Patricia Hurley

Breast Cancer Follow-Up and Management After Primary Treatment: American Society of Clinical Oncology Clinical Practice Guideline Update

PURPOSE To provide recommendations on the follow-up and management of patients with breast cancer who have completed primary therapy with curative intent. METHODS To update the 2006 guideline of the American Society of Clinical Oncology (ASCO), a systematic review of the literature published from March 2006 through March 2012 was completed using MEDLINE and the Cochrane Collaboration Library. An Update Committee reviewed the evidence to determine whether the recommendations were in need of updating. RESULTS There were 14 new publications that met inclusion criteria: nine systematic reviews (three included meta-analyses) and five randomized controlled trials. After its review and analysis of the evidence, the Update Committee concluded that no revisions to the existing ASCO recommendations were warranted. RECOMMENDATIONS Regular history, physical examination, and mammography are recommended for breast cancer follow-up. Physical examinations should be performed every 3 to 6 months for the first 3 years, every 6 to 12 months for years 4 and 5, and annually thereafter. For women who have undergone breast-conserving surgery, a post-treatment mammogram should be obtained 1 year after the initial mammogram and at least 6 months after completion of radiation therapy. Thereafter, unless otherwise indicated, a yearly mammographic evaluation should be performed. The use of complete blood counts, chemistry panels, bone scans, chest radiographs, liver ultrasounds, pelvic ultrasounds, computed tomography scans, [(18)F]fluorodeoxyglucose-positron emission tomography scans, magnetic resonance imaging, and/or tumor markers (carcinoembryonic antigen, CA 15-3, and CA 27.29) is not recommended for routine follow-up in an otherwise asymptomatic patient with no specific findings on clinical examination.

American Society of Clinical Oncology/American Society of Hematology Clinical Practice Guideline Update on the Use of Epoetin and Darbepoetin in Adult Patients With Cancer

PURPOSE To update American Society of Clinical Oncology/American Society of Hematology recommendations for use of erythropoiesis-stimulating agents (ESAs) in patients with cancer. METHODS An Update Committee reviewed data published between January 2007 and January 2010. MEDLINE and the Cochrane Library were searched. RESULTS The literature search yielded one new individual patient data analysis and four literature-based meta-analyses, two systematic reviews, and 13 publications reporting new results from randomized controlled trials not included in prior or new reviews. RECOMMENDATIONS For patients undergoing myelosuppressive chemotherapy who have a hemoglobin (Hb) level less than 10 g/dL, the Update Committee recommends that clinicians discuss potential harms (eg, thromboembolism, shorter survival) and benefits (eg, decreased transfusions) of ESAs and compare these with potential harms (eg, serious infections, immune-mediated adverse reactions) and benefits (eg, rapid Hb improvement) of RBC transfusions. Individual preferences for assumed risk should contribute to shared decisions on managing chemotherapy-induced anemia. The Committee cautions against ESA use under other circumstances. If used, ESAs should be administered at the lowest dose possible and should increase Hb to the lowest concentration possible to avoid transfusions. Available evidence does not identify Hb levels ≥ 10 g/dL either as thresholds for initiating treatment or as targets for ESA therapy. Starting doses and dose modifications after response or nonresponse should follow US Food and Drug Administration-approved labeling. ESAs should be discontinued after 6 to 8 weeks in nonresponders. ESAs should be avoided in patients with cancer not receiving concurrent chemotherapy, except for those with lower risk myelodysplastic syndromes. Caution should be exercised when using ESAs with chemotherapeutic agents in diseases associated with increased risk of thromboembolic complications. Table 1 lists detailed recommendations.

American society of clinical oncology clinical practice guideline update on the use of pharmacologic interventions including tamoxifen, raloxifene, and aromatase inhibition for breast cancer risk reduction.

PURPOSE To update the 2002 American Society of Clinical Oncology guideline on pharmacologic interventions for breast cancer (BC) risk reduction. METHODS A literature search identified relevant randomized trials published since 2002. Primary outcome of interest was BC incidence (invasive and noninvasive). Secondary outcomes included BC mortality, adverse events, and net health benefits. An expert panel reviewed the literature and developed updated consensus guidelines. Results Seventeen articles met inclusion criteria. In premenopausal women, tamoxifen for 5 years reduces the risk of BC for at least 10 years, particularly estrogen receptor (ER) -positive invasive tumors. Women < or = 50 years of age experience fewer serious side effects. Vascular and vasomotor events do not persist post-treatment across all ages. In postmenopausal women, raloxifene and tamoxifen reduce the risk of ER-positive invasive BC with equal efficacy. Raloxifene is associated with a lower risk of thromboembolic disease, benign uterine conditions, and cataracts than tamoxifen in postmenopausal women. No evidence exists establishing whether a reduction in BC risk from either agent translates into reduced BC mortality. Recommendations In women at increased risk for BC, tamoxifen (20 mg/d for 5 years) may be offered to reduce the risk of invasive ER-positive BC, with benefits for at least 10 years. In postmenopausal women, raloxifene (60 mg/d for 5 years) may also be considered. Use of aromatase inhibitors, fenretinide, or other selective estrogen receptor modulators to lower BC risk is not recommended outside of a clinical trial. Discussion of risks and benefits of preventive agents by health providers is critical to patient decision making.

Use of Pharmacologic Interventions for Breast Cancer Risk Reduction: American Society of Clinical Oncology Clinical Practice Guideline

PURPOSE To update the 2009 American Society of Clinical Oncology guideline on pharmacologic interventions for breast cancer (BC) risk reduction. METHODS A systematic review of randomized controlled trials and meta-analyses published from June 2007 through June 2012 was completed using MEDLINE and Cochrane Collaboration Library. Primary outcome of interest was BC incidence (invasive and noninvasive). Secondary outcomes included BC mortality, adverse events, and net health benefits. Guideline recommendations were revised based on an Update Committees review of the literature. RESULTS Nineteen articles met the selection criteria. Six chemoprevention agents were identified: tamoxifen, raloxifene, arzoxifene, lasofoxifene, exemestane, and anastrozole. RECOMMENDATIONS In women at increased risk of BC age ≥ 35 years, tamoxifen (20 mg per day for 5 years) should be discussed as an option to reduce the risk of estrogen receptor (ER) -positive BC. In postmenopausal women, raloxifene (60 mg per day for 5 years) and exemestane (25 mg per day for 5 years) should also be discussed as options for BC risk reduction. Those at increased BC risk are defined as individuals with a 5-year projected absolute risk of BC ≥ 1.66% (based on the National Cancer Institute BC Risk Assessment Tool or an equivalent measure) or women diagnosed with lobular carcinoma in situ. Use of other selective ER modulators or other aromatase inhibitors to lower BC risk is not recommended outside of a clinical trial. Health care providers are encouraged to discuss the option of chemoprevention among women at increased BC risk. The discussion should include the specific risks and benefits associated with each chemopreventive agent.

American Society of Hematology/American Society of Clinical Oncology clinical practice guideline update on the use of epoetin and darbepoetin in adult patients with cancer

PURPOSE To update American Society of Hematology/American Society of Clinical Oncology recommendations for use of erythropoiesis-stimulating agents (ESAs) in patients with cancer. METHODS An Update Committee reviewed data published between January 2007 and January 2010. MEDLINE and the Cochrane Library were searched. RESULTS The literature search yielded one new individual patient data analysis and four literature-based meta-analyses, two systematic reviews, and 13 publications reporting new results from randomized controlled trials not included in prior or new reviews. RECOMMENDATIONS For patients undergoing myelosuppressive chemotherapy who have a hemoglobin (Hb) level less than 10 g/dL, the Update Committee recommends that clinicians discuss potential harms (eg, thromboembolism, shorter survival) and benefits (eg, decreased transfusions) of ESAs and compare these with potential harms (eg, serious infections, immune-mediated adverse reactions) and benefits (eg, rapid Hb improvement) of RBC transfusions. Individual preferences for assumed risk should contribute to shared decisions on managing chemotherapy-induced anemia. The Committee cautions against ESA use under other circumstances. If used, ESAs should be administered at the lowest dose possible and should increase Hb to the lowest concentration possible to avoid transfusions. Available evidence does not identify Hb levels ≥ 10 g/dL either as thresholds for initiating treatment or as targets for ESA therapy. Starting doses and dose modifications after response or nonresponse should follow US Food and Drug Administration-approved labeling. ESAs should be discontinued after 6 to 8 weeks in nonresponders. ESAs should be avoided in patients with cancer not receiving concurrent chemotherapy, except for those with lower risk myelodysplastic syndromes. Caution should be exercised when using ESAs with chemotherapeutic agents in diseases associated with increased risk of thromboembolic complications. Table 1 lists detailed recommendations.

Circulating tumor DNA analysis in patients with cancer: American society of clinical oncology and college of American pathologists joint review

Purpose Clinical use of analytical tests to assess genomic variants in circulating tumor DNA (ctDNA) is increasing. This joint review from ASCO and the College of American Pathologists summarizes current information about clinical ctDNA assays and provides a framework for future research. Methods An Expert Panel conducted a literature review on the use of ctDNA assays for solid tumors, including pre-analytical variables, analytical validity, interpretation and reporting, and clinical validity and utility. Results The literature search identified 1,338 references. Of those, 390, plus 31 references supplied by the Expert Panel, were selected for full-text review. There were 77 articles selected for inclusion. Conclusion The evidence indicates that testing for ctDNA is optimally performed on plasma collected in cell stabilization or EDTA tubes, with EDTA tubes processed within 6 hours of collection. Some ctDNA assays have demonstrated clinical validity and utility with certain types of advanced cancer; however, there is insufficient evidence of clinical validity and utility for the majority of ctDNA assays in advanced cancer. Evidence shows discordance between the results of ctDNA assays and genotyping tumor specimens and supports tumor tissue genotyping to confirm undetected results from ctDNA tests. There is no evidence of clinical utility and little evidence of clinical validity of ctDNA assays in early-stage cancer, treatment monitoring, or residual disease detection. There is no evidence of clinical validity and clinical utility to suggest that ctDNA assays are useful for cancer screening, outside of a clinical trial. Given the rapid pace of research, re-evaluation of the literature will shortly be required, along with the development of tools and guidance for clinical practice.

Addressing Administrative and Regulatory Burden in Cancer Clinical Trials: Summary of a Stakeholder Survey and Workshop Hosted by the American Society of Clinical Oncology and the Association of American Cancer Institutes

Cancer clinical trials are responsible for many of the recent advances in oncology care, including declining mortality rates and increased survivorship; better supportive care; and clinicians’ improved understanding of cancer risk, prevention, and screening. This research has also led to exciting new types of cancer treatments, such as molecularly targeted therapies and immunotherapies. Cancer clinical trials, however, have become more and more challenging to conduct. Research programs must comply with federal and state legal and regulatory requirements that can be inefficient and costly to implement. In addition, institutions and sponsors often interpret these requirements conservatively and thereby add to the complexity and perceived (but often highly theoretical) risk of conducting clinical trials. Elements of the existing requirements are important for protecting trial participants’ safety, for promoting the scientific integrity of research, and for ensuring that trial conduct is efficient and adequately resourced. Such elements are important to preserve. However, taken as a whole, the requirements do not fulfill these goals and, in fact, hinder research and slow patients’ access to safe and effective treatments. To address the problem of administrative and regulatory burden on cancer clinical trials, ASCO partnered with the Association of American Cancer Institutes (AACI) on the Best Practices in Cancer Clinical Trials Initiative (hereafter referred to as the Initiative). ASCO is the leading professional organization to represent oncologists and other health care professionals who care for people with cancer and conduct research to improve cancer treatment. With . 40,000 members, ASCO is committed to the improvement of cancer care through scientific meetings, educational programs, defining and measuring the quality of cancer care, and publishing peerreviewed journals. AACI represents 95 leading cancer research centers in North America. Its mission is to assist cancer centers in keeping pace with the changing landscape of science, technology, and health care through the dissemination of best practices, creation of member forums, and development of policy recommendations and educational material. The purpose of the Initiative was to promote practical solutions to meet existing regulatory and administrative requirements on research. Both ASCO and AACI have previously explored various strategies to streamline the conduct of clinical trials, such as the development of supportive tools and templates, networking sessions, and common guidelines and standards. The Initiative was an opportunity to expand on their current work in this area. A multidisciplinary working group of hematologists/oncologists, research nurses, administrators, and managers as well as industry representatives oversaw the Initiative. Officials from the Food and Drug Administration (FDA) and the National Cancer Institute (NCI), contract research organization (CRO) staff, and patient advocates provided input to the project. The main elements of the project included a stakeholder survey to identify the most pressing issues in clinical trials that could be addressed by the Initiative, assess staff and resources for conducting and managing trials, and gather data on usage of existing tools and resources; an invitational workshop that convened many leading oncology professionals and policymakers to identify potential solutions for improving the efficiency and conduct of cancer clinical trials; dissemination of the recommendations from the workshop through publication and ASCO and AACI annual meetings; and the development of practical resources, toolkits, and follow-up Julie M. Vose, University of Nebraska, Omaha, NE; Laura A. Levit, Patricia Hurley, and Suanna S. Bruinooge, American Society of Clinical Oncology, Alexandria, VA; Carrie Lee, University of North Carolina at Chapel Hill, Chapel Hill, NC; Michael A. Thompson, Aurora Health Care, Milwaukee, WI; Teresa Stewart, New Mexico Cancer Care Alliance, Albuquerque, NM; Janie Hofacker, Association of American Cancer Institutes, Pittsburgh, PA; and Daniel F. Hayes, University of Michigan, Ann Arbor, MI.

Challenges With Research Contract Negotiations in Community-Based Cancer Research

PURPOSE Community-based research programs face many barriers to participation in clinical trials. Although the majority of people with cancer are diagnosed and treated in the community setting, only roughly 3% are enrolled onto clinical trials. Research contract and budget negotiations have been consistently identified as time consuming and a barrier to participation in clinical trials. ASCOs Community Research Forum conducted a survey about specific challenges of research contract and budget negotiation processes in community-based research settings. The goal was to ultimately identify potential solutions to these barriers. METHODS A survey was distributed to 780 community-based physician investigators and research staff. The survey included questions to provide insight into contract and budget negotiation processes and perceptions about related barriers. RESULTS A total of 77% of the 150 respondents acknowledged barriers in the process. Respondents most frequently identified budget-related issues (n = 133), inefficiencies in the process (n = 80), or legal review and negotiation issues (n = 70). Of the respondents, 44.1% indicated that contract research organizations made the contract negotiations process harder for their research program, and only 5% believed contract research organizations made the process easier. The contract negotiations process is perceived to be impeded by sponsors through underestimation of costs, lack of flexibility with the contract language, and excessive delays. CONCLUSION Improving clinical trial activation processes and reducing inefficiencies would be beneficial to all interested stakeholders, including patients who may ultimately stand to benefit from participation in clinical trials. The following key recommendations were made: standardization of contracts and negotiation processes to promulgate transparency and efficiencies, improve sponsor processes to minimize burden on sites, create and promote use of contract templates and best practices, and provide education and consultation.

Circulating Tumor DNA Analysis in Patients With Cancer: American Society of Clinical Oncology and College of American Pathologists Joint Review

PURPOSE.— Clinical use of analytical tests to assess genomic variants in circulating tumor DNA (ctDNA) is increasing. This joint review from the American Society of Clinical Oncology and the College of American Pathologists summarizes current information about clinical ctDNA assays and provides a framework for future research. METHODS.— An Expert Panel conducted a literature review on the use of ctDNA assays for solid tumors, including preanalytical variables, analytical validity, interpretation and reporting, and clinical validity and utility. RESULTS.— The literature search identified 1338 references. Of those, 390, plus 31 references supplied by the Expert Panel, were selected for full-text review. There were 77 articles selected for inclusion. CONCLUSIONS.— The evidence indicates that testing for ctDNA is optimally performed on plasma collected in cell stabilization or EDTA tubes, with EDTA tubes processed within 6 hours of collection. Some ctDNA assays have demonstrated clinical validity and utility with certain types of advanced cancer; however, there is insufficient evidence of clinical validity and utility for the majority of ctDNA assays in advanced cancer. Evidence shows discordance between the results of ctDNA assays and genotyping tumor specimens, and supports tumor tissue genotyping to confirm undetected results from ctDNA tests. There is no evidence of clinical utility and little evidence of clinical validity of ctDNA assays in early-stage cancer, treatment monitoring, or residual disease detection. There is no evidence of clinical validity or clinical utility to suggest that ctDNA assays are useful for cancer screening, outside of a clinical trial. Given the rapid pace of research, reevaluation of the literature will shortly be required, along with the development of tools and guidance for clinical practice.

Sentinel Lymph Node Biopsy for Melanoma: American Society of Clinical Oncology and Society of Surgical Oncology Joint Clinical Practice Guideline

Metastasis to regional nodes is an important prognostic factor in patients with early-stage melanoma.1,2 As such, it is critically important for clinicians to identify patients for whom the expected benefits of resecting regional lymph nodes outweigh the risks of surgical morbidity. Sentinel lymph node (SLN) biopsy is commonly used by surgeons as a valuable staging procedure for patients with melanoma who are at risk of clinically occult nodal metastases, and has been endorsed by the American Joint Committee on Cancer. This highly accurate and low-morbidity staging procedure should be used to guide treatment decisions and entry into clinical trials.3 To develop and formalize clinical practice guideline recommendations for the use of SLN biopsy in oncology practice, ASCO and the Society of Surgical Oncology (SSO) convened a joint expert panel. The guideline addresses two overarching clinical questions: (1) What are the indications for SLN biopsy? and (2) What is the role of completion lymph node dissection?