 April 2013

Annual number of lung cancer deaths potentially avertable by screening in the United States Jiemin Ma, Elizabeth M. Ward, Robert Smith, and Ahmedin Jemal

The National Lung Screening Trial (NLST), conducted between 2002 and 2009, demonstrated that screening with low-dose computed tomography (LDCT) reduced lung cancer mortality by 20% among screening-eligible populations compared with chest x-ray. In this article, the authors provide an estimate of the annual number of lung cancer deaths that can be averted by screening, assuming the screening regimens adopted in the NLST are fully implemented in the United States. The study determined that approximately 8.6 million Americans were eligible for lung-cancer screening in

2010 and that LDCT screening could potentially avert approximately 12,000 lung cancer deaths per year in the United States. The authors note that further studies are needed to estimate the number of avertable lung cancer deaths and the cost-effectiveness of LDCT screening under different scenarios of risk, various screening frequencies, and various screening uptake rates. In addition, they offer a brief literature review on the cost-effectiveness of LDCT screening.

Cancer | Volume 119, Issue 11, pages 2022–2028, 1 Jun 2013

Decreasing incidence of late-stage breast cancer after the introduction of organized mammography screening in Italy Flavia Foca, Silvia Mancini, Lauro Bucchi, Donella Puliti, Marco Zappa, Carlo Naldoni, Fabio Falcini, Maria L. Gambino, Silvano Piffer, Maria E. Sanoja Gonzalez, Fabrizio Stracci, Manuel Zorzi, Eugenio Paci, and the IMPACT Working Group

Read this article to gain a better understanding of the positive impact of organized mammography screening on previously underserved populations. This study evaluates variations in the total incidence of breast cancer and in the incidence of breast cancers with a pathologic tumor (pT) classification of pT2 through pT4 after the introduction of mammography screening in 6 Italian administrative regions.

The study area included 700 municipalities, with a total population of 692,824 women, ages 55 to 74 years, who were targeted by organized mammography screening

between 1991 and 2005. The ratio of the observed 2-year, age-standardized incidence rate to the expected rate was calculated. Expected rates were estimated assuming that the incidence of breast cancer was stable and was equivalent to that in the last 3 years before year 1.

A significant and stable decrease in the incidence of latestage breast cancer was observed from the third year of screening onward.

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Epidemiology CA: A Cancer Journal for Clinicians | Volume 62, Issue 5, pages 283-298, September/October 2012

Cancer statistics for Hispanics/Latinos, 2012 Rebecca Siegel, Deepa Naishadham, and Ahmedin Jemal

Hispanics/Latinos are the largest and fastest growing major demographic group in the United States, accounting for 16.3% (50.5 million/310 million) of the US population in 2010. In this article, the American Cancer Society updates a previous report on cancer statistics for Hispanics using incidence data from the National Cancer Institute, the Centers for Disease Control and Prevention, and the North American Association of Central Cancer Registries and mortality data from the National Center for Health Statistics. In 2012, an estimated 112,800 new cases of cancer will be diagnosed and 33,200 cancer deaths will occur among Hispanics. In 2009, the most recent year for which actual data are available, cancer surpassed heart disease as the leading cause of death among Hispanics. Among US Hispanics during the past 10 years of available data (2000-2009), cancer incidence rates declined by 1.7% per year among men and 0.3% per year among women, while cancer death rates declined by 2.3% per year in men and 1.4% per year in women. Hispanics have lower incidence and death rates than non-Hispanic whites for all cancers combined and for the 4 most common cancers (breast, prostate, lung and bronchus, and colorectum). However, Hispanics have higher incidence and mortality rates for cancers of the stomach, liver, uterine cervix, and gallbladder, reflecting greater exposure to cancer-causing infectious agents, lower rates of screening for cervical cancer, differences in lifestyle and dietary patterns, and possibly genetic factors. Strategies for reducing cancer risk among Hispanics include increasing utilization of screening and available vaccines, as well as implementing effective interventions to reduce obesity, alcohol consumption, and tobacco use. CA: A Cancer Journal for Clinicians | Volume 63, Issue 1, pages 11–30, January/February 2013

Cancer statistics, 2013 Rebecca Siegel, Deepa Naishadham, and Ahmedin Jemal

Trends in Cancer Incidence and Death Rates by Sex, United States, 1975 to 2009.

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Each year, the American Cancer Society estimates the numbers of new cancer cases and deaths expected in the United States in the current year and compiles the most recent data on cancer incidence, mortality, and survival based on incidence data from the National Cancer Institute, the Centers for Disease Control and Prevention, and the North American Association of Central Cancer Registries and mortality data from the National Center for Health Statistics. A total of 1,660,290 new cancer cases and 580,350 cancer deaths are projected to occur in the United States in 2013. During the most recent 5 years for which there are data (20052009), delay-adjusted cancer incidence rates declined slightly in men (by 0.6% per year) and were stable in women, while cancer death rates decreased by 1.8% per year in men and by 1.5% per year in women. Overall, cancer death rates have declined 20% from their peak in 1991 (215.1 per 100,000 population) to 2009 (173.1 per 100,000 population). Death rates continue to decline for all 4 major cancer sites (lung, colorectum, breast, and prostate). Over the past 10 years of data (2000-2009), the largest annual declines in death rates were for chronic myeloid leukemia (8.4%), cancers of the stomach (3.1%) and colorectum (3.0%), and nonHodgkin lymphoma (3.0%). The reduction in overall cancer death rates since 1990 in men and 1991 in women translates to the avoidance of approximately 1.18 million deaths from cancer, with 152,900 of these deaths averted in 2009 alone. Further progress can be accelerated by applying existing cancer control knowledge across all segments of the population, with an emphasis on those groups in the lowest socioeconomic bracket and other underserved populations.


Epidemiology, con’t. VOLUME XX | NUMBER X | MAY/JUNE 2013

CA: A Cancer Journal for Clinicians | Volume 63, Issue 3, pages 151–166, May/June 2013

Cancer statistics for African Americans, 2013 Carol DeSantis, Deepa Naishadham, and Ahmedin Jemal

145,300

52,000

Cancer Deaths Averted

Cancer Deaths Averted

In this article, the American Cancer Society estimates the number of new cancer cases and deaths for African Americans and compiles the most recent In This Issue: data on cancer incidence, mortality, survival, and screening prevalence based upon incidence data from the National Cancer Institute, the Centers for Disease Control and Prevention, and the North American Association of Central Cancer Registries and mortality data from the National Center for Health Statistics. It is estimated that 176,620 new cases of cancer and 64,880 deaths will occur among African Americans in 2013. From 2000 to 2009, the overall cancer death rate among males declined faster among African Americans than whites (2.4% vs 1.7% per year), but among females, the rate of decline was similar (1.5% vs 1.4% per year, respectively). The decrease in cancer death rates among African American males was the largest of any racial or ethnic group. The reduction in overall cancer death rates since 1990 in men and 1991 in women translates to the avoidance of nearly 200,000 deaths from cancer among African Americans. Five-year relative survival is lower for African Americans than whites for most cancers at each stage of diagnosis. The extent to which these disparities reflect unequal access to health care versus other factors remains an active area of research. Overall, progress in reducing cancer death rates has been made, although more can and should be done to accelerate this progress through ensuring equitable access to cancer prevention, early detection, and state-of-the-art treatments.

127

Deaths Averted

139 Males

Females

Year

Year

Total Number of Cancer Deaths Averted From 1991 to 2009 in African American Men and From 1992 to 2009 in African American Women

187

Title Here

142

156

Fine-Needle Aspiration Cancer Cytopathology | Volume 120, Issue 1, pages 44–51, 25 February 2012

Role of BRAFV600E mutation analysis and second cytologic review of fine-needle aspiration for evaluating thyroid nodule Guhyun Kang, Eun Yoon Cho, Jung Hee Shin, Jae-Hoon Chung, Jong Won Kim, and Young Lyun Oh

Thyroid fine-needle aspiration (FNA) is the primary diagnostic tool used for evaluating thyroid nodules. Although most aspirates provide diagnostic cytology, some are classified as indeterminate. This study aimed to determine whether the second review of FNA cytology can improve the diagnostic values and to assess the role of proto-oncogene B-Raf (BRAF) mutation testing in the diagnosis of papillary carcinoma (PC).

Thyroid aspirates from 1060 patients were submitted for cytologic evaluation and BRAFV600E mutation analysis. A second cytologic review was performed by 2 cytopathologists

in light of the mutation status. The sensitivity, accuracy, and negative predictive value (NPV) of the second review were better than those of the first. Mutation analysis significantly improved the NPV for detecting PCs compared with those of cytology alone.

Qualified cytologic diagnosis increases the effectiveness of FNA, forgoing the need for repeat biopsy or intraoperative frozen section evaluation. Preoperative BRAF mutation testing can supplement the routine cytology in the selection of thyroid nodules for surgery.

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Fine-Needle Aspiration, con’t. Cancer Cytopathology | Volume 120, Issue 5, pages 326–333, 25 October 2012

Clinical and pathologic features and clinical impact of false negative thyroid fine-needle aspirations Jerome Jean-Gilles, Andrew H. Fischer, Martin H. Luu, and Christopher L. Owens

False negative results in any test for cancer have the potential to increase patient morbidity due to delayed diagnosis. Although thyroid fine-needle aspiration (TFNA) is an excellent test in evaluating thyroid nodules, there are occasionally false negatives (FN). This article examines both the clinical and pathologic features of FN TFNA and its impact on prognosis and treatment. The findings in this article will be of considerable interest to both clinicians and patients. Although TFNA fails to identify a significant subset of patients with thyroid cancer,

the clinical consequence of FN TFNA is minimal. Thyroid cancers that elude detection with TFNA tend to be low grade, and most are cured despite the false negative cytologic diagnosis. Outcomes are not significantly different between FN TFNAs and true positive TFNAs, despite delayed treatment. These results reemphasize the fact that TFNA is just one factor in the management of nodular thyroid disease and that best patient care incorporates clinical, radiographic, and cytologic findings.

Cancer Cytopathology | Volume 121, Issue 1, pages 29–36, January 2013

Prospective analysis of atypical epithelial cells as a high-risk cytologic feature for malignancy in pancreatic cysts Martha B. Pitman, Kurt A. Yaeger, William R. Brugge, and Mari Mino-Kenudson

Pancreatic cysts are aspirated to assess whether a cyst is mucinous on one hand and malignant on the other. The authors’ retrospective data have indicated that high-grade atypical epithelial cells (AECs) identified on cytology are a high-risk feature and a better threshold than ‘‘positive’’ for detecting malignancy. This article assesses the accuracy of AECs in predicting malignancy in pancreatic cysts.

Cysts aspirated by endoscopic ultrasound (EUS)-guided fine-needle aspiration (EUS-FNAs) obtained between January 2006 and June 2011 were evaluated. Researchers recorded cytologic, histologic, imaging, and cyst fluid analysis

data. AECs were defined as cells that had an increased nuclear-to-cytoplasmic ratio and nuclear hyperchromasia with or without membrane abnormalities and with or without cytoplasmic vacuoles, but of insufficient quality and quantity for a ‘‘positive’’ interpretation. Malignancy included mucinous cysts with high-grade dysplasia and invasive carcinoma. Performance characteristics of cytology with AECs or worse for predicting malignancy were assessed. The lower malignancy threshold with AECs resulted in a 12% increase in malignancy detection.

Cancer Cytopathology | Volume 120, Issue 2, pages 73–86, 25 April 2012

The atypical thyroid fine-needle aspiration: Past, present, and future Massimo Bongiovanni, Jeffrey F. Krane, Edmund S. Cibas, and William C. Faquin

Thyroid fine-needle aspiration has developed into a key test in the evaluation of thyroid nodules. Although the interpretation of thyroid aspirates containing mild abnormalities is problematic, the introduction of the atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) category in The

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Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) has helped to delineate such cases in a systematic and clinically meaningful manner. Herein the authors review the cytomorphologic features associated with the AUS/ FLUS interpretation and summarize the results of studies conducted since the implementation of TBSRTC.


Fine-Needle Aspiration, con’t. Cancer Cytopathology | Volume 120, Issue 5, pages 342–350, 25 October 2012

Cytomorphological and molecular genetic findings in pediatric thyroid fine-needle aspiration Sara E. Monaco, Liron Pantanowitz, Walid E. Khalbuss, Vanessa A. Benkovich, John Ozolek, Marina N. Nikiforova, Jeffrey P. Simons, and Yuri E. Nikiforov

The Bethesda System for Reporting Thyroid Cytopathology is largely based on data from adult studies. Although thyroid nodules in children are rare, the rate of malignancy is high. In this article, the authors analyze the cytomorphology and mutational profiles in pediatric thyroid fine-needle aspirations (FNAs).

Thyroid FNAs from patients 21 years old or younger were identified from the authors’ pathology archive, categorized using the Bethesda System for Reporting Thyroid Cytopathology, and correlated with histological and molecular follow-up. The authors identified 179 samples from 142 patients, including 96 cases with histological follow-up and 66 cases with molecular data. This study demonstrates that pediatric thyroid FNA is a sensitive and highly specific tool. A 17% positivity rate for a genetic mutation correlated with malignancy in all cases. Compared with adults, there was a higher prevalence of RET/PTC mutations and lower prevalence of BRAF mutations, which may in part explain the less aggressive nature of PTCs reported in children.

Genitourinary Disease

Cancer | Volume 119, Issue 8, pages 1547–1554, 15 April 2013

Deletions of chromosomes 3p and 14q molecularly subclassify clear cell renal cell carcinoma Nils Kroeger, Tobias Klatte, Karim Chamie, P. Nagesh Rao, Frédéric D. Birkhäuser, Geoffrey A. Sonn, Joseph Riss, Fairooz F. Kabbinavar, Arie S. Belldegrun, and Allan J. Pantuck

In patients with clear cell renal cell carcinoma, loss of the von Hippel-Lindau (VHL) gene is associated with more favorable pathologic features and with improved recurrencefree and cancer-specific survival, whereas loss of the hypoxiainducible factor 1α (HIF-1α) gene is associated with worse recurrence-free and cancer-specific survival. Combined

loss of chromosome 3p/14q is a strong predictor of disease recurrence in patients with low-stage (pathologic T1) renal cell carcinoma, supporting the hypothesis that HIF-1α functions as a tumor suppressor gene in clear cell renal cell carcinoma.

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Genitourinary Disease, con’t. Cancer | Volume 118, Issue 14, pages 3512–3518, 15 July 2012

Active surveillance for prostate cancer compared with immediate treatment: An economic analysis Kirk A. Keegan, Marc A. Dall’Era, Blythe Durbin-Johnson, and Christopher P. Evans

Prostate cancer is the most common malignancy diagnosed in American men. As health care costs rise, increased attention must be paid to the costs of competing treatment modalities and how these relate to clinical outcomes. Active surveillance has emerged as a viable treatment option for men with tumors of low to intermediate risk. It allows for temporary, often-indefinite, deferment of aggressive therapy for prostate cancer in patients considered at low risk of mortality.

This article explores the health care costs of an active surveillance paradigm versus immediate treatment for prostate cancer. The study created a theoretical cohort of 120,000 men selecting active surveillance for prostate cancer. A Markov model simulated those exiting to each of 5 treatments over 5 years. Estimated total costs after 5 years of active surveillance with subsequent delayed treatment were compared with immediate treatment. The resulting data demonstrate that active surveillance delivers considerable cost savings over immediate treatment for prostate cancer after 5 and 10 years of follow-up.

Guideline CA: A Cancer Journal for Clinicians | Volume 63, Issue 2, pages 106–117, March/April 2013

American Cancer Society lung cancer screening guidelines Richard Wender, Elizabeth T. H. Fontham, Ermilo Barrera Jr, Graham A. Colditz, Timothy R. Church, David S. Ettinger, Ruth Etzioni, Christopher R. Flowers, G. Scott Gazelle, Douglas K. Kelsey, Samuel J. LaMonte, James S. Michaelson, Kevin C. Oeffinger, Ya-Chen Tina Shih, Daniel C. Sullivan, William Travis, Louise Walter, Andrew M. D. Wolf, Otis W. Brawley, and Robert A. Smith

Answer questions and earn free Findings from the National Cancer Institute’s National Lung Screening Trial established that lung cancer mortality in specific high-risk groups can be reduced by annual screening with low-dose computed tomography. These findings indicate that the adoption of lung cancer screening could save many lives. Based on the results of the National Lung Screening Trial, the American Cancer Society is issuing an initial guideline for lung cancer screening. This guideline recommends that clinicians with access to highvolume, high-quality lung cancer screening and treatment centers should initiate a discussion about screening with

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apparently healthy patients aged 55 years to 74 years who have at least a 30–pack-year smoking history and who currently smoke or have quit within the past 15 years. A process of informed and shared decision-making with a clinician related to the potential benefits, limitations, and harms associated with screening for lung cancer with lowdose computed tomography should occur before any decision is made to initiate lung cancer screening. Smoking cessation counseling remains a high priority for clinical attention in discussions with current smokers, who should be informed of their continuing risk of lung cancer. Screening should not be viewed as an alternative to smoking cessation.


Gynecologic Cytopathology Cancer Cytopathology | Volume 120, Issue 6, pages 373–379, 25 December 2012

Should LSIL-H be a distinct cytology category? A study on the frequency and distribution of 40 human papillomavirus genotypes in 808 women Haijun Zhou, Mary R. Schwartz, Donna Coffey, Debora Smith, Dina R. Mody, and Yimin Ge

Read this article to learn why creating an LSIL-H diagnostic category may enable early identification of patients in a highrisk subgroup. The 2001 Bethesda System for gynecologic cervical cytology reporting classifies squamous intraepithelial lesions into low-grade (LSIL) and high-grade (HSIL) lesions. An intermediate term, ‘‘LSIL, cannot exclude high-grade squamous intraepithelial lesion (LSIL-H),’’ has been used in a small percentage of cases. To the authors’ knowledge, little is known regarding the HPV status in patients with LSIL-H.

Of 808 SurePath specimens tested for 40 HPV genotypes using DNA microarray, followed by a confirmatory DNA sequencing assay, those with abnormal cytologic diagnoses included LSIL (20.7%), HSIL (6.9%), and LSIL-H (3.1%). The infection rate of HR-HPV in patients with LSIL-H was strikingly close to that of HSIL (91%). Women found to have LSIL-H appear to have a unique HPV distribution pattern that differs from LSIL and is comparable in risk to that for HSIL.

Cancer Cytopathology | Volume 121, Issue 1, pages 47–53, January 2013

Adherence to practice guidelines for atypical glandular cells on cervical cytology Kathryn E. Sharpless, Cara R. King, and Peter F. Schnatz

Atypical glandular cells (AGC) on cervical cytology are high–risk. Because of the high rate and wide variety of diseases associated with AGC cytology, current practice guidelines recommend an extensive initial evaluation of women with AGC. Historically, however, compliance with practice guidelines for AGC has been low, even when AGC cytology reports contain cytopathologist recommendations for evaluation. This study was launched to determine whether evaluation rates for AGC have improved over time, and whether

cytopathologists’ recommendations correlate with the types of evaluation women receive. It compares evaluation rates from 284 women with AGC (2004-2007) with findings from a similar study covering 1998-2001. Evaluations are compared based on cytology report recommendations. The results indicate that, while adherence to practice guidelines for the evaluation of women with AGC has improved, it continues to be suboptimal. Findings also suggest that continuing education and including practice guidelines on AGC cytology reports may improve compliance.

Cancer Cytopathology | Volume 121, Issue 2, pages 79–85, February 2013

The role of human papillomavirus type 16/18 genotyping in predicting high-grade cervical/vaginal intraepithelial neoplasm in women with mildly abnormal Papanicolaou results Ming Guo, Yun Gong, Jianping Wang, Marilyn Dawlett, Shobha Patel, Ping Liu, Therese B. Bevers, and Nour Sneige

High-risk human papillomavirus (HPV) is responsible for the development of more than 99% of cervical carcinomas. Currently, HPV DNA testing is used as a triage tool for women who have mildly abnormal Papanicolaou (Pap) results, i.e., abnormal squamous cells of undetermined significance (ASCUS). This article compares the predictive value of type 16 and/or 18 human (HPV) versus non-16/18 HPV types for high-grade cervical neoplasm/ vaginal intraepithelial neoplasm and carcinoma in women with mildly abnormal Pap results. The authors retrospectively selected Pap specimens with HPV testing results obtained from 243 women (155 with ASCUS and 88 with LSIL) in their Department of Pathology. HPV genotyping was performed using the EasyChip HPV blot assay. The Pap specimens with HPV16/18 and non-16/18 HPV types were compared with follow-up biopsy results. HPV genotyping for HPV16/18 improved risk assessment for women with ASCUS Pap results and may be used to predict the risk of CIN/VAIN2+ to better guide follow-up management.

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Gynecologic Cytopathology, con’t. Cancer Cytopathology | Volume 121, Issue 5, pages 242–251, May 2013

Pericardial fluid cytology: An analysis of 128 specimens over a 6-year period Ema A. Dragoescu and Lina Liu

Pericardial fluid (PF) accumulates through various mechanisms. Cytology is part of the workup to determine its etiology, primarily to rule malignancy in or out. To the authors’ knowledge, this is the largest systematic evaluation of PF cytology performed to date. Researchers retrieved specimens collected over 6 years, recording clinical history, laboratory, cytologic, and pericardial biopsy results. Examining 128 specimens from 113 patients, the authors established that 95 cases were benign, 2 had “severely atypical cells,” and 31 were malignant. The most common etiologies

for benign PF specimens were neoplasm, idiopathic, infection, and connective tissue disease. The most common neoplasm producing malignant PF in both males and females was lung carcinoma, primarily adenocarcinoma. In females, breast carcinoma was the second most common neoplasm. PF specimens enable specific interpretation in approximately 98.4% of cases. 87% of patients with malignant PF have a known history of malignancy. Although cytology is superior to pericardial biopsy in diagnosing metastatic carcinoma, other tumors may go undetected.

Cancer Cytopathology | Volume 120, Issue 4, pages 238–244, 25 August 2012

Peritoneal washing cytologic analysis of ovarian serous tumors of low malignant potential to detect peritoneal implants and predict clinical outcome Nour Sneige, John B. Thomison, Anais Malpica, Yun Gong, Joe Ensor, and Elvio G. Silva

Patients with ovarian serous tumors of low malignant potential (OSLMP) who have peritoneal implants, especially invasive implants, are at an increased risk of developing tumor recurrence. To the best of the authors’ knowledge, the ability of peritoneal washing (PW) cytology to detect the presence and type of peritoneal implants has not been adequately investigated, and its prognostic significance is unknown. The team reviewed records and PW specimens of 101 patients diagnosed with and treated for OSLMP between 1996 and 2010. Patients’ staging biopsy findings were compared with

the results of the authors’ review of the PWs. Follow-up data were also analyzed. Of the 96 patients whose staging biopsy results were available, 26 had peritoneal implants (17 noninvasive and 9 invasive), 19 had endosalpingiosis, and 51 had negative findings.

Researchers concluded that, while PW cytology detects the presence of peritoneal implants with moderate accuracy, long-term studies are needed to determine whether positive PW cytologic findings are an independent predictor of tumor recurrence.

Head and Neck CA: A Cancer Journal for Clinicians | Volume 63, Issue 4, pages 232-248, July/August 2013

Recent developments in esophageal adenocarcinoma Jesper Lagergren and Pernilla Lagergren

Answer questions and earn free Esophageal adenocarcinoma (EAC) is characterized by 6 striking features: increasing incidence, male predominance, lack of preventive measures, opportunities for early detection, demanding surgical therapy and care, and poor prognosis. Reasons for its rapidly increasing incidence include the rising prevalence of gastroesophageal reflux and obesity, combined with the decreasing prevalence of Helicobacter pylori infection. The strong male predominance remains unexplained, but hormonal influence might play an important role. Future prevention might include the treatment of reflux or obesity or chemoprevention with nonsteroidal antiinflammatory drugs or statins, but no evidence-based preventive measures are currently available. Likely future developments include endoscopic screening of better defined high-risk groups for 16

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EAC. Individuals with Barrett esophagus might benefit from surveillance, at least those with dysplasia, but screening and surveillance strategies need careful evaluation to be feasible and cost-effective. The surgery for EAC is more extensive than virtually any other standard procedure, and postoperative survival, health-related quality of life, and nutrition need to be improved (eg, by improved treatment, better decision-making, and more individually tailored follow-up). Promising clinical developments include increased survival after preoperative chemoradiotherapy, the potentially reduced impact on health-related quality of life after minimally invasive surgery, and the new endoscopic therapies for dysplastic Barrett esophagus or early EAC. The overall survival rates are improving slightly, but poor prognosis remains a challenge.


Head and Neck, con’t. Cancer | Volume 119, Issue 10, pages 1838–1844, 15 May 2013

Early detection of nasopharyngeal carcinoma by plasma Epstein-Barr virus DNA analysis in a surveillance program K. C. Allen Chan, Emily C. W. Hung, John K. S. Woo, Paul K. S. Chan, Sing-Fai Leung, Franco P. T. Lai, Anita S. M. Cheng, Sze Wan Yeung, Yin Wah Chan, Teresa K. C. Tsui, Jeffrey S. S. Kwok, Ann D. King, Anthony T. C. Chan, Andrew C. van Hasselt, and Y. M. Dennis Lo

Nasopharyngeal carcinoma (NPC) is prevalent in Southeast Asia. Over the last decade, plasma Epstein-Barr virus (EBV) DNA has been developed as a tumor marker for NPC. In this study, the authors investigated whether plasma EBV DNA analysis is useful for NPC surveillance.

Among 1318 volunteers, ages 40 to 60 years, three individuals with NPC were identified at enrollment. All were positive for EBV DNA and remained positive in follow-up analysis. Only one was positive for EBV serology. Another patient’s tumor was not detectable on endoscopic examination. A

2-fold increase in plasma EBV DNA on the follow-up analysis prompted MRI, which revealed the tumor. Among participants whose initial plasma EBV DNA results were false positive, two thirds had negative results on follow-up testing. Plasma EBV DNA analysis proved useful for detecting early NPC in individuals without a clinical suspicion of NPC. Repeating the test in those who had initially positive results differentiated those with NPC from those who had falsepositive results.

Hematologic Malignancies Cancer | Volume 119, Issue 6, pages 1186–1194, 15 March 2013

Treatment of adults with acute lymphoblastic leukemia: Do the specifics of the regimen matter? Results from a prospective randomized trial Nicole Lamanna, Leonard T. Heffner, Matt Kalaycio, Gary Schiller, Steven Coutre, Joseph Moore, Karen Seiter, Peter Maslak, Katherine Panageas, David Golde, and Mark A. Weiss

Induction therapy for adults with acute lymphoblastic leukemia (ALL) is similar across all regimens: vincristine, corticosteroids, and anthracyclines intensified with cyclophosphamide, asparaginase, or both. To date, no regimen has emerged as standard. Current regimens induce a complete response/complete remission in approximately 60% to 90% of patients. However, there is a substantial relapse rate. Only 20% to 40% of patients ultimately will be cured of their disease. This article documents a randomized trial of the ALL-2 regimen compared with a standard 4-drug induction

(the L-20 regimen). Patients also received consolidation, maintenance therapy, and central nervous system prophylaxis. Responses were evaluated in 164 patients. The ALL-2 regimen yielded an 83% complete remission rate versus the L-20 regimen (71%). However, ALL-2 did not improve longterm outcomes. Coupled with the reported experience of other studies in adults with ALL, these results raise the possibility that ultimate outcomes in adult ALL may be independent of the specific regimen chosen.

Cancer | Volume 118, Issue 16, pages 3977–3983, 15 August 2012

Pooled analysis of AIDS malignancy consortium trials evaluating rituximab plus CHOP or infusional EPOCH chemotherapy in HIV-associated non-Hodgkin lymphoma Stefan K. Barta, Jeannette Y. Lee, Lawrence D. Kaplan, Ariela Noy, and Joseph A. Sparano

The incidence of aggressive non-Hodgkin lymphoma (NHL) is up to approximately 600-fold greater in individuals with human immunodeficiency virus (HIV) infection. Despite a decrease in the incidence of HIV-associated NHL since the advent of combination antiretroviral therapy (cART), NHL remains the most common HIV-associated malignancy in the United States.

Read this article to learn the results of a pooled analysis of 2 consecutive trials that included 150 patients with HIV-associated NHL who received either R-CHOP or R-EPOCH. Age-adjusted International Prognostic Index

(aaIPI), CD4 count at lymphoma diagnosis, and treatment (R-CHOP vs R-EPOCH) were included as variables in a multivariate logistic regression model for complete response (CR) and in Cox proportional hazards regression models for event-free survival (EFS) and overall survival.

This article provides additional level 2 evidence supporting the use of concurrent R-EPOCH in patients with HIVassociated lymphoma and a CD4 count >50/lL. The results support the design of an ongoing phase 3 trial comparing concurrent R-EPOCH with R-CHOP. American Cancer Society Family of Journals

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Hematologic Malignancies, con’t. Cancer | Volume 118, Issue 24, pages 6079–6088, 15 December 2012

Comparative effectiveness and cost of adding rituximab to first-line chemotherapy for elderly patients diagnosed with diffuse large B-cell lymphoma Robert I. Griffiths, Michelle L. Gleeson, Joseph Mikhael, Martin H. Dreyling, and Mark D. Danese

Clinical trials have demonstrated that adding rituximab to first-line chemotherapy improved survival rates of patients diagnosed with large B-cell lymphoma (DLBCL). Several economic analyses, using multiple data sources have projected cost offsets or outright savings related to these improved clinical outcomes. Given the increasing cost of healthcare and concerns about the future of Medicare, it is important to know whether these benefits accrue to elderly patients as well as to the general population.

chemotherapy for elderly patients diagnosed with DLBCL is similar to its efficacy as measured in randomized trials. However, the survival benefits observed in this study did not translate into cost offsets or savings as previously reported by several studies in the peer-reviewed literature. This suggests that it may not be realistic to expect effective new cancer therapies to attenuate the rising costs of cancer care, especially for elderly populations.

This article reveals that, in routine clinical practice, the comparative effectiveness of adding rituximab to first-line

Histopathology Cancer Cytopathology | Volume 121, Issue 3, pages 111–115, March 2013

Harmony at LAST David C. Wilbur and Teresa M. Darragh

The joint College of American Pathologists/American Society for Colposcopy and Cervical Pathology LAST Project provides evidence-based consensus recommendations for a unified terminology for histopathologic classification

of all human papillomavirus–associated squamous lesions of the lower anogenital tract. It also includes specific recommendations for biomarker use to increase reliability and reproducibility of histopathologic diagnoses.

Immunocytochemistry Cancer Cytopathology | Volume 120, Issue 5, pages 291–293, 25 October 2012

p16INK4a—Is the future of cervical cancer screening rosy? Ann T. Moriarty

The author comments on a meta-analysis in this issue regarding cyclin-dependent kinase inhibitor 2A (p16INK4a) and the triage of women who have minimally abnormal Papanicolaou tests. The meta-analysis provides a framework

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for future research; however, the method is not currently ready for widespread clinical use.


Immunocytochemistry, con’t. Cancer Cytopathology | Volume 121, Issue 3, pages 146–154, March 2013

Endobronchial ultrasound fine-needle aspiration biopsy of pulmonary non–small cell carcinoma with subclassification by immunohistochemistry panel Brian T. Collins

Newer treatment modalities based on kinase inhibitors benefit patients with pulmonary adenocarcinoma (ADCA) but do not help those with squamous cell carcinoma (SCCA). Being able to triage these non-small cell carcinomas (NSCCAs) helps to stratify patients for the appropriate treatment. Endobronchial ultrasound fine-needle aspiration (EBUS FNA) is used for primary evaluation and diagnosis, and can provide a cell block for ancillary testing. This article offers insight into a promising method for subclassifying primary NSCCA of the lung.

The author analyzed EBUS FNA cases from primary pulmonary NSCCA with an immunohistochemical (IHC) panel performed on a cell block with concomitant surgical pathology biopsy. Eighty-one cases were identified from 81 patients. Thirty-five cases were given a specific diagnosis of ADCA, 34 SCCA, and 12 NSCCA, not otherwise specified cases. EBUS FNA with cell block provided a specific subclassification of NSCCA in 85% of cases when used in conjunction with a specific IHC panel including nap-A, TTF-1, CK5/6, and p63.

Lung Cancer | Volume 118, Issue 21, pages 5302–5309, 1 November 2012

Rapid-onset hypogonadism secondary to crizotinib use in men with metastatic nonsmall cell lung cancer Andrew J. Weickhardt, Micol S. Rothman, Smita Salian-Mehta, Katja Kiseljak-Vassiliades, Ana B. Oton, Robert C. Doebele, Margaret E. Wierman, and D. Ross Camidge

This article documents the differences in testosterone (T) levels between crizotinib-treated and noncrizotinib-treated patients with metastatic nonsmall cell lung cancer (NSCLC). Testosterone levels were measured in 19 men with metastatic NSCLC who received crizotinib and in 19 men with metastatic NSCLC who did not receive crizotinib. Clinical characteristics of the patients were compared, and additional hormone assays were performed as appropriate. Two patients who began crizotinib and 4 patients who had dose interruptions or who stopped crizotinib therapy had serial hormone measurements, permitting the documentation of dynamic hormone changes on and off crizotinib treatment. Results indicated that crizotinib therapy caused rapid suppression of T levels in men and that the site of action must include a central (hypothalamic or pituitary) effect. Additional direct testicular effects could not be excluded. Further work is required to assess the correlation between low T levels and crizotinib side effects as well as the exact molecular mechanism and site of drug toxicity.

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Melanoma Cancer | Volume 118, Issue 15, pages 3725–3734, 1 August 2012

Behavioral determinants of successful early melanoma detection: Role of self and physician skin examination Susan M. Swetter, Ricardo A. Pollitt, Timothy M. Johnson, Daniel R. Brooks, and Alan C. Geller

Known factors related to thinner versus thicker cutaneous melanomas at diagnosis involve characteristics related to the patient, tumor, and mode of discovery. Reduced melanoma mortality should result from improved understanding of modifiable factors related to early detection. The authors of this report surveyed 566 adults, who completed questionnaires within 3 months of diagnosis, to identify differences in prediagnosis behavioral and medical care factors associated with thinner versus thicker melanoma. This article reveals the importance of encouraging early

melanoma detection among patients and physicians alike. Skin self-examination (SSE), using a picture aid of a melanoma tumor, and physician skin examination (PSE) during routine medical care were identified as complementary early detection strategies, particularly in men aged >60 years, in whom both partial and full-body PSE were associated with thinner tumors. Given the high rates of physician access, PSE may be a more practical approach for successful early detection in this subgroup with highest mortality.

Cancer | Volume 118, Issue 16, pages 4004–4013, 15 August 2012

Examining the pathways linking lower socioeconomic status and advanced melanoma Ricardo A. Pollitt, Susan M. Swetter, Timothy M. Johnson, Pratima Patil, and Alan C. Geller

Low socioeconomic status (SES) is associated with more advanced melanoma at diagnosis and decreased survival. Exploring the pathways linking lower SES and thicker melanoma will help guide public and professional strategies to reduce deaths. This article suggests that a serious effort to raise melanoma awareness among lower SES individuals and improve physicians’ awareness of the socioeconomic disparities and communication of risk would go a long way toward mitigating this problem. The authors surveyed 566 newly diagnosed patients, assessing SES by education level and obtaining data by self-report among patients within three months of their diagnosis. High school-educated individuals were significantly more likely than college graduates to believe that melanoma was not very serious and were less likely to know the ABCD melanoma rule or the difference between melanoma and ordinary skin growths. Physicians were less likely to have ever told high school-educated versus college-educated individuals that they were at risk for skin cancer. Cancer | Volume 119, Issue 9, pages 1675–1682, 1 May 2013

Patterns of onset and resolution of immune-related adverse events of special interest with ipilimumab: Detailed safety analysis from a phase 3 trial in patients with advanced melanoma Jeffrey S. Weber, Reinhard Dummer, Veerle de Pril, Celeste Lebbé, and F. Stephen Hodi, for the MDX010-20 Investigators

Ipilimumab 3 mg/kg was the first agent to demonstrate improved survival in previously treated patients with metastatic melanoma in a phase 3 trial. However, this treatment produced a characteristic spectrum of immunerelated adverse events (irAEs) of special interest, consistent with its immune-based mechanism of action. This study tracked the onset, development, and resolution of ipilimumab 3 mg/kg related irAEs in 643 patients with unresectable stage III or stage IV melanoma who had received previous treatment. AEs characterized as immune-related 20

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were required to be treatment-related and to be included in a preassembled list of AEs with known inflammatory etiology.

Most ipilimumab-associated irAEs, including grade 3/4 symptoms, developed within 12 weeks of initial dosing and were resolved within 12 weeks of onset. IrAEs were well characterized in their evolution and could be managed using published algorithms. Seven deaths were attributed to irAEs. The authors note the importance of strong staff/patient communication to enable early detection and successful treatment of these irAEs.


Molecular Diagnostics and Cytogenetics Cancer Cytopathology | Volume 120, Issue 1, pages 7–17, 25 February 2012

Cytologic and molecular diagnosis of thyroid cancers: Is it time for routine reflex testing? Lewis A. Hassell, Elizabeth M. Gillies, and S. Terence Dunn

The Bethesda system for standardized reporting of thyroid fine-needle aspiration (FNA) cytology has positively affected the clarity of communication of results and management of patients evaluated for thyroid nodules. Problematic areas still exist in the triage of some of these samples, particularly those in the categories of “follicular lesion with atypia of uncertain significance” and “follicular lesion.” The literature on molecular and genetic abnormalities in thyroid lesions is reviewed. Potentially useful markers for distinguishing currently problematic categories of FNA cytologic samples, especially nondiagnostic samples, atypia of uncertain significance, and follicular lesions, are discussed. The predictive value of the respective molecular analyses in these settings is examined. Evaluation of FNA samples with negative or suboptimal follicular cytology for Ras mutations

may be useful in detecting potentially significant follicular lesions (carcinomas) but is quite low in overall yield. Cytologic samples with atypia of uncertain significance, which may include the possibility of papillary carcinomas, may be fruitfully evaluated using a panel of molecular tests for BRAF, RET/PTC, PAX8/PPARG1, and Ras. Other markers also have potential utility in the workup of thyroid lesions. An era of combined modality testing in thyroid cytology is emerging in which classical cytologic findings can be coupled with molecular data to increase the predictive power of diagnostic interpretations; however, there remains a group of atypical cytologic samples negative for known molecular markers in which the risk of malignancy is too high to simply follow expectantly.

Cancer Cytopathology | Volume 120, Issue 1, pages 62–70, 25 February 2012

Identification of tissue of origin in body fluid specimens using a gene expression microarray assay Gregory A. Stancel, Donna Coffey, Karla Alvarez, Meredith Halks-Miller, Anita Lal, Dina Mody, Tracy Koen, Todd Fairley, and Federico A. Monzon

Body fluid specimens may be the only pathologic specimen available for clinical evaluation in metastatic cancer cases. The challenge of identifying the tissue of origin in metastatic cancer has led to molecular-based assays, such as the microarray-based Pathwork Tissue of Origin gene expression test. Using body fluid specimens in this test would help provide diagnoses to cancer patients without clearly identifiable primary sites. This study evaluated the Tissue of Origin Test for use with malignant effusion specimens. Twenty-seven metastasis-positive body fluid specimens from different body sites were obtained from patients with known diagnoses. Nine specimens from nonmalignant body fluids were included as controls. RNA was extracted from formalin-fixed, paraffin-embedded (FFPE) tissue, and gene expression analysis was performed with the Tissue of Origin Test. The results of this study demonstrate that FFPE cell blocks from cytologic body fluid specimens yield adequate diagnostic material for the Pathwork test and can be used in the workup of patients with unknown primary tumors.

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Molecular Diagnostics and Cytogenetics, con’t. Cancer Cytopathology | Volume 120, Issue 6, pages 390–400, 25 December 2012

Immunoglobulin heavy-chain fluorescence in situ hybridization-chromogenic in situ hybridization DNA probe split signal in the clonality assessment of lymphoproliferative processes on cytological samples Pio Zeppa, Laura Virginia Sosa Fernandez, Immacolata Cozzolino, Valentina Ronga, Rita Genesio, Maria Salatiello, Marco Picardi, Umberto Malapelle, Giancarlo Troncone, and Elena Vigliar

The human immunoglobulin heavy-chain (IGH) locus is frequently involved in different translocations of nonHodgkin lymphoma (NHL), and the detection of any breakage involving the IGH locus should identify a B-cell NHL. The split-signal IGH FISH-CISH DNA probe is a mixture of 2 fluorochrome-labeled DNAs, one red and one green, that bind the telomeric and centromeric segments on the IGH breakpoint. This study tested the capability of the probe to detect IGH translocations and diagnose B-cell lymphoproliferative processes on cytological samples.

Fifty cytological specimens from cases of lymphoproliferative processes were tested, and the results were compared with light-chain assessment by flow cytometry. IGH status was tested by polymerase chain reaction and clinicohistological data. The signal score detected 29 positive, 15 negative, and 6 inadequate cases. The split-signal IGH FISH-CISH DNA probe proved effective in detecting any translocation involving the IGH locus. It can be used on different samples from different B-cell lymphoproliferative processes but is not useful for classifying specific entities.

Cancer Cytopathology | Volume 121, Issue 2, pages 61–71, February 2013

Targeting tyrosine kinases in cancer: The converging roles of cytopathology and molecular pathology in the era of genomic medicine Catherine I. Dumur, Michael O. Idowu, and Celeste N. Powers

Because of knowledge gained in the field of cancer biology, clinicians are currently witnessing an explosion of molecular tests as companion diagnostics to targeted therapies against growth factor receptors and their signaling pathways. Such tests are being applied increasingly to cytology specimens as essential components of genomic medicine, because less invasive diagnostic procedures are becoming the norm.

The objective of this review was to present an overview of the current and future role of cytopathology in molecular diagnostics, including the adequacy of cytology specimens for such studies. The authors also discuss the critical methodologic aspects of the molecular assays used for the selection of tyrosine kinase treatment for oncology patients.

Non-Gynecologic Cytopathology Cancer Cytopathology | Volume 120, Issue 2, pages 134–141, 25 April 2012

The diagnostic value of cell block as an adjunct to liquid-based cytology of bronchial washing specimens in the diagnosis and subclassification of pulmonary neoplasms George R. Collins, Jaiyeola Thomas, Neelam Joshi, and Songlin Zhang

To the authors’ knowledge, the diagnostic value of cell block (CB) as an adjunct to ThinPrep liquid-based cytology (LBC) of bronchial washing specimens in the detection and subclassification of pulmonary neoplasms has not been well evaluated. This article examines the utility of CB in this setting. Seventy-four bronchial washing specimens and concurrently prepared CBs with a diagnosis of malignant or suspicious/ atypical obtained from bronchoscopy procedures performed during 2009 were reviewed along with 28 randomly selected negative cases. LBC and CBs were reviewed independently. 22

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Deeper levels and ancillary studies were performed on CBs for specific tumor classification if needed. LBC and CB diagnoses were correlated with final histology and/or bronchial brushings.

CB combined with LBC was found to improve the rate of detection of malignancy over LBC alone, especially in cases with suspicious or atypical LBC diagnoses. Increased diagnostic yield is observed when CB is used with or without ancillary studies, but the yield is higher with CB using ancillary studies.


Non-Gynecologic Cytopathology, con’t. Cancer Cytopathology | Volume 121, Issue 1, pages 9–14, January 2013

A review of reporting systems and terminology for urine cytology Christopher L. Owens, Christopher J. VandenBussche, Frances H. Burroughs, and Dorothy L. Rosenthal

Urine cytology continues to play an important role in the diagnosis and management of urothelial carcinoma, a common cancer of adults with significant morbidity and mortality. Because of its high sensitivity for highgrade urothelial tumors, including lesions that may be cystoscopically occult, urine cytology nicely compliments cystoscopic examination, a method that detects most lowgrade tumors. Over the decades, several reporting schemes

for urine cytology have been published in the literature, each of which has relative strengths and weaknesses. Unlike cervical cytology, there has not been widespread acceptance and use of any particular reporting scheme for urine cytology studies. Thus, terminology and criteria for urine cytology reporting are not uniform among pathologists, which can frustrate clinicians and hinders interlaboratory comparisons.

Cancer Cytopathology | Volume 121, Issue 5, pages 261–270, May 2013

Subclassification of lymphoproliferative disorders in serous effusions: A 10-year experience Leung Chu Tong, Hyang-Mi Ko, Mauro Ajaj Saieg, Scott Boerner, William R. Geddie, and Gilda da Cunha Santos

Rare studies have reported the application of multiple ancillary tests to the diagnosis of lymphoproliferative disorder in serous effusions. In this study, the authors evaluated the effectiveness of using an algorithm for the triage of serous effusions and the contribution of ancillary studies to achieve a specific diagnosis using the current WHO classification. Serous effusion samples that had a final diagnosis of lymphoproliferative disorder or suspicious for lymphoma were selected from cases that were diagnosed between

2001 and 2010. Data were collected on patient and sample characteristics as well as results from immunophenotype and molecular studies. Immunophenotyping was successful in almost all samples that had a specific subtype with 16 B-cell and 4 T-cell lymphomas being diagnosed.

Successful, specific subtyping of lymphoproliferative disorders was achieved in approximately 33% of cases that were tested for ancillary studies following an approach for the triage and aliquoting of serous effusion samples.

Outcomes and Treatment/Therapies Cancer | Volume 118, Issue 11, pages 2944–2951, 1 June 2012

Lack of benefit of central nervous system prophylaxis for diffuse large B-cell lymphoma in the rituximab era: Findings from a large national database Anita Kumar, Ann Vanderplas, Ann S. LaCasce, Maria A. Rodriguez, Allison L. Crosby, Eva Lepisto, Myron S. Czuczman, Auayporn Nademanee, Joyce Niland, Leo I. Gordon, Michael Millenson, Andrew D. Zelenetz, Jonathan W. Friedberg, and Gregory A. Abel

Little is known about the utility of central nervous system (CNS) prophylaxis for diffuse large B-cell lymphoma (DLBCL) in the rituximab era. This study aimed to characterize patterns of CNS prophylaxis for patients who received combined rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) chemotherapy using the National Comprehensive Cancer Network Non-Hodgkin Lymphoma Outcomes Database, a prospective cohort study that collects clinical and outcomes data for patients at seven participating centers.

Of 989 eligible patients, 117 received CNS prophylaxis, most intrathecally. Involvement of bone marrow, other highrisk site, >1 extranodal site, higher International Prognostic Index score, and higher stage were associated individually with the receipt of prophylaxis. At a median follow-up of 2.5 years, there were 20 CNS recurrences (2%) among all patients, and survival was not affected by prophylaxis. Given the overall low rate of CNS recurrence and lack of prophylaxis-associated survival benefit, the current data called into question the practice of CNS prophylaxis in the rituximab era. American Cancer Society Family of Journals

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Outcomes and Treatment/Therapies, con’t. CA: A Cancer Journal for Clinicians | Volume 62, Issue 5, pages 336–347, September/October 2012

Electronic patient-reported outcome systems in oncology clinical practice Antonia V. Bennett, Roxanne E. Jensen, and Ethan Basch

Answer questions and earn free Patient-reported outcome (PRO) questionnaires assess topics a patient can report about his or her own health. This includes symptoms (eg, nausea, fatigue, diarrhea, pain, or frequent urination), physical functioning (eg, difficulty climbing stairs or difficulty fastening buttons), and mental health (eg, anxiety, fear, or worry). Electronic PRO (ePRO) systems are used in oncology clinical care because of 1) their ability to enhance clinical care by flagging important symptoms and saving clinicians time; 2) the availability of standardized methods for creating and implementing PROs in clinics; and 3) the existence of user-friendly platforms for patient self-reporting like tablet computers and automated telephone surveys. Many ePRO systems can provide actionable links to clinical care such as summary reports in a patient’s electronic medical record and real-time e-mail alerts to providers when patients report acute needs. This review presents 5 examples of ePRO systems currently in use in oncology practice. These systems support multiple clinical activities, including assessment of symptoms and toxicities related to chemotherapy and radiation, postoperative surveillance, and symptom management during palliative care and hospice. Patient self-reporting is possible both at clinical visits and between visits over the Internet or by telephone. The implementation of an ePRO system requires significant resources and expertise, as well as user training. ePRO systems enable regular monitoring of patient symptoms, function, and needs, and can enhance the efficiency and quality of care as well as communication with patients.

CA: A Cancer Journal for Clinicians | Volume 63, Issue 1, pages 31–44, January/February 2013

Hypnosis for cancer care: Over 200 years young Guy H. Montgomery, Julie B. Schnur, and Kate Kravits

Answer questions and earn free Hypnosis has been used to provide psychological and physical comfort to individuals diagnosed with cancer for nearly 200 years. The goals of this review are: 1) to describe hypnosis and its components and to dispel misconceptions; 2) to provide an overview of hypnosis as a cancer prevention and control technique (covering its use in weight management, smoking cessation, as an adjunct to diagnostic and treatment

procedures, survivorship, and metastatic disease); and 3) to discuss future research directions. Overall, the literature supports the benefits of hypnosis for improving quality of life during the course of cancer and its treatment. However, a great deal more work needs to be done to explore the use of hypnosis in survivorship, to understand the mediators and moderators of hypnosis interventions, and to develop effective dissemination strategies.

CA: A Cancer Journal for Clinicians | Volume 63, Issue 4, pages 249–279, July/August 2013

Understanding, recognizing, and managing toxicities of targeted anticancer therapies Grace K. Dy and Alex A. Adjei

Answer questions and earn free Advances in genomics and molecular biology have identified aberrant proteins in cancer cells that are attractive targets for cancer therapy. Because these proteins are overexpressed or dysregulated in cancer cells compared with normal cells, it was assumed that their inhibitors will be narrowly targeted and relatively nontoxic. However, this hope has not been achieved. Current targeted agents exhibit the same frequency

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and severity of toxicities as traditional cytotoxic agents, with the main difference being the nature of the toxic effects. Thus, the classical chemotherapy toxicities of alopecia, myelosuppression, mucositis, nausea, and vomiting have been generally replaced by vascular, dermatologic, endocrine, coagulation, immunologic, ocular, and pulmonary toxicities. These toxicities need to be recognized, prevented, and optimally managed.


Outcomes and Treatment/Therapies, con’t. CA: A Cancer Journal for Clinicians | EarlyView

Impairment-driven cancer rehabilitation: An essential component of quality care and survivorship Julie K. Silver, Jennifer Baima, and R. Samuel Mayer

Adult cancer survivors suffer an extremely diverse and complex set of impairments, affecting virtually every organ system. Both physical and psychological impairments may contribute to a decreased health-related quality of life and should be identified throughout the care continuum. Recent evidence suggests that more cancer survivors have a reduced health-related quality of life as a result of physical impairments than due to psychological ones. Research has also demonstrated that the majority of cancer survivors will have significant impairments and that these often go undetected and/or untreated, and consequently may result in disability. Furthermore, physical disability is a leading cause of distress in this population. The scientific literature has shown that rehabilitation improves pain, function, and quality of life in cancer survivors. In fact, rehabilitation efforts

can ameliorate physical (including cognitive) impairments at every stage along the course of treatment. This includes prehabilitation before cancer treatment commences and multimodal interdisciplinary rehabilitation during and after acute cancer treatment. Rehabilitation appears to be costeffective and may reduce both direct and indirect health care costs, thereby reducing the enormous financial burden of cancer. Therefore, it is critical that survivors are screened for both psychological and physical impairments and then referred appropriately to trained rehabilitation health care professionals. This review suggests an impairment-driven cancer rehabilitation model that includes screening and treating impairments all along the care continuum in order to minimize disability and maximize quality of life.

Palliative Care CA: A Cancer Journal for Clinicians | EarlyView

Early integration of palliative care services with standard oncology care for patients with advanced cancer Joseph A. Greer, Vicki A. Jackson, Diane E. Meier, and Jennifer S. Temel

Answer questions and earn free Scientific advances in novel cancer therapeutics have led to remarkable changes in oncology practice and longer lives for patients diagnosed with incurable malignancies. However, the myriad options for treatment have established a culture of cancer care that has not been matched with a similar availability of efficacious supportive care interventions aimed at relieving debilitating symptoms due to progressive disease and treatment side effects. Accumulating data show that the introduction of palliative care services at the time of diagnosis of advanced cancer leads to meaningful improvement in the experiences of patients and family caregivers by emphasizing symptom management, quality of life, and treatment planning. In this review article, the rationale and evidence base for this model of early palliative care services integrated into standard oncology care are presented. In addition, the implications and limitations of the existing data to 1) elucidate the mechanisms by which early palliative care benefits patients and families; 2) guide the dissemination and application of this model in outpatient settings; and 3) inform health care policy regarding the delivery of high-quality, cost-effective, and comprehensive cancer care are discussed. American Cancer Society Family of Journals

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Pancreas CA: A Cancer Journal for Clinicians | EarlyView

Recent progress in pancreatic cancer Christopher L. Wolfgang, Joseph M. Herman, Daniel A. Laheru, Alison P. Klein, Michael A. Erdek, Elliot K. Fishman, and Ralph H. Hruban

Answer questions and earn free Pancreatic cancer is currently one of the deadliest of the solid malignancies. However, surgery to resect neoplasms of the pancreas is safer and less invasive than ever, novel drug combinations have been shown to improve survival, advances in radiation therapy have resulted in less toxicity, and enormous strides have been made in the understanding

of the fundamental genetics of pancreatic cancer. These advances provide hope but they also increase the complexity of caring for patients. It is clear that multidisciplinary care that provides comprehensive and coordinated evaluation and treatment is the most effective way to manage patients with pancreatic cancer.

Prostate CA: A Cancer Journal for Clinicians | Volume 62, Issue 5, pages 299–308, September/October 2012

Clinical development of novel therapeutics for castration-resistant prostate cancer Matthew D. Galsky, Alexander C. Small, Che-kai Tsao, and William K. Oh

There have been more drugs approved by the US Food and Drug Administration for the treatment of castrationresistant prostate cancer in the past 3 years than in the prior 3 decades, with additional drugs on the verge of approval based on the results of recently reported randomized trials. While an improvement in the understanding of the pathogenesis of castration-resistant prostate cancer has undeniably accelerated the transition of novel approaches from “bench to bedside,” the recent successes in the treatment of prostate

cancer are also a result of the efforts of clinical investigators to redefine the framework in which drugs for castrationresistant disease are evaluated. This review will explore the shifting paradigm in drug development for castrationresistant prostate cancer over the past several decades, and highlight how new definitions, trial designs, and endpoints have facilitated the emergence of new therapies for this challenging disease.

CA: A Cancer Journal for Clinicians | Volume 63, Issue 2, pages 85–86, March/April 2013

Low rate of bone density testing in men receiving androgen deprivation therapy Mary Kay Barton

Although it is well documented that androgen deprivation therapy (ADT) causes a loss of bone density and increases the risk of fractures, this review shows that most men receiving ADT for prostate cancer do not undergo bone mineral density (BMD) testing. The study, using National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) data, was performed between 2001 and 2007. It identified 28,960 men with locoregional prostate cancer who were known to have received ADT continuously for at least 1 year. Only 10.2% underwent BMD testing during the period from 6 months before treatment started, up to 1 year afterward. Factors associated with lower rates of testing included advanced age, race, lower education level, lack of comorbid diseases, and being unmarried. In 2008, the National Comprehensive Cancer Network and the American College of Physicians published guidelines recommending BMD testing for men undergoing ADT. The authors suggest further research to assess the impact of these recommendations. 26

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Psychosocial Oncology Cancer | Volume 119, Issue 11, pages 2067-2073, 1 June 2013

Patient–physician communication about code status preferences: A randomized controlled trial Wadih Rhondali, Pedro Perez-Cruz, David Hui, Gary B. Chisholm, Shalini Dalal, Walter Baile, Eva Chittenden, and Eduardo Bruera

Code status discussions are important in cancer care, but what is the impact on patients’ DNR preferences of a physician ending a code status discussion with a question versus a recommendation?

In this study, patients in a supportive care clinic watched 2 videos showing a physician-patient discussion regarding code status. The videos were identical except for their endings: one ended with the physician asking for the patient’s code status preference and the other with the physician recommending DNR.

Of 78 patients who completed the study, 30 had already chosen DNR for themselves, and 48 had not. All 30 of the first group and 30 of 48 patients in the second group chose DNR for the video patient. Age and white ethnicity predicted DNR choice for the video patient. Ending DNR discussions with a question or a recommendation did not impact DNR choice or perception of physician compassion. Median physician compassion score was very high for both videos.

Radiology CA: A Cancer Journal for Clinicians | Volume 62, Issue 6, pages 364–393, November/December 2012

Advances in oncologic imaging: Update on 5 common cancers Oguz Akin, Sandra B. Brennan, D. David Dershaw, Michelle S. Ginsberg, Marc J. Gollub, Heiko Schöder, David M. Panicek, and Hedvig Hricak

Imaging has become a pivotal component throughout a patient’s encounter with cancer, from initial disease detection and characterization through treatment response assessment and posttreatment follow-up. Recent progress in imaging technology has presented new opportunities for improving clinical care. This article provides updates on the latest approaches to imaging of 5 common cancers: breast, lung, prostate, and colorectal cancers, and lymphoma.

Screening/Early Detection CA: A Cancer Journal for Clinicians | Volume 63, Issue 2, pages 87–105, March/April 2013

Cancer screening in the United States, 2013: A review of current American Cancer Society guidelines, current issues in cancer screening, and new guidance on cervical cancer screening and lung cancer screening Robert A. Smith, Durado Brooks, Vilma Cokkinides, Debbie Saslow, and Otis W. Brawley

Answer questions and earn free Each year the American Cancer Society (ACS) publishes a summary of its recommendations for early cancer detection, a report on data and trends in cancer screening rates, and select issues related to cancer screening. In this issue of the journal, current ACS cancer screening guidelines are summarized, as are updated guidelines on cervical cancer

screening and lung cancer screening with low-dose helical computed tomography. The latest data on the use of cancer screening from the National Health Interview Survey also are described, as are several issues related to screening coverage under the Patient Protection and Affordable Care Act of 2010.

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Surgical Oncology CA: A Cancer Journal for Clinicians | Volume 63, Issue 1, pages 45–56, January/February 2013

The current status of robotic oncologic surgery Hua-yin Yu, David F. Friedlander, Sunil Patel, and Jim C. Hu

Answer questions and earn free The use of robotic assistance facilitates minimally invasive surgery and has been widely adopted across multiple specialties. This article reviews the published literature on use of this technology for treatment of oncologic conditions. PubMed searches were performed for articles published between 2000 and 2012 using the keywords “robotic” or “robotic surgery” in conjunction with

“oncology” or “cancer.” Although the most common use for robotics was to treat urologic oncologic conditions, it has also been widely adopted for gynecologic, general, thoracic, and head and neck surgeries. For several procedures, there is evidence that robotics offers short-term benefits such as shorter lengths of stay and lower intraoperative blood loss, with safety profiles and oncologic outcomes comparable to open or conventional laparoscopic approaches. However, long-term oncologic outcomes are generally lacking, and robotic surgeries are more costly than open or laparoscopic surgeries. Robotic technology is widely used in oncologic surgery with demonstrated short-term advantages. However, whether the benefits of robotics justify the higher costs warrant large comparative effectiveness studies with long-term outcomes.

Symptom Control and Palliative Care Cancer | Volume 119, Issue 5, pages 1098–1105, 1 March 2013

Attrition rates, reasons, and predictive factors in supportive care and palliative oncology clinical trials David Hui, Isabella Glitza, Gary Chisholm, Sriram Yennu, and Eduardo Bruera

Attrition is common among supportive care/palliative oncology clinical trials. To date, however, few studies have documented the reasons and predictors for dropout. In this article, the authors document their process of determining the rate, reasons, and factors associated with attrition both before reaching the primary endpoint and at the end of the study.

The findings revealed in this article have important implications for future clinical trial design, including eligibility criteria and sample size design calculation. Researchers performed a review of all prospective interventional

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supportive care/palliative oncology trials conducted in the Department of Palliative Care and Rehabilitation Medicine at The University of Texas MD Anderson Cancer Center in Houston between 1999 and 2011. A total of 1214 patients were included in 18 clinical trials. The median age was 60 years. The attrition rate was high, and was associated with various patient characteristics and a high baseline symptom burden. Common reasons for primary endpoint dropout were symptom burden, patient preference, hospitalization, and death.


Meet the Editors Celeste N. Powers, MD, PhD Well known throughout the international cytopathology community, Celeste N. Powers is Editor-in-Chief of Cancer Cytopathology, dedicated to advancing cytopathology research for early cancer diagnosis and prevention. Dr. Powers is also the Chair of the Division of Anatomic Pathology at Virginia Commonwealth University Medical Center. Among her many national duties, she has served as President of the American Society of Cytopathology and is currently President Elect of the United States and Canadian Academy of Pathology. In recognition of her dedication to the field of cytopathology, Dr. Powers was presented with the Papanicolaou Award in 2008, the highest award given by the American Society of Cytopathology. Submit to the journal at mc.manuscriptcentral.com/cancercyto

Fadlo R. Khuri, MD Internationally respected for his groundbreaking research into lung, head, and neck cancers, Dr. Fadlo R. Khuri is Deputy Director of the Winship Cancer Institute and Chairman of the Department of Hematology and Medical Oncology at Emory University. A Georgia Cancer Coalition Distinguished Scholar, Dr. Khuri is also Editor-in-Chief of Cancer. His research focuses on the development of molecular, prognostic, therapeutic, and chemopreventive approaches to improve the standard of care for patients with tobacco-related cancers. His research has been supported by peer-reviewed grants from the National Cancer Institute, Department of Defense, and American Cancer Society. Dr. Khuri is the recipient of numerous awards, including the 2006 Naji Sahyoun Memorial Award from the Middle East Medical Assembly, the 2010 Waun Ki Hong Award from the University of Texas MD Anderson Cancer Center, and the 2013 Richard and Hinda Rosenthal Memorial Award from the American Association for Cancer Research. He was inducted into the American Society for Clinical Investigation and is listed among America’s Top Doctors and the Marquis Who’s Who in the World. In addition, Dr. Khuri holds the Roberto C. Goizueta Distinguished Chair for Cancer Research and is Professor of Otolaryngology, Medicine, and Pharmacology. Submit to the journal at mc.manuscriptcentral.com/cancer

Otis Webb Brawley, MD Recognized by Castle Connelly Medical, Ltd. as one of America’s Top Doctors for Cancer, Otis Webb Brawley is the Chief Medical Officer and Executive Vice President of the American Cancer Society. He is also Editor-in-Chief of CA: A Cancer Journal for Clinicians. He is responsible for promoting cancer prevention, early detection, and quality treatment through cancer research and education, championing a variety of efforts, including initiatives to decrease smoking, improve diet, and enhance the ACS’s advocacy programs. Moreover, he is a leader in the Society’s efforts to eliminate disparities in access to quality cancer care. Dr. Brawley also serves as Professor of Hematology, Oncology, Medicine, and Epidemiology at Emory University.

Ted Gansler, MD, MBA, MPH As Director of Medical Content at the American Cancer Society, Ted Gansler heads the ACS Continuing Professional Education program, and provides medical and scientific review of cancer information for patients and the general public. He is also Editor of CA: A Cancer Journal for Clinicians. Prior to joining the ACS, Dr. Gansler directed the Cytopathology Laboratory and Cytopathology Fellowship Program at Emory University, where he is currently an Adjunct Associate Professor of Pathology.

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The American Cancer Society The American Cancer Society (ACS) is the nationwide, community-based, voluntary health organization dedicated to eliminating cancer as a major health problem by preventing cancer, saving lives, and diminishing suffering from cancer, through research, education, advocacy, and service. For further information on the American Cancer Society, please visit cancer.org.

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Now the leading American Cancer Society journals, Cancer, Cancer Cytopathology, and CA: A Cancer Journal for Clinicians, bring you content wherever you are, whenever you want it. Download the ACS Journals App for your mobile device and access instant, real-time updates from the ACS journals, including article abstracts, ACS guidelines, upcoming events, and free content like the three news sections.

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