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

PURPOSE.­: To update key recommendations of the American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) human epidermal growth factor receptor 2 (HER2) testing in breast cancer guideline. METHODS.­: Based on the signals approach, an Expert Panel reviewed published literature and research survey results on the observed frequency of less common in situ hybridization (ISH) patterns to update the recommendations. RECOMMENDATIONS.­: Two recommendations addressed via correspondence in 2015 are included. First, immunohistochemistry (IHC) 2+ is defined as invasive breast cancer with weak to moderate complete membrane staining observed in >10% of tumor cells. Second, if the initial HER2 test result in a core needle biopsy specimen of a primary breast cancer is negative, a new HER2 test may (not "must") be ordered on the excision specimen based on specific clinical criteria. The HER2 testing algorithm for breast cancer is updated to address the recommended workup for less common clinical scenarios (approximately 5% of cases) observed when using a dual-probe ISH assay. These scenarios are described as ISH group 2 ( HER2/chromosome enumeration probe 17 [CEP17] ratio ≥2.0; average HER2 copy number <4.0 signals per cell), ISH group 3 ( HER2/CEP17 ratio <2.0; average HER2 copy number ≥6.0 signals per cell), and ISH group 4 ( HER2/CEP17 ratio <2.0; average HER2 copy number ≥4.0 and <6.0 signals per cell). The diagnostic approach includes more rigorous interpretation criteria for ISH and requires concomitant IHC review for dual-probe ISH groups 2 to 4 to arrive at the most accurate HER2 status designation (positive or negative) based on combined interpretation of the ISH and IHC assays. The Expert Panel recommends that laboratories using single-probe ISH assays include concomitant IHC review as part of the interpretation of all single-probe ISH assay results.

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

Purpose To update key recommendations of the American Society of Clinical Oncology/College of American Pathologists human epidermal growth factor receptor 2 (HER2) testing in breast cancer guideline. Methods Based on the signals approach, an Expert Panel reviewed published literature and research survey results on the observed frequency of less common in situ hybridization (ISH) patterns to update the recommendations. Recommendations Two recommendations addressed via correspondence in 2015 are included. First, immunohistochemistry (IHC) 2+ is defined as invasive breast cancer with weak to moderate complete membrane staining observed in > 10% of tumor cells. Second, if the initial HER2 test result in a core needle biopsy specimen of a primary breast cancer is negative, a new HER2 test may (not "must") be ordered on the excision specimen based on specific clinical criteria. The HER2 testing algorithm for breast cancer is updated to address the recommended work-up for less common clinical scenarios (approximately 5% of cases) observed when using a dual-probe ISH assay. These scenarios are described as ISH group 2 ( HER2/chromosome enumeration probe 17 [CEP17] ratio ≥ 2.0; average HER2 copy number < 4.0 signals per cell), ISH group 3 ( HER2/CEP17 ratio < 2.0; average HER2 copy number ≥ 6.0 signals per cell), and ISH group 4 ( HER2/CEP17 ratio < 2.0; average HER2 copy number ≥ 4.0 and < 6.0 signals per cell). The diagnostic approach includes more rigorous interpretation criteria for ISH and requires concomitant IHC review for dual-probe ISH groups 2 to 4 to arrive at the most accurate HER2 status designation (positive or negative) based on combined interpretation of the ISH and IHC assays. The Expert Panel recommends that laboratories using single-probe ISH assays include concomitant IHC review as part of the interpretation of all single-probe ISH assay results. Find additional information at www.asco.org/breast-cancer-guidelines .

Potentially Curable Pancreatic Cancer: American Society of Clinical Oncology Clinical Practice Guideline Update.

Purpose To update the Potentially Curable Pancreatic Cancer: American Society of Clinical Oncology Clinical Practice Guideline published on May 31, 2016. The October 2016 update focuses solely on new evidence that pertains to clinical question 4 of the guideline: What is the appropriate adjuvant regimen for patients with pancreatic cancer who have undergone an R0 or R1 resection of their primary tumor? Methods The recently published results of a randomized phase III study prompted an update of this guideline. The high quality of the reported evidence and the potential for its clinical impact prompted the Expert Panel to revise one of the guideline recommendations. Results The ESPAC-4 study, a multicenter, international, open-label randomized controlled phase III trial of adjuvant combination chemotherapy compared gemcitabine and capecitabine with gemcitabine monotherapy in 730 evaluable patients with resected pancreatic ductal adenocarcinoma. Median overall survival was improved in the doublet arm to 28.0 months (95% CI, 23.5 to 31.5 months) versus 25.5 months (95% CI, 22.7 to 27.9 months) for gemcitabine alone (hazard ratio, 0.82; 95% CI, 0.68 to 0.98; P = .032). Grade 3 and 4 adverse events were similar in both arms, although higher rates of hand-foot syndrome and diarrhea occurred in patients randomly assigned to the doublet arm. Recommendations All patients with resected pancreatic cancer who did not receive preoperative therapy should be offered 6 months of adjuvant chemotherapy in the absence of medical or surgical contraindications. The doublet regimen of gemcitabine and capecitabine is preferred in the absence of concerns for toxicity or tolerance; alternatively, monotherapy with gemcitabine or fluorouracil plus folinic acid can be offered. Adjuvant treatment should be initiated within 8 weeks of surgical resection, assuming complete recovery. The remaining recommendations from the original 2016 ASCO guideline are unchanged.

2016 Updated American Society of Clinical Oncology/Oncology Nursing Society Chemotherapy Administration Safety Standards, Including Standards for Pediatric Oncology

Purpose: To update the American Society of Clinical Oncology (ASCO)/Oncology Nursing Society (ONS) Chemotherapy Administration Safety Standards and to highlight standards for pediatric oncology. Methods: The ASCO/ONS Chemotherapy Administration Safety Standards were first published in 2009 and updated in 2011 to include inpatient settings. A subsequent 2013 revision expanded the standards to include the safe administration and management of oral chemotherapy. A joint ASCO/ONS workshop with stakeholder participation, including that of the Association of Pediatric Hematology Oncology Nurses and American Society of Pediatric Hematology/Oncology, was held on May 12, 2015, to review the 2013 standards. An extensive literature search was subsequently conducted, and public comments on the revised draft standards were solicited. Results: The updated 2016 standards presented here include clarification and expansion of existing standards to include pediatric oncology and to introduce new standards: most notably, two-person verification of chemotherapy preparation processes, administration of vinca alkaloids via minibags in facilities in which intrathecal medications are administered, and labeling of medications dispensed from the health care setting to be taken by the patient at home. The standards were reordered and renumbered to align with the sequential processes of chemotherapy prescription, preparation, and administration. Several standards were separated into their respective components for clarity and to facilitate measurement of adherence to a standard. Conclusion: As oncology practice has changed, so have chemotherapy administration safety standards. Advances in technology, cancer treatment, and education and training have prompted the need for periodic review and revision of the standards. Additional information is available at http://www.asco.org/chemo-standards.

2016 Updated American Society of Clinical Oncology/Oncology Nursing Society Chemotherapy Administration Safety Standards, Including Standards for Pediatric Oncology.

Purpose To update the ASCO/Oncology Nursing Society (ONS) Chemotherapy Administration Safety Standards and to highlight standards for pediatric oncology. Methods The ASCO/ONS Chemotherapy Administration Safety Standards were first published in 2009 and updated in 2011 to include inpatient settings. A subsequent 2013 revision expanded the standards to include the safe administration and management of oral chemotherapy. A joint ASCO/ONS workshop with stakeholder participation, including that of the Association of Pediatric Hematology Oncology Nurses and American Society of Pediatric Hematology/Oncology, was held on May 12, 2015, to review the 2013 standards. An extensive literature search was subsequently conducted, and public comments on the revised draft standards were solicited. Results The updated 2016 standards presented here include clarification and expansion of existing standards to include pediatric oncology and to introduce new standards: most notably, two-person verification of chemotherapy preparation processes, administration of vinca alkaloids via minibags in facilities in which intrathecal medications are administered, and labeling of medications dispensed from the health care setting to be taken by the patient at home. The standards were reordered and renumbered to align with the sequential processes of chemotherapy prescription, preparation, and administration. Several standards were separated into their respective components for clarity and to facilitate measurement of adherence to a standard. Conclusion As oncology practice has changed, so have chemotherapy administration safety standards. Advances in technology, cancer treatment, and education and training have prompted the need for periodic review and revision of the standards. Additional information is available at http://www.asco.org/chemo-standards .

Locally Advanced, Unresectable Pancreatic Cancer: American Society of Clinical Oncology Clinical Practice Guideline.

PURPOSE: To provide evidence-based recommendations to oncologists and others for treatment of patients with locally advanced, unresectable pancreatic cancer. METHODS: American Society of Clinical Oncology convened an Expert Panel of medical oncology, radiation oncology, surgical oncology, gastroenterology, palliative care, and advocacy experts and conducted a systematic review of the literature from January 2002 to June 2015. Outcomes included overall survival, disease-free survival, progression-free survival, and adverse events. RESULTS: Twenty-six randomized controlled trials met the systematic review criteria. RECOMMENDATIONS: A multiphase computed tomography scan of the chest, abdomen, and pelvis should be performed. Baseline performance status and comorbidity profile should be evaluated. The goals of care, patient preferences, psychological status, support systems, and symptoms should guide decisions for treatments. A palliative care referral should occur at first visit. Initial systemic chemotherapy (6 months) with a combination regimen is recommended for most patients (for some patients radiation therapy may be offered up front) with Eastern Cooperative Oncology Group performance status 0 or 1 and a favorable comorbidity profile. There is no clear evidence to support one regimen over another. The gemcitabine-based combinations and treatments recommended in the metastatic setting (eg, fluorouracil, leucovorin, irinotecan, and oxaliplatin and gemcitabine plus nanoparticle albumin-bound paclitaxel) have not been evaluated in randomized controlled trials involving locally advanced, unresectable pancreatic cancer. If there is local disease progression after induction chemotherapy, without metastasis, then radiation therapy or stereotactic body radiotherapy may be offered also with an Eastern Cooperative Oncology Group performance status ≤ 2 and an adequate comorbidity profile. If there is stable disease after 6 months of induction chemotherapy but unacceptable toxicities, radiation therapy may be offered as an alternative. Patients with disease progression should be offered treatment per the ASCO Metastatic Pancreatic Cancer Treatment Guideline. Follow-up visits every 3 to 4 months are recommended. Additional information is available at www.asco.org/guidelines/LAPC and www.asco.org/guidelines/MetPC and www.asco.org/guidelineswiki.

Potentially Curable Pancreatic Cancer: American Society of Clinical Oncology Clinical Practice Guideline.

PURPOSE: To provide evidence-based recommendations to oncologists and others on potentially curative therapy for patients with localized pancreatic cancer. METHODS: ASCO convened a panel of medical oncology, radiation oncology, surgical oncology, palliative care, and advocacy experts and conducted a systematic review of literature from January 2002 to June 2015. Outcomes included overall survival, disease-free survival, progression-free survival, and adverse events. RESULTS: Nine randomized controlled trials met the systematic review criteria. RECOMMENDATIONS: A multiphase computed tomography scan of the abdomen and pelvis or magnetic resonance imaging should be performed for all patients to assess the anatomic relationships of the primary tumor and for the presence of intra-abdominal metastases. Baseline performance status, comorbidity profile, and goals of care should be evaluated and established. Primary surgical resection is recommended for all patients who have no metastases, appropriate performance and comorbidity profiles, and no radiographic interface between primary tumor and mesenteric vasculature. Preoperative therapy is recommended for patients who meet specific characteristics. All patients with resected pancreatic cancer who did not receive preoperative therapy should be offered 6 months of adjuvant chemotherapy in the absence of contraindications. Adjuvant chemoradiation may be offered to patients who did not receive preoperative therapy with microscopically positive margins (R1) after resection and/or who had node-positive disease after completion of 4 to 6 months of systemic adjuvant chemotherapy. Patients should have a full assessment of symptoms, psychological status, and social supports and should receive palliative care early. Patients who have completed treatment and have no evidence of disease should be monitored. Additional information is available at www.asco.org/guidelines/PCPC and www.asco.org/guidelineswiki.

Metastatic Pancreatic Cancer: American Society of Clinical Oncology Clinical Practice Guideline.

PURPOSE: To provide evidence-based recommendations to oncologists and others for the treatment of patients with metastatic pancreatic cancer. METHODS: American Society of Clinical Oncology convened an Expert Panel of medical oncology, radiation oncology, surgical oncology, gastroenterology, palliative care, and advocacy experts to conduct a systematic review of the literature from April 2004 to June 2015. Outcomes were overall survival, disease-free survival, progression-free survival, and adverse events. RESULTS: Twenty-four randomized controlled trials met the systematic review criteria. RECOMMENDATIONS: A multiphase computed tomography scan of the chest, abdomen, and pelvis should be performed. Baseline performance status and comorbidity profile should be evaluated. Goals of care, patient preferences, treatment response, psychological status, support systems, and symptom burden should guide decisions for treatments. A palliative care referral should occur at first visit. FOLFIRINOX (leucovorin, fluorouracil, irinotecan, and oxaliplatin; favorable comorbidity profile) or gemcitabine plus nanoparticle albumin-bound (NAB) -paclitaxel (adequate comorbidity profile) should be offered to patients with Eastern Cooperative Oncology Group performance status (ECOG PS) 0 to 1 based on patient preference and support system available. Gemcitabine alone is recommended for patients with ECOG PS 2 or with a comorbidity profile that precludes other regimens; the addition of capecitabine or erlotinib may be offered. Patients with an ECOG PS ≥ 3 and poorly controlled comorbid conditions should be offered cancer-directed therapy only on a case-by-case basis; supportive care should be emphasized. For second-line therapy, gemcitabine plus NAB-paclitaxel should be offered to patients with first-line treatment with FOLFIRINOX, an ECOG PS 0 to 1, and a favorable comorbidity profile; fluorouracil plus oxaliplatin, irinotecan, or nanoliposomal irinotecan should be offered to patients with first-line treatment with gemcitabine plus NAB-paclitaxel, ECOG PS 0 to 1, and favorable comorbidity profile, and gemcitabine or fluorouracil should be offered to patients with either an ECOG PS 2 or a comorbidity profile that precludes other regimens. Additional information is available at www.asco.org/guidelines/MetPC and www.asco.org/guidelineswiki.

Extended RAS Gene Mutation Testing in Metastatic Colorectal Carcinoma to Predict Response to Anti-Epidermal Growth Factor Receptor Monoclonal Antibody Therapy: American Society of Clinical Oncology Provisional Clinical Opinion Update 2015.

PURPOSE: An American Society of Clinical Oncology Provisional Clinical Opinion (PCO) offers timely clinical direction after publication or presentation of potentially practice-changing data from major studies. This PCO update addresses the utility of extended RAS gene mutation testing in patients with metastatic colorectal cancer (mCRC) to detect resistance to anti-epidermal growth factor receptor (EGFR) monoclonal antibody (MoAb) therapy. CLINICAL CONTEXT: Recent results from phase II and III clinical trials in mCRC demonstrate that patients whose tumors harbor RAS mutations in exons 2 (codons 12 and 13), 3 (codons 59 and 61), and 4 (codons 117 and 146) are unlikely to benefit from therapy with MoAbs directed against EGFR, when used as monotherapy or combined with chemotherapy. RECENT DATA: In addition to the evidence reviewed in the original PCO, 11 systematic reviews with meta-analyses, two retrospective analyses, and two health technology assessments based on a systematic review were obtained. These evaluated the outcomes for patients with mCRC with no mutation detected or presence of mutation in additional exons in KRAS and NRAS. PCO: All patients with mCRC who are candidates for anti-EGFR antibody therapy should have their tumor tested in a Clinical Laboratory Improvement Amendments-certified laboratory for mutations in both KRAS and NRAS exons 2 (codons 12 and 13), 3 (codons 59 and 61), and 4 (codons 117 and 146). The weight of current evidence indicates that anti-EGFR MoAb therapy should only be considered for treatment of patients whose tumor is determined to not have mutations detected after such extended RAS testing.

Hereditary colorectal cancer syndromes: American Society of Clinical Oncology Clinical Practice Guideline endorsement of the familial risk-colorectal cancer: European Society for Medical Oncology Clinical Practice Guidelines.

PURPOSE: To provide recommendations on prevention, screening, genetics, treatment, and management for people at risk for hereditary colorectal cancer (CRC) syndromes. The American Society of Clinical Oncology (ASCO) has a policy and set of procedures for endorsing clinical practice guidelines that have been developed by other professional organizations. METHODS: The Familial Risk-Colorectal Cancer: European Society for Medical Oncology Clinical Practice Guideline published in 2013 on behalf of the European Society for Medical Oncology (ESMO) Guidelines Working Group in Annals of Oncology was reviewed for developmental rigor by methodologists, with content and recommendations reviewed by an ASCO endorsement panel. RESULTS: The ASCO endorsement panel determined that the recommendations of the ESMO guidelines are clear, thorough, and based on the most relevant scientific evidence. The ASCO panel endorsed the ESMO guidelines and added a few qualifying statements. RECOMMENDATIONS: Approximately 5% to 6% of patient cases of CRC are associated with germline mutations that confer an inherited predisposition for cancer. The possibility of a hereditary cancer syndrome should be assessed for every patient at the time of CRC diagnosis. A diagnosis of Lynch syndrome, familial adenomatous polyposis, or another genetic syndrome can influence clinical management for patients with CRC and their family members. Screening for hereditary cancer syndromes in patients with CRC should include review of personal and family histories and testing of tumors for DNA mismatch repair deficiency and/or microsatellite instability. Formal genetic evaluation is recommended for individuals who meet defined criteria.

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.

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.

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.