1-1 CCO Oncology inPractice: Caring for Patients With Cancer

Author: Ramaswamy Govindan, MD

Date Released: October 01, 2009

2-1 Screening for Breast Cancer

Authors: Joanne E. Mortimer, MD, Sumanta Kumar Pal, MD

Date Released: October 01, 2009

Abstract: Breast cancer is the most common form of cancer in women in the United States, afflicting 1 in 8 women. 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. Seven randomized clinical trials that enrolled one half million 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 chapter describes the risk factors for developing breast cancer, methods for risk assessment, and the evidence-based data leading to the accepted screening guidelines.

2-2 Early Breast Cancer

Author: Joseph A. Sparano, MD

Date Released: October 01, 2009

Abstract: The medical oncologist who treats patients with early breast cancer has several important roles. These include determining the extent of the disease, estimating the risk of recurrence after primary therapy, determining which therapies may reduce the risk of recurrence, educating the patient about their risk of recurrence and the potential benefits and risks of adjuvant therapy, and recommending an adjuvant treatment regimen that reduces the recurrence risk and is consistent with the patient’s therapeutic goals. The approach to the initial management of localized breast cancer includes several essential elements. The National Comprehensive Cancer Network guidelines for the treatment of breast cancer have several key recommendations regarding the treatment of localized breast cancer. Several prognostic factors are associated with an increased risk of local and systemic recurrence. These include the number of axillary lymph nodes harboring metastases, the extent of axillary lymph node involvement, primary tumor size, nuclear and/or histologic grade, estrogen receptor or progesterone receptor expression, HER2/neu protein expression, and other factors. Adjuvant chemotherapy has been consistently shown to reduce the risk of recurrence. Endocrine therapy may produce substantial incremental benefit when added to adjuvant chemotherapy in patients with hormone receptor–positive disease, which accounts for approximately 65% of all breast cancer. Administration of chemotherapy before surgery, called primary systemic chemotherapy or neoadjuvant chemotherapy, offers several potential advantages to postoperative therapy for both practical and theoretical reasons, including a high clinical response rate, a correlation between short-term response and long-term outcomes, and facilitation of breast conservation surgery in patients with a large tumor-to-breast ratio who may not otherwise be optimal candidates for breast conservation. This chapter discusses chemotherapy, hormonal therapy, and immunotherapy (with trastuzumab), which have all been shown to significantly reduce the risk of recurrence when used postoperatively in appropriately selected patients with operable breast cancer who have received primary surgical therapy.

2-3 Locally Advanced and Inflammatory Breast Cancer

Author: Adam M. Brufsky, MD, PhD

Date Released: October 01, 2009

Abstract: When breast cancer has progressed locally but has not yet spread outside of the breast and regional lymph nodes, it is considered locally advanced breast cancer (LABC). LABC includes breast cancers that have evidence of a large mass, that involve the skin of the breast or the underlying muscles of the chest wall, and that have infiltrated into the local lymph nodes. In addition, a growing subset of LABC, termed inflammatory breast cancer (IBC), is becoming increasingly diagnosed. The prognosis of patients with LABC and especially IBC is relatively poor, with 5-year survival rates as low as 40%. According to the National Comprehensive Care Network (NCCN) guidelines, an anthracycline-based regimen is the standard primary neoadjuvant chemotherapy recommended for the treatment of LABC. The majority of clinical trials involving this standard therapy uses doxorubicin combined with cyclophosphamide and 5-fluorouracil. The TAX-301 trial first established the efficacy of the addition of a taxane to this standard therapy in the neoadjuvant setting. For patients with hormone receptor–positive LABC, neoadjuvant endocrine therapy is also considered an acceptable option. Mastectomy has historically been the surgery of choice for patients with LABC. Although the addition of radiotherapy to surgery subsequent to induction chemotherapy results in higher rates of local control, the impact of the addition of radiotherapy on survival is less established. Several treatment strategies have been evaluated for patients with IBC. These include surgical approaches, combine modality, and targeted therapy. An anthracycline-based chemotherapy regimen, with or without a taxane, followed by surgery, radiotherapy, and completion of the chemotherapy regimen, endocrine treatment (if hormone receptor positive), and trastuzumab (if HER2 positive) is the combined modality approach recommended by the NCCN. Ongoing clinical trials are now under way to evaluate the use of novel targeted agents in the treatment of both LABC and IBC, including mTOR inhibitors and antiangiogenesis agents. This chapter focuses on the differentiation, diagnosis, and current and novel treatment approaches for LABC and IBC.

2-4 Metastatic Breast Cancer

Authors: Foluso O. Ademuyiwa, MD, Kathy D. Miller, MD, Lida A. Mina, MD

Date Released: October 01, 2009

Abstract: Breast cancer is the most common malignancy in women in the United States, accounting for an estimated 27% of all female cancers in 2009. 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 (2004-2006), 1 in 8 American women will be diagnosed with breast cancer, making the average lifetime risk 12.1%. According to the American Cancer Society, more than 194,000 new cases of breast cancer are expected to be diagnosed in 2009, and approximately 40,000 deaths are estimated for the same year. Less than 10% of breast cancer patients present with metastasis at the initial diagnosis; instead, the majority of women with metastasis presents as a relapse 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 ultimately develop metastatic 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 chapter discusses clinical trial data reinforcing the standard of care as well as novel treatment approaches. The topic of bone health is also discussed.

2-5 LCIS, DCIS, and Breast Cancer During Pregnancy

Author: Jennifer K. Litton, MD

Date Released: October 01, 2009

Abstract: The incidence of in situ breast carcinomas (lobular carcinoma in situ [LCIS] and ductal carcinoma in situ [DCIS]) has increased over 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 may be useful, but its benefits must be weighed against the adverse effects.

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.

3-1 Esophageal Cancer

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

Date Released: October 01, 2009

Abstract: Esophageal cancer has a case fatality ratio of 83%, making it far more deadly than other common malignancies. A major epidemiologic shift in the location and histologic subtypes of esophageal cancer may be explained by classification changes, increased routine endoscopy, and changing prevalence of risk factors. Optimizing staging tools and classifications 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. Several ongoing trials are integrating targeted agents into chemoradiotherapy regimens for resectable esophageal cancer. 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.

3-2 Stomach Cancer

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

Date Released: October 01, 2009

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 problem throughout Southeast Asia, Eastern Europe, and Central America and is responsible for nearly 700,000 deaths annually. 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. 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 as high as 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.

3-3 Colorectal Cancer: Screening

Author: James E. Allison, MD, FACP, AGAF

Date Released: October 01, 2009

Abstract: This chapter updates 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. Colorectal cancer screening guidelines published by the American Society for Gastrointestinal Endoscopy recommend optical colonoscopy as the preferred screening test. The American Cancer Society guidelines do not specify one screening test as best or preferred but recommend structural examinations (sigmoidoscopy, double-contrast barium enema, computed tomographic colonography, and optical colonoscopy) over fecal tests. Recent findings show that screening colonoscopies typically reveal no adenomas or cancers. They highlight the need to identify a test that can estimate absolute risk for individual persons, which helps target screening colonoscopy to those people with advanced neoplasia. The currently recommended fecal occult blood tests represent such a test. 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 chapter 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.

3-4 Surgical Management of Colon and Rectal Cancer

Author: John M. Skibber, MD

Date Released: October 01, 2009

Abstract: Colorectal cancer is the third most common cancer affecting Americans. An estimated 106,100 cases of colon cancer and 40,870 cases of rectal cancer are expected in 2009, as well as an estimated 49,920 deaths. Five-year survival among patients with localized colorectal cancer is 90%—68% for regional disease and 11% 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.

3-5 Colorectal Cancer: Medical Management

Author: John L. Marshall, MD

Date Released: October 01, 2009

Abstract: Colorectal cancer has gained increased attention over the last 2 decades. It is a common malignancy affecting nearly 1 million people worldwide, and it is known that early detection of colorectal cancer can lead to markedly improved cure rates. When detected in a premalignant state, the incidence of colorectal cancer can be reduced through effective removal of polyps. Unfortunately, the incorporation of effective screening tools for patient populations in the United States and around the world remains a challenge.

Colorectal cancer is staged based on penetration of the tumor through the bowel wall and whether there is lymph node involvement or there are more distant metastases. The staging system evolved over time from an original classification by Duke (A, B, C, and D) to a TNM staging system. Fundamentally, patients with stage I disease who do not have transmural tumor penetration or lymph node involvement have a very high cure rate with surgery alone This group of patients is not routinely offered adjuvant chemotherapy following surgery. However, adjuvant therapy is considered when the tumor penetrates through the bowel wall, constitutes a T3 lesion, or there is lymph node involvement. Distant metastases are unfortunately common in colorectal cancer, with nearly 50,000 patients developing metastatic disease each year in the United States. This chapter examines the current evidence guiding the nonsurgical treatment of advanced colorectal cancer.

Anal carcinoma is a rare type of cancer that is commonly associated with human papillomavirus infection (anal-genital warts) and receptive anal intercourse. Other risk factors include a history of cervical, vulvar, or vaginal cancer; immunosuppression (ie, due to immunosuppressive therapy following transplantation or HIV infection); and smoking. The pathology of most primary anal cancers is squamous cell in origin, and the disease is therefore treated differently from colorectal cancer.

3-6 Hepatocellular Carcinoma

Authors: Ghassan K. Abou-Alfa, MD, Eileen O'Reilly, MD

Date Released: October 01, 2009

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. An overview of the current surgical and therapeutic modalities along with the pitfalls and challenges of the disease are discussed in this chapter.

3-7 Pancreatic Cancer

Author: Andrew H. Ko, MD

Date Released: October 01, 2009

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 35,240 deaths attributable to pancreatic cancer in 2009. Staging is typically conducted using computed tomography or other imaging. The 5-year survival rate of patients with pancreatic cancer is less than 20%. 5-fluorouracil and gemcitabine are standard therapies for pancreatic cancer, and some newer targeted agents (eg, erlotinib) have shown promise in clinical trials. Chemoradiotherapy, although commonly used, remains a controversial treatment modality. Gemcitabine-containing combination chemotherapy regimens are being investigated for the treatment of metastatic disease. No established second-line treatment exists, although the addition of gemcitabine to 5-fluorouracil and folinic acid recently was shown to improve survival as second-line treatment. Managing pancreatic cancer is complex and requires a multidiscliplinary approach including surgery, systemic and/or biologic treatment, and supportive care. Importantly, patients with pancreatic cancer are at high risk of venous thrombolic events. 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.

3-8 Neuroendocrine Tumors

Authors: Nushmia Z. Khokhar, MD, Halla Nimeiri, MD, Al B. Benson III, MD, FACP

Date Released: October 01, 2009

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 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.

4-1 Testicular Cancer

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

Date Released: October 01, 2009

Abstract: Testicular cancer is the most common malignancy in young adult males (aged 15-40 years ) in the United States. Since approximately 95% of testicular tumors are germ cell tumors (GCTs), the terms “testicular cancer” and “GCT” are sometimes used interchangeably. However, a variety of other tumor types can occur in the testis and 10% of GCTs arise in extragonadal locations. Germ cell tumors (GCTs) are derived from primordial germ cells. Consequently, these tumors have the ability to differentiate into a broad range of different embryonic and extraembryonic tissues. Intratubular germ cell neoplasia is the noninvasive precursor lesion to GCT. Upon becoming invasive, GCTs separate into 2 broad histologic categories—seminomas and nonseminomas, each representing approximately 50% of cases. When ultrasound confirms a testicular mass, the initial diagnostic and therapeutic procedure of choice is radical inguinal orchiectomy with clamping and ligation of the spermatic cord at the internal ring. Early-stage carcinoma comprises stage I, IIA, and some IIB tumors. Approximately 80% of seminomas are stage I, with the cure rate approaching 100%, independent of treatment approach. Historically, adjuvant radiation was the mainstay of treatment. However, the reported association between radiation and secondary malignancies and the absence of a survival advantage of radiation over surveillance has led many to favor surveillance. Approximately 20% of patients with germ cell tumors (GCTs) have advanced disease and require chemotherapy. Approximately 20% to 30% of patients will develop progressive disease following initial chemotherapy with or without surgery and will require salvage therapy. This group includes patients refractory to first-line treatment, those relapsing from remission within the first 2 years, and those with late relapse (> 2 years from completion of chemotherapy). This chapter will focus on the clinical presentation, diagnosis, and treatment options for managing different stages of testicular cancer.

4-2 Renal Cell Carcinoma

Author: Brian I. Rini, MD

Date Released: October 01, 2009

Abstract: Renal cell carcinoma (RCC) accounts for 3% to 5% of all new adult malignancies, representing the seventh most common cancer in men and the eighth most common cancer in women. Approximately 2% to 3% of cases are hereditary. Recently, the management of 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 RCC has undergone the most significant transformation. Immunotherapy, although still of benefit in select patients with good prognostic factors, has been supplanted by targeted therapy. An enhanced understanding of the underlying biology of RCC has led to systemic therapy targeted at the vascular endothelial growth factor protein and related pathway 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 RCC.

4-3 Cancer of the GU Tract: Bladder, Urethra, Penis

Author: Derek Raghavan, MD, PhD

Date Released: October 01, 2009

Abstract: Bladder cancer is one of the most common malignancies, with approximately 16 cases per 100,000 males and 5 per 100,000 females. Approximately 90% of incident cases are urothelial carcinoma, also known as transitional cell cancer. The etiology includes cytogenetic changes, including epigenetic alterations. Clinical features, staging, and prognosis are discussed. Treatment of noninvasive bladder cancer includes transurethral resection with adjuvant intravesical therapy. Treatment of invasive or metastatic disease involves cystectomy, lymphadenectomy, chemotherapy, and/or radiotherapy. 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.

4-4 Prostate Cancer

Authors: Maha Hussain, MD, Ted A. Skolarus, MD

Date Released: October 01, 2009

Abstract: Prostate cancer is the most common noncutaneous malignancy occurring in males in the United States. It is estimated that approximately 190,000 men will be diagnosed with prostate cancer in 2009 and 1 in 6 men are likely to receive a diagnosis of prostate cancer in their 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 chapter, we discuss prostate cancer epidemiology, the evolution of prostate cancer screening, the prevention and treatment of localized disease, biochemical recurrence, and advanced disease.

5-1 Lung Cancer Screening and Surveillance

Authors: David E. Midthun, MD, James R. Jett, MD

Date Released: October 01, 2009

Abstract: Unfortunately, the majority of 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 scan have been studied as potential screening tests. Although several studies have shown survival benefit, mortality reduction with screening has yet to be demonstrated. The observed survival benefits are likely a result of inherent screening biases, including lead time, length time, and overdiagnosis bias. Several ongoing clinical studies continue to evaluate screening with the hope of demonstrating mortality benefit for early detection of lung cancer and subsequently changing current clinical practice.

5-2 Small-Cell Lung Cancer

Authors: Manoj Agarwal, MD, MBA, Kishan J. Pandya, MD, FACP

Date Released: October 01, 2009

Abstract: Small-cell lung cancer is expected to comprise 14% of all lung cancers diagnosed in the United States in 2009. 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/toposide) 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.

5-3 Non-Small-Cell Lung Cancer: Epidemiology, Staging, and Resectability

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

Date Released: October 01, 2009

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 majority 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.

5-4 Optimal Management of Stage III Non-Small-Cell Lung Cancer

Authors: Juneko E. Grilley-Olson, MD, Mark Socinski, MD

Date Released: October 01, 2009

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.

5-5 Metastatic Non-Small-Cell Lung Cancer

Authors: Leora Horn, MD, MSc, Alan B. Sandler, MD

Date Released: October 01, 2009

Date Updated: December 03, 2009

Abstract: Non-small cell lung cancer (SCLC) is expected to comprise 80% of all lung cancers diagnosed in the US in 2009 and nearly half of patients present with advanced (stage IIIb or IV disease). Traditional cytotoxic chemotherapy has long been the standard of care for 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, cisplatin-based chemotherapy still appears to be the treatment-of-choice for this diease. However, treatment must be individualized for elderly patients or those with poor performance status. Moreover, tumor histology and EGFR mutational status appear to be important determinants of treatment response and must be considered when selecting therapies. EGFR-targeted agents, such as [erlotinib] and [gefitinib] play a role for EGFR mutation-positive patients. 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. The role of maintenance chemotherapy is not yet clear and its benefits must be weighed against its toxicities. As more treatment choices for patients emerge, clinicians must demonstrate greater discrimination when selecting treatment strategies for advanced NSCLC. In addition, the recent ASCO Clinical Practice Guideline update on chemotherapy in stage IV NSCLC may serve to help oncologists make better informed treatment decisions.

5-6 Management of Thymomas

Author: Tracey Evans, MD

Date Released: October 01, 2009

Abstract: Although quite rare, thymomas 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 inPractice chapter, Tracey Evans, MD, discusses the workup of the anterior mediastinal mass; the pathology and staging of thymic tumors; paraneoplastic syndromes; treatment of thymomas, including radiotherapy and chemotherapy; and the use of novel agents to treat patients with relapsed thymomas.

6-1 The Management of Locoregionally Advanced Head and Neck Cancer

Author: James A. Bonner, MD

Date Released: October 01, 2009

Abstract: The treatment and prognosis of those diagnosed with locoregionally advanced head and neck cancer has changed in the last half of the twentieth century. During the last 30 years, the cornerstone of management for these cancers has partially shifted from surgery to definitive chemoradiotherapy. In addition, the introduction of targeted therapies, such as biologics, into the treatment armamentarium of locoregionally advanced head and neck cancer has created new promise for increasing the cure rate, and has the potential for decreasing treatment-related toxicities. The association of human papillomavirus (HPV) with improved outcomes in oropharyngeal cancer has resulted in new optimism for patients with HPV-associated head and neck cancer as these HPV-related tumors appear to be more readily treated than their HPV-negative counterparts. This chapter reviews past and current management strategies for the treatment of locoregionally advanced head and neck cancer, including a discussion of the role of altered fractionated radiotherapy, intensity modulated radiotherapy, chemoradiotherapy, combinations of altered fractionated radiotherapy and chemotherapy, elective neck dissection, and targeted therapies.

6-2 The Management of Metastatic or Recurrent Head and Neck Cancer

Authors: Barbara Burtness, MD, Mohamedtaki Tejani, MD

Date Released: October 01, 2009

Date Updated: March 01, 2010

Abstract: An estimated 644,000 new cases of head and neck cancer are diagnosed each year worldwide, with the majority occurring in developing countries. According to the American Cancer Society, head and neck cancers will account for 35,720 new cancer diagnoses and 7600 cancer deaths in the United States in 2009. Squamous cell carcinomas of the lip/oral cavity, nasopharynx, oropharynx, hypopharynx, and larynx make up the majority—greater than 90%—of head and neck cancers. Despite aggressive treatment of these tumors, 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. Thirty percent to 40% of patients develop locoregional recurrences, and distant metastases occur in 20% to 30%. The majority of recurrences appear 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 use, including smoking and/or chewing tobacco, and alcohol use are the most common risk factors for head and neck squamous cell carcinoma (HNSCC). In addition, approximately 25% of HNSCC cases diagnosed in recent years—mostly involving the oral cavity and tonsils—have been associated with human papillomavirus infection. In this chapter, Barbara Burtness, MD, and Mohamedtaki Tejani, MD, describe diagnosis, staging, and treatment of advanced head and neck cancer.

7-1 Ovarian Cancer

Author: Maurie Markman, MD

Date Released: October 01, 2009

Date Updated: March 03, 2010

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.

7-2 Cervical, Endometrial, Vulvar, and Vaginal Cancers

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

Date Released: October 01, 2009

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. Targeted 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.

8-1 Nonmelanoma Skin Cancers

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

Date Released: October 01, 2009

Date Updated: November 24, 2009

Abstract: Nonmelanoma skin cancer is the most common type of malignancy in the United States, with more than 1 million cases diagnosed 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 hosts, and some that are intrinsically more aggressive (eg, Merkel cell carcinoma). This chapter 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.

8-2 Surgical Management of Malignant Melanoma

Author: Robert H. I. Andtbacka, MD, CM

Date Released: October 01, 2009

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 chapter 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.

8-3 Medical Management of Cutaneous Melanoma

Author: Ahmad Tarhini, MD, MS

Date Released: October 01, 2009

Abstract: Among new cancer cases in the United States in 2009, melanoma is estimated to be the fifth most common cancer in men and sixth most common in women. For the year 2009, there are projected to be 68,720 new cases of melanoma. The vast majority of these will be early stage and therefore curable. However, it is estimated that 8650 patients will die from this disease in 2009.^{[Jemal 2009]} Approximately 8000 patients are found to have metastatic melanoma annually, closely approximating the annual number of deaths from this disease, illustrating the lack of progress that has been made in the treatment of stage IV melanoma during the last several decades. This chapter reviews the risk factors, clinical diagnosis, and nonsurgical treatment options of cutaneous melanoma.

9-1 Soft Tissue Sarcomas

Authors: Elizabeth Baldini, MD, MPH, Bartosz Chmielowski, MD, PhD, William Tap, MD

Date Released: October 01, 2009

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.

9-2 Bone Sarcomas

Authors: David M. Thomas, MD, FRACP, PhD , Francis J. Hornicek, MD, PhD

Date Released: October 01, 2009

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.

9-3 Gastrointestinal Stromal Tumors

Authors: Margaret von Mehren, MD, Neeta Somaiah, MD, Chandrajit P. Raut, MD, MSc

Date Released: October 01, 2009

Date Updated: March 02, 2010

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.

10-1 High-Grade Glioma

Authors: Patrick Y. Wen, MD, Ryan T. Merrell, MD

Date Released: October 01, 2009

Abstract: Patrick Y. Wen, MD, and Ryan T. Merrell, 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.

11-1 Hodgkin Lymphoma

Author: David J. Straus, MD

Date Released: October 01, 2009

Abstract: Hodgkin’s lymphoma is an uncommon B-cell malignancy representing approximately 0.6% of all cancers. It is occurs in 2 broad categories: classical Hodgkin’s lymphoma and nodular lymphocyte predominant Hodgkin’s lymphoma. There are 4 subtypes of classical Hodgkin’s lymphoma; 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 Hodgkin’s lymphoma. 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 Hodgkin’s lymphoma.

11-2 Non-Hodgkin Lymphoma

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

Date Released: October 01, 2009

Abstract: The 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 the majority of cases and, more rarely, the natural killer cell. NHL is the fifth most common malignancy in the United States, accounting for 5% of cancer diagnoses and 3% 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, aggressive lymphomas by diffuse large B-cell, peripheral T-cell, and mantle cell types, whereas Burkitt’s 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 the 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, including T-cell lymphomas for which no successful targeted monoclonal antibody has been identified. This chapter provides a comprehensive overview of the etiology, diagnosis, staging, and treatment of the various NHLs.

11-3 Acute Leukemias

Authors: Elias Jabbour, MD, Hagop M. Kantarjian, MD, Amber C. Fullmer, PharmD

Date Released: October 01, 2009

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 only approximately 30% to 40% of adult patients with ALL achieve long-term disease-free survival. 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.

11-4 Myelodysplastic Syndromes

Authors: Rami Komrokji, MD, Alan F. List, MD

Date Released: October 01, 2009

Abstract: Myelodysplastic syndromes (MDS) are a spectrum of hematopoietic stem cell malignancies that present as bone marrow failure disorders with 1 or more cytopenias and associated complications; namely, anemia, transfusion dependency, infection, and bleeding. MDS have a variable tendency to progress to acute myeloid leukemia. The incidence of MDS is approximately 10,000 cases/year in the United States, with a median age at diagnosis of 76 years and approximately a 2:1 male-to-female ratio. Risk factors are family history of hematopoietic disease, exposure to pesticides or solvents, and smoking. MDS may also occur secondary to treatment for other malignancies. Several classification systems to guide risk stratification and prognosis continue to be developed based on morphologic features, cytogenetics, and number of cytopenias and include the French-British-American classification system, the World Health Organization classification system, the International Prognostic Scoring System, and the World Health Organization–based Prognostic Scoring System.

In this chapter treatment options, which include allogeneic stem cell transplantation, red blood cell transfusions, and supportive measures with erythroid growth factors, are discussed. In addition, the recently introduced treatment options, which include the immunomodulatory drug lenalidomide, the hypomethylating agents 5-azacytidine and decitabine, and immunosuppressive therapy, are reviewed. Treatment of iron overload in transfusion-dependent patients is explained as are management of neutropenia and thrombocytopenia, which are common in MDS.

11-5 Chronic Lymphocytic Leukemia

Authors: Matthew Kaufman, MD, Kanti Rai, MD

Date Released: October 01, 2009

Date Updated: November 23, 2009

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 covers incidence, epidemiology, molecular markers, and treatment of both newly diagnosed and relapsed CLL.

11-6 Chronic Myeloid Leukemia

Authors: Alfonso Quintás-Cardama, MD, Hagop M. Kantarjian, MD, Jorge E. Cortes, MD

Date Released: October 01, 2009

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. 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 tyrosine kinase inhibitors. Most adverse events associated with these agents are manageable and frequently transient. Patients with the T315I mutation currently have no established and effective treatment options and should be considered for stem cell transplantation as soon as this abnormality is identified. Adequate management of patients with CML requires opportune identification of adverse events as well as measures to minimize unnecessary treatment interruptions and dose reductions.

11-7 Multiple Myeloma

Authors: Jacob P. Laubach, MD, MPP, Irene M. Ghobrial, MD, Constantine S. Mitsiades, MD, PhD, Paul G. Richardson, MD, Kenneth Anderson, MD

Date Released: October 01, 2009

Abstract: This CCO inPractice chapter reviews the etiology and risk factors for multiple myeloma, as well presentation, diagnosis, and current staging and risk-stratification strategies. General clinical management of myeloma is summarized. Novel treatments for this hematologic malignancy, including thalidomide, lenalidomide, and bortezomib, are discussed in relation to their use in both relapsed/refractory and newly diagnosed disease settings. The authors also explain 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.

12-1 Supportive Care: Nausea, Vomiting, and Diarrhea

Authors: Constance Engelking, RN, MS, OCN, Rita Wickham, PhD, RN

Date Released: October 01, 2009

Abstract: Nausea, vomiting, and diarrhea represent 3 of the greatest concerns among cancer patients, their families, and their care givers. Because they are so common—and can be so severe—nausea, vomiting, and diarrhea can lead to a host of problems that can impede the success of cancer therapies and cause additional morbidity and mortality in oncology patients. Problems related to nausea and vomiting can include serious metabolic disturbances, anorexia and nutritional deficiencies, deteriorating physical and mental status, esophageal tears, wound dehiscence, discontinuation of potentially useful and curative cancer treatments, and patients’ neglect of self-care and loss of functional abilities. Diarrhea can occur at many points throughout the development, diagnosis, and treatment of cancer. Diarrhea can interfere with patients’ dietary patterns, trigger dehydration, create electrolyte imbalances, impair daily functional abilities, cause fatigue, impair skin integrity, limit activity, and, in some cases, can even be life threatening. This chapter reviews the pathogenesis, incidence, and risks for nausea, vomiting, and diarrhea in cancer patients and discusses the most up-to-date findings regarding both pharmacologic and nonpharmacologic management approaches.

12-2 Pulmonary Toxicity

Authors: Nicholas J. Pastis, Jr., MD, Gerard A. Silvestri, MD, MS

Date Released: October 01, 2009

Abstract: As the number of available cancer therapies continues to expand, clinicians must stay abreast of potential treatment-related pulmonary complications, some of which may lead to respiratory failure and death. In the 1960s, the first drug to induce chemotherapy-related lung disease was busulfan. Since that time, several chemotherapeutic agents are now known to cause pulmonary toxicity. In addition, both radiation and surgery have been associated with severe and fatal pulmonary disease. In this clinically oriented chapter, Gerard A. Silvestri, MD, MS, and Nicholas J. Pastis, Jr., MD, review a broad spectrum of pulmonary complications that result from a variety of cancer therapies.

12-3 Cardiotoxicity of Anticancer Treatments

Authors: Michael S. Ewer, MD, MPH, JD, Steven M. Ewer, MD

Date Released: October 01, 2009

Abstract: Heart disease and cancer are the 2 leading causes of death in developed countries. To a large extent, both are associated with advancing age; consequently, patients with malignancy often either have overt cardiovascular problems or they are at increased cardiovascular risk. In addition, malignancy and its treatment places stress on body systems that are often already compromised by underlying primary cardiac or pulmonary disease. The cardiac effects of cancer treatment represent a diverse group of responses to chemical, biological, physical, and hormonal agents. The risk of serious toxicity is related to the type of agent, but is influenced by the stability and reserves of the patient. Decision making in this setting depends on the likelihood of response or cure of the underlying malignancy, and the risk/benefit relationship must be considered as an essential part of the process.

12-4 Management of Neutropenia in the Cancer Patient

Author: Jeffrey Crawford, MD

Date Released: October 01, 2009

Abstract: The most common dose-limiting toxicity in cancer chemotherapy is neutropenia. Neutropenia is the primary risk factor for development of febrile neutropenia, which can be either a self-limiting process that resolves quickly or one that is associated with serious infection, prolonged hospitalization, and risk of mortality. If patients recover fully from febrile neutropenia, the consequences from hospitalization and infection may lead to subsequent chemotherapy delays or dose reductions, either of which can reduce the overall relative dose intensity (RDI) of chemotherapy. Even without a febrile component, neutropenia may be prolonged and delay the start of subsequent chemotherapy cycles, which can also reduce RDI. Overall reductions in RDI have also been associated with reduced efficacy of chemotherapy. Both the infectious complications of neutropenia and its impact on chemotherapy dose delivery can lead to overall reduction in the survival of a cancer patient who is receiving chemotherapy. The management of chemotherapy-induced neutropenia can involve preventive strategies, treatment strategies, or both. The US Food and Drug Administration has approved the myeloid growth factors filgrastim, sargramostim, and pegfilgrastim for neutropenia management. This chapter reviews the risk factors associated with the development of neutropenia in cancer patients receiving chemotherapy; discusses neutropenia as a pharmacodynamic endpoint; evaluates the effect of neutropenia on clinical outcomes; assesses use of antibiotics and colony-stimulating factors to prevent and treat neutropenia; and identifies adverse effects associated with use of colony-stimulating factors.

12-5 Anemia and Erythropoiesis-Stimulating Agents

Author: John Glaspy, MD

Date Released: October 01, 2009

Abstract: Anemia is a frequent and important issue faced by many cancer patients, especially those receiving chemotherapy. Because of its potential deleterious effects on patient quality of life, performance score, and therapeutic outcomes, treating anemia is an important component of the overall care of the cancer patient. Treatment interventions include iron supplementation, blood transfusion, and recombinant human erythropoietin. Worldwide, 3 major preparations of recombinant human erythropoietin are used to treat anemia in cancer patients—epoetin alfa, epoetin beta, and darbepoetin alfa. Of these, only epoetin alfa and darbepoetin alfa are approved for this use in the United States. Together, these preparations are referred to as erythropoiesis-stimulating agents (ESAs). This chapter provides an overview of the impact of anemia on the cancer patient, the positive benefits on clinical outcomes associated with the use of ESA in cancer patients with anemia, and the risks associated with the use of ESAs in this setting.

12-6 Cancer-Related Fatigue

Author: Barbara F. Piper, DNSc, RN, AOCN, FAAN

Date Released: October 01, 2009

Abstract: Cancer-related fatigue is one of the most common and distressing symptoms experienced by cancer patients. Patients report cancer-related fatigue as being more distressing than pain, nausea, or vomiting, most likely because cancer-related fatigue can negatively affect all aspects of patients’ quality of life and can limit their ability to fully engage in activities that give meaning and value to their lives. Cancer-related fatigue can have negative effects on a patient’s and family’s employment and financial status, but these effects have not been well studied. Cancer-related fatigue may be dose- limiting and may compromise the timing and frequency of treatments. It may also affect treatment adherence and survival. Despite its frequency and its negative impact, cancer-related fatigue remains under-reported, under-diagnosed, and under-treated. Prevalence rates, case definitions, and general principles of treatment are discussed. Common contributing factors to cancer-related fatigue such as anemia, comorbidities, deconditioning, emotional distress, nutritional problems, pain, and sleep disturbances need to be assessed and treated. Validated methods to screen, assess, and measure cancer-related fatigue are presented. Several proven nonpharmacologic therapeutic strategies to reduce cancer-related fatigue exist such as psychoeducational programs, exercise, and cognitive-behavioral approaches. Pharmacologic strategies such as using psychotropic medications that include psychostimulants, wakefulness-promoting agents, antidepressants, and cholinesterase inhibitors are reviewed and are being studied for cancer-related fatigue treatment with varying degrees of success. Gaps in the evidence are mentioned, as are implications for practice and future research.

12-7 Nutritional Support and Oncology

Authors: Diana Bearden, MS, RD, LD, CNSD, Carol Frankmann, MS, RD, CSO, LD, CNSD, Linda J. Pataki, MS, RD, LD, CNSC, Virginia Schierman, MS, RD, LD, CNSC, Kimberlee Taylor, MS, RD, CSO, LD, CNSD

Date Released: October 01, 2009

Abstract: A cancer patient’s nutritional status is gravely affected by his or her disease; in addition, a patient’s nutrition during treatment may aid or hamper recovery. Many forms of cancer contribute to nutritional compromise. Survival outcomes are affected by patients’ ability to sustain themselves nutritionally during and after treatment. Kwashiorkor (severe protein malnutrition, especially in children after weaning), marasmus (protein-energy malnutrition, chiefly occurring in the first year of life), and obesity are linked not only to the occurrence of cancer but to the response to treatment. Cancer, particularly types that affect the gastrointestinal tract, can impact nutrient absorption and utilization as well as metabolic rate. Cancer treatment and its multiple adverse effects can also interfere with a patient’s own ability or desire to ingest food. This chapter reviews guidelines and tools available for the assessment of a patient’s nutritional status and summarizes important nutritional interventions that can be implemented during cancer treatment. Detailed interventions tailored to nutritional adverse effects associated with particular cancer types, including head and neck cancers, esophageal and gastrointestinal cancers, pancreatic cancer, colorectal cancer, and hematologic malignancies are presented.

12-8 Cancer Pain Management

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

Date Released: October 01, 2009

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 chapter, Robert A. Swarm, MD, provides 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.

12-9 Hospice and Palliative Care

Authors: Eduardo Bruera, MD, David Hui, MD, MSc, FRCPC

Date Released: October 01, 2009

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.

13-1 Molecular Biology for the Clinician: The Essentials

Authors: Michael Franklin, MSc, Robert Kratzke, MD

Date Released: October 01, 2009

Abstract: The development of a cancer cell requires the acquisition of a variety of characteristics not generally found in nontransformed cells. In this review, Robert Kratzke, MD, and Michael Franklin, MSc, highlight developing targets and therapeutic approaches designed to exploit these characteristics of cancer cells. In addition, evasion of immune surveillance is discussed, as tumors must develop this capacity in order to proliferate. Therapies, both in the pipeline and already in the clinic, are also reviewed, including representatives from each class of agents targeting the unique characteristics of the cancer cell.

13-2 Molecular Diagnostics for the Practicing Clinician: Applications in Lung Cancer and Other Tumor Types

Authors: Fred R. Hirsch, MD, PhD, Celine Mascaux, MD, PhD, Nir Peled, MD, PhD

Date Released: October 01, 2009

Abstract: After years of using chemotherapy to fight cancer, the last decade has witnessed the introduction of tumor-specific targeted therapies, including hormone therapies for breast cancer and prostate cancer; epidermal growth factor receptor inhibitors for lung, colon, and head and neck cancer; and imatinib for chronic myeloid leukemia. Therefore, a new era of cancer treatment is evolving to include personalized, customized therapy.

Biomarker research aims to characterize prognostic factors and to determine predictive markers of benefit that can be derived from systemic treatments. These biomarkers can be used to select the patient groups who will most likely benefit from treatment and can help avoid the toxicities associated with noneffective therapies. This chapter will discuss molecular diagnostic platforms and their utility in assessing patient treatment options. It will also include established and ongoing studies of biomarkers in several tumor types with a particular focus on lung cancer.

13-3 Cancer of Unknown Primary Site

Author: F. Anthony Greco, MD

Date Released: October 01, 2009

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, future treatment may rely on molecular assays to better differentiate patients for therapy.

13-4 HIV and Cancer

Authors: Liron Pantanowitz, MD, Bruce J. Dezube, MD

Date Released: October 01, 2009

Abstract: HIV-infected individuals are at an increased risk of developing several cancers, 3 of which are classified as AIDS-defining malignancies: Kaposi’s sarcoma; high-grade B-cell non-Hodgkin’s lymphoma, including primary central nervous system lymphoma; and invasive cervical cancer. The management of HIV-infected patients with these cancers is frequently complicated by treatment-induced immunosuppression, comorbid disease, drug interactions, and social issues. Multidisciplinary cooperation between oncologists and HIV physicians is often needed to ensure that patients with AIDS-defining malignancies are suitably managed. Early referral of HIV-infected patients with malignancy to centers with expertise in the management of these diseases appears to be associated with more favorable outcomes. Recently, both the spectrum and incidence of various non-AIDS malignancies being reported among persons infected with HIV have increased. This emerging and crucial problem has contributed to the mortality of HIV-positive persons in the pre-HAART era. Even in resource-poor settings where antiretroviral therapy is limited in its availability, non–AIDS-defining cancers have increased along with AIDS-defining cancers in the growing HIV-infected population. In this chapter, Bruce J. Dezube, MD, and Liron Pantanowitz, MD, focus on several of the non–AIDS-defining cancers likely to be encountered in clinical practice and the current management of the 3 AIDS-defining cancers.

13-5 Oncologic Emergencies

Authors: Michael C. Perry, MD, MS, MACP, Shadi Haddadin, MD

Date Released: October 01, 2009

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 production, 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.

13-6 Interpreting Clinical Trial Results

Author: Maurie Markman, MD

Date Released: October 01, 2009

Abstract: Interpreting results of cancer clinical trials is both critically important and quite complex. The intent of this chapter, written for the practicing oncologist or trainee, is to briefly discuss levels of evidence and to describe a number of relevant pitfalls associated with the interpretation of clinical trial results. How should an individual oncologist evaluate the results of a trial that claims or suggests “treatment A” is superior to or less toxic than “treatment B”? What level of evidence should be required for a physician to either accept a new approach or modify/abandon an existing strategy?

13-7 Resources for the Caregivers

Authors: Paula R. Sherwood, RN, PhD, CNRN, Jennifer S. Prince, RN, BSN, BA

Date Released: October 01, 2009

Abstract: Historically, the primary focus of cancer care has been to prevent recurrence and slow tumor progression. However, the growing number of cancer survivors has brought diagnosis- and treatment-related psychosocial issues to the attention of both caregivers and their advocates. Depression, caregiver distress, and financial worries are common to patients undergoing active treatment as well as to long-term survivors. In this chapter, Paula R. Sherwood, RN, PhD, CNRN, and Jennifer S. Prince, RN, BSN, BA, review several key psychosocial issues faced by cancer patients and their families.