inPractice Oncology

  • Editor in Chief: Ramaswamy Govindan, MD

  1. 1. Breast Cancer

    1. 1-1

      Breast Cancer Screening

      • Authors: Joanne E. Mortimer, MD;

      • Last Reviewed: 4/1/2016

      • Abstract: Breast cancer is treatable and curable when caught at an early stage with mammog... (more)

        Abstract: Breast cancer is treatable and curable when caught at an early stage with mammography screening. A Cochrane analysis was performed that included only controlled randomized trials assessing mammography in women with no history of breast cancer and for whom mortality was an endpoint. Eight randomized clinical trials that enrolled more than 600,000 women were included in the analysis. The findings support the use of screening mammography in women older than 40 years of age; screening mammography has been shown to be effective in identifying early-stage breast cancer and in decreasing the risk of dying from the disease. By contrast, the benefits of screening mammography in women at higher risk for breast cancer are less clear. Because mammographic screening may be less effective in identifying early cancers in women at high risk for breast cancer, newer radiologic technologies may be advocated in that setting. This module describes risk factors for developing breast cancer, methods for risk assessment, and the evidence-based data leading to the accepted screening guidelines. ( less )

    2. 1-2

      Localized and Locally Advanced Breast Cancer

      • Authors: Joseph A. Sparano, MD;

      • Last Reviewed: 2/21/2018

      • Abstract: Invasive nonmetastatic breast cancer, including stage I and II localized breast ... (more)

        Abstract: Invasive nonmetastatic breast cancer, including stage I and II localized breast cancer (LBC) and stage III locally advanced breast cancer (LABC), is best managed using a multidisciplinary approach including local therapy (ie, surgery, radiation) and systemic therapy (ie, chemotherapy, endocrine therapy, anti-HER2 therapy). Initial management includes 1) estimating the risk of local and systemic recurrence after primary surgical therapy (if operable), 2) determining whether additional local therapy (eg, radiation, axillary dissection) and/or systemic therapies (eg, hormonal therapy, chemotherapy, anti-HER2 therapy) are indicated to reduce the risk of local and systemic recurrence, 3) educating the patient about their risk of recurrence and the potential benefits and risks of additional local therapy and adjuvant systemic therapy, and 4) recommending a treatment program that reduces the recurrence risk and is consistent with the patient’s therapeutic goals. Treatment recommendations are based on prognostic factors associated with recurrence risk regardless of therapy (eg, number of axillary lymph nodes with metastases, primary tumor size, and nuclear and/or histologic grade), and predictive factors that are identify patients who benefit from specific therapies, including hormonal therapy (eg, estrogen receptor or PgR expression), anti-HER2–directing therapy (eg, HER2 protein overexpression and/or gene amplification), and chemotherapy (eg, multiparameter gene expression assays). This module discusses evidence-based guideline medical management of patients with EBC and patients with LABC including inflammatory breast cancer (IBC). ( less )

    3. 1-3

      Metastatic/Advanced Breast Cancer

      • Authors: Tiffany A. Traina, MD;

      • Last Reviewed: 2/27/2018

      • Abstract: Breast cancer is the most common malignancy in women in the United States, accou... (more)

        Abstract: Breast cancer is the most common malignancy in women in the United States, accounting for an estimated 29% of all female cancers in 2017. Breast cancer also accounts for 15% of cancer deaths in women, making it the second leading cause of cancer death following lung cancer. According to data from the Surveillance, Epidemiology and End Results database (2006-2010), 1 in 8 American women will be diagnosed with breast cancer, making the average lifetime risk 12.3%. According to the American Cancer Society, 255,180 new cases of breast cancer were expected to be diagnosed in 2017, and approximately 40,890 deaths are estimated for the same year. Less than 10% of patients with breast cancer present with metastases at the initial diagnosis; instead, the majority of women with metastases presents as recurrence after definitive treatment for early-stage breast cancer. Among patients with apparently localized disease, approximately 25% with lymph node–negative and one half with lymph node–positive breast cancer will develop distant recurrences of disease. Some patients develop evidence of systemic disease concurrently with diagnosis, whereas others may experience recurrent disease more than 20 years later. Metastatic breast cancer is unlikely to be cured and complete remission from chemotherapy is rarely achieved; the median survival of patients with metastatic disease is 18-24 months. Treatment options for this patient population include surgery, cytotoxic chemotherapy, hormonal therapy, and novel targeted agents. This module discusses clinical trial data reinforcing the standard of care as well as novel treatment approaches. The topic of triple-negative breast cancer is also discussed in greater detail. ( less )

    4. 1-4

      Special Situations in Breast Diseases: LCIS, DCIS, and Breast Cancer During Pregnancy

      • Authors: Jennifer K. Litton, MD;

      • Last Reviewed: 4/1/2016

      • Abstract: Advances in screening have contributed to a high incidence of in situ breast car... (more)

        Abstract: Advances in screening have contributed to a high incidence of in situ breast carcinomas (lobular carcinoma in situ [LCIS] and ductal carcinoma in situ [DCIS]) has during the past 2 decades. In addition, delays in childbearing have led to an increased incidence of breast cancer during pregnancy. Taken together, more women are affected by in situ carcinomas and pregnancy-associated breast cancer, warranting a greater understanding of these special issues in breast health.

        The pathologic and molecular features of LCIS are distinct, and the risk for invasive cancer is increased. Because of this increased risk, women with LCIS should be encouraged to have enhanced screening and to participate in a high-risk screening program. Prophylactic mastectomy and chemoprevention are other management strategies to reduce risk.

        DCIS also presents with distinct mammography features as well as molecular markers. Surgery and radiation therapy is the preferred management strategy for most women. A risk of subsequent invasive cancer exists with DCIS, and chemoprevention with tamoxifen or an aromatase inhibitor may be useful, but its benefits must be weighed against the AEs..

        Breast cancer during pregnancy is associated with several specific issues, including the sensitivity of screening, the safety of diagnostic procedures and staging studies, and the safety and efficacy of treatment options. Other important considerations are outcomes in offspring of women treated for breast cancer during pregnancy, and the safety of pregnancy subsequent to breast cancer treatment. ( less )

  2. 2. Gastrointestinal Cancer

    1. 2-1

      Esophageal Cancer: Diagnosis, Workup, and Management

      • Authors: David H. Ilson, MD, PhD; Derek Power, BSc (Pharm), MD;

      • Last Reviewed: 4/1/2016

      • Abstract: Esophageal cancer carries a significant worldwide healthcare burden. A major epi... (more)

        Abstract: Esophageal cancer carries a significant worldwide healthcare burden. A major epidemiologic shift in the location and histologic subtypes of esophageal cancer has occurred and may be explained by classification changes, increased routine endoscopy, and changing prevalence of risk factors. Optimizing staging tools and classification is imperative because outcome of localized disease correlates directly with initial stage. Surgery is the gold standard of treatment for patients with resectable disease and can be curative. Radiation therapy, an integral part of esophageal cancer treatment, can be given in definitive, preoperative, postoperative, and palliative settings. Chemotherapy is the therapeutic mainstay for metastatic disease and is also an important component of preoperative therapy. Chemotherapy combined with radiation therapy before surgery is the most common approach for patients with resectable esophageal cancer. The integration of targeted agents into chemoradiotherapy regimens for resectable esophageal cancer has been a subject of interest in recent years, although results to date have been mixed. Trastuzumab is now approved in combination with chemotherapy (cisplatin plus either capecitabine or fluorouracil) for treatment of HER2-positive metastatic cancer of the stomach or gastroesophageal junction (GEJ) in patients who have not received prior treatment in the metastatic setting. Ramucirumab was also approved for patients with advanced gastric cancer or GEJ adenocarcinoma, as a single-agent or in combination with paclitaxel after previous fluoropyrimidine- or platinum-containing chemotherapy. Identifying predictive markers that can determine who will respond to treatment is especially pertinent for patients with localized esophageal cancer because they proceed to a potentially life-threatening surgery after neoadjuvant therapy. ( less )

    2. 2-2

      Gastric Cancer: An Overview of Diagnosis, Treatment, and Recent Advances in Care

      • Authors: Manish A. Shah, MD; Vivian E. Strong, MD;

      • Last Reviewed: 1/30/2018

      • Abstract: Gastric cancer is a global disease that presents an enormous health burden world... (more)

        Abstract: Gastric cancer is a global disease that presents an enormous health burden worldwide. Although the incidence of gastric cancer in the United States has declined during the past several decades, it remains a significant health. Although gastric malignancies are often grouped together, there are considerable clinical and pathologic differences within the disease, and various subtypes can be distinguished by disease location, histology, and molecular characteristics. Of note, the diffuse subtype is increasing in incidence in the United States. As oncologists improve their understanding of this heterogeneous disease and its specific biologic variants, improvements in patient outcomes through better characterization of distinct biologic subtypes is anticipated. There are now widely accepted standard staging algorithms, recommended standards for adequate surgery with improved nodal dissection, and numerous options for systemic therapy. Modern combination chemotherapy regimens for advanced disease are easier to administer, are better tolerated, and have demonstrated modest but real gains in response rates and patient outcomes compared with earlier regimens. Moreover, long-term survival is possible: Many studies report 10% to 15% rates of patient survival out to 2 years and beyond, and a 5-year survival rate up to 3% has been reported for individuals with metastatic disease. Finally, with the integration of molecular targeted therapy, survival rates are expected to improve even further for patients with advanced disease. This review summarizes the current standard of care in the management of gastric cancer, with an eye on eagerly anticipated future developments. ( less )

    3. 2-3

      Screening for Colorectal Cancer

      • Authors: Lukejohn Day, MD;

      • Last Reviewed: 4/1/2016

      • Abstract: This module provides clinical oncologists on the available and recommended scree... (more)

        Abstract: This module provides clinical oncologists on the available and recommended screening tests for colorectal cancer, explores the evidence behind each recommendation, and argues that there is no one best test. Three major colorectal cancer screening guidelines are available: 1) US Preventive Services Task Force, 2) American Cancer Society, US Multi-Society Task Force on Colorectal Cancer, and American College of Radiology, and 3) the National Comprehensive Cancer Network. This module presents information—similarities and differences—from all 3 guidelines. In 2012, a guidance statement from the American College of Physicians stated that “shared decision making is important when selecting a screening test because the currently available colorectal cancer screening tests are believed to be similarly efficacious.” Despite efforts to increase screening rates, by 2005 only 50% of insured Americans of screening age were up to date with colorectal cancer screening. This module emphasizes that that no screening test is perfect, that any test is better than none, and that the best screening test remains the one that gets done. ( less )

    4. 2-4

      Surgical Management of Colon and Rectal Cancer

      • Authors: John M. Skibber, MD;

      • Last Reviewed: 4/1/2016

      • Abstract: Colorectal cancer is the third most common cancer affecting Americans. An estima... (more)

        Abstract: Colorectal cancer is the third most common cancer affecting Americans. An estimated 136,830 cases of colorectal cancer and an estimated 50,310 deaths from the disease are expected in 2014. Five-year survival among patients with localized colorectal cancer is 90%—70% for regional disease and 12% for metastatic disease. Patients may present with adenomatous polyps, precancerous lesions that should be biopsied or removed during colonoscopy. Surgical management is required for most patients with colon carcinoma, and is determined by the extent of disease and comorbidities. Radical resection with curative intent is an appropriate management strategy for 80% to 90% of patients with colon carcinoma. Imaging techniques are applied to assist staging and detect metastases. The use of modern chemotherapy regimens is associated with significant response at the primary tumor site and probably reduces local complications of the primary tumor. The goal of treatment for patients with rectal carcinoma is cure or local control of disease, with maintenance of quality of life. The biology of a patient’s tumor is the most important factor in overall outcome. Appropriate adjuvant therapies can enhance local control, reduce systemic recurrence, and increase organ preservation. ( less )

    5. 2-5

      Medical Management of Colorectal Cancer

      • Authors: John L. Marshall, MD;

      • Last Reviewed: 1/30/2018

      • Abstract: Colorectal cancer is a common malignancy, with 139,970 new cases and 50,710 deat... (more)

        Abstract: Colorectal cancer is a common malignancy, with 139,970 new cases and 50,710 deaths expected in the United States in 2015. Early detection can lead to markedly improved cure rates, and when detected in a premalignant state, the incidence of colorectal cancer can be reduced through effective removal of polyps. Staging for colorectal cancer has evolved over time from the classification by Dukes (A, B, C, and D) to a more detailed TNM staging system. Patients with stage I disease have a very high cure rate with surgery alone and are not routinely offered adjuvant chemotherapy following surgery. Adjuvant therapy is considered in stage II/III colorectal cancer, though its use remains controversial in stage II patients. An increasing number of patients are recognized as having metastatic disease that may be cured by surgical techniques, with additional benefits provided with perioperative use of chemotherapy. Novel small-molecule kinase inhibitors offer a new alternative for patients with late-stage metastatic colorectal cancer. This module examines the current evidence and best practices in the nonsurgical treatment of advanced colorectal cancer. Anal carcinoma is also discussed with respect to clinical features, staging, and current treatment modalities. ( less )

    6. 2-6

      Hepatocellular Carcinoma

      • Authors: David Kaplan, MD, MSc;

      • Last Reviewed: 10/31/2017

      • Abstract: The management of hepatocellular carcinoma in the United States is challenging d... (more)

        Abstract: The management of hepatocellular carcinoma in the United States is challenging due to a rise in epidemiologic factors, low cure rates achievable through surgical interventions, and a paucity of effective biological and chemotherapeutic agents. Emergent therapies provide new hope in the treatment of advanced disease. This module provides an overview of the current surgical and therapeutic modalities and describes the pitfalls and challenges of this disease. ( less )

    7. 2-7

      Pancreatic Adenocarcinoma

      • Authors: Andrew H. Ko, MD;

      • Last Reviewed: 4/1/2016

      • Abstract: Pancreatic ductal adenocarcinoma represents the fourth leading cause of cancer-r... (more)

        Abstract: Pancreatic ductal adenocarcinoma represents the fourth leading cause of cancer-related mortality both in males and females in the United States, with an estimated 37,660 deaths attributable to pancreatic cancer in 2011. Staging is typically conducted using computed tomography or other imaging tools, including endoscopic ultrasonography where available. For patients diagnosed at an early stages of the disease who are able to undergo resection, 5-year survival is still less than 20%. In the postoperative setting, gemcitabine has a demonstrable survival advantage compared with no further therapy whereas the role of radiation remains controversial. For patients with inoperable but nonmetastatic disease, the addition of chemoradiotherapy to chemotherapy does appear to confer some benefit, although the sequencing of these modalities is a key question that still needs to be addressed. In the metastatic setting, gemcitabine-based therapy has remained the standard of care for more than a decade, with certain doublets (such as combining gemcitabine with erlotinib, a platinum agent, or capecitabine) are now recommended, at least in the subset of patients with good performance scores. Recently, a nongemcitabine-containing combination called FOLFIRINOX was shown in a phase III trial to improve survival in patients with metastatic pancreatic cancer compared with gemcitabine alone and is also recommended, although FOLFIRINOX is associated with greater toxicities. No established second-line treatment exists for advanced pancreatic cancer, although the combination of oxaliplatin, 5-fluorouracil, and folinic acid (OFF) is emerging as a standard approach. In summary, managing pancreatic cancer is complex and requires a multidiscliplinary approach including surgery, systemic and/or radiation treatment, and supportive care. There is a pressing need for earlier detection methods, identification of modifiable risk factors, and effective chemopreventive agents that may decrease both the incidence and mortality associated with this disease. ( less )

    8. 2-8

      Neuroendocrine Tumors

      • Authors: Al B. Benson III, MD, FACP, FASCO; Halla Nimeiri, MD;

      • Last Reviewed: 4/1/2016

      • Abstract: The incidence of neuroendocrine tumors, although relatively low compared with th... (more)

        Abstract: The incidence of neuroendocrine tumors, although relatively low compared with that of other carcinomas, has risen in recent years due to improved diagnostic detection. In addition, neuroendocrine tumors (NETs) occur in a variety of organ systems and exhibit diverse behavior. Neuroendocrine tumors include carcinoid tumors of the bronchi, lungs, and upper-, mid-, and lower-gastrointestinal systems; pancreatic neuroendocrine tumors; insulinomas; gastrinomas; vasoactive intestinal peptide tumors; and pheochromocytomas/paragangliomas. Biochemical evaluation of NETs includes levels of urinary or plasma 5-hydroxyindolacetic acid, and whole blood levels of chromogranin A and serotonin. Histochemical markers of neuroendocrine differentiation include chromogranin, synaptophysin, CD56, protein gene product 9.5, and neuron-specific enolase. Topographical location and determination of the extent of NETs are important for management and can be accomplished by standard endoscopy, colonoscopy, capsule endoscopy; fiberoptic bronchoscopy; and imaging techniques such as magnetic resonance imaging, computed tomography, and positron emission tomography. The use of radiolabeled octreotide and somatostatin analogues has been useful for not only detecting NETs, but also predicting the efficacy of somatostatin analogues as therapy. Functional NETs may secrete products that lead to symptoms in patients, and therefore, treatment is individualized for each patient to reduce NET burden and ameliorate symptoms. Key treatments include surgery, chemotherapy, somatostatin analogues, interferon, angiogenesis inhibitors, and mammalian target of rapamycin (mTOR) inhibitors. In addition to the above, this chapter also includes a discussion on treatment of hepatic metastases, as well as additional care and follow-up care. The genetic syndromes associated with NET are addressed. In conclusion, future developments of new and improved treatments show promising evidence of tumor and symptom reduction. Ongoing clinical trials are clarifying treatment options and adding to the armamentarium of effective agents. ( less )

    9. 2-9

      Biliary Tract Cancers

      • Authors: Rachna T. Shroff, MD;

      • Last Reviewed: 4/1/2016

      • Abstract: Biliary tract cancers are relatively rare in the United States. Surgery offers t... (more)

        Abstract: Biliary tract cancers are relatively rare in the United States. Surgery offers the sole opportunity for long-term survival, but most patients with biliary tract cancers present with inoperable disease. Neoadjuvant and adjuvant techniques have had only limited success at improving survival. Nevertheless, advances in diagnosis, imaging, surgery, radiotherapy, and chemotherapy continue to slowly improve outcomes for patients with biliary tract cancers. In the module Rachna T. Shroff, MD, discusses current diagnostic methods and treatment options and future therapeutic directions in gallbladder cancer, cholangiocarcinoma, and ampulla of Vater cancer. ( less )

  3. 3. Genitourinary Cancer

    1. 3-1

      Testicular Cancer

      • Authors: Darren R. Feldman, MD; George J. Bosl, MD;

      • Last Reviewed: 4/1/2016

      • Abstract: Testicular cancer is the most common malignancy in young adult males (aged 15-40... (more)

        Abstract: Testicular cancer is the most common malignancy in young adult males (aged 15-40 years) in the United States. The incidence of testicular cancer has been steadily rising in the United States during the past 40 years with approximately 8430 new cases predicted to be diagnosed in 2015. This inPractice module reviews the histology and pathophysiology of testicular cancer, as well as disease presentation, diagnosis, staging, and prognostic stratification. George J. Bosl, MD, and Darren R. Feldman, MD, discuss patient management strategies, guideline-based treatment options, and standards of care for testicular cancer based on histologic subtype and disease stage. ( less )

    2. 3-2

      Renal Cell Carcinoma

      • Authors: Brian Rini, MD, FACP;

      • Last Reviewed: 4/26/2018

      • Abstract: The management of renal cell carcinoma (RCC) has undergone substantial changes, ... (more)

        Abstract: The management of renal cell carcinoma (RCC) has undergone substantial changes, with innovative surgical and systemic strategies revolutionizing the approach to this disease. In localized RCC, partial nephrectomy for small tumors and radical nephrectomy for larger tumors continue to be the gold standard. Surgical practice has reduced morbidity and has advanced toward more limited and less invasive resection approaches. In addition, cytoreductive nephrectomy is often indicated before embarking on systemic treatment in patients with metastatic disease.

        The management of metastatic RCC has undergone the most significant transformation. Since the early 2000s, sunitinib and pazopanib have been the standard therapy for first-line treatment of advanced RCC, and the newer TKIs axitinib and cabozantinib have expanded treatment options for patients with advanced RCC. In the last few years, new approvals of immune checkpoint inhibitor therapies have changed the way clinicians select treatment for their patients, and optimal sequencing of these new-generation immunotherapies with current targeted therapy options continues to evolve. In this module, Brian I. Rini, MD, discusses clinical evidence and recommendations for the diagnosis and treatment of RCC.
        ( less )

    3. 3-3

      Cancers of the Bladder, Urethra, and Penis

      • Authors: Daniel Petrylak, MD;

      • Last Reviewed: 9/6/2017

      • Abstract: Bladder cancer is one of the most common malignancies, with approximately 90% of... (more)

        Abstract: Bladder cancer is one of the most common malignancies, with approximately 90% of incident cases being urothelial carcinoma, formerly known as transitional cell cancer. The etiology includes cytogenetic changes, such as epigenetic alterations. Clinical features, staging, and prognosis are discussed. Treatment of noninvasive bladder cancer includes transurethral resection with or without adjuvant intravesical therapy (Bacillus Calmette-Guérin, cytotoxics). Treatment of invasive disease involves cystectomy with or without lymphadenectomy, chemotherapy, and/or radiotherapy. Treatment of metastatic disease is focused on chemotherapy and immunotherapy. Molecular biology is playing an increasing role in the prediction of response to treatment and prognosis and is identifying targets for potential therapeutic intervention. In addition to improved staging and diagnostic techniques, the introduction of multimodal treatment protocols appears to be yielding improved prognosis. Carcinoma of the urethra and penis are also discussed, including epidemiology, etiology, staging, treatment, and prognosis.. ( less )

    4. 3-4

      Prostate Cancer

      • Authors: Gary R. MacVicar, MD;

      • Last Reviewed: 2/23/2018

      • Abstract: Prostate cancer is the most common noncutaneous malignancy occurring in males in... (more)

        Abstract: Prostate cancer is the most common noncutaneous malignancy occurring in males in the United States. It is estimated that approximately 221,000 men will be diagnosed with prostate cancer in 2015, and 1 in 7 men is likely to receive a diagnosis of prostate cancer in his lifetime. With cancer-specific survival approaching 100% at 5 years, death from prostate cancer is rare, and most men live with the disease and die from other causes rather than from prostate cancer. The consequences of prostate cancer screening and treatment are substantial, and affect quality of life as well as urinary, sexual, and bowel function. Moreover, the optimal diagnosis and treatment approaches remain controversial. In this module, the author discusses prostate cancer epidemiology, the evolution of prostate cancer screening, the prevention and treatment of localized disease, biochemical recurrence, and advanced disease. ( less )

  4. 4. Lung Cancer

    1. 4-1

      Lung Cancer Screening and Surveillance

      • Authors: David E. Midthun, MD;

      • Last Reviewed: 4/1/2016

      • Abstract: Most lung cancer cases are diagnosed at an advanced stage when curative treatmen... (more)

        Abstract: Most lung cancer cases are diagnosed at an advanced stage when curative treatment is no longer an option. A number of clinical studies have evaluated the effectiveness of screening for early detection of lung cancer with the goal of reducing mortality from lung cancer. Sputum cytology, chest radiography, and computed tomography (CT) scan have been studied as potential screening tests. Recent findings from the National Lung Screening Trial (NLST) have demonstrated a 20% reduction in mortality associated with computed tomography screening, prompting several prominent guidelines-issuing organizations to endorse annual low-dose CT screening in high-risk individuals. Based on the NLST, screening with low-dose CT has been endorsed in guidelines and recommendations from various organizations. Major concerns include false positives, radiation exposure, cost, overdiagnosis, and implementation of screening in community centers. Several ongoing clinical studies continue to evaluate low-dose CT screening and use of biomarkers in various populations and clinical contexts in order to improve outcomes in patients with lung cancer. ( less )

    2. 4-2

      Small-Cell Lung Cancer

      • Authors: David W. Dougherty, MD; Kishan J. Pandya, MD, FACP;

      • Last Reviewed: 4/1/2016

      • Abstract: Small-cell lung cancer is expected to comprise approximately 15% of all lung can... (more)

        Abstract: Small-cell lung cancer is expected to comprise approximately 15% of all lung cancers diagnosed. It is characterized by an abrupt clinical presentation and often accompanied by widespread metastases at diagnosis. Unfortunately, local treatment modalities have not been very successful; therefore, systemic chemotherapy has become the gold standard for treatment. Although thoracic and prophylactic cranial irradiation are given to some patients with limited-stage disease, combination cytotoxic chemotherapy (platinum/etoposide) has been the backbone of treatment for nearly 5 decades. Several new treatment strategies have been attempted, including the addition of a third cytotoxic agent, substitution of etoposide with another active agent, dose intensification, and maintenance chemotherapy, but unfortunately very little progress has been made. Current research is focusing on improving outcomes by employing novel molecular therapies, both as single agents and in combination with conventional cytotoxic chemotherapy. ( less )

    3. 4-3

      Non-Small-Cell Lung Cancer: Epidemiology, Staging, and Resectability

      • Authors: Betty C. Tong, MD, MHS; David H. Harpole, Jr., MD;

      • Last Reviewed: 4/1/2016

      • Abstract: Although the incidence has declined for men and stabilized for women, lung cance... (more)

        Abstract: Although the incidence has declined for men and stabilized for women, lung cancer remains the leading cause of cancer mortality in the United States. Eighty percent of cases are non-small-cell lung cancer (NSCLC) and the most are linked to cigarette smoking. Several imaging modalities, including chest radiography, computed tomography, positron emission tomography, and magnetic resonance imaging, are commonly used to assist with the diagnosis and staging of the disease. The TNM staging system is currently employed as the primary staging system. Treatment of NSCLC largely depends upon stage of disease and frequently involves a multidisciplinary team; the gold standard for early stage disease remains surgical resection, while platinum-based chemotherapy and/or chemoradiation is incorporated into the treatment strategy of those patients with higher-stage disease. The role of targeted therapies continues to emerge. ( less )

    4. 4-4

      Optimal Management of Stage III Non-Small-Cell Lung Cancer

      • Authors: Mark A. Socinski, MD;

      • Last Reviewed: 2/20/2018

      • Abstract: Locally advanced non-small-cell lung cancer (NSCLC) remains a complex and hetero... (more)

        Abstract: Locally advanced non-small-cell lung cancer (NSCLC) remains a complex and heterogeneous disease and treatment approaches continue to evolve. Several treatment approaches can be considered for Stage III NSCLC, including surgical resection, chemoradiotherapy, radiation therapy (RT), targeted treatments, and immunotherapies. Concurrent chemoradiotherapy is accepted as a standard of care in stage III NSCLC, and compared with radiotherapy alone provides a small survival benefit. By contrast, surgery should be reserved for select patients. There has been recent optimism over the integration of targeted therapies into treatment and their potential benefit over traditional cytotoxic chemotherapies in combination with radiation. Targeted agents currently approved for use in NSCLC include erlotinib and cetuximab, and bevacizumab. Many other targeted agents are being explored in clinical trials. In this review, key challenges and recent data regarding the staging and treatment of stage III NSCLC and clinical recommendations for patient management will be discussed. ( less )

    5. 4-5

      Metastatic Non-Small-Cell Lung Cancer

      • Authors: Leora Horn, MD, MSc;

      • Last Reviewed: 4/27/2018

      • Abstract: Non-small-cell lung cancer (NSCLC) comprises approximately 80% of all lung cance... (more)

        Abstract: Non-small-cell lung cancer (NSCLC) comprises approximately 80% of all lung cancers diagnosed in the United States, and one half of patients present with advanced (stage IIIb or IV) disease at diagnosis. Tumor histology and mutational status are important determinants of treatment response and must be considered when selecting therapies for metastatic NSCLC. EGFR-targeted agents, such as erlotinib, gefitinib, and afatinib play a role for EGFR mutation–positive patients, with osimertinib approved for second-line therapy for patients who develop the EGFR T790M mutation. Patients with tumors that harbor the ALK rearrangement have superior PFS when treated with crizotinib, and ceritinib and alectinib are approved at the time of progression. Crizotinib is also approved for patients with ROS1 fusions. Furthermore, targeted therapies are also becoming available for other rare driver mutations in NSCLC, including RET rearrangements, MET amplifications, and BRAF V600E or HER2 mutations. Traditional cytotoxic chemotherapy remains the frontline standard of care for EGFR and ALK wild-type patients with advanced NSCLC. A multitude of studies have evaluated various combinations, most of which are platinum based, with similar results. For the vast majority, platinum-based chemotherapy still appears to be the treatment of choice for this disease. Moreover, patients with nonsquamous cell histology may benefit from the addition of bevacizumab, an antiangiogenic agent targeting vascular endothelial growth factor, to standard platinum-based chemotherapy; while patients with squamous cell histology may benefit from the addition of necitumumab, a monoclonal antibody that inhibits EGFR signaling, to chemotherapy with gemcitabine and cisplatin. Maintenance chemotherapy is considered standard of care in patients with disease control following first-line platinum-based chemotherapy. The benefits of switch maintenance therapy remain controversial. Immune checkpoint inhibitors have emerged as an exciting new standard of care in patients with NSCLC who have progressed after platinum-based chemotherapy, regardless of histology. Ramucirumab is also approved for second-line therapy in combination with docetaxel and has been shown to be beneficial and safe regardless of tumor histology. As more treatment choices for patients emerge, clinicians must demonstrate greater discrimination when selecting treatment strategies for advanced NSCLC. In addition, the recent NCCN guidelines and ASCO clinical practice guideline update on therapy in stage IV NSCLC may serve to help oncologists make better informed treatment decisions. ( less )

    6. 4-6

      Management of Thymomas

      • Authors: Tracey Evans, MD;

      • Last Reviewed: 4/1/2016

      • Abstract: Although quite rare, tumors of the thymus (consisting of thymomas and thymi... (more)

        Abstract: Although quite rare, tumors of the thymus (consisting of thymomas and thymic carcinomas) represent the most common primary neoplasm of the anterior mediastinum. There are many unique features of thymomas, including a frequent association with autoimmune paraneoplastic syndromes. All thymomas have the capability to be invasive and to metastasize, although they are more likely to spread to the pleural lining via so-called drop metastases, rather than hematogenously or through the lymphatic system. Thymic carcinomas, by contrast, have a malignant histologic appearance and tend to follow a more aggressive disease course. In this module, Tracey Evans, MD, discusses the workup of the anterior mediastinal mass; the pathology and staging of thymic tumors; paraneoplastic syndromes; treatment of thymic tumors, including radiotherapy and chemotherapy; and the use of novel agents to treat patients with relapsed thymic tumors. ( less )

    7. 4-7

      Mesothelioma

      • Authors: Anne S. Tsao, MD;

      • Last Reviewed: 4/1/2016

      • Abstract: Mesothelioma is a rare cancer originating from the mesothelial cell monolayer th... (more)

        Abstract: Mesothelioma is a rare cancer originating from the mesothelial cell monolayer that forms the mesothelium, a nonadhesive membrane lining the body cavities. The main causative factor linked to the development of mesothelioma is environmental exposure to the mineral asbestos through inhalation or ingestion of airborne particles. Although the incidence of mesothelioma in the United States is estimated to have reached a peak in recent years as a result of reduced asbestos exposure during the last several decades, approximately 2000-3000 new cases continue to be diagnosed each year. In many other countries, the incidence continues to increase. As mesothelioma is a rare diagnosis, it is often overlooked or mistaken for other cancer types or benign conditions, thereby adversely delaying the appropriate diagnosis and treatment of patients. Once a diagnosis has been made, the management of mesothelioma also presents a considerable challenge to the healthcare community because the efficacy of currently available treatment approaches is limited, and prognosis remains poor for most patients diagnosed with this disease. This chapter reviews established methods for the accurate diagnosis and staging of mesothelioma and provides a detailed assessment of currently available treatment approaches as well as investigational studies aimed at improving outcomes for patients diagnosed with malignant mesothelioma. ( less )

  5. 5. Head and Neck Cancer

    1. 5-1

      Medical Management of Head and Neck Cancer

      • Authors: Barbara Burtness, MD;

      • Last Reviewed: 11/30/2016

      • Abstract: An estimated 650,000 new cases of head and neck cancer are diagnosed each year w... (more)

        Abstract: An estimated 650,000 new cases of head and neck cancer are diagnosed each year worldwide, with the majority occurring in developing countries. Squamous cell carcinomas (HNSCC) of the lip/oral cavity, nasopharynx, oropharynx, hypopharynx, and larynx make up the majority (> 90%) of head and neck cancers. Despite aggressive treatment of HNSCC, only 35% to 55% of patients remain alive and free of disease 3 years after standard curative treatment, even if only locally advanced at presentation. Locoregional recurrences are seen in 30% to 40% of patients and distant metastases occur in 20% to 30%. The majority of recurrences appears quickly (within 2 years of initial treatment) and an additional 10% of patients will have evidence of distant metastases at the time of first presentation. Tobacco and alcohol use are the most common risk factors for HNSCC; in addition, approximately 25% of HNSCC cases have been associated with human papillomavirus infection and have a significantly better prognosis when locally advanced compared with human papillomavirus–negative cases. Early-stage disease is often treated with surgery, but radiotherapy and chemoradiotherapy may be considered. Advanced disease or recurrent/metastatic disease often requires a multimodality approach. Several studies are exploring novel pathways, targets, and immunotherapy. Complex treatment requires a multidisciplinary approach to address the unique issues affecting quality of life. In this module, Barbara Burtness, MD, describes the diagnosis, staging, and treatment of head and neck cancer. ( less )

    2. 5-2

      Management of Thyroid Cancer

      • Authors: Corey J. Langer, MD, FACP;

      • Last Reviewed: 4/1/2016

      • Abstract: Thyroid cancer is the most common type of endocrine malignancy, and it accounts ... (more)

        Abstract: Thyroid cancer is the most common type of endocrine malignancy, and it accounts for nearly 3% of all malignancies. Thyroid cancer can be divided into three general subtypes based on pathology: differentiated (papillary, follicular, and Hürthle cell), medullary, and anaplastic thyroid cancers, with the differentiated subtypes accounting for more than 90% of thyroid cancers. With the exception of those with anaplastic cancer, the prognosis is excellent for most patients with thyroid cancer, with an overall survival rate of 85% at 10 years. Despite low mortality, local recurrence occurs in up to 20% of patients, and distant metastases occur in approximately 10% at 10 years. Emerging clinical trial data suggest that advanced or metastatic thyroid cancer can be effectively treated with targeted agents, particularly kinase inhibitors. In this chapter, Corey Langer, MD, FACP, describes the diagnosis, staging, and treatment of differentiated, medullary, and anaplastic thyroid cancers. ( less )

  6. 6. Gynecologic Cancer

    1. 6-1

      Ovarian Cancer

      • Authors: Maurie Markman, MD;

      • Last Reviewed: 9/7/2017

      • Abstract: Epithelial ovarian cancer is the most common cause of death arising from a femal... (more)

        Abstract: Epithelial ovarian cancer is the most common cause of death arising from a female pelvic malignancy and the sixth most frequent cancer in women. Risk factors such as infertility and oral contraceptive use have supported the hypothesized role of ovulation in the pathogenesis of the disease, and the presence of BRCA mutations has also been associated with increased risk of developing the disease. Screening has not played a significant role in managing ovarian cancer patients, and although the disease has long been considered a “silent” disease, this perception is likely incorrect, as findings from recent retrospective studies show that symptoms of ovarian cancer are much more common during the early stages. In this chapter, Maurie Markman, MD, discusses the current therapeutic approaches for ovarian cancer, including surgical cytoreduction, chemotherapy in the first and second lines of treatment, maintenance therapy, and treatment strategies for platinum-sensitive vs platinum-resistant recurrent disease and addresses the management of carboplatin hypersensitivity reactions. ( less )

    2. 6-2

      Nonovarian Cancer

      • Authors: Bradley J. Monk, MD, FACS, FACOG; Lyndsay J. Willmott, MD, FACOG;

      • Last Reviewed: 10/3/2017

      • Abstract: Endometrial carcinoma is the most common cause of gynecologic cancer and the sec... (more)

        Abstract: Endometrial carcinoma is the most common cause of gynecologic cancer and the second most common cause of death among female genital tract cancers. It is surgically staged, and adjuvant radiation therapy in early high-risk disease is controversial. Advanced and metastatic disease benefit from surgical cytoreduction. Cervical cancer has declined in incidence and mortality in the United States. Human papillomavirus vaccination will likely decrease rates even more, but Pap smears and HPV DNA testing remain important. Staging is based on clinical assessment, but advanced imaging modalities can be used for treatment planning. Early lesions are treated with radical surgical excision and subsequent adjuvant therapy as appropriate. Locally advanced disease is treated with radiation and cisplatin-based chemotherapy. The cisplatin/paclitaxel doublet is the standard of care for metastatic and recurrent disease. Antiangiogenic agents will likely have an important role in cervical cancer. Annual physical examinations and biopsies of suspicious lesions are key to early diagnosis and treatment of vulvar cancer. Surgery is the primary therapy for local lesions, but advanced lesions may require adjuvant radiation therapy. Neoadjuvant chemoradiotherapy can improve resectability in advanced disease. Vaginal cancer is relatively rare. Squamous cell carcinoma is the most common histologic subtype. Treatment is surgical for only the earliest lesions. More advanced stages are typically treated with radiation with or without chemotherapy. ( less )

  7. 7. Skin Cancer

    1. 7-1

      Nonmelanoma Skin Cancers

      • Authors: Caroline C. Kim, MD; Clara Curiel-Lewandrowski, MD;

      • Last Reviewed: 4/1/2016

      • Abstract: Nonmelanoma skin cancers are the most common type of malignancy in the United St... (more)

        Abstract: Nonmelanoma skin cancers are the most common type of malignancy in the United States, with more than 3.5 million cases each year. More than 75% of these tumors are basal cell carcinomas, whereas approximately 20% are squamous cell carcinomas. The majority of nonmelanoma skin cancers are curable with a variety of treatment options; however, some cases can be fatal, including those tumors found at later stages, those detected in immunocompromised individuals, and some that are intrinsically more aggressive (eg, Merkel cell carcinoma). This module reviews the clinical diagnosis, histopathologic subtypes, treatment options, and prognosis of nonmelanoma skin cancers, including basal cell carcinoma, squamous cell carcinoma, cutaneous T-cell lymphoma, and Merkel cell carcinoma. Understanding these subtypes will help clinicians refer patients to appropriate disciplines for treatment and manage patients’ risk of developing future skin cancers, recurrence, and metastasis. ( less )

    2. 7-2

      Surgical Management of Malignant Melanoma

      • Authors: Robert H. I. Andtbacka, MD, CM;

      • Last Reviewed: 4/1/2016

      • Abstract: The management of primary cutaneous melanoma has changed dramatically in the pas... (more)

        Abstract: The management of primary cutaneous melanoma has changed dramatically in the past 40 years. Traditionally, many institutions promoted wide local excisions of melanomas with 3- to 5-cm margins and the routine use of elective lymph node dissections. Most of these recommendations were not based on scientific data but rather on anecdotal evidence that patients treated with wider excisions experienced lower likelihood of recurrence at the resection site, and patients treated with elective lymph node dissections had a lower rate of regional lymph node recurrences. Surgery remains the main treatment modality for primary cutaneous melanoma, but the optimal excision margins for removal of primary tumors and methods for the evaluation of regional lymph node metastasis have now been established through well-conducted clinical trials. This module will review the current surgical management of primary cutaneous melanoma and will highlight recent changes in our understanding of this disease, including a discussion of prognostic factors for recurrence and survival. ( less )

    3. 7-3

      Medical Management of Melanoma

      • Authors: Ahmad Tarhini, MD, PhD;

      • Last Reviewed: 3/9/2017

      • Abstract: Among new cancer cases in the United States in 2015, melanoma is estimated to be... (more)

        Abstract: Among new cancer cases in the United States in 2015, melanoma is estimated to be the fifth most common cancer in men and seventh most common in women. For the year 2015, there are projected to be 73,870 new cases of melanoma. The vast majority of these will be early stage and therefore curable. However, it is estimated that 9940 patients will die from this disease in 2015. Approximately 8000 patients are found to have metastatic melanoma annually, closely approximating the annual number of deaths from this disease. This illustrates the lack of progress that has been made, up until very recently, in the treatment of stage IV melanoma during the last several decades. Nonetheless, new data from multiple recently completed clinical trials testing novel therapeutic strategies have raised real hopes about finally changing the outcome of advanced melanoma. This module reviews the risk factors, clinical diagnosis, and nonsurgical treatment options of cutaneous melanoma. ( less )

  8. 8. Sarcomas

    1. 8-1

      Soft Tissue Sarcomas

      • Authors: Sandra P. D’Angelo, MD;

      • Last Reviewed: 11/3/2016

      • Abstract: Sarcomas are a heterogeneous group of mesenchymally derived tumors that can aris... (more)

        Abstract: Sarcomas are a heterogeneous group of mesenchymally derived tumors that can arise anywhere in the body in soft tissues or bone. Soft tissue sarcomas are the most frequent sarcomas, although even these malignancies are relatively rare. Surgery is the primary treatment for soft tissue sarcomas. Radiotherapy (preoperative or postoperative) also plays a role for intermediate- and high-grade sarcomas and in cases where adequate resection is precluded by the location and extent of the tumor, or by anticipated functional deficits. The role of adjuvant chemotherapy is unclear, although some studies have shown a benefit with [doxorubicin]-based regimens, particularly for patients with soft tissue sarcomas of the extremities. New chemotherapeutic agents and targeted agents are showing activity in patients with soft tissue sarcomas, and clinical trials of these agents are ongoing. This chapter will discuss current surgical, radiation therapy, and medical options for the management of soft tissue sarcomas. ( less )

    2. 8-2

      Bone Sarcomas

      • Authors: David M. Thomas, MD, FRACP, PhD ;

      • Last Reviewed: 4/1/2016

      • Abstract: Bone sarcomas are rare cancers that illustrate many fundamental principles of mu... (more)

        Abstract: Bone sarcomas are rare cancers that illustrate many fundamental principles of multidisciplinary care. They can be categorized into 3 common types based on their tissue of origin: osteosarcomas, arising from the osteoblast lineage; chondrosarcomas, arising from cartilage; and primitive neuroectodermal tumors, also called Ewing’s sarcoma. Bone tumors present complex challenges to the clinician not only because of the range and complexity of diagnostic and treatment processes, but also because the rarity of the diseases means that management of the individual patient occurs in the absence of a strong evidence base. Treatment requires access to highly specialized resources, including state-of-the-art diagnostic imaging, skilled radiologists with experience in image-guided sampling techniques, experienced pathologists, dedicated surgeons, radiation and medical oncologists, and a committed supportive care team assembled into a dedicated multidisciplinary team.

        Outcomes for bone sarcomas, particularly Ewing’s and osteosarcoma, have markedly improved during the past 30 years. This is in no small part due to multidisciplinary care of patients and to dramatic improvements in imaging, molecular pathology, and surgical and medical techniques. However, improvements have plateaued in the past decade, despite the introduction of aggressive chemotherapy into osteosarcoma and Ewing’s sarcoma regimens and in the absence of effective systemic therapies for chondrosarcomas. ( less )

    3. 8-3

      Gastrointestinal Stromal Tumors

      • Authors: Neeta Somaiah, MD;

      • Last Reviewed: 4/1/2016

      • Abstract: Gastrointestinal stromal tumors (GIST) are the most common type of mesenchymal m... (more)

        Abstract: Gastrointestinal stromal tumors (GIST) are the most common type of mesenchymal malignancy, but are relatively rare, accounting for less than 1% of all gastrointestinal cancers. Recently, the management of GIST has undergone substantial changes, with innovative surgical and systemic strategies revolutionizing the approach to this disease. In localized GIST, wedge resection for small tumors and radical resection for larger tumors continue to be the gold standard. Surgical practice has reduced morbidity and has advanced toward more limited and less invasive resection approaches. Cytoreductive surgery is no longer indicated before embarking on systemic treatment in patients with metastatic disease. The management of advanced or metastatic GIST has undergone the most significant transformation. Surgery as primary therapy for advanced disease has been supplanted by targeted therapy. Nevertheless, the appropriate use of surgery as an “adjuvant” therapy in advanced disease remains an active area of investigation. An enhanced understanding of the underlying biology of GIST has led to systemic therapy targeted at the KIT tyrosine kinase receptor and the vascular endothelial growth factor and related pathways as well as the mammalian target of rapamycin pathway. Agents blocking these pathway elements have demonstrated robust efficacy and offer new strategic options for patients with metastatic GIST. In addition, GISTS that are deficient in succinate dehydrogenase (SDH) have demonstrated overexpression of IGF-1R, elucidating yet another potential therapeutic target. ( less )

  9. 9. Brain and CNS Malignancies

    1. 9-1

      Management of Gliomas

      • Authors: Ryan T. Merrell, MD; David A. Reardon, MD;

      • Last Reviewed: 10/3/2017

      • Abstract: Ryan T. Merrell, MD, and David Reardon, MD, review the current understanding of ... (more)

        Abstract: Ryan T. Merrell, MD, and David Reardon, MD, review the current understanding of the epidemiology and pathology of high-grade glioma in adults, including the histologic features and molecular pathogenesis. The authors also examine the medical management of the symptoms of high-grade glioma and discuss the most up-to-date treatment regimens, including surgery, radiation, and chemotherapy. New therapeutic approaches are explored, including approved and investigational agents and targets. ( less )

  10. 10. Hematologic Malignancies

    1. 10-1

      Hodgkin's Lymphoma

      • Authors: David J. Straus, MD;

      • Last Reviewed: 4/25/2018

      • Abstract: Hodgkin’s lymphoma (HL) is an uncommon B-cell malignancy representing appr... (more)

        Abstract: Hodgkin’s lymphoma (HL) is an uncommon B-cell malignancy representing approximately 0.6% of all cancers. It is occurs in 2 broad categories: classical HL and nodular lymphocyte predominant HL. There are 4 subtypes of classical HL; nodular sclerosis, mixed cellularity, lymphocyte depleted, and lymphocyte rich are characterized by the presence of the Reed-Sternberg cell. This disease has 2 age-specific incidence peaks in developed countries: 15-34 years of age and older than 50 years of age. Although higher socioeconomic status, smaller sibship size, and the Epstein-Barr virus have been suggested, no clear risk factors have been identified. However, a genetic component has been identified in twin registry studies. The use of extended field radiation therapy, introduced more than 40 years ago, and of combination chemotherapy in the mid-1960s has been major success stories in medical oncology. Combinations of chemotherapy with radiation therapy have been widely used during the past 20 years, resulting in further improvements in outcome, particularly in patients with early stages of HL. More recently, chemotherapy alone has been used in many patients with excellent results. Reducing the amount of radiation in combination with chemotherapy or eliminating radiation when it is not required can reduce the amount of late toxicity in patients cured of their HL. ( less )

    2. 10-2

      Non-Hodgkin’s Lymphoma

      • Authors: Paul M. Barr, MD; Richard I. Fisher, MD;

      • Last Reviewed: 10/31/2017

      • Abstract: Non-Hodgkin’s lymphomas (NHL) are a diverse group of lymphoproliferative d... (more)

        Abstract: Non-Hodgkin’s lymphomas (NHL) are a diverse group of lymphoproliferative disorders in which the cell of origin is a B or T lymphocyte in most cases and, more rarely, the natural killer cell. NHL is the seventh most common malignancy in the United States, accounting for 4.0% of cancer diagnoses and 2.0% of cancer-related deaths. In such a heterogeneous group of diseases, classification is based on cell type, morphology, and disease characteristics, with the most common indolent lymphomas represented by follicular and marginal zone types and aggressive lymphomas by diffuse large B-cell, peripheral T-cell, and mantle cell types, whereas Burkitt lymphoma is classified as highly aggressive. The identification and successful therapeutic exploitation of the B-cell surface marker CD20 in the form of the chimeric monoclonal antibody rituximab has revolutionized therapy for B-cell lymphomas; however, in most cases the disease remains incurable. Optimization of targeted and cytotoxic chemotherapies is an active area of clinical research across the spectrum of NHLs. This module provides a comprehensive overview of the etiology, diagnosis, staging, and treatment of various NHLs. ( less )

    3. 10-3

      Acute Leukemias

      • Authors: Elias Jabbour, MD;

      • Last Reviewed: 10/6/2017

      • Abstract: Acute leukemias are clonal malignant hematopoietic disorders resulting from gene... (more)

        Abstract: Acute leukemias are clonal malignant hematopoietic disorders resulting from genetic alterations in normal hematopoietic stem cells. These alterations induce differentiation arrest and/or excessive proliferation of abnormal “leukemic” cells or “blasts”. Acute leukemias are classified as those of myeloid or lymphoid lineage. Over the past several decades, improvements in chemotherapeutic regimens have improved outcomes in both acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). A better understanding of the biology of both AML and ALL has resulted in the identification of new therapeutic targets. However, despite current optimism, most patients with AML still die of their disease, and of adults with ALL, only 35% to 40% aged 60 years or younger and 5% to 15% aged older than 60 years will be cured. With better molecular definition and elucidation of the physiopathology of AML and ALL subtypes, and the development of new and targeted therapies, a better outcome for acute leukemias may be achievable in the future. ( less )

    4. 10-4

      Myelodysplastic Syndromes

      • Authors: Eric Padron, MD; Rami S. Komrokji, MD;

      • Last Reviewed: 4/1/2016

      • Abstract: Myelodysplastic syndromes (MDS) are a spectrum of hematopoietic stem cell malign... (more)

        Abstract: Myelodysplastic syndromes (MDS) are a spectrum of hematopoietic stem cell malignancies that present as bone marrow failure with 1 or more cytopenias and associated complications, namely, anemia, transfusion dependency, infection, and bleeding. MDS have a variable tendency to progress to AML. The incidence of MDS is approximately 14,000 cases/year in the United States, with a median age at diagnosis of 76 years, with a 2:1 male-to-female ratio. Risk factors are exposure to benzene, pesticides, or solvents and smoking. MDS may also occur secondary to chemotherapy or radiation treatment for other malignancies. Several classification systems and clinical models to guide risk stratification and prognosis continue to be developed based on morphologic features, cytogenetics, and number of cytopenias.

        In this module, Rami S. Komrokji, MD, and Eric Padron, MD, discuss treatment options, including supportive measures, the immunomodulatory drug lenalidomide, the hypomethylating agents 5-azacitidine and decitabine, and immunosuppressive therapy. Allogeneic stem cell transplantation remains the only curative option. Treatment of iron overload in transfusion-dependent patients is discussed. This module also includes discussion of the diagnosis, genetics, risk factors, and current optimal treatment of one of the MDS/myeloproliferative neoplasms, chronic myelomonocytic leukemia. ( less )

    5. 10-5

      Chronic Lymphocytic Leukemia

      • Authors: Jacqueline Barrientos, MD; Kanti Rai, MD;

      • Last Reviewed: 9/10/2016

      • Abstract: Chronic lymphocytic leukemia (CLL) is a monoclonal B-cell lymphoproliferative di... (more)

        Abstract: Chronic lymphocytic leukemia (CLL) is a monoclonal B-cell lymphoproliferative disease derived from antigen-experienced B-lymphocytes that differ in their level of immunoglobulin heavy chain variable region (IgVH) gene mutations. CLL accounts for 35% of all leukemias. Recent evidence shows that CLL is a heterogeneous disorder, with some cases demonstrating IgVH gene mutations and others not. The enhanced understanding of CLL biology has enabled the discovery of several markers that predict the course of disease. The introduction of purine analogues, monoclonal antibodies, and other targeted therapies has shifted the treatment paradigm for CLL in recent years. These modern therapies commonly achieve complete remissions and even eradication of minimal residual disease. This chapter includes information on the incidence, epidemiology, molecular markers, and treatment of both newly diagnosed and relapsed CLL. ( less )

    6. 10-6

      Chronic Myeloid Leukemia

      • Authors: Elias Jabbour, MD;

      • Last Reviewed: 1/31/2018

      • Abstract: Chronic myeloid leukemia (CML) is a clonal disorder of a pluripotent stem cell t... (more)

        Abstract: Chronic myeloid leukemia (CML) is a clonal disorder of a pluripotent stem cell that affects several cell lineages. The cytogenetic hallmark of CML is the Philadelphia chromosome, a balanced translocation between chromosomes 9 and 22. This module focuses on chronic-phase CML since more than 85% of patients are diagnosed in the chronic phase, which is usually asymptomatic and historically (ie, in the pre-imatinib era) was associated with a median survival of 4-5 years. Without adequate therapy, all patients will eventually go to an end-stage blast phase with a median survival of only 3-6 months. Universal expression of the chimeric BCR-ABL gene in patients with CML led to development of agents specifically targeted at inhibiting the resulting tyrosine kinase. These agents, such as imatinib, have significantly changed the natural history of the disease. Although most patients respond well to imatinib, some will exhibit resistance or intolerance to this treatment. Options for patients with imatinib failure include dose modification or treatment with other, newer second-generation tyrosine kinase inhibitors: dasatinib, nilotinib, or bosutinib. Most adverse events associated with these agents are manageable and frequently transient. Adequate management of patients with CML requires opportune identification of adverse events as well as measures to minimize unnecessary treatment interruptions and dose reductions. ( less )

    7. 10-7

      Philadelphia Chromosome–Negative Myeloproliferative Neoplasms: Polycythemia Vera, Essential Thrombocythemia, and Primary Myelofibrosis

      • Authors: Eric Padron, MD;

      • Last Reviewed: 4/10/2017

      • Abstract: In 2008, the World Health Organization designated the myeloproliferative neoplas... (more)

        Abstract: In 2008, the World Health Organization designated the myeloproliferative neoplasms (MPNs) into either carriers of the Philadelphia chromosome (ie, chronic myeloid leukemia) or those that do not carry the Philadelphia chromosome (ie, polycythemia vera [PV], essential thrombocythemia [ET], primary myelofibrosis [PMF]). These MPNs are collectively characterized by hypercellularity, megakaryocytic atypia, and clonality in the bone marrow along with myeloproliferation in the peripheral blood and/or spleen. Myeloproliferation can be seen in all 3 main myeloid lineages, but it is the characteristic predominance of myeloproliferation in the erythroid lineage (PV), megakaryocyte/platelet lineage (ET) and megakaryocyte/granulocytic lineage (PMF) that distinguishes each individual classical MPN. Distinguishing the classical MPNs is useful as they confer different prognoses and treatment recommendations but can be difficult due to many overlapping clinical and pathologic characteristics. This module focuses on the management of the Philadelphia chromosome negative MPNs: PV, ET, and PMF. ( less )

    8. 10-8

      Management of Multiple Myeloma

      • Authors: Kenneth Anderson, MD;

      • Last Reviewed: 3/2/2017

      • Abstract: This inPractice module reviews the etiology and risk factors for multiple m... (more)

        Abstract: This inPractice module reviews the etiology and risk factors for multiple myeloma, as well as presentation, diagnosis, and current staging and risk-stratification strategies. General clinical management of myeloma is summarized, and newly approved treatments for this hematologic malignancy are discussed. Dr. Anderson also explains standards of care such as stem cell transplantation and evolving therapeutic strategies such as regimens that combine novel agents with each other and with stem cell transplantation. Although multiple myeloma remains an incurable illness associated with significant morbidity and mortality, the introduction of novel therapies has improved outcomes for patients with the disease and, moreover, provided a paradigm for the development of new agents in other malignancies. ( less )

    9. 10-9

      Peripheral and Cutaneous T-Cell Lymphomas

      • Authors: Daniel O. Persky, MD;

      • Last Reviewed: 4/1/2016

      • Abstract: T-cell lymphoma is a type of non-Hodgkin’s lymphoma that arises from the T... (more)

        Abstract: T-cell lymphoma is a type of non-Hodgkin’s lymphoma that arises from the T lymphocytes in the immune system. T-cell lymphoma is relatively rare, accounting for only 15% of all non-Hodgkin’s lymphomas and approximately 5% of all lymphoid neoplasms. T-cell lymphoma is largely classified as either peripheral T-cell lymphoma (PTCL) or cutaneous T-cell lymphoma (CTCL). PTCL and CTCL differ primarily in their presentation; PTCL can occur both systemically and cutaneously, and CTCL first manifests in the skin before progressing to other sites. Both PTCL and CTCL are further divided into multiple subtypes. Each subtype is unique, with a different clinical presentation, pathologic findings, and prognosis. Although CTCL generally responds well to treatment, PTCL is considered to be aggressive and difficult to treat. Whereas PTCL has traditionally been unresponsive to standard chemotherapies, new insights into the molecular and immunologic characteristics of PTCL have allowed the development of new treatment options for these patients. This module discusses the diagnosis, presentation, workup, prognosis, pathology, and therapeutic options associated with treating patients with the numerous subtypes of PTCL and CTCL. ( less )

    10. 10-10

      Immune Thrombocytopenia

      • Authors: Howard Liebman, MD, FACP;

      • Last Reviewed: 4/1/2016

      • Abstract: Immune thrombocytopenia is a heterogeneous autoimmune disorder characterized by ... (more)

        Abstract: Immune thrombocytopenia is a heterogeneous autoimmune disorder characterized by thrombocytopenia with or without mucocutaneous bleeding manifestations. Because of its complex pathophysiology and association with a variety of other disorders, immune thrombocytopenia is best described as a syndrome with a common clinical phenotype of thrombocytopenia. Although the clinical manifestations of immune thrombocytopenia have been known for more than a century, it is only in the last 20 years that our increased understanding of normal immune regulation has led to improved awareness of its pathophysiology. The mechanisms that underlie immune thrombocytopenia involve aberrant interactions of antigen presenting cells, B lymphocytes, and regulatory thymic lymphocytes, leading to increased platelet destruction and ineffective platelet production. This new understanding of the pathogenesis of immune thrombocytopenia has resulted in new therapeutic interventions with improved treatment outcomes, particularly for patients with disease that is refractory to traditional therapies. ( less )

    11. 10-11

      Waldenström’s Macroglobulinemia

      • Authors: Steven P. Treon, MD, MA, PhD;

      • Last Reviewed: 4/1/2016

      • Abstract: Waldenström’s macroglobulinemia (WM) arises from the accumulation of ... (more)

        Abstract: Waldenström’s macroglobulinemia (WM) arises from the accumulation of clonally related IgM-secreting lymphoplasmacytic cells, primarily in the marrow. Approximately 20% of patients demonstrate a familial predisposition. MYD88 L265P is a highly recurring somatic mutation (> 90%) that can help distinguish WM from other overlapping B-cell LPD. CXCR4 WHIM-like somatitic mutations are present in 30% to 35% of patients with WM. Observation is suitable for asymptomatic patients, whereas treatment should be considered for patients with a disease-related hemoglobin level < 10 g/L, platelet count < 100 x 109/L, bulky adenopathy or organomegaly, symptomatic hyperviscosity, peripheral neuropathy, amyloidosis, cryoglobulinemia, cold-agglutinin disease, or evidence of disease transformation. Plasmapheresis should be for patients with symptomatic hyperviscosity, and as a prophylactic measure prior to rituximab administration in selected patients. Frontline therapies include rituximab alone or in combination with alkylating agents, proteasome inhibitors, nucleoside analogues, and ibrutinib. The reuse or use of an alternative frontline regimen, ibrutinib, everolimus, or stem cell transplantation can be considered as salvage therapy. Novel therapies for WM include agents that target MYD88, CXCR4, BCL2, and CD27/CD70 as well as novel proteasome inhibitors, and chimeric antigen receptor modified T-cell therapy. ( less )

  11. 11. Supportive Care

    1. 11-1

      Management of Cancer Pain

      • Authors: Rahul Rastogi, MD; Robert A. Swarm, MD;

      • Last Reviewed: 4/1/2016

      • Abstract: Earlier cancer diagnoses and better treatments have improved survival among canc... (more)

        Abstract: Earlier cancer diagnoses and better treatments have improved survival among cancer patients; however, with increasing survival from advancements in cancer care, cancer is becoming an important cause of chronic pain. In some cases, pain associated with cancer may be more devastating than cancer itself. Up to 50% of cancer patients have severe pain at some point in the disease process, even with new treatments and improved awareness of cancer-pain management. Cancer patients usually have at least 2 chronically painful anatomical sites, but 40% of patients have more than 4 painful sites. The etiology of cancer pain is usually multifactorial. Cancer pain may be related to the tumor itself, cancer treatments, or noncancer preexisting disease. Because of the multidimensional nature of pain, management must include a multidisciplinary approach. Cancer-pain management is not simply a matter of administering systemic analgesics but may also require psychological therapies, physical therapies, and other treatments. In this module, Robert A. Swarm, MD, and Rahul Rastogi, MD, provide a comprehensive review of current approaches to managing pain in cancer patients. Topics include an analysis of optimized use of opioids, nonopioids, and adjuvant analgesics in the pharmacologic management of cancer pain as well as an evaluation of the role of interventional pain therapies for the treatment of refractory cancer pain and a discussion of complementary and alternative medical approaches. ( less )

    2. 11-2

      Palliative Care

      • Authors: David Hui, MD, MSc;

      • Last Reviewed: 4/1/2016

      • Abstract: The diagnosis of cancer is associated with significant morbidity and mortality, ... (more)

        Abstract: The diagnosis of cancer is associated with significant morbidity and mortality, with more than one half of all cancer patients eventually dying of their illness. Complications such as thromboembolism and infections frequently result in acute deterioration. In addition, antineoplastic therapies such as chemotherapy and radiation are associated with significant adverse effects, adding to the already heavy symptom burden. Faced with a life-threatening illness, uncertainties of treatment outcomes, and financial stress, cancer patients and their families frequently experience psychosocial and existential distress, which can further affect their quality of life. Given the universal nature of physical and emotional concerns among cancer patients, it is essential to ensure that they have access to effective symptom management and psychosocial interventions. Over the past few decades, the discipline of palliative care has accumulated substantial expertise and scientific evidence in areas relating to symptom control, patient-clinician communication, and healthcare decision making, particularly for patients with advanced cancer. Integration of palliative care under a comprehensive cancer-care model not only helps to improve patient quality of life but also enables them to better tolerate cancer treatments. ( less )

    3. 11-3

      Cancer-Associated Thrombosis

      • Authors: Alok A. Khorana, MD, FACP;

      • Last Reviewed: 4/1/2016

      • Abstract: Cancer-associated thrombosis occurs commonly in patients with cancer, especially... (more)

        Abstract: Cancer-associated thrombosis occurs commonly in patients with cancer, especially those receiving anticancer treatment. Venous thromboembolism, which includes deep vein thrombosis and pulmonary embolism, has important consequences for the cancer patient: requirement for long-term anticoagulation, increased risk of major bleeding complications, and increased risk of recurrent venous thromboembolism. It also can affect chemotherapy delivery and patient quality of life. Most important, thrombotic events are the second leading cause of death in cancer patients (after cancer itself) and are associated with decreased short-term and long-term survival. The past decade has seen important strides in the understanding of cancer-associated thrombosis. Identification of new clinical risk factors as well as biomarkers, development of a risk assessment tool for chemotherapy-associated thrombosis, large new clinical trials of thromboprophylaxis in cancer populations, and new oral agents for treatment of cancer-associated thrombosis have all moved the field forward. This module will focus on risk assessment, prevention, and treatment of cancer-associated thrombosis. ( less )

    4. 11-4

      Supportive Care Issues in Cancer Care

      • Authors: Christine Rimkus, RN, MSN, AOCN;

      • Last Reviewed: 4/1/2016

      • Abstract: Physicians and other providers have a significant role in managing the AEs of ca... (more)

        Abstract: Physicians and other providers have a significant role in managing the AEs of cancer and its treatment. Because of the potential deleterious effects on patient quality of life, performance score, and therapeutic outcomes, treating AEs is an important component of the overall care of the patient with cancer. This module covers the latest information in the prevention and management of neutropenia, anemia, fatigue, nausea/vomiting, diarrhea, and nutritional challenges in addition to cardiac and pulmonary toxicity. With better control of AEs, patients may not only have improved comfort and quality of life but may be better able to tolerate therapy, which can result in improved treatment outcomes. ( less )

  12. 12. General Oncology Topics

    1. 12-1

      Cancer of Unknown Primary Site

      • Authors: F. Anthony Greco, MD;

      • Last Reviewed: 4/1/2016

      • Abstract: Cancer of unknown primary site (CUPS) accounts for up to 5% of advanced cancers ... (more)

        Abstract: Cancer of unknown primary site (CUPS) accounts for up to 5% of advanced cancers each year in the United States. However, the management of patients with these tumors is unresolved, primarily because traditional oncologic principles regarding the treatment of known primary tumor sites are not applicable to these patients. Cytotoxic chemotherapeutic agents have traditionally been used, with limited success. More recently, advancements in targeted therapies have improved the prognosis of these patients. Research into the genetic features of CUPS suggests that many share molecular characteristics attributed to certain known primary tumors. Thus, treatment now relies on diagnostic immunohistochemistry and molecular cancer classifier assays to better differentiate patients for site-specific therapy. ( less )

    2. 12-2

      Oncologic Emergencies

      • Authors: Carl E. Freter, MD, PhD, FACP; Shadi Haddadin, MD;

      • Last Reviewed: 4/1/2016

      • Abstract: Oncologic emergencies are an uncommon yet important complication experienced by ... (more)

        Abstract: Oncologic emergencies are an uncommon yet important complication experienced by cancer patients. When not promptly diagnosed and effectively treated, these complications may progress and become long-term or even fatal consequences of their cancer. This chapter provides an overview of the most frequently encountered oncologic emergencies, including malignant spinal cord compression, cardiac tamponade, superior vena cava syndrome, cancer-associated hypercalcemia, syndrome of inappropriate antidiuretic hormone secretion, and acute tumor lysis syndrome. The authors describe the clinical presentation and diagnosis of these complications and discuss the treatment options. By completing this activity, providers will be able to more effectively recognize and treat oncologic emergencies, thus preventing potentially devastating complications in their cancer patients. ( less )

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      Adolescents and Young Adults With Cancer

      • Authors: Keri B. Zabokrtsky, BA, MS; Leonard S. Sender, MD;

      • Last Reviewed: 4/1/2016

      • Abstract: Of the 1.6 million Americans diagnosed with cancer each year, approximately 70,0... (more)

        Abstract: Of the 1.6 million Americans diagnosed with cancer each year, approximately 70,000 are adolescent and young adults (AYAs) aged 15-39 years. The AYA cancers can broadly be classified into 3 categories that are strongly correlated with the age of the patient: classic “pediatric” cancers, classic “adult” cancers, and cancers that uniquely peak in the AYA population. As knowledge of cancer grows, so does awareness of the cancer’s host—not only are children different from adults, but there are key developmental stages present over the course of a lifetime that should be taken into consideration when planning patient care. Adolescents and young adults differ from their younger and older peers; this module defines the AYAs who develop cancers, discusses what we know about them and their diseases, and provides a guide to their diagnoses and treatment in this group of patients. ( less )