Pamela B. Mangu

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.

Recommendations for human epidermal growth factor receptor 2 testing in breast cancer: American Society of Clinical Oncology/College of American Pathologists clinical practice guideline update.

PURPOSE To update the American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guideline recommendations for human epidermal growth factor receptor 2 (HER2) testing in breast cancer to improve the accuracy of HER2 testing and its utility as a predictive marker in invasive breast cancer. METHODS ASCO/CAP convened an Update Committee that included coauthors of the 2007 guideline to conduct a systematic literature review and update recommendations for optimal HER2 testing. RESULTS The Update Committee identified criteria and areas requiring clarification to improve the accuracy of HER2 testing by immunohistochemistry (IHC) or in situ hybridization (ISH). The guideline was reviewed and approved by both organizations. RECOMMENDATIONS The Update Committee recommends that HER2 status (HER2 negative or positive) be determined in all patients with invasive (early stage or recurrence) breast cancer on the basis of one or more HER2 test results (negative, equivocal, or positive). Testing criteria define HER2-positive status when (on observing within an area of tumor that amounts to > 10% of contiguous and homogeneous tumor cells) there is evidence of protein overexpression (IHC) or gene amplification (HER2 copy number or HER2/CEP17 ratio by ISH based on counting at least 20 cells within the area). If results are equivocal (revised criteria), reflex testing should be performed using an alternative assay (IHC or ISH). Repeat testing should be considered if results seem discordant with other histopathologic findings. Laboratories should demonstrate high concordance with a validated HER2 test on a sufficiently large and representative set of specimens. Testing must be performed in a laboratory accredited by CAP or another accrediting entity. The Update Committee urges providers and health systems to cooperate to ensure the highest quality testing. This guideline was developed through a collaboration between the American Society of Clinical Oncology and the College of American Pathologists and has been published jointly by invitation and consent in both Journal of Clinical Oncology and the Archives of Pathology & Laboratory Medicine.

Fertility Preservation for Patients With Cancer: American Society of Clinical Oncology Clinical Practice Guideline Update

PURPOSE To update guidance for health care providers about fertility preservation for adults and children with cancer. METHODS A systematic review of the literature published from March 2006 through January 2013 was completed using MEDLINE and the Cochrane Collaboration Library. An Update Panel reviewed the evidence and updated the recommendation language. RESULTS There were 222 new publications that met inclusion criteria. A majority were observational studies, cohort studies, and case series or reports, with few randomized clinical trials. After review of the new evidence, the Update Panel concluded that no major, substantive revisions to the 2006 American Society of Clinical Oncology recommendations were warranted, but clarifications were added. RECOMMENDATIONS As part of education and informed consent before cancer therapy, health care providers (including medical oncologists, radiation oncologists, gynecologic oncologists, urologists, hematologists, pediatric oncologists, and surgeons) should address the possibility of infertility with patients treated during their reproductive years (or with parents or guardians of children) and be prepared to discuss fertility preservation options and/or to refer all potential patients to appropriate reproductive specialists. Although patients may be focused initially on their cancer diagnosis, the Update Panel encourages providers to advise patients regarding potential threats to fertility as early as possible in the treatment process so as to allow for the widest array of options for fertility preservation. The discussion should be documented. Sperm and embryo cryopreservation as well as oocyte cryopreservation are considered standard practice and are widely available. Other fertility preservation methods should be considered investigational and should be performed by providers with the necessary expertise.

Recommendations for Human Epidermal Growth Factor Receptor 2 Testing in Breast Cancer: American Society of Clinical Oncology/College of American Pathologists Clinical Practice Guideline Update

PURPOSE To update the American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guideline recommendations for human epidermal growth factor receptor 2 (HER2) testing in breast cancer to improve the accuracy of HER2 testing and its utility as a predictive marker in invasive breast cancer. METHODS ASCO/CAP convened an Update Committee that included coauthors of the 2007 guideline to conduct a systematic literature review and update recommendations for optimal HER2 testing. RESULTS The Update Committee identified criteria and areas requiring clarification to improve the accuracy of HER2 testing by immunohistochemistry (IHC) or in situ hybridization (ISH). The guideline was reviewed and approved by both organizations. RECOMMENDATIONS The Update Committee recommends that HER2 status (HER2 negative or positive) be determined in all patients with invasive (early stage or recurrence) breast cancer on the basis of one or more HER2 test results (negative, equivocal, or positive). Testing criteria define HER2-positive status when (on observing within an area of tumor that amounts to >10% of contiguous and homogeneous tumor cells) there is evidence of protein overexpression (IHC) or gene amplification (HER2 copy number or HER2/CEP17 ratio by ISH based on counting at least 20 cells within the area). If results are equivocal (revised criteria), reflex testing should be performed using an alternative assay (IHC or ISH). Repeat testing should be considered if results seem discordant with other histopathologic findings. Laboratories should demonstrate high concordance with a validated HER2 test on a sufficiently large and representative set of specimens. Testing must be performed in a laboratory accredited by CAP or another accrediting entity. The Update Committee urges providers and health systems to cooperate to ensure the highest quality testing.

American Society of Clinical Oncology 2009 Clinical Evidence Review on Radiofrequency Ablation of Hepatic Metastases From Colorectal Cancer

PURPOSE To review the evidence about the efficacy and utility of radiofrequency ablation (RFA) for hepatic metastases from colorectal cancer (CRHM). METHODS The American Society of Clinical Oncology (ASCO) convened a panel to conduct and analyze a comprehensive systematic review of the RFA literature from Medline and the Cochrane Collaboration Library. RESULTS Because data were considered insufficient to form the basis of a practice guideline, ASCO has instead published a clinical evidence review. The evidence is from single-arm, retrospective, and prospective trials. No randomized controlled trials have been included. The following three clinical issues were considered by the panel: the efficacy of surgical hepatic resection versus RFA for resectable tumors; the utility of RFA for unresectable tumors; and RFA approaches (open, laparoscopic, or percutaneous). Evidence suggests that hepatic resection improves overall survival (OS), particularly for patients with resectable tumors without extrahepatic disease. Careful patient and tumor selection is discussed at length in the literature. RFA investigators report a wide variability in the 5-year survival rate (14% to 55%) and local tumor recurrence rate (3.6% to 60%). The reported mortality rate was low (0% to 2%), and the major complications rate was commonly reported to be between 6% and 9%. RFA is currently performed with all three approaches. CONCLUSION There is a compelling need for more research to determine the efficacy and utility of RFA to increase local recurrence-free, progression-free, and disease-free survival as well as OS for patients with CRHM. Clinical trials have established that hepatic resection can improve OS for patients with resectable CRHM.

Appropriate Chemotherapy Dosing for Obese Adult Patients With Cancer: American Society of Clinical Oncology Clinical Practice Guideline

PURPOSE To provide recommendations for appropriate cytotoxic chemotherapy dosing for obese adult patients with cancer. METHODS The American Society of Clinical Oncology convened a Panel of experts in medical and gynecologic oncology, clinical pharmacology, pharmacokinetics and pharmacogenetics, and biostatistics and a patient representative. MEDLINE searches identified studies published in English between 1996 and 2010, and a systematic review of the literature was conducted. A majority of studies involved breast, ovarian, colon, and lung cancers. This guideline does not address dosing for novel targeted agents. RESULTS Practice pattern studies demonstrate that up to 40% of obese patients receive limited chemotherapy doses that are not based on actual body weight. Concerns about toxicity or overdosing in obese patients with cancer, based on the use of actual body weight, are unfounded. RECOMMENDATIONS The Panel recommends that full weight-based cytotoxic chemotherapy doses be used to treat obese patients with cancer, particularly when the goal of treatment is cure. There is no evidence that short- or long-term toxicity is increased among obese patients receiving full weight-based doses. Most data indicate that myelosuppression is the same or less pronounced among the obese than the non-obese who are administered full weight-based doses. Clinicians should respond to all treatment-related toxicities in obese patients in the same ways they do for non-obese patients. The use of fixed-dose chemotherapy is rarely justified, but the Panel does recommend fixed dosing for a few select agents. The Panel recommends further research into the role of pharmacokinetics and pharmacogenetics to guide appropriate dosing of obese patients with cancer.

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.

Central Venous Catheter Care for the Patient With Cancer: American Society of Clinical Oncology Clinical Practice Guideline

PURPOSE To develop an evidence-based guideline on central venous catheter (CVC) care for patients with cancer that addresses catheter type, insertion site, and placement as well as prophylaxis and management of both catheter-related infection and thrombosis. METHODS A systematic search of MEDLINE and the Cochrane Library (1980 to July 2012) identified relevant articles published in English. RESULTS The overall quality of the randomized controlled trial evidence was rated as good. There is consistency among meta-analyses and guidelines compiled by other groups as well. RECOMMENDATIONS There is insufficient evidence to recommend one CVC type or insertion site; femoral catheterization should be avoided. CVC should be placed by well-trained providers, and the use of a CVC clinical care bundle is recommended. The use of antimicrobial/antiseptic-impregnated and/or heparin-impregnated CVCs is recommended to decrease the risk of catheter-related infections for short-term CVCs, particularly in high-risk groups; more research is needed. The prophylactic use of systemic antibiotics is not recommended before insertion. Data are not sufficient to recommend for or against routine use of antibiotic flush/lock therapy; more research is needed. Before starting antibiotic therapy, cultures should be obtained. Some life-threatening infections require immediate catheter removal, but most can be treated with antimicrobial therapy while the CVC remains in place. Routine flushing with saline is recommended. Prophylactic use of warfarin or low-molecular weight heparin is not recommended, although a tissue plasminogen activator (t-PA) is recommended to restore patency to occluded catheters. CVC removal is recommended when the catheter is no longer needed or if there is a radiologically confirmed thrombosis that worsens despite anticoagulation therapy.

Follow-Up Care, Surveillance Protocol, and Secondary Prevention Measures for Survivors of Colorectal Cancer: American Society of Clinical Oncology Clinical Practice Guideline Endorsement

PURPOSE The American Society of Clinical Oncology (ASCO) has a policy and set of procedures for endorsing recent clinical practice guidelines that have been developed by other professional organizations. METHODS The Cancer Care Ontario (CCO) Guideline on Follow-up Care, Surveillance Protocol, and Secondary Prevention Measures for Survivors of Colorectal Cancer was reviewed by ASCO for methodologic rigor and considered for endorsement. RESULTS The ASCO Panel concurred with the CCO recommendations and recommended endorsement, with the addition of several qualifying statements. CONCLUSION Surveillance should be guided by presumed risk of recurrence and functional status of the patient (important within the first 2 to 4 years). Medical history, physical examination, and carcinoembryonic antigen testing should be performed every 3 to 6 months for 5 years. Patients at higher risk of recurrence should be considered for testing in the more frequent end of the range. A computed tomography scan (abdominal and chest) is recommended annually for 3 years, in most cases. Positron emission tomography scans should not be used for surveillance outside of a clinical trial. A surveillance colonoscopy should be performed 1 year after the initial surgery and then every 5 years, dictated by the findings of the previous one. If a colonoscopy was not preformed before diagnosis, it should be done after completion of adjuvant therapy (before 1 year). Secondary prevention (maintaining a healthy body weight and active lifestyle) is recommended. If a patient is not a candidate for surgery or systemic therapy because of severe comorbid conditions, surveillance tests should not be performed. A treatment plan from the specialist should have clear directions on appropriate follow-up by a nonspecialist.

ACCF/AHA clinical practice guideline methodology summit report: A report of the American college of cardiology foundation/American heart association task force on practice guidelines

Alice K. Jacobs, MD, FACC, FAHA, Immediate Past Chair Jeffrey L. Anderson, MD, FACC, FAHA, Chair Jonathan L. Halperin, MD, FACC, FAHA, Chair-Elect Nancy M. Albert, PhD, CCNS, CCRN, FAHA Mark A. Creager, MD, FACC, FAHA David L. DeMets, PhD Steven M. Ettinger, MD, FACC Robert A. Guyton, MD,