bluuebunny/crossref_metadata_2025 huggingface dataset:
Hodgkin Disease/Lymphoma
Authors: _ _
Published: April 2017

Hodgkin disease/lymphoma (HD/HL) is an uncommon malignancy; in 2008, an estimated 8220 new diagnoses and 1350 deaths will occur in the United States. The past few decades have seen significant progress in the management of HL; it is now curable in at least 80% of patients. In fact, cure rates for HL have increased so extensively that the overriding treatment considerations often relate to long-term toxicity, especially for patients with early- or intermediate-stage disease. The World Health Organization classification divides HL into 2 main types: classical and lymphocyte-predominant HL (CHL and LPHL). These guidelines discuss clinical management, focusing exclusively on patients from postadolescence through the seventh decade of life who do not have serious intercurrent disease.

For the most recent version of the guidelines, please visit NCCN.org
VTE as a Quality Indicator
Authors: Goldsmith Myron , Whitelaw George , Cannaday Denise A.
Published: April 2017

Venous thromboembolism (VTE) is still the most common preventable cause of hospital death, with cancer a known significant risk factor for its development. Prophylaxis to prevent VTE in hospitalized surgical and medical patients has been suboptimal, and efforts for improvement have been unsuccessful. Recent practice guidelines on VTE in oncology from the National Comprehensive Cancer Network and American Society of Clinical Oncologists have further highlighted this relationship and could bridge performance measures and outcomes that can affect the strategies for preventing deep venous thrombosis and pulmonary embolism in oncology patients. Hospitals and physicians with poor performance data will have problems with payment from the Centers for Medicare & Medicaid Services and contracting the best rates from other payors. Hospital accreditation from The Joint Commission could be an issue for poorly performing institutions, as could consumer acceptance. The authors believe that specific oncology VTE measures should be developed to help decrease the current poor rates of VTE prophylaxis and also improve hospital and physician compliance.
The Role of Cytoreductive/Debulking Surgery in Ovarian Cancer
Authors: Wakabayashi Mark T. , Lin Paul S. , Hakim Amy A.
Published: April 2017

Ovarian cancer is the fifth most common cause of cancer-related death among women in the United States, although the median survival of patients has been increasing over the past few decades. In patients with epithelial ovarian cancer, chemotherapy has increased survival. Platinum agents combined with taxanes have become standard treatment. Intraperitoneal chemotherapy has also increased survival. Cytoreductive surgery to optimally debulk a tumor or, ideally, remove any gross disease has also been shown to increase survival. Each 10% increase in cytoreduction correlates with a 5.5% increase in median survival. The ability to successfully perform optimal cytoreduction ranges from 20% to 90%. Many institutions have recently begun to perform aggressive/ultraradical procedures to achieve this result. Interval cytoreduction may also benefit patients whose initial surgery is suboptimal, especially if the first procedure was performed by a surgeon unfamiliar with the disease. Secondary cytoreduction can increase survival in patients with low-volume disease and a long disease-free interval. All of these procedures should be performed by a specialist trained in ovarian cancer surgery.
Modern Staging and Utility of PET Imaging in Esophageal Cancer Management
Authors: Chang Kwang-Yu , Chang Jang-Yang , Chao Joseph , Yen Yun
Published: April 2017

Esophageal cancer is the eighth most common cancer worldwide, and one of the most fatal diseases despite modern medical treatment. Because correct staging and surveillance of neoadjuvant therapy for esophageal cancer is mandatory for further treatment planning, choosing a modern imaging system is important. The development of 18F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET) has provided alternate means of tumor detection distinct from more conventional methods. This modality has extraordinary performance in detecting locoregional lymph node involvement and distant metastatic disease, and has been introduced as a powerful tool in many guidelines. However, some factors still lead to false-negative or -positive results, raising questions of its accuracy. This article discusses the clinical efficacy of PET in staging and surveillance of neoadjuvant therapy in esophageal cancer, comparing its accuracy with conventional imaging modalities.
Minimally Invasive Surgery for Esophageal Cancer
Authors: Santillan Alfredo A. , Farma Jeffrey M. , Meredith Kenneth L. , Shah Nilay R. , Kelley Scott T.
Published: April 2017

Esophageal cancer represents a major public health problem worldwide. Several minimally invasive esophagectomy (MIE) techniques have been described and represent a safe alternative for the surgical management of esophageal cancer in selected centers with high volume and expertise in them. This article reviews the most recent and largest series evaluating MIE techniques. Recent larger series have shown MIE to be equivalent in postoperative morbidity and mortality rates to conventional surgery. MIE has been associated with less blood loss, less postoperative pain, and decreased intensive care unit and hospital length of stay compared with conventional surgery. Despite limited data, conventional surgery and MIE have shown no significant difference in survival, stage for stage. The myriad of MIE techniques complicates the debate of defining the optimal surgical approach for treating esophageal cancer. Randomized controlled trials comparing MIE with conventional open esophagectomy are needed to clarify the ideal procedure with the lowest postoperative morbidity, best quality of life after surgery, and long-term survival.
An Update on Biochemotherapy of Advanced Gastric and Gastroesophageal Adenocarcinoma
Authors: Haghighat Peyman , Bekaii-Saab Tanios
Published: April 2017

Gastric and gastroesophageal adenocarcinoma (GGA) are significant worldwide health problems. With most patients presenting with advanced disease, palliative chemotherapy plays a significant role in treatment. Results from recent phase III studies of cytotoxic agents in combination therapy, such as docetaxel, oxaliplatin, irinotecan, capecitabine, and S-1, have been encouraging and provide patients with additional therapeutic options. Although these forthcoming regimens have allowed for more flexible patient-tailored therapy, survival continues to be suboptimal. Although still in its infancy, targeted biotherapy, including inhibitors of the vascular endothelial and epidermal growth factor receptors, seems to be promising and its incorporation into the next generation of clinical trials will hopefully improve outcomes and help advance future treatments. This article reviews current active chemotherapeutic regimens and explores the role of novel targeted therapies in advanced GGA.
Strategy for Incorporating Molecular and Cytogenetic Markers into Acute Myeloid Leukemia Therapy
Authors: Frattini Mark G. , Maslak Peter G.
Published: April 2017

Acute myeloid leukemia is a heterogeneous disease. Standard treatments may be applied to biologically distinct subgroups, resulting in different treatment outcomes. The concept of risk-adapted therapy allows for recognition of this biologic diversity by incorporating key biologic features, such as cytogenetic and molecular markers, when formulating treatment regimens and investigating emerging targeted therapies based on disease characteristics.
Optimizing Therapy for Acute Myeloid Leukemia
Authors: Kohrt Holbrook E. , Coutre Steven E.
Published: April 2017

The 10-year overall survival for younger patients with newly diagnosed acute myeloid leukemia has improved threefold in the past 2 decades. This improvement has occurred in large part because of advances in supportive care and efforts to optimize standard induction and consolidation therapies applied in a stratified approach based on predictors of individual patient risk. Innovations in diagnostic technologies have broadened the understanding of key prognostic factors, including cytogenetic and molecular status, which define the extensive interpatient heterogeneity of this clonal disease. Despite this progress, only approximately 25% of patients who experience a complete remission with cytotoxic chemotherapy (50%–70% of patients with newly diagnosed disease) remain disease-free. Efforts to develop novel agents are actively ongoing, particularly for older patients (age ≥ 60), and targeted therapies, for specific subsets of patients are being based on a better understanding of the biology of the disease.
Therapy of Adenocarcinoma of Unknown Primary: Are We Making Progress?
Authors: Greco F. Anthony
Published: April 2017

Therapy for patients with unknown primary carcinoma is evolving and requires a detailed understanding of the various clinicopathologic subsets with more favorable prognoses. For the remainder, and most patients with unfavorable prognoses, data on current empiric chemotherapy with the newer drugs seems to show improved overall survival compared with older historical data, including comparisons with large retrospective series and prospective phase II trial results. Several recent clinical trials have recently documented long-term survival for a minority of patients. The survival of patients with several metastatic adenocarcinomas of known primary sites, including colon/rectum, lung, and pancreas, has been improved by the administration of chemotherapy alone or combined with biologic targeted drugs (bevacizumab, erlotinib). Approximately 60% of the patients with unknown primary adenocarcinoma have clinically occult primary sites of colon/rectum, lung, and pancreas. Many of these patients will also benefit from therapeutic regimens now proven to be useful for patients with these known primary sites. All available data make a convincing argument that progress is being made for the commonly seen patients with adenocarcinoma of unknown primary site, and is likely to continue as understanding of these and other neoplasms further evolves.
Evaluation and Management of the Unknown Primary Carcinoma of the Head and Neck
Authors: Galer Chad E. , Kies Merrill S.
Published: April 2017

Squamous cell carcinoma of unknown primary origin in the head and neck is encountered as a recurring clinical problem in head and neck cancer clinics, affecting 3% to 25% of patients. This article describes the clinical presentation, appropriate evaluation, and treatment strategies for this important subgroup. Treatment—best carried out with multidisciplinary teams of specialists experienced in the care of head and neck cancer patients—is curative for most of these patients.
Review of Evidence-Based Support for Pretreatment Imaging in Melanoma
Authors: Sabel Michael S. , Wong Sandra L.
Published: April 2017

When making a new diagnosis of melanoma, clinicians often obtain imaging studies to rule out clinically occult distant disease. These studies range from inexpensive tests, such as chest radiographs, to more expensive studies, such as PET/CT. The impetus for ordering these studies is usually the desire to identify potentially resectable distant disease, avoid surgery when curative resection is not possible, and assuage patient anxiety by showing that no evidence of distant disease is present. However, some detrimental aspects to these studies are less apparent, including cost and potential for false-positive findings. Although routine use seems reasonable, the true benefit of these studies depends on the probability of clinically occult disease being present, likelihood that disease will be detected with the available technology, and impact of earlier detection on outcome. Contrary to current practice patterns, available evidence suggests that preoperative imaging studies are associated with significant costs and minimal benefit in most patients with melanoma. This article reviews available literature on the role of pretreatment imaging in patients with newly diagnosed cutaneous melanoma.
Where Are We With Adjuvant Therapy of Stage III and IV Melanoma in 2009?
Authors: Fecher Leslie A. , Flaherty Keith T.
Published: April 2017

Adjuvant therapy options for advanced melanoma in 2009 remain active observation, high-dose interferon, or clinical trial participation. Close observation is currently the only required adjuvant management, with the purpose of detecting the emergence of regional or metastatic disease early, when surgical management may still be possible. The National Comprehensive Cancer Network guidelines for the workup and follow-up of all stages of melanoma must be tailored to specific patients by the treating physician. This article explores the factors to consider when individualizing care within the scope of these guidelines.
Role of Sentinel Lymph Node Biopsy in Patients with Thin Melanoma
Authors: Andtbacka Robert H. I. , Gershenwald Jeffrey E.
Published: April 2017

Sentinel lymph node (SLN) biopsy has emerged over the past 2 decades as a rational approach for staging regional lymph nodes in patients with clinically node-negative melanoma (stage I and II disease). Large multi-institutional studies have confirmed that when performed by experienced surgeons, it is an accurate, reliable technique for identifying occult regional nodal disease, and that SLN status is the most important prognostic factor in patients with stage I and II melanoma. However, the incidence of occult regional nodal metastasis in patients with thin melanoma (≤ 1.0 mm; approximately 70% of patients with newly diagnosed melanoma) is low, and whether to perform SLN biopsy in these patients remains controversial. Several predictors of SLN metastasis in patients with thin melanoma have been suggested, but none widely accepted. This article reviews current literature on these predictors in patients with thin melanoma. Although the ability to draw conclusions was limited by the size and design of the available studies, the authors tentatively conclude that SLN biopsy can be considered for patients with melanomas 0.75 mm or larger, those with T1b melanomas (i.e., ≤ 1.0 mm; Clark level IV/V and/or ulcerated), and those with thin melanomas with an increased tumor mitotic rate (especially ≥ 1 mitosis/mm2). Including younger age (e.g., ≤ 40 years) in the decision also seems reasonable, particularly if the primary tumor is associated with a high tumor mitotic rate. Tumor regression does not seem to be associated with an increased risk for SLN metastasis. Firm conclusions on the predictive value of vertical growth phase, absence of tumor-infiltrating lymphocytes, or male gender were not possible, particularly if used as a sole criterion for offering this procedure. SLN biopsy should be discussed with all patients with newly diagnosed thin melanoma.
Increasing Incidence of Intrahepatic Cholangiocarcinoma and its Relationship to Chronic Viral Hepatitis
Authors: Chang Kwang-Yu , Chang Jang-Yang , Yen Yun
Published: April 2017

Primary liver cancer is the sixth most common cancer and third most common cause of cancer death worldwide. Cholangiocarcinoma is the second most common primary liver tumor after hepatocellular carcinoma. Because the incidence of intrahepatic cholangiocarcinoma is rising in most areas worldwide, identification of the main causes of this problem is urgently needed. Despite well-known risk factors in the development of intrahepatic cholangiocarcinoma, recent reports focus on chronic hepatitis B and C viral infections because an increasing number of studies have observed an association. The relationship, however, is still not conclusive because of the diversity in clinical reports and the lack of in vitro evidences. This issue should be emphasized and further investigation is required for clarification.
Palliative Care Across the Continuum of Cancer Care
Authors: Sanft Tara B. , Von Roenn Jamie H.
Published: April 2017

Optimal oncology care requires the integration of palliative medicine into oncology care across the disease trajectory. All patients require screening for palliative care services at the initial oncologic visit and reassessment throughout the continuum of care. As a result of the increasing attention focused on palliative care nationally and internationally, the domains of palliative cancer care have been elucidated and have fostered the development of guidelines for quality palliative care. The recent recognition of palliative medicine as a subspecialty in the United States, the growing number of hospital-based palliative care programs, and the accreditation of palliative medicine fellowship programs by the Accreditation Council for Graduate Medical Education highlight the increased visibility of palliative medicine. This provides hope for the future of oncologic care. The palliative approach is subsumed in cancer care—it provides assistance with decision-making, symptom management, and access to financial, emotional, and spiritual services. A fully integrated program of oncology and palliative care provides the greatest opportunity for care and cure.
Issues of Imatinib and Pregnancy Outcome
Authors: Apperley Jane
Published: April 2017

The introduction of tyrosine kinase inhibitors into clinical practice now offers most patients with chronic myelogenous leukemia lengthy remissions and the possibility of normal life expectancies. These improved survivals have resulted in the need to address issues relating to quality of life, including fertility and procreation. Treatment may require lifelong daily therapy with drugs that might inhibit proteins essential to gonadal function, implantation, and embryogenesis. Animal data suggest that imatinib at standard dosages is unlikely to impair fertility in either adult male or female animals. However, human data remain limited, particularly in children and adolescents. Children born to men who are actively taking imatinib at conception seem healthy, and current advice is not to discontinue treatment. In contrast, data are less encouraging for children born to women exposed to imatinib during pregnancy. Although numbers are small, a disturbing cluster of rare congenital malformations has prevented imatinib from being recommended safely, particularly during the period of organogenesis. Alternative strategies for managing pregnancy in chronic myelogenous leukemia include one or both of regular leukapheresis and interferon-α. Pregnancy in advanced-phase disease presents particular problems.
NCCN Task Force Report: Molecular Markers in Leukemias and Lymphomas
Authors: Radich Jerald P. , Zelenetz Andrew D. , Chan Wing C. , Croce Carlo M. , Czuczman Myron S. , Erba Harry P. , Horning Sandra J. , Houldsworth Jane , Smith B. Douglas , Snyder David S. , Sundar Hema M. , Wetzler Meir , Winter Jane N.
Published: April 2017

The introduction of targeted therapies has revolutionized treatment and improved outcomes in patients with leukemias and lymphomas. However, many patients experience relapse caused by the persistence of residual malignant cells. Cytogenetic and molecular techniques are increasingly being used to assess and quantify minimal residual disease (MRD). The emergence of advanced technologies has led to the discovery of multiple novel molecular markers that can be used to detect MRD and predict outcome in patients with leukemias and lymphomas. Gene expression signatures that predict clinical outcomes in patients with non-Hodgkin's lymphoma have been identified. In chronic myelogenous leukemia, molecular monitoring has become more important in assessing response and detecting resistance to therapy. In acute leukemias, several new markers have shown potential in prognostication and monitoring treatment. In leukemias and lymphomas, microRNAs have been identified that may be useful in diagnostics and prognostication. To address these issues, the National Comprehensive Cancer Network (NCCN) organized a task force consisting of a panel of experts in leukemia and lymphoma to discuss recent advances in the field of molecular markers and monitoring MRD.
Use of Nomograms for Early Detection in Prostate Cancer
Authors: Snow Devon C. , Klein Eric A.
Published: April 2017

Since the first introduction of prostate-specific antigen (PSA) as a screening tool in the 1980s, the accurate diagnoses of clinically significant prostate cancer remains a challenge. Analysis of a correlation between PSA levels and prostate biopsies of men with PSA 3 ng/mL or less in the placebo group of the Prostate Cancer Prevention Trial suggested that no “normal” PSA level exists. With the acknowledgement that PSA level is considered a continuum rather than a dichotomous marker, accurately diagnosing clinically significant prostate cancer is even more challenging. Nomograms are increasingly being used as tools in the clinical setting to address this challenge. Through incorporating multiple clinical factors, such as PSA, digital rectal examination, age, race, prostate volume, family history, and previous negative biopsy, risk calculators can improve sensitivity of diagnosis over using a PSA cutoff alone. This article discusses the rational for the use of nomograms and the advantages and limitations for the most commonly used nomograms.
Does Adjuvant Bisphosphonate in Early Breast Cancer Modify the Natural Course of the Disease? A Meta-Analysis of Randomized Controlled Trials
Authors: Mauri Davide , Valachis Antonis , Polyzos Nikolaos P. , Tsali Lamprini , Mavroudis Dimitris , Georgoulias Vassilis , Casazza Giovanni
Published: April 2017

To address whether the use of bisphosphonates in the adjuvant setting of breast cancer might have any effect on the natural course of the disease, a meta-analysis was conducted of published and unpublished randomized controlled trials found in PubMed, the Cochrane Central Register of Controlled Trials, the ISI Web of Knowledge, and abstracts of major international conferences up to January 2009. All trials that randomized patients with primary breast cancer to undergo adjuvant treatment with any bisphosphonate versus non-use were considered eligible. Analysis included data from 13 eligible trials involving 6886 patients randomized to treatment with bisphosphonates (n = 3414) or either placebo or no treatment (n = 3472). Compared with no use, adjuvant breast cancer treatment with bisphosphonates did not reduce the overall number of deaths (odds ratio [OR], 0.708; 95% CI, 0.482–1.041; P = .079), bone metastases (OR, 0.925; 95% CI, 0.768–1.114; P = .413), overall disease recurrences (OR, 0.843; 95% CI, 0.602–1.181; P = .321), distant relapse (OR, 0.896; 95% CI, 0.674–1.192; P = .453), visceral recurrences (OR, 1.051; 95% CI, 0.686–1.609; P = .820), or local relapses (OR, 1.056; 95% CI, 0.750–1.487; P = .756). No significant heterogeneity was observed among the trials except for estimates of deaths and disease recurrences (P = .034 and P = .016, respectively). In subgroup analyses, use of zoledronic acid was associated with a statistically significant lower risk for disease recurrence (OR, 0.675; 95% CI, 0.479–0.952; P = .025). However, these results should be interpreted with caution because the statistical significance for this association was weak and might be attributed to chance from multi-test analyses. Use of zoledronic acid was not associated with any significant difference in death (OR, 0.642; 95% CI, 0.388–1.063) and bone metastasis rates (OR, 0.661; 95% CI, 0.379–1.151). Currently available evidence does not support the hypothesis that use of bisphosphonates in adjuvant treatment of early breast cancer will alter the natural course of the disease. Nonetheless, a nonsignificant trend seems to exist for better outcomes in patients undergoing bisphosphonate treatment. Until further evidence from new clinical trials becomes available, adjuvant bisphosphonates should not be recommended routinely.
Gastric Cancer: A Primer on the Epidemiology and Biology of the Disease and an Overview of the Medical Management of Advanced Disease
Authors: Shah Manish A. , Kelsen David P.
Published: April 2017

Gastric cancer is a cause of significant morbidity and cancer-related mortality worldwide. Despite recent advances in targeted therapy and understanding of the biology and development of the malignancy, progress in the treatment of gastric cancer has been limited. Most newly diagnosed patients will present with incurable disease, and have a median survival of less than 1 year. Although the disease has widespread ethnic and epidemiologic differences, medical management of gastric cancer does not distinguish among the various disease subtypes. The recent report of the ToGA phase III study has validated Her2 as a molecular target in this disease, supporting the concept that a greater understanding of the biology of gastric cancer subsets may improve treatment selection and overall outcome of individual patients. This article summarizes the epidemiology and ethnic variation of this disease to crystalize subtypes of gastric cancer in the context of current and future medical management of advanced disease.
Point: Justification for Lynch Syndrome Screening Among All Patients With Newly Diagnosed Colorectal Cancer
Authors: Hampel Heather
Published: April 2017

Either microsatellite instability testing or immunohistochemical staining for the 4 mismatch repair proteins (MLH1, MSH2, MSH6, and PMS2) should be performed on all newly diagnosed colorectal cancers. This testing will identify tumors that are microsatellite unstable, which has implications for patient prognosis and possibly treatment. In addition, it will identify patients who are more likely to have Lynch syndrome. Of every 35 colorectal cancer patients, 1 has Lynch syndrome, the most common hereditary cause of colorectal and endometrial cancers. Diagnosis of Lynch syndrome affects the medical management of the patient and their relatives, with potentially life-saving ramifications. Although screening only a subset of patients with colorectal cancer based on age at diagnosis, family history, or histologic criteria will reduce the number of screening tests necessary, it will miss a significant proportion of patients with microsatellite unstable colorectal cancer and many patients with Lynch syndrome. Given that universal screening of all patients with newly diagnosed colorectal cancer using immunohistochemistry as the initial test was recently shown to be cost-effective and comparable with other widely accepted preventive services, it is not necessary to try to reduce costs by restricting screening to a subset of patients, which leads to a reduction in the efficacy of the screening program.
Counterpoint: Implementing Population Genetic Screening for Lynch Syndrome Among Newly Diagnosed Colorectal Cancer Patients—Will the Ends Justify the Means?
Authors: Hall Michael J.
Published: April 2017

Inherited mutations in 1 of 4 known mismatch repair genes (MLH1, MSH2, MSH6, PMS2) are associated with various cancer risks collectively referred to as Lynch syndrome. Roughly 3 of every 100 new colorectal cancers (CRCs) have an underlying Lynch mutation. Tumor-based screening for Lynch among all patients with newly diagnosed CRC could theoretically improve the ability to identify Lynch and prevent cancer among at-risk family members, but the patient-level and social implications of this approach must be carefully considered before adopting this strategy. Poorly addressed issues include the role/timing of informed consent for testing, access and cost barriers associated with genetic counseling and DNA testing, psychosocial burdens to the thousands of middle-aged and elderly patients with CRC coping with surgical and chemotherapy treatments and poor prognosis, the need for providers to warn third-party relatives of risk for Lynch syndrome, limited effectiveness of screening, and the cost burden to society when poor DNA testing uptake, test limitations, and modest screening compliance are considered. Diverse barriers to the success of a population-based Lynch screening program in the United States remain (e.g., clinical resource needs, financial limitations, clinical expertise gaps, educational deficits). Data supporting clinical efficacy (feasibility) and effectiveness (real-life performance) are critical before important policy changes are adopted, especially where issues of hereditary cancer risk and genetic privacy are involved.
Operative Techniques in Early-Stage Lung Cancer
Authors: D'Amico Thomas A.
Published: April 2017

Lung cancer is the most common cause of death by malignancy, responsible for more deaths than the next 4 causes combined and predicted to account for nearly 220,000 new cancer diagnoses and 160,000 deaths in 2009. The cornerstone of therapy for early-stage lung cancer is lobectomy and mediastinal lymph node dissection. Although lobectomy is considered the standard procedure, segmentectomy may be appropriate for selected patients. Conventional approaches to resection may be used, including posterolateral and muscle-sparing thoracotomy. However, minimally invasive lobectomy and segmentectomy procedures are now commonly used with superior outcomes.
Biomarkers with Predictive and Prognostic Function in Non–Small Cell Lung Cancer: Ready for Prime Time?
Authors: Aggarwal Charu , Somaiah Neeta , Simon George R.
Published: April 2017

Lung cancer is the leading cause of cancer-related mortality in the United States. Non–small cell lung cancer (NSCLC) accounts for approximately 85% of all lung cancers. Most patients with NSCLC present with locoregionally advanced or metastatic disease, for which response rates and median overall survival remain poor. Platinum-based chemotherapy is the mainstay of treatment for NSCLC in both adjuvant and metastatic disease. Personalized chemotherapy and targeted biologic therapy based on a tumor's histologic and molecular profile have already shown promise in optimizing efficacy. Various markers are currently being investigated for their ability to guide treatment decision-making and management. This article describes these predictive and prognostic markers and details their current role, benefit, and potential future use in the management of patients with NSCLC.
Radiation Therapy in Operable and Locally Advanced Pancreatic Cancer
Authors: Ko Andrew H. , Crane Christopher H.
Published: April 2017

It is well established that the development of distant metastatic disease represents the dominant pattern of tumor recurrence/progression among patients with operable and locally advanced pancreatic cancer. However, the contribution of localized or locoregional tumor burden to pancreatic cancer–associated morbidity and mortality may be underappreciated, and therefore balancing competing considerations of systemic versus local disease control becomes important in therapeutic decision-making. The role of local therapies, particularly radiation therapy, has remained somewhat controversial in this disease context. Several phase II and III trials have sought to address the relative importance and role of radiation in both the localized and locally advanced settings, including the sequencing of this modality relative to systemic therapy and its optimal means of administration. However, differences and limitations in study design have produced mixed results, particularly in terms of the contribution of radiation to overall survival benefit. An emerging paradigm that makes conceptual sense and remains the subject of active investigation is to start with a defined period of systemic treatment, thus limiting radiation to the subset of patients who do not manifest with metastatic disease during initial therapy and are therefore most likely to benefit from local control.
Clinical Assessment of Breast Cancer Risk Based on Family History
Authors: Ready Kaylene , Arun Banu
Published: April 2017

Family history is a key component of breast cancer risk assessment. Family history provides clues as to the likelihood of a hereditary breast cancer syndrome and the need for a cancer genetics referral and can be used in the setting of a breast cancer risk assessment model to estimate a woman's risk. Appropriate breast cancer screening and risk reduction management plans rely on an accurate assessment of a patient's family history. This article reviews the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Breast Cancer Risk Reduction and provides insight into the application of the guidelines in clinical practice.
Nonhormonal Management of Hot Flashes for Women on Risk Reduction Therapy
Authors: Sideras Kostandinos , Loprinzi Charles L.
Published: April 2017

Hot flashes are very common in women in menopause and can have a detrimental effect on quality of life. Women on risk reduction therapy are particularly prone because treatments, such as tamoxifen, raloxifene, or oophorectomy, have the potential to exacerbate these symptoms. Hormonal treatments, despite the fact that they represent the most effective therapies, are not used for the treatment of hot flashes in these women because of concerns that they may increase the risk for breast cancer. As a result, several nonhormonal therapies have been tested in randomized placebo-controlled trials and shown to be effective, such as paroxetine, venlafaxine, desvenlafaxine, fluoxetine, citalopram, gabapentin, and pregabalin. In addition, several nonpharmacologic therapies have been tested with various successes. An additional consideration is how some of those drugs, especially fluoxetine and paroxetine, interact with the metabolism of tamoxifen. This article discusses these issues, and provides some recommendations regarding use of nonhormonal therapies for treating hot flashes in women on risk reduction therapy, with an emphasis on pharmacogenomic considerations.
Risk Reduction Strategies for Ductal Carcinoma In Situ
Authors: Cohen Adam L. , Ward John H.
Published: April 2017

Ductal carcinoma in situ (DCIS) is a premalignant condition that, if left untreated, may progress to invasive breast cancer. After lumpectomy, DCIS can recur, and about half of recurrences are invasive. In 4 randomized trials, radiation has been shown to decrease the local recurrence rate by about half, though it does not change survival. Based on the results of 3 randomized trials, tamoxifen probably decreases cancer recurrence by about 30%, particularly in young women. Low fat diets, weight loss, and physical activity decrease invasive breast cancer recurrence and may be recommended to certain women with DCIS. Prognostic factors include age, extent of DCIS, margin status, grade, and presence of necrosis, although how these affect adjuvant therapy is unclear. Research evaluating other drugs to reduce recurrence risk and on different ways of delivering radiation continues.
Perspectives on Margins in DCIS: Pathology
Authors: Lester Susan
Published: April 2017

All breast carcinomas must originate within the ductal/lobular system as carcinoma in situ, but only a subset of these lesions progress to invasive carcinoma. Although pathologic evaluation of the extent of ductal carcinoma in situ (DCIS), the distance to margins, and the degree of margin involvement provides an estimation of the likelihood of residual disease, the amount of disease in the remaining breast cannot be predicted with certainty. Factors other than residual disease may be more important in determining whether patients with DCIS survive or succumb to breast cancer, including biologically new ipsilateral cancers, contralateral cancers, and the degree of resistance of the normal stroma to invasion.
Preliminary Report: The Development of the NCCN Comparative Therapeutic Index™ as a Clinical Evaluative Process for Existing Data in Oncology
Authors: Li Edward C. , DeMartino Jessica
Published: April 2017

The National Comprehensive Cancer Network (NCCN) develops and communicates the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) to oncologists and other clinicians. The NCCN Guidelines are widely recognized and applied as the standard for clinical policy in the United States. These guidelines and related documents, such as the NCCN Drugs & Biologics Compendium (NCCN Compendium), are used extensively by public and private payors as the basis for the setting of coverage policies. Given the demand for comparative effectiveness (CE) analyses, as described and discussed in this report, the NCCN has begun work on a paradigm to integrate evidence-based CE analysis into the NCCN Guidelines deliberative process. This report presents NCCN's initial thinking on the use of NCCN expert panel members in developing a process that can be used to compare health care technologies (e.g., radiation modalities, chemotherapy regimens) in a formal, systematic way. Draft considerations are provided to stimulate discussion and feedback, particularly in the oncology community, as NCCN moves through processes such as methodologic review, validation of rating scales, and review of implications for public policy, toward finalization of an NCCN CE analytic paradigm.
Indications for Minimally Invasive Surgery for Ovarian Cancer
Authors: Han Ernest S. , Wakabayashi Mark
Published: April 2017

Epithelial ovarian cancer is often diagnosed in advanced stages and typically managed with surgical debulking followed by chemotherapy. For patients with presumed early-stage ovarian cancer, comprehensive surgical staging is essential for management, because 31% are upstaged. Over the past 15 years, minimally invasive techniques have improved and are increasingly being used to treat patients with ovarian cancer. Currently, only retrospective data support laparoscopic staging of patients with a suspicious adnexal mass or those surgically diagnosed with presumed early-stage ovarian cancer. Laparoscopy is also used in patients undergoing second-look procedures and to help evaluate whether patients should undergo optimal tumor debulking procedures or be initially managed with neoadjuvant chemotherapy. Randomized clinical studies are needed to further support the role of minimally invasive surgery in the treatment of ovarian cancer.
Controversies in the Locoregional Management of Head and Neck Cancer
Authors: Brizel David M. , Lydiatt William , Colevas A. Dimitrios
Published: April 2017

Head and neck cancer (HNC) is a heterogeneous combination of various sites and types of disease. This manuscript elaborates on 3 important and current issues: the emerging role of human papilloma virus (HPV) in oropharyngeal cancer (OPC), current considerations in systemic therapy for advanced disease, and evolving treatment of the neck. Exogenous carcinogens, most notably tobacco, have classically been implicated in the development of HNC. A large increase in the incidence of OPC has occurred in the past few decades, predominantly in nontobacco users, and is caused by HPV. This disease is unique in many respects and presents an opportunity for novel therapeutic approaches. Because the prognosis for HPV-related HNC is better, regardless of whether surgery or radiation is used as the primary therapy, the reduction of treatment-related morbidity has assumed increasing importance and provides unique opportunities and challenges for de-escalation of therapies. Radiotherapy (RT) and concurrent cisplatin is the most commonly used nonsurgical platform for locally advanced disease. New data suggest that viable alternatives exist to the typical 3 cycles of bolus high-dose cisplatin. The role of RT and concurrent taxanes remains less understood. Similarly, the value of integrating epidermal growth factor inhibition and concurrent chemoradiation is under continuing investigation. The use of PET scanning is changing the traditional use of adjuvant neck dissection after RT or chemoradiation. Recent data support the use of surgery in the presence of a positive posttreatment PET, and observation in the setting of a negative posttreatment scan.
The Epidemic of HPV-Associated Oropharyngeal Cancer Is Here: Is It Time to Change Our Treatment Paradigms?
Authors: Sturgis Erich M. , Ang K. Kian
Published: April 2017

Although relatively uncommon, oropharyngeal cancers are increasing in incidence despite declining prevalence of smoking and in direct opposition to a decreasing incidence of all other head and neck cancers. An epidemic of human papillomavirus (HPV)–associated oropharyngeal cancers seems to account for these incidence trends. Important demographic, behavioral, and prognostic characteristics define this unique population. Changes in prevention, diagnosis, evaluation, staging, and treatment are needed. This article summarizes the epidemiology and clinical behavior of HPV-associated oropharyngeal cancer and discusses evolving/potential paradigms of treatment. However, data are currently insufficient to change treatment paradigms for HPV-associated oropharyngeal cancer outside of a closely monitored clinical trial.
Current Recommendations for Systemic Therapy of Recurrent and/or Metastatic Head and Neck Squamous Cell Cancer
Authors: Fury Matthew G. , Pfister David G.
Published: April 2017

For palliation of patients with recurrent and/or metastatic head and neck squamous cell cancer (R/M HNSCC), the major classes of commonly used cytotoxic chemotherapeutic agents are platinum agents (cisplatin, carboplatin), taxanes (paclitaxel, docetaxel), and antimetabolic agents (methotrexate, 5-fluorouracil). Cetuximab, a monoclonal antibody directed against the extracellular domain of the epidermal growth factor receptor, also shows modest activity against R/M HNSCC. Because the overall management of patients with R/M HNSCC often involves multidisciplinary input, this review focuses on data that help guide decision-making in scenarios in which palliative chemotherapy is planned. Avenues for ongoing research are also presented.
Modern Approaches to Localized Cancer of the Esophagus
Authors: Glasgow Robert E. , Ilson David H. , Hayman James A. , Gerdes Hans , Mulcahy Mary F. , Ajani Jaffer A.
Published: April 2017

The clinical spectrum of esophageal cancer has changed dramatically over the past couple of decades. Most notably, a profound rise in esophageal adenocarcinoma and decrease in the incidence of squamous carcinomas have occurred. An understanding of the factors that influence survival for patients with localized esophageal cancer has evolved concomitantly with these changes in epidemiology. Significant advancement in endoscopic and radiographic staging allows for more selective use of treatment modalities. The treatment of localized esophageal cancer mandates a multidisciplinary approach, with treatment tailored to disease extent, location, histology, and an accurate assessment of pretreatment staging. Despite these improvements in the staging and use of multimodality therapy, only modest improvements in patient survival have been observed. This article summarizes these modern approaches to localized cancer of the esophagus.
Selecting Targeted Therapies for Patients With Renal Cell Carcinoma
Authors: Plimack Elizabeth R. , Hudes Gary R.
Published: April 2017

Advanced renal cell carcinoma (RCC) is a heterogeneous disease with variable histology, biology, and response to treatment. In the past 5 years, 6 new agents have been approved for the treatment of RCC, and many more are in clinical development. With an ever-increasing number of treatment options, selecting among them for a particular patient can be a daunting task for clinicians. This article describes how treatment choice can be guided by the disease setting and histology, as well as patient characteristics, comorbidities, and preference within the context of available data. Results from clinical trials are combined with practical considerations to make recommendations for first-line and subsequent treatment of patients with clear cell and non-clear cell RCC. These recommendations should supplement the current NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for the treatment of advanced RCC.
The Role of Autologous and Allogeneic Hematopoietic Stem Cell Transplantation for Hodgkin Lymphoma
Authors: Holmberg Leona , Maloney David G.
Published: April 2017

Patients with Hodgkin lymphoma are usually cured by primary therapy using chemotherapy alone or combined modality therapy with external beam radiation. Patients who do not experience a complete remission or those who experience relapse may by salvaged by high-dose therapy and autologous hematopoietic stem cell transplantation (ASCT). Success of this approach is largely dependent on the tumor being sensitive to salvage chemotherapy before transplant. More studies are showing the predictive value of functional imaging in this setting. Allogeneic hematopoietic stem cell transplantation has greater risk of nonrelapse mortality and is generally reserved for patients who experience relapse post-ASCT, but may provide long-term survival for some patients through graft-versus-tumor immune effects.
Large-Cell Neuroendocrine Carcinoma: Controversies in Diagnosis and Treatment
Authors: Glisson Bonnie S. , Moran Cesar A.
Published: April 2017

The diagnosis and treatment of large cell neuroendocrine carcinoma are controversial, difficult, and clearly still evolving. Diagnosing this particular entity can be hampered by the limitations and restrictions imposed by its own definition in the current WHO classification. These complexities in the semantics of diagnostic criteria can puzzle not only the pathologist but also the treating physician, and lead to difficulties in choosing treatment for individual patients. Because of its low incidence (2%-3% of non-small cell carcinomas) and the difficulties in diagnosis, data regarding treatment outcomes are based on series in which the diagnosis is frequently made retrospectively in reclassification, the numbers of patients are small, and the determinants of therapy choice (e.g., treatment with or without adjuvant chemotherapy postresection) cannot be known. Thus, the evidence on which to base recommendations for stage-based treatment paradigms is flawed in many respects. This article discusses these difficult issues for pathologists and oncologists, offers a perspective regarding approaches in treatment, and suggests ways in which prospective data on this uncommon cancer can be gathered to inform treatment guidelines and improve patient outcomes.
Surgery for Early-Stage Small Cell Lung Cancer
Authors: Schneider Bryan J. , Saxena Ashish , Downey Robert J.
Published: April 2017

Limited-stage small cell lung cancer remains one of the more frustrating malignancies to treat. Current standard of care typically includes platinum-based chemotherapy with thoracic radiation, and although response to therapy is high, most patients will ultimately experience relapse and die of recurrent disease. No high-level data exist supporting surgical resection of early-stage disease; however, several retrospective reviews and small single-arm studies suggest surgery may benefit patients with very limited extent of disease. This article reviews the available literature, and proposes guidelines for including potentially curative resection in the management of patients with limited-stage small cell lung cancer.
Biomarker Use in Colorectal Cancer Therapy
Authors: Kelley Robin K. , Wang Grace , Venook Alan P.
Published: April 2017

Biomarkers reflective of the molecular and genetic heterogeneity in colorectal cancers now guide certain aspects of clinical management and offer great potential for enrichment, stratification, and identification of novel therapeutic targets in drug development. Using case-based examples, this article reviews biomarkers that have an established role in the clinical management of colorectal cancer: mismatch repair protein testing and KRAS and BRAF mutational analysis. A selection of biomarkers undergoing validation for future clinical application is presented, and the dynamic and challenging interface between biomarkers in research and clinical practice is discussed.