bluuebunny/crossref_metadata_2025 huggingface dataset:
Novel Targets for Therapeutic Agents in Small Cell Lung Cancer
Authors: Ma Patrick C. , Salgia Ravi
Published: April 2017

Small cell lung cancer (SCLC) is known to have an aggressive phenotype and often presents with distant metastasis. Despite frequent initial response to chemotherapy, it inevitably relapses within 2 years in the majority of patients. Because of the poor overall prognosis of the disease and its unique tumor biology, the opportunity for improving clinical outcome of patients with development of novel therapeutics is great. This review provides current insights into the novel molecular targets in SCLC. Cellular signal transduction pathways and their relationship to cellular functions also are discussed. Discussion of the role receptor tyrosine kinases (RTKs) have in SCLC therapeutic inhibition is emphasized. In particular, the recent development of small molecule inhibitors of RTKs such as c-Kit, c-Met, and VEGF-R and the potential for clinical trials are highlighted.
Point: Fluoroquinolone-Based Antibacterial Chemoprophylaxis in Neutropenic Cancer Patients Works for Defined Outcomes in Defined Populations, but Must Be Used Wisely
Authors: Bow Eric J.
Published: April 2017

Fluoroquinolone-based antibacterial chemoprophylaxis administered in situations in which the prevalence of fluoroquinolone-resistant Escherichia coli is low (<3% to 5%) can reliably reduce the risk for invasive gram-negative bacillary infection, and, if supplemented by gram-positive agents such as rifampin, penicillin, or macrolides, can reduce the risk of developing invasive infections caused by gram-positive microorganisms, including Viridans streptococci and coagulase-negative staphylococci. In the published literature, fluoroquinolone-based chemoprophylaxis does not reliably reduce the incidence of febrile neutropenic episodes, neutropenic episode-related mortality, or physician-initiated systemic antimicrobial prescribing behavior. Prophylaxis should only be prescribed in defined patient populations from the first day of cytotoxic therapy until neutrophil regeneration in environments in which the prevalence of gram-negative bacillary resistance to the prophylaxis strategy is low. Small phase II clinical trials suggest that empirical antibacterial therapy of unexplained fevers in neutropenic patients receiving effective fluoroquinolone-based prophylaxis under defined epidemiologic circumstances may be safely discontinued early. Better discriminators of infection in febrile neutropenic patients are needed.
Counterpoint: Routine Anti-Bacterial Prophylaxis Is Not Indicated in Neutropenic Patients With Hematological Malignancies
Authors: Kleinberg Michael
Published: April 2017

Preventing bacterial infections by prescribing prophylactic antibiotics is seen by many as an important strategy for decreasing infectious mortality in the most profoundly immunosuppressed patients with hematologic malignancies. Comparative studies show consistently that neutropenic patients treated with prophylactic fluoroquinolone antibiotics develop fewer bacteremias than patients treated with placebo or less-potent antibacterials. However, these same studies fail to show increased survival rates in fluoroquinolone-treated patients. This repeated observation is the basis for the continued controversy concerning universal antibacterial prophylaxis of neutropenic patients, namely, the inability to translate the observed reduction in culture-proven bacterial infections with prophylaxis into improved clinical outcomes. The answer to this controversy lies in the effectiveness of empiric antibacterial therapy in response to neutropenic fevers. Mortality from bacterial infections is 1% or less for patients enrolled in empiric treatment trials who do not receive prophylactic antibacterials. Therefore, routine fluoroquinolone prophylaxis offers essentially no potential survival benefit to neutropenic patients with hematologic malignancies. In fact, the increasing potential for fluoroquinolones to select for resistant bacterial pathogens should give pause to the practice of routine prophylaxis of neutropenic patients.
Antiemetic Studies on the NK1 Receptor Antagonist Aprepitant
Authors: Stoutenburg John P. , Raftopoulos Harry
Published: April 2017

Aprepitant (Emend, Merck Inc., Whitehouse Station, NJ), a neurokin-1 (NK1) receptor antagonist, is a first-in-class agent approved for the prevention of acute and delayed chemotherapy-induced nausea and vomiting (CINV). It competitively binds to NK1 receptors, blocks the binding of substance P, the natural ligand, and prevents signal transduction. Early clinical trials showed that aprepitant combined with standard therapy (corticosteroids and serotonin receptor antagonists) provided improved antiemetic protection in patients receiving highly emetogenic chemotherapy. The results of three randomized, double blind, placebo-controlled trials that compared aprepitant plus standard therapy with standard therapy plus placebo showed significant improvements in complete response rates (defined as no emesis and no use of rescue medication) with the addition of aprepitant (58.8% to 71% vs. 43.3% to 52.3%; P < .05 for all). Benefits were found in the acute phases, delayed phases, and in the overall study periods. Multiple secondary endpoints also favored the addition of aprepitant, particularly in the delayed phases and overall study periods. In extended trials in which treatment was continued for up to 6 cycles of highly emetogenic chemotherapy, the antiemetic effect was maintained and remained statistically greater for the aprepitant plus standard therapy group compared with standard therapy and placebo. The addition of aprepitant was well tolerated, and common adverse events were similar to those seen with standard therapy plus placebo. A clinically significant drug interaction with CYP3A4-metabolized cytotoxic agents was reported in one trial, but not confirmed in the others. The additional protection confirmed by aprepitant translated into a decreased impact of CINV on patients' daily lives as measured by the Functional Living Index-Emesis questionnaire. Aprepitant adds additional antiemetic protection to standard therapy and should be considered in all patients receiving highly emetogenic chemotherapy.
Point: Intraperitoneal Chemotherapy in the Management of Ovarian Cancer
Authors: Markman Maurie
Published: April 2017

Both preclinical considerations and results of phase I safety and pharmacokinetic studies provided support for the argument that intraperitoneal antineoplastic drug delivery should be a rational approach to the management of ovarian cancer. Subsequently conducted phase II trials exploring regional treatment revealed surgically documented objective responses when the approach was employed as a second-line therapy. Recently, the results of three randomized phase III trials have shown that the use of primary cisplatin-based intraperitoneal therapy leads to superior survival compared with intravenous cisplatin-based treatment in patients with small-volume residual advanced ovarian cancer after initial surgical cytoreduction. Further exploration of this unique management strategy is indicated to develop an optimal approach that maintains the demonstrated enhanced efficacy while reducing the toxicity (principally because of cisplatin) of treatment.
Counterpoint: Intraperitoneal Chemotherapy: An Investigational Treatment in Ovarian Cancer
Authors: Ozols Robert F.
Published: April 2017

Intraperitoneal (IP) chemotherapy in ovarian cancer has been studied since 1978. Numerous phase II trials have been performed, which have shown that higher levels can be obtained in the peritoneal cavity compared with systemic circulation after administration of cytoxic agents in a large volume via a semi-permanent catheter. Three randomized trials have been performed in patients with ovarian cancer comparing different IP regimens to standard therapy with intravenous agents. The last two trials from the Gynecologic Oncology Group (GOG) and the Southwest Oncology Group (SWOG) compared two different IP regimens versus standard therapy with intravenous cisplatin plus paclitaxel. Although an improvement in progression-free survival was reported for the IP regimens, they have been associated with unacceptable toxicity, and no IP regimen can be considered standard therapy. Maintenance therapy with IP cisplatin also failed to improve survival in patients who obtained complete remission after intravenous chemotherapy. The GOG is considering another phase III trial of IP therapy that will compare a carboplatin-based regimen versus standard therapy with intravenous paclitaxel plus carboplatin. Unless such a trial shows an improvement in clinical outcome, intravenous carboplatin plus paclitaxel remains the standard of care and IP chemotherapy should not be used outside of a clinical trial.
Surgery for Ovarian Cancer: Rationale and Guidelines
Authors: Greer Benjamin E. , Swensen Ron E. , Gray Heidi J.
Published: April 2017

Ovarian cancer is the second most common gynecologic cancer in women and the leading cause of death caused by gynecologic malignancy. Surgery plays a fundamental role in treating this challenging disease. Goals of primary surgery for ovarian cancer are to establish diagnosis, proper staging, determination of prognosis, and optimal cytoreduction of gross disease before chemotherapy for improved outcome. In addition to standard removal of the ovaries, uterus, omentum, and pelvic and para-aortic lymph nodes for early disease, extended surgical techniques used to debulk advanced disease include bowel resection, splenectomy, partial liver resection, peritoneal or diaphragmatic stripping, and use of laser or ultrasound (CUSA). Secondary surgery is used in a variety of situations. Second-look procedures were performed historically to determine response to chemotherapy to delineate duration of treatment, but now are best used in a research setting with the advent of improved chemotherapeutic agents. As a high percentage of patients have a gynecologic malignancy recurrence after primary treatment, many practitioners perform secondary cytoreductive procedures for recurrent disease. Additionally, in the recurrent setting, surgery may be necessary for relief of bowel obstruction and palliation of symptoms. Surgical management of ovarian cancer must be performed by surgeons, such as gynecologic oncologists, who have a firm understanding of the disease process, display good clinical judgment, and are adequately trained to perform the complex surgery that commonly is required for appropriate care.
Management of Metastatic Renal Cancer
Authors: Thompson Patricia , Fishman Mayer
Published: April 2017

The purpose of this article is to review the systemic management options for patients with metastatic renal cancer. We reviewed the literature regarding systemic management of metastatic renal cancer. Treatment options of chemotherapy agents, immunotherapy, molecularly targeted agents, allogeneic stem cell transplantation, vaccines, and other manipulations of the immune system are discussed. No chemotherapy agent used alone or in combination has consistently produced responses to substantiate its routine use. Interleukin-2 (IL-2) and interferon-α (IFN-α) have shown response rates ranging from 10% to 20%. Some studies have shown that retinoids may enhance the antitumor activity of IFN-α. Molecularly targeted agents and angiogenic agents are being actively pursued and several studies are showing response rates above 30%. Although nonmyeloablative allogeneic stem cell transplantation shows some promising results, they also have limitations to its use. Therapy strategies that incorporate vaccines as part of comprehensive immune manipulations are also being studied. The systemic treatment of patients with advanced renal cell cancer continues to be a significant challenge. Immunotherapy treatment has shown response in up to 20% of patients. Unfortunately, most do not respond. The current technologies are promising and may be the key step for introduction of better treatments for renal cancer care.
Elucidation of the Molecular Mechanisms of Malignant Bone Tumors: Refining Diagnosis and Identifying Novel Targets for Treatment
Authors: Casas-Ganem Jorge , Healey John H.
Published: April 2017

Primary bone tumors are rare, accounting for less than 0.2% of all cancers diagnosed yearly in the United States. Study of the molecular mechanisms of these diseases has given insight into their pathobiology. It has also identified molecular alterations that, if present, may be used in conjunction with histologic evaluation to further refine diagnosis, allowing cases to be stratified into prognostic groups more or less likely to show response to current cytotoxic protocols. Recent findings have lead to the identification of molecular pathways that may serve as targets of novel therapies, especially in the case of Ewing sarcoma. Telomere maintenance mechanisms are also emerging as potential targets for anticancer therapy. As the molecular mechanisms underlying malignant bone tumors are better understood, new anticancer agents targeting specific pathways are likely to emerge. This may make it possible to tailor treatment for each individual patient, using a combination of cytotoxic and targeted therapies based on the histologic and molecular profile of the patient's tumor.
Aromatase Inhibitors in Postmenopausal Breast Cancer Patients
Authors: Rieber Alyssa G. , Theriault Richard L.
Published: April 2017

Aromatase inhibitors (AIs) have greatly enriched the treatment of hormone receptor-positive breast cancer in postmenopausal patients. Before the introduction of the well-tolerated third-generation AIs, tamoxifen was the mainstay of endocrine therapy for hormone receptor-positive breast cancer. Many clinical trials have shown the superiority of AIs compared with tamoxifen in adjuvant breast cancer treatment, as well as their benefit in metastatic breast cancer. NCCN guidelines recommendations for their use are based on the evidence provided by these clinical trials. This discussion reviews the evidence supporting the current guidelines for use of AI therapy in the treatment of hormone receptor-positive postmenopausal breast cancer patients.
Surgical Management of Thyroid Carcinoma
Authors: Kouvaraki Maria A. , Shapiro Suzanne E. , Lee Jeffrey E. , Evans Douglas B. , Perrier Nancy D.
Published: April 2017

Thyroid carcinoma has a unique biologic behavior characterized by early spread to regional lymph nodes and occasional extrathyroidal soft tissue extension but a low incidence of distant metastasis and infrequent disease-related death. Therefore, controversy exists over the proper extent of thyroidectomy and regional lymph node dissection in patients with differentiated thyroid carcinoma (DTC) and medullary thyroid carcinoma (MTC). The modest disease-specific mortality makes it unlikely that the extent of surgery will ever be the subject of a prospective randomized trial. Although more extensive cervical surgery may have only a limited effect on the duration of survival in patients with DTC, it may significantly improve quality of life by minimizing cervical recurrence. The high rates of cervical recurrence in patients with DTC and MTC have alerted physicians to the importance of fine-needle aspiration biopsy and ultrasonography for the diagnosis, preoperative staging, and follow-up of thyroid cancer. In patients with MTC, death caused by disease is uncommon in the absence of radiographically evident distant metastasis at the time of thyroidectomy. Cervical recurrence is even more common with MTC, and the need for compartment-oriented lymphadenectomy is accepted as standard surgical treatment to minimize disease recurrence. Postoperatively, calcitonin (CT) levels can be used to guide clinical management, but basal CT levels should not be used to direct the timing of prophylactic thyroidectomy in affected high-risk patients with familial MTC.
Chemotherapy for Metastatic Colorectal Cancer
Authors: Rosales Joseph , Leong Lucille A.
Published: April 2017

The past decade has seen a significant survival improvement for patients with metastatic colorectal cancer, fueled in large part by the arrival of active novel chemotherapeutic drugs and their incorporation into combination regimens. Several randomized trials have successfully integrated oxaliplatin and irinotecan into previously existing 5-fluorouracil (5-FU)-based regimens for advanced colorectal cancer, resulting in median survivals that have risen from 9 months to almost 2 years. Even as the ideal combinations and sequences of these regimens are elucidated, targeted therapies such as recently approved bevacizumab and cetuximab have been added to treatment protocols, with favorable consequences. We review the evolution of primary chemotherapy for advanced colorectal cancer, focusing on the trials that have led to the new standard first-line treatments. We also review the data on newer targeted therapies, especially in combination with cytotoxic therapy.
Guidelines of the National Comprehensive Cancer Network on the Use of Myeloid Growth Factors with Cancer Chemotherapy: A Review of the Evidence
Authors: Lyman Gary H.
Published: April 2017

The prophylactic use of myeloid growth factors reduces the risk of chemotherapy-induced neutropenia and its complications, including febrile neutropenia and infection-related mortality. Perhaps most importantly, the prophylactic use of colony-stimulating factors (CSFs) has been shown to reduce the need for chemotherapy dose reductions and delays that may limit chemotherapy dose intensity, thereby increasing the potential for prolonged disease-free and overall survival in the curative setting. National surveys have shown that the majority of patients with potentially curable breast cancer or non-Hodgkin's lymphoma (NHL) do not receive prophylactic CSF support. In this issue, the National Comprehensive Cancer Network presents guidelines for the use of myeloid growth factors in patients with cancer. These guidelines recommend a balanced clinical evaluation of the potential benefits and harms associated with chemotherapy to define the treatment intention, followed by a careful assessment of the individual patient's risk for febrile neutropenia and its complications. The decision to use prophylactic CSFs is then based on the patient's risk and potential benefit from such treatment. The routine prophylactic use of CSFs in patients receiving systemic chemotherapy is recommended in patients at high risk (>20%) of developing febrile neutropenia or related complications that may compromise treatment. Where compelling clinical indications are absent, the potential for CSF prophylaxis to reduce or offset costs by preventing hospitalization for FN should be considered. The clinical, economic, and quality of life data in support of these recommendations are reviewed, and important areas of ongoing research are highlighted.
Treatment of Metastatic Pancreatic Cancer
Authors: Ko Andrew H. , Tempero Margaret A.
Published: April 2017

Pancreatic adenocarcinoma represents the fourth-leading cause of cancer-related mortality in the United States. The vast majority of patients are diagnosed at advanced stages of the disease when surgery is no longer an option. For these patients, systemic therapy remains the mainstay of care. Although single-agent gemcitabine has remained the standard of care since its approval in 1997, improvements in patient outcomes may potentially be realized by (1) applying pharmacokinetic principles to optimize drug delivery, such as the administration of gemcitabine at a “fixed-dose rate” infusion; (2) combining gemcitabine with other cytotoxic agents for which evidence of synergy exists, such as platinum compounds; and (3) integrating novel targeted agents such as bevacizumab, erlotinib, and cetuximab into treatment paradigms, based on an increasing understanding of the molecular pathways that govern pancreatic tumor growth and maintenance. This article provides the evidence to support each of these approaches and highlights future directions in the management of metastatic pancreatic cancer.
The Current Status of Combined Radiotherapy and Chemotherapy for Locally Advanced or Resected Pancreas Cancer
Authors: Mulcahy Mary F. , Wahl Andrew O. , Small William
Published: April 2017

Pancreas cancer is the fourth most common cause of cancer deaths. Even for the small percentage of patients who can undergo surgical resection of the primary tumor, the risk of recurrence remains unacceptably high. For patients with localized disease that is not amenable to surgical resection, pain related to the primary tumor can significantly impair quality of life. Attempts to improve the duration and quality of life for these patients have included both chemotherapy and radiotherapy. The addition of chemotherapy to radiation may enhance the local effects of radiation or provide treatment of disease outside the radiation field. The results of clinical trials evaluating the appropriate therapy for locally advanced or resected disease have been inconsistent. In some instances, the methods used in these studies became outdated before the results were available. Hopefully, advances in radiation techniques and systemic drug therapy will provide more durable and clinically relevant results. Meanwhile, treatment decisions should be tailored to the clinical situation, including consideration of treatment toxicity and therapy goals. Recognizing which patients are likely to benefit from combination therapy or systemic therapy alone is a subject of future and ongoing clinical trials.
Leptomeningeal Metastases: Current Concepts and Management Guidelines
Authors: Chowdhary Sajeel , Chamberlain Marc
Published: April 2017

Neoplastic infiltration of the meninges occurs when malignant cells gain entry into the cerebrospinal fluid (CSF). This is clinically recognized in 4% to 7% of all cancer patients. Leptomeningeal metastases may involve any part of the neural axis via tumor seeding; thus, a multitude of clinical presentations involving one or more domains exist, including the cerebral hemisphere, cranial nerves, and spinal cord and roots. The diagnosis of CSF metastases is often delayed and not appreciated until fixed neurologic deficits become evident. Adequate cytologic analysis of CSF fluid, neuroradiography of brain and spine, and an appropriate clinical context are the key element in diagnosing leptomeningeal metastases. A major challenge of treating neoplastic meningitis is the importance of treating the entire neural axis and stratifying patients in poor risk or good risk categories. Treatment is palliative and involves stabilizing neurologic status and prolonging survival. Median survival for untreated patients is 4 to 6 weeks. Treatment in a broad perspective entails radiotherapy and chemotherapy (systemic and intra-CSF). Commonly used intra-CSF chemotherapy regimens use drugs such as methotrexate, cytarabine, thiotepa, and a sustained-release liposome-encapsulated form of cytarabine (Depocyt, SkyePharma, London, UK). Patients with neoplastic meningitis usually experience a limited survival, even when treated using close adherence to evaluation algorithms and treatment protocols. In randomized controlled clinical trials using currently available intra-CSF chemotherapeutic agents, median survival in carefully selected, study-eligible groups of patients was 2 to 6 months.
Metastatic Spinal Cord Compression
Authors: Schmidt Meic H. , Klimo Paul , Vrionis Frank D.
Published: April 2017

Approximately 70% of cancer patients have metastatic disease at death. The spine is involved in up to 40% of those patients. Spinal cord compression may develop in 5% to 10% of cancer patients and up to 40% of patients with preexisting nonspinal bone metastasis (>25,000 cases/y). Given the increasing survival times of patients with cancer, greater numbers of patients are likely to develop this complication. The role of surgery in the management of metastatic spinal cord compression is expanding. The management of metastatic spine disease can consist of a combination of surgery, radiation treatment, and chemotherapy. Treatment modalities are not mutually exclusive and must be individualized for patients evaluated in a multidisciplinary setting.
Local Treatment of Malignant Brain Tumors Using Implantable Chemotherapeutic Polymers
Authors: Gallia Gary L. , Brem Steven , Brem Henry
Published: April 2017

Malignant gliomas are among the most devastating human cancers. The infiltrating nature of these malignancies makes complete surgical resection nearly impossible. Conventional therapy for malignant gliomas consists primarily of surgical debulking followed by radiation therapy and possibly chemotherapy. The major factor limiting intracranial therapeutic levels of systemically administered chemotherapeutics is the physiologic barriers of the brain. This has led to the development of novel methods of drug delivery such as implantable polymers containing chemotherapeutic agents. Several phase III clinical trials show that implantation of carmustine-containing biodegradable polymers prolongs survival in patients with both recurrent and newly diagnosed malignant gliomas. In this article, we summarize these trials and discuss ongoing clinical trials involving implantable chemotherapy-containing polymers in the treatment of patients with malignant gliomas.
Surviving the Perfect Storm: An RVU-Based Model to Evaluate the Continuing Impact of MMA on the Practice of Oncology
Authors: Dunning David M. , Paivanas Thomas A.
Published: April 2017

The Resource-Based Relative Value Scale (RBRVS) system instituted by Centers for Medicare and Medicaid Services has lead to the implementation of a new financial analysis paradigm based on relative value units (RVUs). RVU-based financial tools have great potential to allow in-depth analysis of all components of the cancer care delivery system. Because all medical oncology practices must become conversant in RVU terminology and methodology, RVU-based financial tools will allow standardization and benchmarking for intra- and interpractice comparisons. Understanding this approach is essential for sound business management. The emotional and financial pressures facing the medical oncologist in private practice are enormous, with no real relief in sight. The complexity of managing the business of private practice oncology rivals that of managing the complexity of cancer care. With anticipated reductions in total net revenue per clinical treatment protocol per course of care, funds available for providers and their practices will be severely reduced. Only those practices with superlative RVU-based cost and revenue accounting systems will be able to prospectively and efficiently manage their businesses. Clearly, management of the Oncology Practice Econometric Model (OPEM) expense RVU or similar RVU-based data will be required for survival. The purpose of this article is to explore an RVU-based model to analyze the professional, infusion, and therapeutic components of contemporary cancer care.
Six (or More) Drugs in Search of a Mechanism: DNA Methyltransferase and Histone Deacetylase Inhibitors in the Treatment of Myelodysplastic Syndromes
Authors: Gore Steven D.
Published: April 2017

The clinical activity of the DNA methyltransferase inhibitors 5-azacitidine and 2′-deoxy-5-azacytidine in myelodysplastic syndromes (MDS) suggests that epigenetic modulation of gene transcription may play an important pathogenetic role in the development and expression of these diseases. Approximately 50% of patients treated with these compounds experience hematologic improvement, making these the most active single agents for unselected patients with MDS. Responses include complete and partial hematologic responses. Two randomized trials have shown that the use of these drugs significantly alters the natural history of MDS compared with supportive care. Histone deacetylase inhibitors, which may also impact the expression of genes through epigenetic mechanisms, seem to have measurable activity in MDS in preliminary studies. Histone deacetylase inhibitors are most likely used in combination with other agents, including DNA methyltransferase inhibitors. Despite the clinical activity of these classes of drugs, there is no conclusive evidence that their clinical activity is attributable to their impact on the epigenome. Such information will be critical in the development of more effective congeners and drug combinations in ongoing attempts to improve the outcome of patients with MDS.
Surgery for Gastrinoma and Insulinoma in Multiple Endocrine Neoplasia Type 1
Authors: Norton Jeffrey A. , Fang Tony D. , Jensen Robert T.
Published: April 2017

The surgical management of pancreatic endocrine tumors in patients with multiple endocrine neoplasia type 1 remains controversial. Gastrinoma and insulinoma are the 2 most common functional pancreatic neuroendocrine tumors in patients with multiple endocrine neoplasia type 1. Gastrinomas cause gastric acid hypersecretion and peptic ulcer disease that are best managed using proton pump inhibitors. Surgery to remove the gastrinoma in patients with multiple endocrine neoplasia type 1 is seldom curative unless a more extensive Whipple pancreaticoduodenectomy is performed. Because the prognosis is excellent, aggressive resections such as a Whipple procedure are only indicated for large, locally metastatic, advanced tumors. Furthermore, surgery to remove imageable tumors that are 2 cm in diameter is associated with excellent outcomes and decreased probability of liver metastases. Because gastrinomas are commonly multiple and most originate in the duodenum and develop lymph node metastases, the duodenum should be opened and all tumors and lymph nodes excised. Insulinomas cause hypoglycemia that results in neuroglycopenic symptoms. Medical management of the hypoglycemia is less effective than that of the gastric acid hypersecretion. Fortunately, the insulinoma is usually clearly identified using routine pancreatic imaging studies. There is a high likelihood of cure when the insulinoma is excised surgically. However, recurrent hypoglycemia may occur, and careful follow-up is indicated.
Ethical Obligations and Counseling Challenges in Cancer Genetics
Authors: Burke Wylie , Press Nancy
Published: April 2017

Cancer genetics is creating new practice opportunities in medical genetics, oncology, and primary care. The ethical and counseling challenges of this new area of practice are not unique but sometimes take new form in the context of genetic risk. This article uses cases to explore the issues associated with shared family risk, including competing concerns of family members, duty to warn relatives of genetic risk, and testing of children and other relatives. The ethical obligations of clinicians start with the need to maintain competence in the face of rapidly evolving science. Clinicians should be able to identify patients within their practice who are candidates for genetic testing. When genetic susceptibility to cancer is identified, patients should be offered counseling and follow-up, with referral as appropriate, to ensure delivery of care consistent with current standards. When patients experience barriers to needed health care, clinicians should advocate for their needs. Clinicians must ensure the autonomy and informed decision-making of all members of cancer-prone families. Clinicians must also provide emotional support and accurate information about cancer risks and cancer risk reduction measures, including uncertainties. Teamwork among different specialties is important in addressing these challenges.
Hodgkin Disease/Lymphoma Clinical Practice Guidelines
Authors: _ _
Published: April 2017

Cure rates for Hodgkin disease/lymphoma have increased to such an extent that the overriding treatment considerations often relate to long-term toxicity, especially for patients with early- or intermediate-stage disease. Current management programs are based on comprehensive clinical staging followed by combined modality therapy for patients with favorable and intermediate prognosis, or chemotherapy alone for patients with advanced disease. Relapse is uncommon, but secondary management with peripheral stem cell transplantation may be effective. The excellent prognosis for these patients mandates careful long-term follow-up to detect late treatment effects.

For the most recent version of the guidelines, please visit NCCN.org
Marginal Zone Lymphoma
Authors: Shaye Omid S. , Levine Alexandra M.
Published: April 2017

Marginal zone lymphomas (MZLs) comprise 3 distinct entities: extranodal MZL of mucosa-associated lymphoid tissue (MALT), splenic MZL, and nodal MZL. Gastric MALT lymphoma is the most common extranodal MZL and often develops as a result of chronic Helicobacter pylori gastritis. Such cases frequently respond to antibiotics directed against H. pylori. Antigen-driven lymphomatous disease can also be seen in the association of Borrelia burgdorferi with MALT lymphoma of the skin, Chlamydia psittaci with MALT lymphoma of the ocular adnexa, Campylobacter jejuni with immunoproliferative disease of the small intestine, and hepatitis C with splenic MZL. This article discusses the pathogenesis and clinical features of MZL and the treatment options available to patients.
Esophageal Cancer Clinical Practice Guidelines
Authors: _ _
Published: April 2017

Carcinomas originating in the upper gastrointestinal (GI) tract (esophagus, gastroesophageal junction, and stomach) constitute a worldwide major health problem. Unfortunately, esophageal carcinoma is often diagnosed late, and most therapeutic approaches are palliative, although advances have been made in staging procedures and therapy. The guidelines emphasize that palpable advances have been made in the treatment of locoregional esophageal carcinoma. Similarly, endoscopic palliation of esophageal carcinoma has improved substantially because of improving technology.

For the most recent version of the guidelines, please visit NCCN.org
Gastric Cancer Clinical Practice Guidelines
Authors: _ _
Published: April 2017

Gastric carcinoma is rampant in many countries around the world. An estimated 36,380 new cases of upper GI carcinomas and 25,120 deaths from these tumors will occur in the United States in 2005. These guidelines provide a systematic approach to gastric cancer and discuss advances in staging procedures such as laparoscopy and endoscopic ultrasonography and in possible functional imaging techniques. The guidelines also discuss the new standard in the United States: combination chemotherapy and radiotherapy in the adjuvant setting for a select group of patients.

For the most recent version of the guidelines, please visit NCCN.org
Combined Modality Therapy of Localized Gastric and Esophageal Cancers
Authors: Das Prajnan , Fukami Norio , Ajani Jaffer A.
Published: April 2017

Gastric and esophageal cancers continue to be a significant health problem. The incidence of proximal gastric and distal esophageal cancers has been increasing, especially in white men. Gastric and esophageal cancers have high rates of locoregional and distant failure, resulting in poor overall survival. Therefore, patients with gastric and esophageal cancer may benefit from combined modality therapy. Adjuvant chemoradiation has been shown to improve survival in gastric and gastroesophageal cancers in a phase III trial. In esophageal cancer, most randomized trials have not shown a survival benefit for preoperative chemotherapy or chemoradiation, although these approaches are widely used. This article reviews the role of staging, surgery, and adjuvant and preoperative therapies in the management of localized gastric and esophageal cancers.
Current Approaches in Familial Colorectal Cancer: A Clinical Perspective
Authors: Lynch Patrick M.
Published: April 2017

Individuals with a family history of colorectal cancer or
colorectal adenomas have an increased risk for colorectal cancer. When no hereditary syndrome is evident, screening is based on empiric risk estimates. The risk is greatest for individuals with specific inherited cancer-predisposing disorders. When conditions such as familial adenomatous polyposis or hereditary nonpolyposis colorectal cancer are diagnosed, specific neoplasm risk estimates can usually be performed based on advances in molecular genetics. These estimates lead to more straightforward and cost-effective approaches to surveillance and management. The National Comprehensive Cancer Center Network (NCCN) and other groups have provided detailed guidelines for evaluating patients based on recognition of clinical syndrome characteristics, followed by appropriate genetic counseling, genetic testing, and optimal surveillance. The NCCN guidelines are used as a frame of reference for this discussion of selected recent advances in human cancer genetics as they apply to clinical practice.
Uterine Cancers Clinical Practice Guidelines
Authors: _ _
Published: April 2017

Adenocarcinoma of the endometrium is the most common malignancy of the female genital tract in the United States. Many physicians believe that adenocarcinoma of the endometrium is a relatively benign disease because of the early symptoms of irregular vaginal bleeding in this predominantly postmenopausal patient population, the often-localized nature of the disease, and the generally high survival rate. However, the estimated number of deaths from endometrial cancer continues to increase, indicating the need for a critical reassessment of the guidelines for managing endometrial cancer. Physicians must identify high-risk patients and tailor treatment appropriately to provide the best opportunity for long-term survival.

For the most recent version of the guidelines, please visit NCCN.org
Expanding Role of Positron Emission Tomography in Cancer of the Uterine Cervix
Authors: Rajendran Joseph G. , Greer Benjamin E.
Published: April 2017

Molecular imaging through positron emission tomography (PET) is playing a very important role in the management of several different cancers. Its noninvasive nature and ability to study biologic function are ideal for oncology practice. PET is establishing itself in staging, guiding therapy, and follow-up of patients with cervical cancer. The emergence and widespread availability of combined PET/computed tomography technology has further consolidated the role of molecular scanning in managing these patients. This technology is now accessible to every cancer center in the United States and is also available in most countries. Although it is approved for staging patients with cervical cancer, its use in other clinical management situations is being evaluated. The real power of molecular imaging will be to predict treatment response and guide therapy and applications of novel PET tracers for studying complex cellular functions that characterize the tumor for individualized treatment approaches. Although PET technology is beyond the reach of many developing countries, the experience gained in major centers would help devise more effective and simpler treatments that can be introduced.
Evolving Concepts in the Management of Lobular Neoplasia
Authors: Anderson Benjamin O. , Calhoun Kristine E. , Rosen Eric L.
Published: April 2017

Lobular neoplasia broadly defines the spectrum of changes within the lobule, ranging from atypical lobular hyperplasia (ALH) to lobular carcinoma in situ (LCIS). This continuum of lesions is associated with an increased risk for developing subsequent invasive breast cancer, with the magnitude of that risk corresponding to the degree of proliferative change. The associated risk for developing invasive breast cancer after a diagnosis of lobular neoplasia is multicentric, bilateral, and equal in both breasts. Lobular neoplasia itself may transform into invasive carcinoma, although the frequency of this occurrence is unknown. Thus, lobular neoplasia is a risk factor for invasive breast cancer and may be a precursor lesion in unusual circumstances. The management of ALH and LCIS depends on the setting in which they are encountered. When ALH and LCIS are diagnosed after core needle breast biopsy, wire localization for surgical excision is required for definitive diagnosis because rates of histologic underestimation approach those of atypical ductal hyperplasia (ADH). When diagnosed on surgical biopsy, ALH and LCIS generally do not require further intervention, even when present at a surgical margin. However, bilateral breast cancer risk must be considered, especially when patients have a family history of breast cancer. In selected situations, bilateral prophylactic mastectomy with or without reconstruction may be considered when atypical hyperplasia or LCIS is diagnosed. Although this reduces risk for developing subsequent breast carcinoma by 90%, patients selected for prophylactic mastectomy represent a small subgroup of lobular neoplasia patients and generally have other risk factors, such as strong family history or evidence of genetic predisposition.
Employee Attitudes and Smoking Behavior at the City of Hope National Medical Center Smoke-Free Campus
Authors: Lin David , Stahl Douglas C. , Iklé David , Grannis Frederic W.
Published: April 2017

Since 1989, City of Hope National Medical Center (COH), located in Duarte, California, and a member of the National Comprehensive Cancer Network, has prohibited smoking anywhere on the 100-acre campus. Because little published information is available on smoke-free campuses (SFCs), we investigated the attitudes of COH employees toward the SFC and attempted to answer the question of whether a difference in employee smoking behavior occurred and was attributable to the SFC policy. An anonymous survey was sent to all 2787 campus employees using both Web-based data entry and scannable paper forms. Employees with network access were contacted by e-mail and those without computers were contacted in person. Respondents were asked questions regarding their attitudes toward the SFC and about their smoking history and current smoking behavior. A total of 1356 responses (48.7%) were received. One hundred (7.4%) respondents were current smokers, 242 (17.8%) were ex-smokers, and 1014 (74.8%) were nonsmokers. Smokers and ex-smokers smoked a mean of 2.4 fewer cigarettes (95% CI, 1.8 to 3.1; P < .0001) on workdays than on days off, with evidence of a small amount of compensatory smoking (one cigarette per day). Of the smoking employees, 61.6% believed that the SFC reduced their cigarette consumption, and 42.2% quit smoking while employed at COH between 1989 and 2002. Of all respondents, 92.6% supported the COH SFC policy. High acceptance was consistent across gender, ethnicity, job type, and educational level. COH's SFC policy is strongly supported by employees and may decrease cigarette consumption and facilitate smoking cessation among smoking employees. This information may be useful to NCCN and other medical centers in assessing current and planning future campus smoking policies.
Update on Immunotherapy for Melanoma
Authors: Ribas Antoni
Published: April 2017

Several experimental immunotherapy approaches and standard therapy with high doses of interleukin (IL)-2 can cause prolonged objective responses in some patients with metastatic melanoma. Experimental immunotherapy approaches in clinical development include 1) cytokines such as IL-7 and IL-21, 2) cytokine–antibody fusion proteins or immunocytokines, 3) whole tumor cell vaccines, 4) genetically modified tumor cells, 5) heat shock protein vaccines, 6) peptide vaccines, 7) dendritic cells pulsed with tumor antigens, 8) tumor antigen-naked DNA vectors, 9) recombinant viral vectors (either alone or in a prime boost schedule), 10) adoptive transfer of cloned tumor antigen-specific T cells, 11) Toll-like receptor ligands, 12) antagonistic antibodies to the cytotoxic T-lymphocyte antigen 4 (CTLA4, CD152), and 13) activating antibodies to CD40 and CD137 (41-BB). These improved approaches to induce cytotoxic T-cell responses to tumors are based on a more detailed understanding of the immune system activation and regulation. The higher response rates with modern immunotherapy approaches may allow exploration of the molecular mechanisms that make tumor targets sensitive or resistant to immunotherapy.
Hepatobiliary Cancers
Authors: _ _
Published: April 2017

Hepatobiliary cancers are common worldwide and highly lethal. Hepatocellular carcinoma is the most common hepatobiliary malignancy and the seventh most common cancer worldwide. Gallbladder cancer is the most common biliary tract malignancy, accounting for approximately 5000 newly diagnosed cases in the United States. Cholangiocarcinomas are diagnosed throughout the biliary tree and are usually classified as intrahepatic or extrahepatic. Intrahepatic cholangiocarcinomas arise from intrahepatic small-duct radicals, whereas extrahepatic cholangiocarcinomas encompass hilar carcinomas (including Klatskin's tumors). These guidelines discuss these subtypes of hepatobiliary cancer and the epidemiology, pathology, etiology, staging, diagnosis, and treatment of each subtype.

For the most recent version of the guidelines, please visit NCCN.org
Liver Transplantation for Hepatocellular Carcinoma: An Update
Authors: Botha Jean F. , Langnas Alan N.
Published: April 2017

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death worldwide and the most common primary hepatic malignancy. It arises on a background of hepatic cirrhosis in approximately 95% of the cases in the United States. A wide variety of treatment modalities have been applied in the treatment of HCC. Liver transplantation has emerged as the preferred treatment for patients with small HCC. Transplantation for patients whose tumors do not exceed the Milan criteria yields results equivalent to those of transplantation for non-HCC indications. Controversy now exists regarding the use of living donors, expansion of selection criteria, and role of adjuvant therapy.
Integrating POLST into Palliative Care Guidelines: A Paradigm Shift in Advance Care Planning in Oncology
Authors: Bomba Patricia A. , Vermilyea Daniel
Published: April 2017

Because predicting and outlining guidance for all possible scenarios is difficult, advance directives are rarely sufficiently precise to dictate patient preferences in specific situations as a disease progresses. Nonetheless, advance care planning is an essential process that should begin at the time of diagnosis, if not already initiated, to ensure that all patient and family rights are preserved. Communicating effectively with the patient and family and having the patient designate a surrogate decision-maker are critical. Attention must be paid to resolving conflicts among patient values and preferences and those of family and the health care team. Patient-centered goals for care and expectations should be elicited at first assessment and reassessed frequently as conditions change. As a disease progresses, advance directives are rarely precise enough to predict all possible scenarios and outline guidance for care. Therefore, for patients with advanced metastatic cancer and a potential life expectancy of less than 1 year, converting patient-centered treatment goals into actionable medical orders while the patient maintains capacity is a more effective way to ensure that patient preferences are honored. Physician Orders for Life-Sustaining Treatment (POLST) and similar medical order forms provide explicit direction about resuscitation status (“code status”) if the patient is pulseless and apneic. POLST also includes directions about additional interventions the patient may or may not want. A decade of research in Oregon has proved that the POLST Paradigm Program more accurately conveys end-of-life preferences that are more likely to be followed by medical professionals than traditional advance directives alone.