Selected Health Conditions and Likelihood of Improvement with Treatment (2020) / Chapter Skim
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3 Cancer
3 Cancer
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Cancer-related functional impairment can be caused by the cancer itself (e.g., a direct invasion of the lungs causing compromised breathing, or of the bone marrow causing anemia) or caused by cancer treatments such as surgery, radiation therapy (RT)
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) , melanoma, renal cancer, head and neck cancers, advanced epithelial ovary cancer, non-small-cell lung cancer (NSCLC)
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. The incidence rates of lung cancer have seen a steady decline among both men and women across all age groups since 1985, in part reflecting the effectiveness of public health and regulatory tobacco control programs and policies (Farrelly, 2008; Siegel et al., 2019)
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48 FIGURE 3-1 Average annual cancer incidence rates and case distribution by age, United States, 2011–2015.
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. As a result, the number of cancer survivors is steadily increasing -- from 14 million in 2014 to almost 18 million expected by 2022 (Fuentes et al., 2017)
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Overall survival rates do not specify whether cancer survivors are still undergoing treatment at 5 years or if they have achieved remission, meaning they have become cancer free. The following cancers have overall 5-year survival rates of 80 percent or higher: uterine, Hodgkin lymphoma, breast, melanoma, testis, thyroid, and prostate (NCI, 2019a)
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The table shows small increases in survival rates for selected cancers. TABLE 3-1 5-Year Relative Survival Rates (%)
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52 TABLE 3-2 Trends in Cancer 5-Year Survival Rates (Percent by Year of Diagnosis) Non Small-Cell Oral Lung and Cavity All Bronchus Ovarian Hodgkin and Cancers Breast Thyroid Melanoma (Invasive)
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. Specifically, the death rate for lung cancer dropped by 45 percent from 1990 to 2015 among males and by 19 percent from 2002 to 2015 among females; the death rate for breast cancer dropped by 39 percent from 1989 to 2015; for prostate cancer, the death rate dropped by 52 percent from 1993 to 2015; and for colorectal cancer the death rate dropped by 52 percent from 1970 to 2015 (ACS, 2018)
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of selected cancers, based on U.S. prevalence on January 1, 2016.
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This section covers the following topics broadly as they relate across all of the selected cancers: diagnostic criteria, medical professionals involved in cancer care, cancer treatments, treatment settings, a framework for understanding length of time from treatment to functional improvement, standard measures of outcomes for the selected cancers, and pain. Whether and how these characteristics differ for each of the selected cancers and any additional specifics relevant to the Statement of Task are described in the sections that follow devoted to each of the selected cancers.
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. Diagnostic criteria specific to each of the selected cancers are discussed in the cancer-specific sections and summarized in Tables 3-5 through 3-13.
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Sputum cytology is used to look for the presence of lung cancer. Tumor marker tests are used to identify a broad range of specific proteins or genes in tissue, blood, or other bodily fluids that may be signs of cancer or certain benign
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Cancer patients may see, over the course of their treatment, surgeons, medical oncologists, radiation oncologists, interventional radiologists, internal medical subspecialties such as endocrinology and dermatology, advanced practice providers such as nurse practitioners and physician assistants, nurses, social workers, clinical trials coordinators, patient navigators, and genetics counselors. During and after treatment the patients may see registered dietitians; physical, speech, and occupational therapists; and rehabilitation physicians (Fennell et al., 2010; IOM, 2013; Ko and Chaudhry, 2002; Litton et al., 2010)
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. Cancer Treatments for Selected Cancers There are many types of treatments used in cancer therapy.
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Chemotherapy Chemotherapy is a drug treatment that uses chemicals to kill fastgrowing cells. Many different chemotherapy drugs are available, and they TABLE 3-4 Selected Cancers and Commonly Used Treatments Cancers Cutaneous Melanoma Non-Small-Cell Lung Diffuse Large B-Cell Advanced Epithelial Head and Neck Invasive Breast Lymphoma Ovary Renal Therapy Chemotherapy √ √ √ √ √ √ Hormone therapy √ √ Immune √ √ √ √ √ √ √ modulators Radiation therapy √ √ √ √ √ √ √ Surgery √ √ √ √ √ √ √ Targeted therapy √ √ √ √ √ √ √ SOURCES: NCCN, 2019a,b,c,d,e,f,g.
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Hormone Therapy Hormone therapy, also called endocrine therapy, is a cancer treatment that slows or stops the growth of cancers that use hormones to grow, such as breast, thyroid, and ovarian cancers. Hormone therapy is most often used in combination with other cancer treatments.
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. Radiation Therapy RT is a type of cancer therapy that uses X-rays and other types of high-energy particles or waves to destroy or damage cancer cells.
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Cancer treatment settings specific to each cancer site are noted in the sections devoted to the selected cancers. Length of Time from Treatment to Functional Improvement The length of time from start of cancer treatment until a person's functioning improves to the point that the condition is no longer disabling involves two timeframes: (1)
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Standard Measures of Outcomes for the Selected Cancers Outcomes to monitor for patients with cancer include the various lengths of remission and progression, depending on the cancer site and stage. The ideal outcome of cancer treatment is complete remission, meaning that the treatment has resulted in the disappearance of all measurable signs of cancer.
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Additionally, limited research has been devoted to accurately distinguishing the etiologic contributors to different pain syndromes that might inform their treatment. All cancer treatments, including surgery, radiation, and systemic therapies, have the potential to produce chronic pain among disease-free survivors.
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For example, among a cohort of 175 head and neck cancer survivors at a median of 6.6 years after diagnosis, 45.1 percent reported pain, and 11.5 percent reported severe pain (Cramer et al., 2018)
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Table 3-5 describes the diagnostics, therapy, outcome, and monitoring for invasive breast cancer, excluding DCIS. Professionally Accepted Diagnostic Criteria for Breast Cancer Breast cancer is typically detected during either a screening mammographic or an MRI examination, either before symptoms have developed or after a woman has noticed a lump.
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• Diagnostic bilateral Same as early stage • Chest CT, abdominal/pelvic CT or MRI, bone scan, FDG mammogram/ultrasound, PET/CT breast MRI • Biopsy with ER/PR/HER2 tissue testing, tumor PIK3CA • Tumor biopsy with ER/ mutation testing if ER/PR positive and HER2 negative; PR/HER2 tissue testing germline BRCA 1/2 testing if HER2 negative; PDL-1 • Axillary ultrasound/ biomarker testing for triple negative (HR and HER2 imaging plus percutaneous negative) , genetic counseling biopsy if suspicious node • Brain/spine MRI, symptomatic and long and weight • Genetic counseling and bearing bone X-rays if clinically indicated testing as indicated, tumor multigene assay (if ER/ PR positive and HER2 negative)
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(capecitabine) Disease • Complete remission Same as early stage • Complete remission (rare)
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polymerase; PET = positron emission tomography; PIK3CA = a protein coding gene; RT = radiation therapy. Routine lab studies/all CT and MRI imaging is with contrast unless otherwise designated.
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. Treatments for Breast Cancer The medical professionals involved in the care of individuals with breast cancer include surgeons, radiation oncologists, medical oncologists,
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In fact, the treatment itself could reduce functioning. Length of Treatment Time for Breast Cancer A treatment using non-hormonal therapy for early or locally advanced disease that achieves complete remission is generally complete in 12 to 18
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Breast cancer patients with early-stage and locally advanced disease achieving complete remission should receive frequent (one to four times per year) physical examinations for the first 5 years post-treatment, then yearly physical examinations after the first 5 years to assess for possible metastatic recurrence and tolerance to ongoing therapies, and to monitor or treat any treatment effects.
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SOURCE: NCCN, 2019b. Professionally Accepted Diagnostic Criteria for Cutaneous Melanoma A clinical suspicion of a melanoma is based on the visual appearance of a skin lesion.
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Standard Measures of Outcomes for Cutaneous Melanoma For early-stage and locally advanced melanoma, the ideal outcome of cancer therapy is complete remission. For advanced-stage diseases, complete remission is rare; other possible outcomes of therapy include partial remission or progressive disease (NCCN, 2019b)
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Professionally Accepted Diagnostic Criteria for Renal Cancer With the expansion of routine imaging for many disorders, patients with renal cell carcinoma are increasingly being identified incidentally. Only 30 percent of patients are diagnosed on the basis of symptoms (Capitanio and Montorsi, 2016)
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for variety • Kinase inhibitor small lesions • Immunotherapy • Antiangiogenics • High-dose interleukin-2 Disease • Complete Same as early stage • Partial remission outcomes of remission • Complete remission (rare) treatment • Recurrence • Stable disease • Disease progression Post-treatment • Postoperative Same as early stage • Chest, abdominal, pelvic monitoring abdominal CT or MRI imaging every CT, MRI, or 6–16 weeks ultrasound and • Head CT/MRI baseline then annually for and then as clinically 3 years indicated • Chest X-ray or • Bone scan, spine MRI as CT annually for 5 clinically indicated years NOTES: *
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. Standard Measures of Outcomes for Renal Cancer For early-stage and locally advanced renal cancer, the ideal outcome of cancer therapy is complete remission.
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Professionally Accepted Diagnostic Criteria for Head and Neck Squamous Cell Cancer The diagnostic criteria are the same for all stages of head and neck cancer and may include biopsy (such as fine-needle aspiration of the neck) , HPV tissue testing for oropharynx cancer, Epstein-Barr virus (EBV)
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• Mirror and fiberoptic exam • Examination under anesthesia with endoscopy • CT/MRI of primary and neck • Dental evaluation • As clinically indicated: chest CT; PET/CT; nutritional, speech, swallowing evaluation/therapy Treatment • Primary resection • Primary resection • Chemotherapy • RT • Neck sentinel • Targeted agent node biopsy therapy • Neck node • Immunotherapy dissection • RT • Chemotherapy • Targeted agent therapy Disease • Complete remission • Complete • Complete outcomes of • Recurrence remission remission treatment • Partial remission • Partial remission • Progressive Disease
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In addition to history and physical examination and laboratory tests. CT = computed tomography; EBV = Epstein-Barr virus; FNA = fine needle aspiration; HPV = human papillomavirus; MRI = magnetic resonance imaging; PET = positron emission tomography; RT = radiation therapy; TSH = thyroid-stimulating hormone.
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. Treatments for Head and Neck Squamous Cell Cancer Medical professionals involved in the care of individuals with head and neck squamous cell cancer include surgeons, radiation oncologists, medical oncologists, and dentists (NCCN, 2019b)
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. Standard Measures of Outcomes for Head and Neck Squamous Cell Cancer For all stages of head and neck cancer, the ideal outcome of cancer therapy is complete remission.
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Professionally Accepted Diagnostic Criteria for Advanced Epithelial Ovary Cancer Diagnostics for advanced epithelial ovarian cancer include CT of the chest, abdomen, and pelvis using the CA-125 (carbohydrate antigen 125) marker and genetic counseling and testing (NCCN, 2019e; Pepin et al., 2014)
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Chemotherapy, targeted agent, hormonal therapy, immunotherapy, palliative RT for persistent/progressive disease Disease outcomes • Complete or partial remission of treatment • Persistent and progressive disease Post-treatment • Complete remission: monitoring o History and physical examination (including pelvic exam) every 2–4 months for 2 years, 3–6 months for 3 years, and then annually o CA-125 monitoring o Imaging and labs as clinically indicated o Genetic counseling if not done initially • Relapsed, progressive disease o Chest/abdomen/pelvic CT, MRI, PET/CT, or PET o CA-125 monitoring, labs as therapy and clinically indicated o Tumor molecular testing NOTES: *
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. Standard Measures of Outcomes for Advanced Epithelial Ovary Cancer For those with advanced epithelial ovary cancer, the ideal outcome of cancer therapy is complete remission, although partial remission and persistent and progressive disease are also possible (NCCN, 2019e)
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Professionally Accepted Diagnostic Criteria for Non-Small-Cell Lung Cancer Often, NSCLC is not diagnosed until advanced-stage disease is present. Cough, seen in 50 percent to 75 percent of patients, is the most common symptom, followed by hemoptysis, chest pain, and dyspnea.
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stent/laser • Orthopedic bone stabiliza tion, skeletal directed agents for bone metastases Disease • Complete remission • Complete remission • Complete outcomes of • Recurrence • Persistent disease remission treatment • Partial remission, stable disease • Progressive disease Post- • History and physical For complete remission: • History and treatment and low-dose non- History and physical and physical and monitoring contrast chest CT chest CT every 3–6 months labs every cycle annually for 3 years, then every • Imaging every • Chest CT every 6 6 months for 2 years, then three cycles months for 2–3 years history and physical and low-dose non-contrast chest CT annually NOTES: * In addition to history and physical examination and laboratory tests.
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. Treatments for Non-Small-Cell Lung Cancer The medical professionals involved in the care of individuals with NSCLC include surgeons, radiation oncologists, medical oncologists, pulmonologists, and radiologists (NCCN, 2019f)
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Length of Treatment Time for Non-Small-Cell Lung Cancer Disease therapy for early-stage disease requiring surgery is usually complete in 12 weeks, therapy for early-stage disease requiring adjuvant therapy is complete in 6 months, and therapy for locally advanced disease that achieves complete remission with combination therapy is complete in up to 15 months (NCCN, 2019f)
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. Professionally Accepted Diagnostic Criteria for Diffuse Large B-Cell Lymphoma Diffuse large B-cell lymphoma is best diagnosed from an excisional biopsy of a suspicious lymph node, which shows sheets of large cells that disrupt the underlying structural integrity of the follicle center and stain positive for pan-B-cell antigens, such as CD20 and CD79a.
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• General blood Same as early stage Same as early stage laboratory studies, incisional or excisional biopsy • Tissue for immunohistochemistry, flow cytometry, PCR for IGH and TCR gene rearrangements, karyotype, FISH for major translocations, next-generation sequencing • Whole body PET/CT with or without C/A/P CT, bone marrow biopsy, International Prognostic Score calculation • Hep B testing, echocardiogram or MUGA scan, International Prognostic Index calculation • As clinically indicated: head CT/MRI, neck CT/MRI, HIV and hep C testing, beta-2 microglobulin level, lumbar puncture, pregnancy testing (as indicated)
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. C/A/P = chest/abdomen/pelvis; CNS = central nervous system; CT = computed tomography; FISH = fluorescence in situ hybridization; IGH = immunoglobulin heavy chain; MUGA = multiplegated acquisition scan; PCR = polymerase chain reaction; PET = positron emission tomography; RT = radiation therapy; TCR = T-cell receptor.
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. Monitoring for all stages of disease with complete remission includes a history and physical and laboratory tests (including a comprehensive metabolic panel and a complete blood count)
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DISABLING IMPAIRMENTS RELATED TO THE SELECTED CANCERS AND CANCER TREATMENTS Cancer treatments are well known to cause morbidity in cancer survivors. Although the treatments have generally improved to the point that they are both more effective and less debilitating than previously, treatmentrelated impairments are still common and, in many instances, expected.
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. About 58 percent of breast cancer survivors experience chemotherapy-induced peripheral neuropathy (CIPN)
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. Among disease-free cancer survivors, disablement is less often due to a single symptom or impairment than to the toxic interplay and reinforcing effects of multiple mild to moderate issues (Sarfarti et al., 2016)
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The following sections describe key symptoms and impairments that have been empirically implicated in cancer-related disablement. TABLE 3-12 Selected Cancers and Associated Impairments Caused by Cancer or Cancer Treatment Impairments Nerve Dysfunction Cardiotoxicity Lymphedema Dysfunction Dysfuction Pulmonary Cognitive Fatigue Pain Cancers Advanced epithelial √ √ √ √ √ √ √ ovary Cutaneous melanoma √ √ √ √ √ √ √ Diffuse large B-cell √ √ √ √ √ √ √ lymphoma Head and neck √ √ √ √ √ √ Invasive breast √ √ √ √ √ √ √ Non-small-cell lung √ √ √ √ √ √ √ Renal √ √ √ NOTE: Many impairments are mediated by cancer treatments and are not caused by the cancers themselves (see Table 3-13)
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Physical and cognitive functions are particularly susceptible to the damaging effects of pain, which affects survivors' ability to work. Professionally Accepted Diagnostic Criteria for Pain The diagnosis of cancer-related pain is most commonly made through patient report.
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Primary care providers may coordinate pain management, with the assistance of the aforementioned professionals, among disease-free cancer survivors who
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. Multimodal chronic pain management programs have been proven effective in reducing pain and opioid use among diverse clinical populations, including cancer survivors (Pollak et al., 2018)
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Despite clear evidence that patient-reported outcomes accurately and precisely measure pain, they are not routinely captured during the care of cancer survivors, making it difficult to define an individual's trajectory over time and thus challenging to define a length of time from start of treatment until functioning improves. Pain's adverse effects on other QOL domains make assessment of these domains a reasonable surrogate for gauging treatment response when pain ratings are not available.
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. Moderate or severe fatigue was found in 45 percent of patients undergoing active outpatient treatment and in 29 percent of patients with complete remission from breast, prostate, colorectal, or lung cancer (Wang et al., 2014)
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. All members of the oncology and rehabilitation teams, including medical oncologists, oncologic surgeons, radiation oncologists, rehabilitation physicians, nurses, physical therapists, occupational therapists, social workers, and psychologists, should take an active part in screening for CRF.
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. CARDIOTOXICITY A number of cancer treatments, including anthracyclines, trastuzumab and other HER2 receptor blockers, antimetabolites, alkylating agents, tyrosine kinase inhibitors, angiogenesis inhibitors, checkpoint inhibitors, and thoracic irradiation, are associated with significant cardiotoxicity (Jain et al., 2017)
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. Professionally Accepted Diagnostic Criteria for Cardiotoxicity The evaluation and management of cancer treatment–related cardiotoxicity is an emerging field.
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Standard Measures of Outcomes for Cardiotoxicity The expected benefits of a comprehensive cancer rehabilitation program include improvements in exercise tolerance, skeletal muscle strength, psychological status, and QOL. Though little literature exists for patients with cardiac disease resulting from cancer treatment, it is likely that similar benefits would be conferred by cardiac rehabilitation (Bonsignore et al., 2017)
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. Professionally Accepted Diagnostic Criteria for Chemotherapy-Induced Peripheral Neuropathy The diagnosis of CIPN is generally made on clinical grounds.
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. All members of the oncology and rehabilitation teams, including medical oncologists, oncologic surgeons, radiation oncologists, neurologists, rehabilitation physicians, nurses, physical therapists, and occupational therapists, should take an active part in screening for signs and symptoms of CIPN.
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110 SELECTED HEALTH CONDITIONS AND LIKELIHOOD OF IMPROVEMENT TABLE 3-14 Common Agents for Pain Management in Neuropathy Duration of Starting Maximum Adequate Potential Side Drug Dose Titration Dose Trial Effects Duloxetine 20–30 mg/ No 120 mg/ 2 weeks Nausea, day evidence day xerostomia, that higher constipation, dose is diarrhea more effective Gabapentin* 100–300 Increase by 3,600 mg 1–2 week Somnolence, mg nightly 100–300 (depending at max dizziness, GI or 100–300 mg 3 times/ on tolerated symptoms, mild mg 3 times/ day, every absorption)
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. LYMPHEDEMA Lymphedema is a late or long-term side effect of cancer that is caused by the compromise of lymph nodes or vessels during cancer treatment.
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This subgroup has proven conducive to study because they are numerous and generally have an uninvolved upper extremity for comparison. Incidence rates vary contingent on the lymphedema diagnostic criteria and cancer treatment specifics, ranging from 5 percent, after sentinel node procedures to as high as 25–40 percent following full axillary dissection with radiation (Armer and Stewart, 2005; Norman et al., 2009)
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Incidence rates also vary by the type and extent of cancer treatment, with the use of radiation and the number of lymph nodes surgically removed being principal risk factors. Many patients (e.g., those with gynecologic and prostate cancers)
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whose treatment involves lymph node removal. There is currently no evidence of a gender difference in lymphedema incidence among patients for head and neck cancer or melanoma, malignancies whose treatment also requires lymph node removal.
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Several microsurgeries, including lymphovenous bypass and vascularized lymph node transplant, have gained traction over the past decade as a means of further temporizing lymphedema. These surgeries do not necessarily cure lymphedema or obviate the requirement that patients wear compression garments (Garza et al., 2017)
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Plastic surgeons who perform lymphedema surgeries are often situated in large medical centers to ensure sufficient volume for their specialty practices. Cancer survivors are identified for treatment through various routes.
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. A number of cancer treatments can cause pulmonary dysfunction with severity ranging from mild to life threatening (Stubblefield, 2018)
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Training modalities may include a treadmill, a stationary bicycle, NU-Step, upper body resistance training, and training in breathing techniques. Evidence suggests that PR is safe and effective before, during, and after lung cancer treatment (Rivas-Perez and NanaSinkam, 2015)
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In addition, neurologic complications associated with brain cancer, including seizures, increased intracranial pressure, hydrocephalus, and stroke, can cause CD. It is widely accepted that cancer treatments can also result in CD.
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Standard Measures of Outcomes for Cognitive Dysfunction A variety of neurocognitive assessments are available to assess improvement or deterioration of cognitive function in cancer survivors (Lange and
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. NEW AND DEVELOPING CANCER TREATMENTS The development of anticancer drugs has changed radically from designing chemotherapies to maximize damage to cancer cells to developing therapeutics based on our greater understanding of tumor biology.
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In the IMPACT study, the targeted therapy resulted in slower cancer growth and prolonged survival across a diverse set of cancer types, including gastrointestinal cancer, gynecologic cancer, breast cancer, melanoma, lung cancer, and thyroid cancer (ASCO, 2018)
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Some monoclonal antibodies mark cancer cells so that they will be better seen and destroyed by the immune system, and this is a type of immunotherapy. Other monoclonal antibodies that are used in cancer treatment do not cause a response from the immune system.
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, are proteins that enhance the immune system's abil ity to respond to cancer. IFNα and IFNβ are involved in innate immune response and increase the resistance of normal cells to natural killer cells and make cancer cells more vulnerable to kill ing by cytotoxic T cells.
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. FDA has approved several new immunotherapies for use in cancer patients in the past year, including atezolizumab combination for lung cancer and triple-negative breast cancer, and pembrolizumab for head and neck cancer, first-line treatment of lung cancer, and pre-surgical treatment for advanced melanoma (CRI, 2020)
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Within cancers of a specific organ system, there are differences by specific cancer cell type and by cancer stage. For example, triple-negative2 invasive breast cancer is much more aggressive and has lower survival rates than other invasive breast cancer cell types.
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RETURN TO WORK AFTER CANCER While this chapter addresses the effect of cancer treatments on disease status and functional ability, there is not a clear linkage to return to work. This section reviews reports studying the effects of surviving cancer on long-term employment and return to work.
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Several studies reviewed return-to-work data across cancer survivors of multiple cancer sites. Moran and colleagues (2011)
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The committee acknowledges that other cancers might also fit the criteria. In addition to the effects of the medical condition itself, cancer treatments are well known to cause morbidity in cancer survivors.
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The residual effects of cancer treatments can present decades after treatment. Studies have shown that the majority will improve after treatment completion although the time course is patient specific.
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Second, success in cancer treatment does not predict improved functional outcomes. Long-term cancer survivors often experience multiple comorbidities and impairments related to the toxic effects of cancer therapies, including surgery, radiation, and systemic therapy (chemotherapy, biologic therapy)
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2016. Risk factors, prevalence, and course of severe fatigue after breast cancer treatment: A meta-analysis involving 12,327 breast cancer survivors.
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2016. Long-term chemotherapy-induced peripheral neuropathy among breast cancer survivors: Prevalence, risk factors, and fall risk.
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2019. Modern radiation further improves survival in non-small cell lung cancer: An analysis of 288,670 patients.
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2016a. American Cancer Society head and neck cancer survivorship care guideline.
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2018. Predicting cardiovascular disease among testicular cancer survivors after modern cisplatin-based chemotherapy: Application of the Framingham Risk Score.
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2011. Cancer-related chronic pain: Examin ing quality of life in diverse cancer survivors.
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2014. Fac tors associated with return to work of breast cancer survivors: A systematic review.
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2019. Chronic pain in breast cancer survivors: Nociceptive, neuropathic, or central sensitization pain?
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2018. Associations between perceived stress and chemotherapy-induced peripheral neuropathy and otoxicity in adult cancer survivors.
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2019f. NCCN clinical practice guidelines in oncology: Non-small cell lung cancer, version 5.2019.
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2016. Pain following cancer treatment: Guidelines for the clinical classification of predominant neuropathic, nociceptive and central sensitization pain.
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2018. A smoking cessation and pain management program for cancer survivors.
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2016. American Cancer Society/American Society of Clinical Oncology breast cancer survivorship care guideline.
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2018. Targeted therapies in non-small cell lung cancer: A focus on ALK/ROS tyrosine kinase inhibitors.
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2016. Targeted therapies for lung cancer.
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2019. Comparison of survival rates after a combination of local treatment and systemic therapy vs systemic therapy alone for treatment of stage IV non-small cell lung cancer.
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2019. Age-related differences in patient-reported and objective measures of chemotherapy induced peripheral neuropathy among cancer survivors.
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