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  • Recent progress in Lynch syndrome and other familial colorectal cancer syndromes
    CA: Cancer J. Clin. (IF 187.04) Pub Date : 2018-02-27
    Patrick M. Boland; Matthew B. Yurgelun; C. Richard Boland

    The current understanding of familial colorectal cancer was limited to descriptions of affected pedigrees until the early 1990s. A series of landscape‐altering discoveries revealed that there were distinct forms of familial cancer, and most were related to genes previously not known to be involved in human disease. This review largely focuses on advances in our understanding of Lynch syndrome because of the unique relationship of this disease to defective DNA mismatch repair and the clinical implications this has for diagnostics, prevention, and therapy. Recent advances have occurred in our understanding of the epidemiology of this disease, and the advent of broad genetic panels has altered the approach to germline and somatic diagnoses for all of the familial colorectal cancer syndromes. Important advances have been made toward a more complete mechanistic understanding of the pathogenesis of neoplasia in the setting of Lynch syndrome, and these advances have important implications for prevention. Finally, paradigm‐shifting approaches to treatment of Lynch‐syndrome and related tumors have occurred through the development of immune checkpoint therapies for hypermutated cancers. CA Cancer J Clin 2018. © 2018 American Cancer Society.

  • The financial burden and distress of patients with cancer: Understanding and stepping‐up action on the financial toxicity of cancer treatment
    CA: Cancer J. Clin. (IF 187.04) Pub Date : 2018-01-16
    Pricivel M. Carrera; Hagop M. Kantarjian; Victoria S. Blinder

    “Financial toxicity” has now become a familiar term used in the discussion of cancer drugs, and it is gaining traction in the literature given the high price of newer classes of therapies. However, as a phenomenon in the contemporary treatment and care of people with cancer, financial toxicity is not fully understood, with the discussion on mitigation mainly geared toward interventions at the health system level. Although important, health policy prescriptions take time before their intended results manifest, if they are implemented at all. They require corresponding strategies at the individual patient level. In this review, the authors discuss the nature of financial toxicity, defined as the objective financial burden and subjective financial distress of patients with cancer, as a result of treatments using innovative drugs and concomitant health services. They discuss coping with financial toxicity by patients and how maladaptive coping leads to poor health and nonhealth outcomes. They cover management strategies for oncologists, including having the difficult and urgent conversation about the cost and value of cancer treatment, availability of and access to resources, and assessment of financial toxicity as part of supportive care in the provision of comprehensive cancer care. CA Cancer J Clin 2018;68:153‐165. © 2018 American Cancer Society.

  • Factors influencing risk‐based care of the childhood cancer survivor in the 21st century
    CA: Cancer J. Clin. (IF 187.04) Pub Date : 2018-01-29
    Stephanie B. Dixon; Kari L. Bjornard; Nicole M. Alberts; Gregory T. Armstrong; Tara M. Brinkman; Wassim Chemaitilly; Matthew J. Ehrhardt; Israel Fernandez‐Pineda; Lisa M. Force; Todd M. Gibson; Daniel M. Green; Carrie R. Howell; Sue C. Kaste; Anne C. Kirchhoff; James L. Klosky; Kevin R. Krull; John T. Lucas; Daniel A. Mulrooney; Kirsten K. Ness; Carmen L. Wilson; Yutaka Yasui; Leslie L. Robison; Melissa M. Hudson
  • Hodgkin lymphoma: A review and update on recent progress
    CA: Cancer J. Clin. (IF 187.04) Pub Date : 2017-12-01
    Satish Shanbhag; Richard F. Ambinder

    Hodgkin lymphoma (HL) is a unique hematopoietic neoplasm characterized by cancerous Reed‐Sternberg cells in an inflammatory background. Patients are commonly diagnosed with HL in their 20s and 30s, and they present with supradiaphragmatic lymphadenopathy, often with systemic B symptoms. Even in advanced‐stage disease, HL is highly curable with combination chemotherapy, radiation, or combined‐modality treatment. Although the same doxorubicin, bleomycin, vinblastine, and dacarbazine chemotherapeutic regimen has been the mainstay of therapy over the last 30 years, risk‐adapted approaches have helped de‐escalate therapy in low‐risk patients while intensifying treatment for higher risk patients. Even patients who are not cured with initial therapy can often be salvaged with alternate chemotherapy combinations, the novel antibody‐drug conjugate brentuximab, or high‐dose autologous or allogeneic hematopoietic stem cell transplantation. The programmed death‐1 inhibitors nivolumab and pembrolizumab have both demonstrated high response rates and durable remissions in patients with relapsed/refractory HL. Alternate donor sources and reduced‐intensity conditioning have made allogeneic hematopoietic stem cell transplantation a viable option for more patients. Future research will look to integrate novel strategies into earlier lines of therapy to improve the HL cure rate and minimize long‐term treatment toxicities. CA Cancer J Clin 2018;68:116‐132. © 2017 American Cancer Society.

  • Who's still smoking? Disparities in adult cigarette smoking prevalence in the United States
    CA: Cancer J. Clin. (IF 187.04) Pub Date : 2018-01-31
    Jeffrey Drope; Alex C. Liber; Zachary Cahn; Michal Stoklosa; Rosemary Kennedy; Clifford E. Douglas; Rosemarie Henson; Jacqui Drope

    The continuing high prevalence of cigarette smoking among specific subpopulations, many of them vulnerable, is one of the most pressing challenges facing the tobacco control community. These populations include individuals in lower education and/or socioeconomic groups; from certain racial/ethnic groups; in the lesbian, gay, bisexual, and transgender community; with mental illness; and in the military, particularly among those in the lowest pay grades. Although traditional tobacco control measures are having positive health effects for most groups, the effects are not sufficient for others. More attention to and support for promising novel interventions, in addition to new attempts at reaching these populations through conventional interventions that have proven to be effective, are crucial going forward to find new ways to address these disparities. CA Cancer J Clin 2018;68:106‐115. © 2018 American Cancer Society.

  • The incidental thyroid nodule
    CA: Cancer J. Clin. (IF 187.04) Pub Date : 2018-01-25
    Sarah B. Fisher; Nancy D. Perrier

    Incidental thyroid nodules that are found on an imaging study performed for reasons other than thyroid pathology represent a common scenario encountered by health care providers. The initial workup for these nodules comprises a thorough history and physical examination, thyroid function tests, a dedicated thyroid ultrasound, and fine‐needle aspiration of any suspicious lesions. Management ranges from observation and reassurance to surgical resection and depends on the cytologic diagnosis. In cases of cytologically indeterminate or discordant nodules, surgical excision (lobectomy) offers a definitive diagnosis, although molecular testing or a reasonable period of observation may be useful as less invasive adjuncts. CA Cancer J Clin 2018;68:97‐105. © 2018 American Cancer Society.

  • Patient selection in major upper abdominal surgery for cancer in octogenarians
    CA: Cancer J. Clin. (IF 187.04) Pub Date : 2018-01-10
    Lara C. Pullen

    The overall rates of major upper abdominal cancer resections in octogenarians have increased over time. The number of major liver and pancreatic resections for cancer in this demographic has more than doubled from 2001 to 2011. This trend may be the result of an emboldened surgical approach within the context of increasingly favorable inpatient mortality rates from elective surgeries of the pancreas and liver.

  • Decision making in breast cancer risk reduction
    CA: Cancer J. Clin. (IF 187.04) Pub Date : 2018-01-10
    Lara C. Pullen

    The DMP‐1 study examined women in the United States who were counseled regarding the use of SERMs as part of their regular care. Patient perceptions regarding drug‐based therapy played an important role in the choice of therapy. The findings suggest that HCPs should not only present medical information, but also communicate with patients regarding their beliefs and experiences.

  • Cancer statistics, 2018
    CA: Cancer J. Clin. (IF 187.04) Pub Date : 2018-01-04
    Rebecca L. Siegel, Kimberly D. Miller, Ahmedin Jemal

    Abstract Each year, the American Cancer Society estimates the numbers of new cancer cases and deaths that will occur in the United States and compiles the most recent data on cancer incidence, mortality, and survival. Incidence data, available through 2014, were collected by the Surveillance, Epidemiology, and End Results Program; the National Program of Cancer Registries; and the North American Association of Central Cancer Registries. Mortality data, available through 2015, were collected by the National Center for Health Statistics. In 2018, 1,735,350 new cancer cases and 609,640 cancer deaths are projected to occur in the United States. Over the past decade of data, the cancer incidence rate (2005-2014) was stable in women and declined by approximately 2% annually in men, while the cancer death rate (2006-2015) declined by about 1.5% annually in both men and women. The combined cancer death rate dropped continuously from 1991 to 2015 by a total of 26%, translating to approximately 2,378,600 fewer cancer deaths than would have been expected if death rates had remained at their peak. Of the 10 leading causes of death, only cancer declined from 2014 to 2015. In 2015, the cancer death rate was 14% higher in non-Hispanic blacks (NHBs) than non-Hispanic whites (NHWs) overall (death rate ratio [DRR], 1.14; 95% confidence interval [95% CI], 1.13-1.15), but the racial disparity was much larger for individuals aged <65 years (DRR, 1.31; 95% CI, 1.29-1.32) compared with those aged ≥65 years (DRR, 1.07; 95% CI, 1.06-1.09) and varied substantially by state. For example, the cancer death rate was lower in NHBs than NHWs in Massachusetts for all ages and in New York for individuals aged ≥65 years, whereas for those aged <65 years, it was 3 times higher in NHBs in the District of Columbia (DRR, 2.89; 95% CI, 2.16-3.91) and about 50% higher in Wisconsin (DRR, 1.78; 95% CI, 1.56-2.02), Kansas (DRR, 1.51; 95% CI, 1.25-1.81), Louisiana (DRR, 1.49; 95% CI, 1.38-1.60), Illinois (DRR, 1.48; 95% CI, 1.39-1.57), and California (DRR, 1.45; 95% CI, 1.38-1.54). Larger racial inequalities in young and middle-aged adults probably partly reflect less access to high-quality health care. CA Cancer J Clin 2018. © 2018 American Cancer Society.

  • Older adults may not consider life expectancy an important factor in cancer screening
    CA: Cancer J. Clin. (IF 187.04) Pub Date : 2017-11-20
    Clement Chung

    Key Points Although many elderly individuals considered their age and health status to be relevant in making decisions regarding cancer screening, they often did not understand the role of life expectancy. It is important for providers to incorporate patient preference into communication strategies regarding cancer screening. In the context of good physician-patient relationships, discussions regarding discontinuing cancer screening generally do not negatively affect older adults' views of their physicians.

  • Risk of ovarian function recovery should be considered when switching from treatment with adjuvant tamoxifen to aromatase inhibitor therapy in women with chemotherapy-induced amenorrhea
    CA: Cancer J. Clin. (IF 187.04) Pub Date : 2017-11-20
    Clement Chung

    Key Points In this study, the risk of a return to menses and/or premenopausal estradiol/follicle-stimulating hormone levels by 30 months after a switch from adjuvant tamoxifen to aromatase inhibitor therapy in women with postmenopausal estradiol levels at the time of the switch was 15.2% (38 of 250 patients) for women who had chemotherapy-induced amenorrhea and were aged younger than 50 years at the time of breast cancer diagnosis. The risk was 1.2% (1 in 79 women) for women who were aged 50 to 54 years but still were premenopausal at the time of breast cancer diagnosis.

  • Higher cigarette pricing encourages older smokers to quit
    CA: Cancer J. Clin. (IF 187.04) Pub Date : 2017-10-10
    Lara C. Pullen

    Key Points Cigarette price increases are associated with a reduction in smoking rates in smokers aged 65 years and older. Although cigarette price increases have been shown to discourage smoking in younger individuals, to the authors' knowledge this is the first study that demonstrates the effect in older smokers. Cigarette price increases now join the enforcement of smoke-free laws as an important public health tool to limit smoking.

  • Falls and disability among female cancer survivors
    CA: Cancer J. Clin. (IF 187.04) Pub Date : 2017-10-10
    Lara C. Pullen

    Key Points Approximately one-half of women have symptoms of CIPN 6 years after treatment. Women with persistent CIPN symptoms were found to have poorer physical functioning, more disability, and nearly twice the rate of falls as asymptomatic women. Women with neuropathy, pain, and weakness frequently lose their ability to perform even basic exercises correctly.

  • Weight management and physical activity throughout the cancer care continuum
    CA: Cancer J. Clin. (IF 187.04) Pub Date : 2017-11-22
    Wendy Demark-Wahnefried, Kathryn H. Schmitz, Catherine M. Alfano, Jennifer R. Bail, Pamela J. Goodwin, Cynthia A. Thomson, Don W. Bradley, Kerry S. Courneya, Christie A. Befort, Crystal S. Denlinger, Jennifer A. Ligibel, William H. Dietz, Melinda R. Stolley, Melinda L. Irwin, Marcas M. Bamman, Caroline M. Apovian, Bernardine M. Pinto, Kathleen Y. Wolin, Rachel M. Ballard, Andrew J. Dannenberg, Elizabeth G. Eakin, Matt M. Longjohn, Susan D. Raffa, Lucile L. Adams-Campbell, Joanne S. Buzaglo, Sharyl J. Nass, Greta M. Massetti, Erin P. Balogh, Elizabeth S. Kraft, Anand K. Parekh, Darshak M. Sanghavi, G. Stephen Morris, Karen Basen-Engquist

    Mounting evidence suggests that weight management and physical activity (PA) improve overall health and well being, and reduce the risk of morbidity and mortality among cancer survivors. Although many opportunities exist to include weight management and PA in routine cancer care, several barriers remain. This review summarizes key topics addressed in a recent National Academies of Science, Engineering, and Medicine workshop entitled, “Incorporating Weight Management and Physical Activity Throughout the Cancer Care Continuum.” Discussions related to body weight and PA among cancer survivors included: 1) current knowledge and gaps related to health outcomes; 2) effective intervention approaches; 3) addressing the needs of diverse populations of cancer survivors; 4) opportunities and challenges of workforce, care coordination, and technologies for program implementation; 5) models of care; and 6) program coverage. While more discoveries are still needed for the provision of optimal weight-management and PA programs for cancer survivors, obesity and inactivity currently jeopardize their overall health and quality of life. Actionable future directions are presented for research; practice and policy changes required to assure the availability of effective, affordable, and feasible weight management; and PA services for all cancer survivors as a part of their routine cancer care. CA Cancer J Clin 2017. © 2017 American Cancer Society.

  • Proportion and number of cancer cases and deaths attributable to potentially modifiable risk factors in the United States
    CA: Cancer J. Clin. (IF 187.04) Pub Date : 2017-11-21
    Farhad Islami, Ann Goding Sauer, Kimberly D. Miller, Rebecca L. Siegel, Stacey A. Fedewa, Eric J. Jacobs, Marjorie L. McCullough, Alpa V. Patel, Jiemin Ma, Isabelle Soerjomataram, W. Dana Flanders, Otis W. Brawley, Susan M. Gapstur, Ahmedin Jemal

    Contemporary information on the fraction of cancers that potentially could be prevented is useful for priority setting in cancer prevention and control. Herein, the authors estimate the proportion and number of invasive cancer cases and deaths, overall (excluding nonmelanoma skin cancers) and for 26 cancer types, in adults aged 30 years and older in the United States in 2014, that were attributable to major, potentially modifiable exposures (cigarette smoking; secondhand smoke; excess body weight; alcohol intake; consumption of red and processed meat; low consumption of fruits/vegetables, dietary fiber, and dietary calcium; physical inactivity; ultraviolet radiation; and 6 cancer-associated infections). The numbers of cancer cases were obtained from the Centers for Disease Control and Prevention (CDC) and the National Cancer Institute; the numbers of deaths were obtained from the CDC; risk factor prevalence estimates were obtained from nationally representative surveys; and associated relative risks of cancer were obtained from published, large-scale pooled analyses or meta-analyses. In the United States in 2014, an estimated 42.0% of all incident cancers (659,640 of 1570,975 cancers, excluding nonmelanoma skin cancers) and 45.1% of cancer deaths (265,150 of 587,521 deaths) were attributable to evaluated risk factors. Cigarette smoking accounted for the highest proportion of cancer cases (19.0%; 298,970 cases) and deaths (28.8%; 169,180 deaths), followed by excess body weight (7.8% and 6.5%, respectively) and alcohol intake (5.6% and 4.0%, respectively). Lung cancer had the highest number of cancers (184,970 cases) and deaths (132,960 deaths) attributable to evaluated risk factors, followed by colorectal cancer (76,910 cases and 28,290 deaths). These results, however, may underestimate the overall proportion of cancers attributable to modifiable factors, because the impact of all established risk factors could not be quantified, and many likely modifiable risk factors are not yet firmly established as causal. Nevertheless, these findings underscore the vast potential for reducing cancer morbidity and mortality through broad and equitable implementation of known preventive measures. CA Cancer J Clin 2017. © 2017 American Cancer Society.

  • Differentiated and anaplastic thyroid carcinoma: Major changes in the American Joint Committee on Cancer eighth edition cancer staging manual
    CA: Cancer J. Clin. (IF 187.04) Pub Date : 2017-11-01
    Nancy D. Perrier, James D. Brierley, R. Michael Tuttle

    Answer questions and earn CME/CNE This is a review of the major changes in the American Joint Committee on Cancer staging manual, eighth edition, for differentiated and anaplastic thyroid carcinoma. All patients younger than 55 years have stage I disease unless they have distant metastases, in which case, their disease is stage II. In patients aged 55 years or older, the presence of distant metastases confers stage IVB, while cases without distant metastases are further categorized based on the presence/absence of gross extrathyroidal extension, tumor size, and lymph node status. Patients aged 55 years or older whose tumor measures 4 cm or smaller (T1-T2) and is confined to the thyroid (N0, NX) have stage I disease, and those whose tumor measures greater than 4 cm and is confined to the thyroid (T3a) have stage II disease regardless of lymph node status. Patients aged 55 years or older whose tumor is confined to the thyroid and measures 4 cm or smaller (T1-T2) with any lymph node metastases present (N1a or N1b) have stage II disease. In patients who demonstrate gross extrathyroidal extension, the disease is considered stage II if only the strap muscles are grossly invaded (T3b); stage III if there is gross invasion of the subcutaneous tissue, larynx, trachea, esophagus, or recurrent laryngeal nerve (T4a); or stage IVA if there is gross invasion of the prevertebral fascia or tumor encasing the carotid artery or internal jugular vein (T4b). The same T definitions will be used for both differentiated and anaplastic thyroid cancer, but the basic premise of the anatomic stage groups will remain the same. CA Cancer J Clin 2017. © 2017 American Cancer Society.

  • Breast cancer statistics, 2017, racial disparity in mortality by state
    CA: Cancer J. Clin. (IF 187.04) Pub Date : 2017-10-03
    Carol E. DeSantis, Jiemin Ma, Ann Goding Sauer, Lisa A. Newman, Ahmedin Jemal

    In this article, the American Cancer Society provides an overview of female breast cancer statistics in the United States, including data on incidence, mortality, survival, and screening. Approximately 252,710 new cases of invasive breast cancer and 40,610 breast cancer deaths are expected to occur among US women in 2017. From 2005 to 2014, overall breast cancer incidence rates increased among Asian/Pacific Islander (1.7% per year), non-Hispanic black (NHB) (0.4% per year), and Hispanic (0.3% per year) women but were stable in non-Hispanic white (NHW) and American Indian/Alaska Native (AI/AN) women. The increasing trends were driven by increases in hormone receptor-positive breast cancer, which increased among all racial/ethnic groups, whereas rates of hormone receptor-negative breast cancers decreased. From 1989 to 2015, breast cancer death rates decreased by 39%, which translates to 322,600 averted breast cancer deaths in the United States. During 2006 to 2015, death rates decreased in all racial/ethnic groups, including AI/ANs. However, NHB women continued to have higher breast cancer death rates than NHW women, with rates 39% higher (mortality rate ratio [MRR], 1.39; 95% confidence interval [CI], 1.35-1.43) in NHB women in 2015, although the disparity has ceased to widen since 2011. By state, excess death rates in black women ranged from 20% in Nevada (MRR, 1.20; 95% CI, 1.01-1.42) to 66% in Louisiana (MRR, 1.66; 95% CI, 1.54, 1.79). Notably, breast cancer death rates were not significantly different in NHB and NHW women in 7 states, perhaps reflecting an elimination of disparities and/or a lack of statistical power. Improving access to care for all populations could eliminate the racial disparity in breast cancer mortality and accelerate the reduction in deaths from this malignancy nationwide. CA Cancer J Clin 2017;67:439-448. © 2017 American Cancer Society.

  • Key issues surrounding the health impacts of electronic nicotine delivery systems (ENDS) and other sources of nicotine
    CA: Cancer J. Clin. (IF 187.04) Pub Date : 2017-09-29
    Jeffrey Drope, Zachary Cahn, Rosemary Kennedy, Alex C. Liber, Michal Stoklosa, Rosemarie Henson, Clifford E. Douglas, Jacqui Drope

    Answer questions and earn CME/CNE Over the last decade, the use of electronic nicotine delivery systems (ENDS), including the electronic cigarette or e-cigarette, has grown rapidly. More youth now use ENDS than any tobacco product. This extensive research review shows that there are scientifically sound, sometimes competing arguments about ENDS that are not immediately and/or completely resolvable. However, the preponderance of the scientific evidence to date suggests that current-generation ENDS products are demonstrably less harmful than combustible tobacco products such as conventional cigarettes in several key ways, including by generating far lower levels of carcinogens and other toxic compounds than combustible products or those that contain tobacco. To place ENDS in context, the authors begin by reviewing the trends in use of major nicotine-containing products. Because nicotine is the common core—and highly addictive—constituent across all tobacco products, its toxicology is examined. With its long history as the only nicotine product widely accepted as being relatively safe, nicotine-replacement therapy (NRT) is also examined. A section is also included that examines snus, the most debated potential harm-reduction product before ENDS. Between discussions of NRT and snus, ENDS are extensively examined: what they are, knowledge about their level of “harm,” their relationship to smoking cessation, the so-called gateway effect, and dual use/poly-use. CA Cancer J Clin 2017;67:449-471. © 2017 American Cancer Society.

  • Melanoma staging: Evidence-based changes in the American Joint Committee on Cancer eighth edition cancer staging manual
    CA: Cancer J. Clin. (IF 187.04) Pub Date : 2017-10-13
    Jeffrey E. Gershenwald, Richard A. Scolyer, Kenneth R. Hess, Vernon K. Sondak, Georgina V. Long, Merrick I. Ross, Alexander J. Lazar, Mark B. Faries, John M. Kirkwood, Grant A. McArthur, Lauren E. Haydu, Alexander M. M. Eggermont, Keith T. Flaherty, Charles M. Balch, John F. Thompson,

    Answer questions and earn CME/CNE To update the melanoma staging system of the American Joint Committee on Cancer (AJCC) a large database was assembled comprising >46,000 patients from 10 centers worldwide with stages I, II, and III melanoma diagnosed since 1998. Based on analyses of this new database, the existing seventh edition AJCC stage IV database, and contemporary clinical trial data, the AJCC Melanoma Expert Panel introduced several important changes to the Tumor, Nodes, Metastasis (TNM) classification and stage grouping criteria. Key changes in the eighth edition AJCC Cancer Staging Manual include: 1) tumor thickness measurements to be recorded to the nearest 0.1 mm, not 0.01 mm; 2) definitions of T1a and T1b are revised (T1a, <0.8 mm without ulceration; T1b, 0.8-1.0 mm with or without ulceration or <0.8 mm with ulceration), with mitotic rate no longer a T category criterion; 3) pathological (but not clinical) stage IA is revised to include T1b N0 M0 (formerly pathologic stage IB); 4) the N category descriptors “microscopic” and “macroscopic” for regional node metastasis are redefined as “clinically occult” and “clinically apparent”; 5) prognostic stage III groupings are based on N category criteria and T category criteria (ie, primary tumor thickness and ulceration) and increased from 3 to 4 subgroups (stages IIIA-IIID); 6) definitions of N subcategories are revised, with the presence of microsatellites, satellites, or in-transit metastases now categorized as N1c, N2c, or N3c based on the number of tumor-involved regional lymph nodes, if any; 7) descriptors are added to each M1 subcategory designation for lactate dehydrogenase (LDH) level (LDH elevation no longer upstages to M1c); and 8) a new M1d designation is added for central nervous system metastases. This evidence-based revision of the AJCC melanoma staging system will guide patient treatment, provide better prognostic estimates, and refine stratification of patients entering clinical trials. CA Cancer J Clin 2017;67:472-492. © 2017 American Cancer Society.

  • Missed therapeutic and prevention opportunities in women with BRCA-mutated epithelial ovarian cancer and their families due to low referral rates for genetic counseling and BRCA testing: A review of the literature
    CA: Cancer J. Clin. (IF 187.04) Pub Date : 2017-09-07
    Paul J. Hoskins, Walter H. Gotlieb

    Answer questions and earn CME/CNE Fifteen percent of women with epithelial ovarian cancer have inherited mutations in the BRCA breast cancer susceptibility genes. Knowledge of her BRCA status has value both for the woman and for her family. A therapeutic benefit exists for the woman with cancer, because a new family of oral drugs, the poly ADP-ribose polymerase (PARP) inhibitors, has recently been approved, and these drugs have the greatest efficacy in women who carry the mutation. For her family, there is the potential to prevent ovarian cancer in those carrying the mutation by using risk-reducing surgery. Such surgery significantly reduces the chance of developing this, for the most part, incurable cancer. Despite these potential benefits, referral rates for genetic counseling and subsequent BRCA testing are low, ranging from 10% to 30%, indicating that these therapeutic and prevention opportunities are being missed. The authors have reviewed the relevant available literature. Topics discussed are BRCA and its relation to ovarian cancer, the rates of referral for genetic counseling/BRCA testing, reasons for these low rates, potential strategies to improve on those rates, lack of effectiveness of current screening strategies, the pros and cons of risk-reducing surgery, other prevention options, and the role and value of PARP inhibitors. CA Cancer J Clin 2017;67:493-506. © 2017 American Cancer Society.

  • Treatment of renal cell carcinoma: Current status and future directions
    CA: Cancer J. Clin. (IF 187.04) Pub Date : 2017-09-29
    Pedro C. Barata, Brian I. Rini

    Answer questions and earn CME/CNE Over the past 12 years, medical treatment for renal cell carcinoma (RCC) has transitioned from a nonspecific immune approach (in the cytokine era), to targeted therapy against vascular endothelial growth factor (VEGF), and now to novel immunotherapy agents. Multiple agents—including molecules against vascular endothelial growth factor, platelet-derived growth factor, and related receptors; inhibitors of other targets, such as the mammalian target of rapamycin and the MET and AXL tyrosine-protein kinase receptors; and an immune-checkpoint inhibitor—have been approved based on significant activity in patients with advanced RCC. Despite these advances, important questions remain regarding biomarkers of efficacy, patient selection, and the optimal combination and sequencing of agents. The purpose of this review is to summarize present management and future directions in the treatment of metastatic RCC. CA Cancer J Clin 2017;67:507-524. © 2017 American Cancer Society.

  • Obesity and adverse breast cancer risk and outcome: Mechanistic insights and strategies for intervention
    CA: Cancer J. Clin. (IF 187.04) Pub Date : 2017-08-01
    Manuel Picon-Ruiz, Cynthia Morata-Tarifa, Janeiro J. Valle-Goffin, Eitan R. Friedman, Joyce M. Slingerland

    Recent decades have seen an unprecedented rise in obesity, and the health impact thereof is increasingly evident. In 2014, worldwide, more than 1.9 billion adults were overweight (body mass index [BMI], 25-29.9 kg/m2), and of these, over 600 million were obese (BMI ≥30 kg/m2). Although the association between obesity and the risk of diabetes and coronary artery disease is widely known, the impact of obesity on cancer incidence, morbidity, and mortality is not fully appreciated. Obesity is associated both with a higher risk of developing breast cancer, particularly in postmenopausal women, and with worse disease outcome for women of all ages. The first part of this review summarizes the relationships between obesity and breast cancer development and outcomes in premenopausal and postmenopausal women and in those with hormone receptor-positive and -negative disease. The second part of this review addresses hypothesized molecular mechanistic insights that may underlie the effects of obesity to increase local and circulating proinflammatory cytokines, promote tumor angiogenesis and stimulate the most malignant cancer stem cell population to drive cancer growth, invasion, and metastasis. Finally, a review of observational studies demonstrates that increased physical activity is associated with lower breast cancer risk and better outcomes. The effects of recent lifestyle interventions to decrease sex steroids, insulin/insulin-like growth factor-1 pathway activation, and inflammatory biomarkers associated with worse breast cancer outcomes in obesity also are discussed. Although many observational studies indicate that exercise with weight loss is associated with improved breast cancer outcome, further prospective studies are needed to determine whether weight reduction will lead to improved patient outcomes. It is hoped that several ongoing lifestyle intervention trials, which are reviewed herein, will support the systematic incorporation of weight loss intervention strategies into care for patients with breast cancer. CA Cancer J Clin 2017;. © 2017 The Authors. CA A Cancer Journal for Clinicians published by Wiley Periodicals, Inc. on behalf of American Cancer Society. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

  • The importance of immunization in cancer prevention, treatment, and survivorship
    CA: Cancer J. Clin. (IF 187.04) Pub Date : 2017-07-28
    Elizabeth M. Ward, Christopher R. Flowers, Ted Gansler, Saad B. Omer, Robert A. Bednarczyk

    A measles outbreak originating in California during 2014 and 2015 called attention to the potential for infectious disease outbreaks related to underimmunized populations in the United States and the potential risk to pediatric patients with cancer attending school when such outbreaks occur. Compliance with vaccine recommendations is important for the prevention of hepatitis B-related and human papillomavirus-related cancers and for protecting immunocompromised patients with cancer, and these points are often overlooked, resulting in the continued occurrence of vaccine-preventable neoplastic and infectious diseases and complications. This article provides an overview of the importance of vaccines in the context of cancer and encourages clinician, health system, and public policy efforts to promote adherence to immunization recommendations in the United States. CA Cancer J Clin 2017. © 2017 American Cancer Society.

  • Frailty and cancer: Implications for oncology surgery, medical oncology, and radiation oncology
    CA: Cancer J. Clin. (IF 187.04) Pub Date : 2017-07-21
    Cecilia G. Ethun, Mehmet A. Bilen, Ashesh B. Jani, Shishir K. Maithel, Kenneth Ogan, Viraj A. Master

    The concept of frailty has become increasingly recognized as one of the most important issues in health care and health outcomes and is of particular importance in patients with cancer who are receiving treatment with surgery, chemotherapy, and radiotherapy. Because both cancer itself, as well as the therapies offered, can be significant additional stressors that challenge a patient's physiologic reserve, the incidence of frailty in older patients with cancer is especially high—it is estimated that over one-half of older patients with cancer have frailty or prefrailty. Defining frailty can be challenging, however. Put simply, frailty is a state of extreme vulnerability to stressors that leads to adverse health outcomes. In reality, frailty is a complex, multidimensional, and cyclical state of diminished physiologic reserve that results in decreased resiliency and adaptive capacity and increased vulnerability to stressors. In addition, over 70 different measures of frailty have been proposed. Still, it has been demonstrated that frail patients are at increased risk of postoperative complications, chemotherapy intolerance, disease progression, and death. Although international standardization of frailty cutoff points are needed, continued efforts by oncology physicians and surgeons to identify frailty and promote multidisciplinary decision making will help to develop more individualized management strategies and optimize care for patients with cancer. CA Cancer J Clin 2017. © 2017 American Cancer Society.

  • The oncologic burden of hepatitis C virus infection: A clinical perspective
    CA: Cancer J. Clin. (IF 187.04) Pub Date : 2017-07-06
    Harrys A. Torres, Terri Lynn Shigle, Nassim Hammoudi, James T. Link, Felipe Samaniego, Ahmed Kaseb, Vincent Mallet

    Chronic hepatitis C virus (HCV) infection affects millions of people worldwide and is associated with cancer. Direct-acting antivirals (DAAs) have changed HCV treatment paradigms, but little is known about the management of HCV infection in patients with cancer. The substantial burden of HCV infection and the inconclusive evidence regarding its detection and management in patients with cancer prompted the authors to review the literature and formulate recommendations. Patients for whom HCV screening is recommended included all patients with hematologic malignancies, hematopoietic cell transplantation candidates, and patients with liver cancer. There is a lack of consensus-based recommendations for the identification of HCV-infected patients with other types of cancer, but physicians may at least consider screening patients who belong to groups at heightened risk of HCV infection, including those born during 1945 through 1965 and those at high risk for infection. Patients with evidence of HCV infection should be assessed by an expert to evaluate liver disease severity, comorbidities associated with HCV infection, and treatment opportunities. DAA therapy should be tailored on the basis of patient prognosis, type of cancer, cancer treatment plan, and hepatic and virologic parameters. HCV-infected patients with cancer who have cirrhosis (or even advanced fibrosis) and those at risk for liver disease progression, especially patients with HCV-associated comorbidities, should have ongoing follow-up, regardless of whether there is a sustained virologic response, to ensure timely detection and treatment of hepatocellular carcinoma. HCV infection and its treatment should not be considered contraindications to cancer treatment and should not delay the initiation of an urgent cancer therapy. CA Cancer J Clin 2017. © 2017 American Cancer Society.

  • The burden of rare cancers in the United States
    CA: Cancer J. Clin. (IF 187.04) Pub Date : 2017-05-19
    Carol E. DeSantis, Joan L. Kramer, Ahmedin Jemal

    There are limited published data on the burden of rare cancers in the United States. By using data from the North American Association of Central Cancer Registries and the Surveillance, Epidemiology, and End Results program, the authors provide information on incidence rates, stage at diagnosis, and survival for more than 100 rare cancers (defined as an incidence of fewer than 6 cases per 100,000 individuals per year) in the United States. Overall, approximately 20% of patients with cancer in the United States are diagnosed with a rare cancer. Rare cancers make up a larger proportion of cancers diagnosed in Hispanic (24%) and Asian/Pacific Islander (22%) patients compared with non-Hispanic blacks (20%) and non-Hispanic whites (19%). More than two-thirds (71%) of cancers occurring in children and adolescents are rare cancers compared with less than 20% of cancers diagnosed in patients aged 65 years and older. Among solid tumors, 59% of rare cancers are diagnosed at regional or distant stages compared with 45% of common cancers. In part because of this stage distribution, 5-year relative survival is poorer for patients with a rare cancer compared with those diagnosed with a common cancer among both males (55% vs 75%) and females (60% vs 74%). However, 5-year relative survival is substantially higher for children and adolescents diagnosed with a rare cancer (82%) than for adults (46% for ages 65-79 years). Continued efforts are needed to develop interventions for prevention, early detection, and treatment to reduce the burden of rare cancers. Such discoveries can often advance knowledge for all cancers. CA Cancer J Clin 2017. © 2017 American Cancer Society. CA Cancer J Clin 2017;67:261–272. © 2017 American Cancer Society.

  • Disparities in liver cancer occurrence in the United States by race/ethnicity and state
    CA: Cancer J. Clin. (IF 187.04) Pub Date : 2017-06-06
    Farhad Islami, Kimberly D. Miller, Rebecca L. Siegel, Stacey A. Fedewa, Elizabeth M. Ward, Ahmedin Jemal

    Liver cancer is highly fatal, and death rates in the United States are increasing faster than for any other cancer, having doubled since the mid-1980s. In 2017, it is estimated that the disease will account for about 41,000 new cancer cases and 29,000 cancer deaths in the United States. In this article, data from the Surveillance, Epidemiology, and End Results (SEER) Program and the National Center for Health Statistics are used to provide an overview of liver cancer incidence, mortality, and survival rates and trends, including data by race/ethnicity and state. The prevalence of major risk factors for liver cancer is also reported based on national survey data from the Centers for Disease Control and Prevention. Despite the improvement in liver cancer survival in recent decades, only 1 in 5 patients survives 5 years after diagnosis. There is substantial disparity in liver cancer death rates by race/ethnicity (from 5.5 per 100,000 in non-Hispanic whites to 11.9 per 100,000 in American Indians/Alaska Natives) and state (from 3.8 per 100,000 in North Dakota to 9.6 per 100,000 in the District of Columbia) and by race/ethnicity within states. Differences in risk factor prevalence account for much of the observed variation in liver cancer rates. Thus, in contrast to the growing burden, a substantial proportion of liver cancer deaths could be averted, and existing disparities could be dramatically reduced, through the targeted application of existing knowledge in prevention, early detection, and treatment, including improvements in vaccination against hepatitis B virus, screening and treatment for chronic hepatitis C virus infections, maintaining a healthy body weight, access to high-quality diabetes care, preventing excessive alcohol drinking, and tobacco control, at both the state and national levels. CA Cancer J Clin 2017;67:273–289. © 2017 American Cancer Society.

  • Breast Cancer—Major changes in the American Joint Committee on Cancer eighth edition cancer staging manual
    CA: Cancer J. Clin. (IF 187.04) Pub Date : 2017-03-14
    Armando E. Giuliano, James L. Connolly, Stephen B. Edge, Elizabeth A. Mittendorf, Hope S. Rugo, Lawrence J. Solin, Donald L. Weaver, David J. Winchester, Gabriel N. Hortobagyi

    The revision of the eighth edition of the primary tumor, lymph node, and metastasis (TNM) classification of the American Joint Commission of Cancer (AJCC) for breast cancer was determined by a multidisciplinary team of breast cancer experts. The panel recognized the need to incorporate biologic factors, such as tumor grade, proliferation rate, estrogen and progesterone receptor expression, human epidermal growth factor 2 (HER2) expression, and gene expression prognostic panels into the staging system. AJCC levels of evidence and guidelines for all tumor types were followed as much as possible. The panel felt that, to maintain worldwide value, the tumor staging system should remain based on TNM anatomic factors. However, the recognition of the prognostic influence of grade, hormone receptor expression, and HER2 amplification mandated their inclusion into the staging system. The value of commercially available, gene-based assays was acknowledged and prognostic input added. Tumor biomarkers and low Oncotype DX recurrence scores can alter prognosis and stage. These updates are expected to provide additional precision and flexibility to the staging system and were based on the extent of published information and analysis of large, as yet unpublished databases. The eighth edition of the AJCC TNM staging system, thus, provides a flexible platform for prognostic classification based on traditional anatomic factors, which can be modified and enhanced using patient biomarkers and multifactorial prognostic panel data. The eighth edition remains the worldwide basis for breast cancer staging and will incorporate future online updates to remain timely and relevant. CA Cancer J Clin 2017;67:290–303. © 2017 American Cancer Society.

  • Cancer of the esophagus and esophagogastric junction—Major changes in the American Joint Committee on Cancer eighth edition cancer staging manual
    CA: Cancer J. Clin. (IF 187.04) Pub Date : 2017-05-26
    Thomas W. Rice, Donna M. Gress, Deepa T. Patil, Wayne L. Hofstetter, David P. Kelsen, Eugene H. Blackstone

    New to the eighth edition of the American Joint Committee on Cancer (AJCC) Cancer Staging Manual for epithelial cancers of the esophagus and esophagogastric junction are separate, temporally related cancer classifications: 1) before treatment decision (clinical); 2) after esophagectomy alone (pathologic); and 3) after preresection therapy followed by esophagectomy (postneoadjuvant pathologic). The addition of clinical and postneoadjuvant pathologic stage groupings was driven by a lack of correspondence of survival, and thus prognosis, between both clinical and postneoadjuvant pathologic cancer categories (facts about the cancer) and pathologic categories. This was revealed by a machine-learning analysis of 6-continent data from the Worldwide Esophageal Cancer Collaboration, with consensus of the AJCC Upper GI Expert Panel. Survival is markedly affected by histopathologic cell type (squamous cell carcinoma and adenocarcinoma) in clinically and pathologically staged patients, requiring separate stage grouping for each cell type. However, postneoadjuvant pathologic stage groups are identical. For the future, more refined and granular data are needed. This requires: 1) more accurate clinical staging; 2) innovative solutions to pathologic staging challenges in endoscopically resected cancers; 3) integration of genomics into staging; and 4) precision cancer care with targeted therapy. It is the responsibility of the oncology team to accurately determine and record registry data, which requires eliminating both common errors and those related to incompleteness and inconsistency. Despite the new complexity of eighth edition staging of cancers of the esophagus and esophagogastric junction, these key concepts and new directions will facilitate precision cancer care. CA Cancer J Clin 2017;67:304–317. © 2017 American Cancer Society.

  • A review of family caregiving intervention trials in oncology
    CA: Cancer J. Clin. (IF 187.04) Pub Date : 2017-03-20
    Betty Ferrell, Elaine Wittenberg

    This article contains a review of literature published from 2010 to 2016 on family caregiving in oncology. An analysis of 810 citations resulted in 50 randomized trials. These trials describe the need to prepare family caregivers for the complex role they play in cancer care. Several studies have demonstrated improved quality of life for family caregivers and improved emotional support from interventions. Several studies addressed communication and relational intimacy, which are key concerns. An additional focus of these trials was in the area of caregiving tasks and ways to diminish the burden of caregiving and preparedness for this role. Further research is needed in this area given the shift to outpatient care and as family caregivers become the primary providers of care. Future research should include expanding tested models of family caregiver support in clinical practice and in diverse populations. CA Cancer J Clin 2017. © 2017 American Cancer Society. CA Cancer J Clin 2017;67:318–325. © 2017 American Cancer Society.

  • The role of the microbiome in cancer development and therapy
    CA: Cancer J. Clin. (IF 187.04) Pub Date : 2017-05-08
    Aadra P. Bhatt, Matthew R. Redinbo, Scott J. Bultman

    The human body harbors enormous numbers of microbiota that influence cancer susceptibility, in part through their prodigious metabolic capacity and their profound influence on immune cell function. Microbial pathogens drive tumorigenesis in 15% to 20% of cancer cases. Even larger numbers of malignancies are associated with an altered composition of commensal microbiota (dysbiosis) based on microbiome studies using metagenomic sequencing. Although association studies cannot distinguish whether changes in microbiota are causes or effects of cancer, a causative role is supported by rigorously controlled preclinical studies using gnotobiotic mouse models colonized with one or more specific bacteria. These studies demonstrate that microbiota can alter cancer susceptibility and progression by diverse mechanisms, such as modulating inflammation, inducing DNA damage, and producing metabolites involved in oncogenesis or tumor suppression. Evidence is emerging that microbiota can be manipulated for improving cancer treatment. By incorporating probiotics as adjuvants for checkpoint immunotherapy or by designing small molecules that target microbial enzymes, microbiota can be harnessed to improve cancer care. CA Cancer J Clin 2017;67:326–344. © 2017 American Cancer Society.

Some contents have been Reproduced with permission of the American Chemical Society.
Some contents have been Reproduced by permission of The Royal Society of Chemistry.
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