American Society of Clinical Oncology Road to Recovery Report: Learning From the COVID-19 Experience to Improve Clinical Research and Cancer Care.

This report presents the American Society of Clinical Oncology's (ASCO's) evaluation of the adaptations in care delivery, research operations, and regulatory oversight made in response to the coronavirus pandemic and presents recommendations for moving forward as the pandemic recedes. ASCO organized its recommendations for clinical research around five goals to ensure lessons learned from the COVID-19 experience are used to craft a more equitable, accessible, and efficient clinical research system that protects patient safety, ensures scientific integrity, and maintains data quality. The specific goals are: (1) ensure that clinical research is accessible, affordable, and equitable; (2) design more pragmatic and efficient clinical trials; (3) minimize administrative and regulatory burdens on research sites; (4) recruit, retain, and support a well-trained clinical research workforce; and (5) promote appropriate oversight and review of clinical trial conduct and results. Similarly, ASCO also organized its recommendations regarding cancer care delivery around five goals: (1) promote and protect equitable access to high-quality cancer care; (2) support safe delivery of high-quality cancer care; (3) advance policies to ensure oncology providers have sufficient resources to provide high-quality patient care; (4) recognize and address threats to clinician, provider, and patient well-being; and (5) improve patient access to high-quality cancer care via telemedicine. ASCO will work at all levels to advance the recommendations made in this report.

Results of the 2013 American Society of Clinical Oncology National Oncology Census.

PURPOSE: The American Society of Clinical Oncology (ASCO) National Oncology Census (Census) provides a mechanism for ASCO to systematically gather and analyze information about current practice structures and potential changes at a time when practices are working to adapt to increasing administrative and financial pressures. The Census is conducted annually and reports on new and trending data. METHODS: The 2013 Census was launched on May 30, 2013, as a national survey of oncology practices. The survey required practices to answer 11 questions and provided additional optional questions. RESULTS: The Census collected 530 useable responses in 2013 compared with 632 respondents in 2012. Practices reporting in 2013, however, represented a total of 8,011 physicians compared with only 5,018 in 2012. CONCLUSION: The pace of policy change in oncology practice is changing the landscape of how practices are organized. A greater number of practices with more than seven physicians responded in 2013, which could indicate overall growth in the size of oncology practice. Practices reported increased affiliations with hospitals through a variety of contractual mechanisms. In subsequent census efforts, ASCO will have the capability to match 2013 respondents to future respondents, allowing for increased precision in comparison of longitudinal data.

American Society of Clinical Oncology National Census of Oncology Practices: preliminary report.

In response to reports of increasing financial and administrative burdens on oncology practices and a lack of systematic information related to these issues, American Society of Clinical Oncology (ASCO) leadership started an effort to collect key practice-level data from all oncology practices in the United States. The result of the effort is the ASCO National Census of Oncology Practices (Census) launched in June 2012. The initial Census work involved compiling an inventory of oncology practices from existing lists of oncology physicians in the United States. A comprehensive, online data collection instrument was developed, which covered a number of areas, including practice characteristics (staffing configuration, organizational structure, patient mix and volume, types of services offered); organizational, staffing, and service changes over the past 12 months; and an assessment of the likelihood that the practice would experience organizational, staffing, and service changes in the next 12 months. More than 600 practices participated in the Census by providing information. In this article, we present preliminary highlights from the data gathered to date. We found that practice size was related to having experienced practice mergers, hiring additional staff, and increasing staff pay in the past 12 months, that geographic location was related to having experienced hiring additional staff, and that practices in metropolitan areas were more likely to have experienced practice mergers in the past 12 months than those in nonmetropolitan areas. We also found that practice size and geographic location were related to higher likelihoods of anticipating practice mergers, sales, and purchases in the future.

Systematic review on hormone receptor testing in breast cancer.

Assessment of hormone receptors (estrogen and progesterone) helps to direct therapy for women with breast cancer. Immunohistochemistry is most commonly used to assess hormone receptor status and it is essential that these tests are performed accurately and reliably within and across laboratories. The overall purpose of this guideline is to improve the quality and accuracy of hormone receptor testing and its utility as a prognostic and predictive marker for invasive and in situ breast cancer. Medline, EMBASE, the Cochrane Database of Systematic Reviews, and abstracts from the San Antonio Breast Cancer Symposium were searched. An environmental scan of the internet and of international guideline developers and key organizations was performed. Preanalytic elements such as the collection, fixation, and storage of samples, and analytic elements such as selection of antibodies and scoring methods that seem to offer the best results for immunohistochemical assessment of hormone receptors are presented. Proficiency testing or quality assurance of immunohistochemistry is described.

5-α-Reductase inhibitors for prostate cancer chemoprevention: an updated Cochrane systematic review.

OBJECTIVE: • To estimate the benefits and harms of 5-α-reductase inhibitors (5-α-RIs) in preventing prostate cancer. MATERIALS AND METHODS: • We searched MEDLINE and the Cochrane Collaboration Library through June 2010 to identify randomized trials. • We included articles if they examined 5-α-RI vs control, were ≥ 1 year in duration and provided clinical outcomes. • Our primary outcome was prostate cancer period-prevalence 'for-cause'. RESULTS: • Eight studies met inclusion criteria but only the Prostate Cancer Prevention Trial and the Reduction by Dutasteride of Prostate Cancer Events were designed to assess the impact of 5-α-RIs on prostate cancer period-prevalence. The mean age of enrolees was 64 years, 92% were White, and mean PSA level was 3.1 ng/mL. For-cause prostate cancers comprised 54% of all cancers detected in placebo-controlled studies. • Compared with placebo, 5-α-RI resulted in a 25% relative risk (RR) reduction in prostate cancers detected for-cause [RR 0.75, 95% confidence interval (CI) 0.67-0.83; 1.4% absolute risk reduction (3.5% vs 4.9%)]. One BPH trial reported that the risk of prostate cancers detected for-cause was significantly reduced with dutasteride and combined dutasteride plus tamsulosin compared with tamsulosin monotherapy. • Six trials vs placebo assessed prostate cancers detected overall. There was a 26% RR reduction favouring 5-α-RI [RR 0.74, 95% CI 0.55-1.00; 2.9% absolute risk reduction (6.3% vs 9.2%)]. There were reductions across categories of age, race and family history of prostate cancer. • One placebo-controlled trial of men that investigators considered at greater risk for prostate cancer (based on age, elevated PSA level and having a previous suspicion of prostate cancer leading to a prostate biopsy) reported that dutasteride did not reduce prostate cancers detected for-cause based on needle-biopsy but did reduce risk of overall incident prostate cancer detected by biopsy by 23%[RR 0.77, 95% CI 0.70-0.85; absolute reduction 16.1% vs 20.8%]. There were reductions across age, family history of prostate cancer, PSA level, and prostate volume subgroups. • Incidences of erectile dysfunction, ejaculate volume, decreased libido, and gynaecomastia were greater with 5-α-RI vs placebo. CONCLUSIONS: • 5-α-RIs reduce the risk of being diagnosed with prostate cancer among men who are screened regularly for prostate cancer. • Information is inadequate to assess the effect of 5-α-RIs on prostate cancer or all-cause mortality. • 5-α-RIs increase sexual and erectile dysfunction.

American Society of Clinical Oncology/College of American Pathologists guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer (unabridged version).

PURPOSE: To develop a guideline to improve the accuracy of immunohistochemical (IHC) estrogen receptor (ER) and progesterone receptor (PgR) testing in breast cancer and the utility of these receptors as predictive markers. METHODS: The American Society of Clinical Oncology and the College of American Pathologists convened an international Expert Panel that conducted a systematic review and evaluation of the literature in partnership with Cancer Care Ontario and developed recommendations for optimal IHC ER/PgR testing performance. RESULTS: Up to 20% of current IHC determinations of ER and PgR testing worldwide may be inaccurate (false negative or false positive). Most of the issues with testing have occurred because of variation in pre-analytic variables, thresholds for positivity, and interpretation criteria. RECOMMENDATIONS: The Panel recommends that ER and PgR status be determined on all invasive breast cancers and breast cancer recurrences. A testing algorithm that relies on accurate, reproducible assay performance is proposed. Elements to reliably reduce assay variation are specified. It is recommended that ER and PgR assays be considered positive if there are at least 1% positive tumor nuclei in the sample on testing in the presence of expected reactivity of internal (normal epithelial elements) and external controls. The absence of benefit from endocrine therapy for women with ER-negative invasive breast cancers has been confirmed in large overviews of randomized clinical trials.

American Society of Clinical Oncology/College of American Pathologists guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer.

PURPOSE: To develop a guideline to improve the accuracy of immunohistochemical (IHC) estrogen receptor (ER) and progesterone receptor (PgR) testing in breast cancer and the utility of these receptors as predictive markers. METHODS: The American Society of Clinical Oncology and the College of American Pathologists convened an international Expert Panel that conducted a systematic review and evaluation of the literature in partnership with Cancer Care Ontario and developed recommendations for optimal IHC ER/PgR testing performance. RESULTS: Up to 20% of current IHC determinations of ER and PgR testing worldwide may be inaccurate (false negative or false positive). Most of the issues with testing have occurred because of variation in preanalytic variables, thresholds for positivity, and interpretation criteria. RECOMMENDATIONS: The Panel recommends that ER and PgR status be determined on all invasive breast cancers and breast cancer recurrences. A testing algorithm that relies on accurate, reproducible assay performance is proposed. Elements to reliably reduce assay variation are specified. It is recommended that ER and PgR assays be considered positive if there are at least 1% positive tumor nuclei in the sample on testing in the presence of expected reactivity of internal (normal epithelial elements) and external controls. The absence of benefit from endocrine therapy for women with ER-negative invasive breast cancers has been confirmed in large overviews of randomized clinical trials.

American Society of Clinical Oncology/College Of American Pathologists guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer.

PURPOSE: To develop a guideline to improve the accuracy of immunohistochemical (IHC) estrogen receptor (ER) and progesterone receptor (PgR) testing in breast cancer and the utility of these receptors as predictive markers. METHODS: The American Society of Clinical Oncology and the College of American Pathologists convened an international Expert Panel that conducted a systematic review and evaluation of the literature in partnership with Cancer Care Ontario and developed recommendations for optimal IHC ER/PgR testing performance. RESULTS: Up to 20% of current IHC determinations of ER and PgR testing worldwide may be inaccurate (false negative or false positive). Most of the issues with testing have occurred because of variation in preanalytic variables, thresholds for positivity, and interpretation criteria. RECOMMENDATIONS: The Panel recommends that ER and PgR status be determined on all invasive breast cancers and breast cancer recurrences. A testing algorithm that relies on accurate, reproducible assay performance is proposed. Elements to reliably reduce assay variation are specified. It is recommended that ER and PgR assays be considered positive if there are at least 1% positive tumor nuclei in the sample on testing in the presence of expected reactivity of internal (normal epithelial elements) and external controls. The absence of benefit from endocrine therapy for women with ER-negative invasive breast cancers has been confirmed in large overviews of randomized clinical trials.

APPRISE Oncology Program for Erythropoiesis-Stimulating Agents.

The FDA recently announced an oncology-specific Risk Evaluation and Mitigation Strategy for erythropoiesis-stimulating agents prescribed under approved indications: The APPRISE program.

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 5-alpha-reductase inhibitors for prostate cancer chemoprevention: American Society of Clinical Oncology/American Urological Association 2008 Clinical Practice Guideline.

PURPOSE To develop an evidence-based guideline on the use of 5-alpha-reductase inhibitors (5-ARIs) for prostate cancer chemoprevention. METHODS The American Society of Clinical Oncology (ASCO) Health Services Committee (HSC), ASCO Cancer Prevention Committee, and the American Urological Association Practice Guidelines Committee jointly convened a Panel of experts, who used the results from a systematic review of the literature to develop evidence-based recommendations on the use of 5-ARIs for prostate cancer chemoprevention. Results The systematic review completed for this guideline identified 15 randomized clinical trials that met the inclusion criteria, nine of which reported prostate cancer period prevalence. CONCLUSION Asymptomatic men with a prostate-specific antigen (PSA)

Use of 5alpha-reductase inhibitors for prostate cancer chemoprevention: American Society of Clinical Oncology/American Urological Association 2008 Clinical Practice Guideline.

PURPOSE: To develop an evidence-based guideline on the use of 5-alpha-reductase inhibitors (5-ARIs) for prostate cancer chemoprevention. METHODS: The American Society of Clinical Oncology (ASCO) Health Services Committee (HSC), ASCO Cancer Prevention Committee, and the American Urological Association Practice Guidelines Committee jointly convened a Panel of experts, who used the results from a systematic review of the literature to develop evidence-based recommendations on the use of 5-ARIs for prostate cancer chemoprevention. RESULTS: The systematic review completed for this guideline identified 15 randomized clinical trials that met the inclusion criteria, nine of which reported prostate cancer period prevalence. CONCLUSION: Asymptomatic men with a prostate-specific antigen (PSA)

American Society of Clinical Oncology 2008 clinical practice guideline update: use of chemotherapy and radiation therapy protectants.

PURPOSE: To update a clinical practice guideline on the use of chemotherapy and radiation therapy protectants for patients with cancer. METHODS: An update committee reviewed literature published since the last guideline update in 2002. RESULTS: Thirty-nine reports met the inclusion criteria: palifermin and dexrazoxane, three reports (two studies) each; amifostine, 33 reports (31 studies); and mesna, no published randomized trials identified since 2002. RECOMMENDATIONS: Dexrazoxane is not recommended for routine use in breast cancer (BC) in adjuvant setting, or metastatic setting with initial doxorubicin-based chemotherapy. Consider use with metastatic BC and other malignancies, for patients who have received more than 300 mg/m(2) doxorubicin who may benefit from continued doxorubicin-containing therapy. Cardiac monitoring should continue in patients receiving doxorubicin. Amifostine may be considered for prevention of cisplatin-associated nephrotoxicity, reduction of grade 3 to 4 neutropenia (alternative strategies are reasonable), and to decrease acute and late xerostomia with fractionated radiation therapy alone for head and neck cancer. It is not recommended for protection against thrombocytopenia, prevention of platinum-associated neurotoxicity or ototoxicity or paclitaxel-associated neuropathy, prevention of radiation therapy-associated mucositis in head and neck cancer, or prevention of esophagitis during concurrent chemoradiotherapy for non-small-cell lung cancer. Palifermin is recommended to decrease severe mucositis in autologous stem-cell transplantation (SCT) for hematologic malignancies with total-body irradiation (TBI) conditioning regimens, and considered for patients undergoing myeloablative allogeneic SCT with TBI-based conditioning regimens. Data are insufficient to recommend use in the non-SCT setting.

American Society of Clinical Oncology clinical practice guidelines: opportunities and challenges.

The American Society of Clinical Oncology (ASCO) published its first clinical practice guideline, which focused on the use of hematopoietic colony-stimulating factors, in 1994. Since then, ASCO has published 24 additional guidelines or technology assessments on a range of topics and is developing 11 additional guidelines. Guidelines are among ASCO's most valued products, according to membership surveys and data from the JCO.org Web site. However, the same data from ASCO members have highlighted a number of limitations to the guideline program. These relate to the timelines of guideline updates, difficulties locating guidelines and related products, and challenges to implementing ASCO guidelines in everyday clinical practice. This article outlines the concrete steps that the ASCO Health Services Committee (HSC) is taking to address these limitations, including the institution of a more aggressive guideline updating schedule, a transition from narrative to systematic literature reviews to support the practice recommendations, a new Board of Directors-approved policy to permit endorsement of other groups' guidelines, and a robust Clinical Tools and Resources program that offers a range of guideline dissemination and implementation aids. Additional work is underway to establish stronger and deeper collaborations with practicing oncologists to expand their role in the review, field testing, and implementation of guideline clinical tools and resources. Finally, the HSC is discussing evaluation of the guidelines program to maximize the impact of ASCO clinical practice guidelines on clinical decision making and, ultimately, the quality of cancer care.

Continued regulatory actions affecting the use of erythropoiesis-stimulating agents.

The FDA sent a "Complete Response and Safety Labeling Change Order" to the sponsors of ESAs on July 30, ordering changes to ESA labels in three important ways. For the first time, the FDA used its statutory authority to order a sponsor to make revisions to a product label.

Use of epoetin and darbepoetin in patients with cancer: 2007 American Society of Hematology/American Society of Clinical Oncology clinical practice guideline update.

PURPOSE: To update the American Society of Clinical Oncology/American Society of Hematology (ASCO/ASH) recommendations for the use of epoetin. The guideline was expanded to address use of darbepoetin and thromboembolic risk associated with these agents. METHOD: An Update Committee ("Committee") reviewed and analyzed data published since 2002 through July 2007. MEDLINE and the Cochrane Collaboration Library databases were searched. RECOMMENDATIONS: For patients with chemotherapy-associated anemia, the Committee continues to recommend initiating an erythropoiesis-stimulating agent (ESA) as hemoglobin (Hb) approaches, or falls below, 10 g/dL, to increase Hb and decrease transfusions. ESA treatment continues to be recommended for patients with low-risk myelodysplasia for similar reasons. There is no evidence showing increased survival as a result of ESA treatment. Conclusive evidence is lacking that, absent clinical circumstances necessitating earlier treatment, initiating ESAs at Hb levels greater than 10 g/dL either spares more patients from transfusion or substantially improves their quality of life. Starting doses and dose modifications based on response or lack thereof should follow the package insert. Continuing ESAs beyond 6 to 8 weeks in the absence of response, assuming appropriate dose increase has been attempted in nonresponders as per US Food and Drug Administration-approved label, does not seem to be beneficial, and ESA therapy should be discontinued. The Committee recommends monitoring iron stores and supplementing iron intake for ESA-treated patients. ESAs should be used cautiously with chemotherapy, or in clinical states, associated with elevated risk for thromo-embolic complications. The Committee also cautions against ESA use for patients with cancer who are not receiving chemotherapy, since recent trials report increased thromboembolic risks and decreased survival under these circumstances.

Use of epoetin and darbepoetin in patients with cancer: 2007 American Society of Clinical Oncology/American Society of Hematology clinical practice guideline update.

PURPOSE: To update the American Society of Clinical Oncology/American Society of Hematology (ASCO/ASH) recommendations for the use of epoetin. The guideline was expanded to address use of darbepoetin and thromboembolic risk associated with these agents. METHOD: An Update Committee ("Committee") reviewed and analyzed data published since 2002 through July 2007. MEDLINE and the Cochrane Collaboration Library databases were searched. RECOMMENDATIONS: For patients with chemotherapy-associated anemia, the Committee continues to recommend initiating an erythropoiesis-stimulating agent (ESA) as hemoglobin (Hb) approaches, or falls below, 10 g/dL, to increase Hb and decrease transfusions. ESA treatment continues to be recommended for patients with low-risk myelodysplasia for similar reasons. There is no evidence showing increased survival as a result of ESA treatment. Conclusive evidence is lacking that, absent clinical circumstances necessitating earlier treatment, initiating ESAs at Hb levels greater than 10 g/dL either spares more patients from transfusion or substantially improves their quality of life. Starting doses and dose modifications based on response or lack thereof should follow the package insert. Continuing ESAs beyond 6 to 8 weeks in the absence of response, assuming appropriate dose increase has been attempted in nonresponders as per US Food and Drug Administration-approved labeling, does not seem to be beneficial, and ESA therapy should be discontinued. The Committee recommends monitoring iron stores and supplementing iron intake for ESA-treated patients. ESAs should be used cautiously with chemotherapy, or in clinical states, associated with elevated risk for thromboembolic complications. The Committee also cautions against ESA use for patients with cancer who are not receiving chemotherapy, since recent trials report increased thromboembolic risks and decreased survival under these circumstances.

American Society of Clinical Oncology clinical evidence review on the ongoing care of adult cancer survivors: cardiac and pulmonary late effects.

PURPOSE: To review the evidence on the incidence of long-term cardiac or pulmonary toxicity secondary to chemotherapy, radiotherapy, or trastuzumab in symptomatic and asymptomatic cancer survivors. METHODS: An American Society of Clinical Oncology Panel reviewed pertinent information from the literature through February 2006. RESULTS: Few studies directly addressing the benefits of screening for long-term cardiac or pulmonary toxicity in asymptomatic cancer survivors who received chemotherapy, radiotherapy, or trastuzumab were identified. The reviewed literature included primarily retrospective and cross-sectional studies describing the incidence of cardiac and pulmonary late effects. Anatomic and/or functional abnormalities have been associated with use of all currently available anthracyclines and their derivatives. Trastuzumab-related cardiac dysfunction rarely causes death, and in most cases is reversible with improvement in cardiac function on drug discontinuation and/or treatment with cardiac medications. The estimated aggregate incidence of radiation-induced cardiac disease is 10% to 30% by 5 to 10 years post-treatment, although the incidence may be lower with modern techniques. Radiation pneumonitis is reported in 5% to 15% of lung cancer patients receiving definitive external-beam radiation therapy. A minority of patients may develop progressive pulmonary fibrosis; late complications include cor pulmonale and respiratory failure. Bleomycin-induced pneumonitis is an acute rather than late effect of treatment. Late pulmonary complications in bone marrow or stem cell transplantation patients who develop interstitial pneumonitis include idiopathic pneumonia syndrome and bronchiolitis obliterans. CONCLUSION: An increased incidence of cardiac and/or pulmonary dysfunction is observed in cancer survivors. Research is needed to identify high-risk patients, and to determine the optimal screening strategies and subsequent treatment.