ASCO Guidelines Research Articles

Use of Endocrine Therapy for Breast Cancer Risk Reduction: ASCO Clinical Practice Guideline Update.

To update the ASCO guideline on pharmacologic interventions for breast cancer risk reduction and provide guidance on clinical issues that arise when deciding to use endocrine therapy for breast cancer risk reduction. An Expert Panel conducted targeted systematic literature reviews to identify new studies. A randomized clinical trial that evaluated the use of anastrozole for reduction of estrogen receptor-positive breast cancers in postmenopausal women at increased risk of developing breast cancer provided the predominant basis for the update. In postmenopausal women at increased risk, the choice of endocrine therapy now includes anastrozole (1 mg/day) in addition to exemestane (25 mg/day), raloxifene (60 mg/day), or tamoxifen (20 mg/day). The decision regarding choice of endocrine therapy should take into consideration age, baseline comorbidities, and adverse effect profiles. Clinicians should not prescribe anastrozole, exemestane, or raloxifene for breast cancer risk reduction to premenopausal women. Tamoxifen 20 mg/day for 5 years is still considered standard of care for risk reduction in premenopausal women who are at least 35 years old and have completed childbearing. Data on low-dose tamoxifen as an alternative to the standard dose for both pre- and postmenopausal women with intraepithelial neoplasia are discussed in the Clinical Considerations section of this article. Additional information is available at www.asco.org/breast-cancer-guidelines.

ASCO Guidelines Direct Clinical Decisions for Biliary Tract Cancer

ASCO Guidelines Direct Clinical Decisions for Biliary Tract Cancer

Abstract 3148: Identification and establishment of an 18-gene redox signature for recurrence prediction in colorectal cancer

Abstract Purpose: Colorectal cancer (CRC) is the third most common cancers worldwide. The immediate clinical challenge is the identification of high-risk CRC patients, particularly stage II and III, who are genuine candidates for adjuvant chemotherapy, while sparing the low-risk patients from the toxicity and expense of such treatment modalities. According to ASCO guidelines, the high-risk stage II CRC patients are currently defined by specific clinicopathological risk factors. However, the prognosis of patients, even with similar clinicopathological features varies significantly; highlighting their inadequacy in identifying true high-risk CRC patients. Accumulating evidence shows that redox adaptation provides survival benefit to cancer cells and enhances resistance to conventional chemotherapy. Therefore, in this study we performed a comprehensive evaluation of the clinical potential of redox-related genes as recurrence prediction biomarkers in CRC patients. Experimental Design: We undertook a rigorous biomarker discovery effort (GSE33113, n=90), followed by validation of a redox gene signature for recurrence prediction in two datasets (GSE39582, n=461 and GSE14333, n=185) of stage II and III CRC patients. The 18-gene signature discovered from the genome wide discovery effort was subsequently validated in an independent in-house clinical cohort (n=128) by qRT-PCR assays. Univariate and multivariate analyses were performed using CoxPH regression by including various clinicopathological features. Results: A systematic analysis of 312 redox-related genes in three public datasets of 736 CRC patients led to the identification of an 18-gene panel for predicting recurrence free survival (RFS) in stage II and III CRC patients. This gene signature could successfully discriminate high vs. low risk patients in the discovery cohort (AUC=0.88, HR=17.0, p<0.0001), as well as two validation cohorts (GSE39582: AUC=0.70; HR=3.1, p<0.0001; GSE14333: AUC=0.63; HR=3.8, p<0.0001). Subsequent validation in an independent CRC clinical cohort (n=128) confirmed that this gene signature was significantly associated with RFS (AUC=0.81; HR=9.3, CI=3.8 to 22.5, p<0.0001). Univariate analysis identified tumor stage, tumor infiltration, and TNM stage as significant predictors of RFS, and multivariate analysis further confirmed that our gene signature was a significant predictor of RFS in stage II/III CRC patients (p<0.0001). A risk-assessment model by combining the 18-gene signature and the three clinical factors exhibited an even superior prediction for RFS (AUC = 0.877; HR=10.34, CI=4.2 to 25.6, p<0.0001). Conclusions: We identified and established a novel 18-gene redox signature for the prediction of tumor recurrence in high-risk stage II/III CRC patients, which has the potential for translation into the clinic for improved risk-assessment and stratification in CRC patients. Citation Format: Priyanka Sharma, Jasjit K. Banwait, Luis Bujanda, Ajay Goel. Identification and establishment of an 18-gene redox signature for recurrence prediction in colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3148.

Role of Patient and Disease Factors in Adjuvant Systemic Therapy Decision Making for Early-Stage, Operable Breast Cancer: Update of the ASCO Endorsement of the Cancer Care Ontario Guideline.

To update the American Society of Clinical Oncology endorsement of the Cancer Care Ontario recommendations on the Role of Patient and Disease Factors in Adjuvant Systemic Therapy Decision Making for Early-Stage, Operable Breast Cancer. Two phase III trials-the Trial Assigning Individualized Options for Treatment (TAILORx) in women with hormone receptor-positive, node-negative tumors and the Microarray in Node-Negative and 1 to 3 Positive Lymph Node Disease May Avoid Chemotherapy (MINDACT) trial-provided the evidence for this update. Shared decision making between clinicians and patients is appropriate for adjuvant systemic therapy for breast cancer. For patients older than age 50 years and whose tumors have Oncotype DX recurrence scores less than 26, and for patients age 50 years or younger whose tumors have Oncotype DX recurrence scores less than 16, there is little to no benefit from chemotherapy. Clinicians may offer endocrine therapy alone for these patients. For patients age 50 years or younger with recurrence scores of 16 to 25, clinicians may offer chemoendocrine therapy. Patients with recurrence scores greater than 30 should be considered candidates for chemoendocrine therapy. Based on informal consensus, the Panel recommends that oncologists may offer chemoendocrine therapy to patients with Oncotype DX scores of 26 to 30.The MammaPrint assay could be used to guide decisions on withholding adjuvant systemic chemotherapy in patients with hormone receptor-positive lymph node-negative breast cancer and in select patients with lymph node-positive cancers. In both patients with node-positive and node-negative disease, evidence of clinical utility of the MammaPrint assay was only apparent in those determined to be at high clinical risk; the Panel thus did not recommend use of MammaPrint assay in patients determined to be at low clinical risk. Remaining recommendations from the 2016 ASCO guideline endorsement are unchanged.Additional information is available at www.asco.org/breast-cancer-guidelines.

Tobacco cessation practices among primary care physicians in northern Illinois.

e23054 Background: Tobacco cessation is an acknowledged key component of cancer survivorship programs, but significant barriers to program implementation exist. In a 2012 ASCO member survey, 86% of respondents agreed that tobacco cessation should be a routine part of clinical care. However, only 29% reported adequate training. A 2013 survey of physicians at NCI Cancer Centers also showed high levels of support for such programs, but only 1% of oncologists personally engaged themselves. This view is in line with ASCO guidelines that recommend cessation interventions by primary care (PCPs). There is a disconnect between the oncologist’s desire to provide high quality tobacco cessation support for cancer patients and the delegation and delivery of such support. The goal of our study is to evaluate current tobacco cessation practices of PCPs in a large integrated healthcare system. Methods: An electronic survey was sent to all PCPs (n = 165) of the NorthShore Medical Group (Northern Illinois) with questions about their views and practices regarding tobacco cessation. Results: 53 PCPs responded to the survey (response rate of 32%). 94% of respondents believe that PCPs are primarily responsible for addressing tobacco cessation with general patients. 89% believe that PCPs are also responsible for cancer patients, although 34% believe the responsibility should be shared with oncologists. 100% believe that tobacco use affects cancer outcomes in their patients, and 98% report sufficient training in providing cessation support. 90% always ask their patients about tobacco status at the initial visit; this drops to 21% at follow-up visits. For current smokers, 57% of PCPs recommend tobacco cessation all the time and 36% recommend services most of the time. Lack of patient willingness was the most frequently cited barrier to tobacco cessation efforts (74%), followed by lack of time (46%) and lack of resources (42%). Conclusions: PCPs view themselves as primarily responsible for addressing tobacco cessation with their patients but are limited by multiple factors. This primary care-based approach is endorsed by ASCO and other clinical guidelines. More financial and clinical support should be allocated for successful efforts against tobacco dependency.

Randomized controlled trial (RCT) of a patient navigation (PN) intervention to increase early access to supportive care (SC) for patients with metastatic cancer in a resource-limited setting.

11505 Background: Early integration of SC to the treatment of advanced cancer can improve outcomes, but this may be challenging in developing countries due to a lack of resources and knowledge. In this RCT, we examined whether PN could improve early access to SC among Mexican patients with metastatic solid tumors as recommended by ASCO guidelines. Methods: Adult patients with newly-diagnosed metastatic cancer were randomly assigned to PN or standard oncologic care. At baseline, a navigator assessed the patients’ SC needs (depression, anxiety, fatigue, pain, caregiver burden) using validated questionnaires administered with an electronic tablet. For those in the PN arm, a personalized SC plan was created and implemented by a multidisciplinary team (palliative care, physical therapy, geriatrics, psychology, psychiatry). The primary outcome was access to SC, defined as receipt of SC interventions in the first 3 months (mo) after diagnosis. Secondary outcomes included advanced directive (AD) completion (for patients with expected survival ≤6 mo in accordance to Mexican law), changes in SC needs, and changes in quality of life (assessed using FACT-G). Results: 133 patients (median age 60, range 23-93; 52% male) were randomized (66 PN, 67 control). 61% of patients had gastrointestinal tumors. 94% of patients in the PN arm completed baseline assessments and received recommendations from the navigator. At 3 mo, 37 patients died or were lost to follow-up (16 PN, 21 control; p = 0.45), and 96 completed assessments. SC interventions were provided to 73% of patients in the PN arm and 24% of controls (p < 0.01). In the PN arm, 48% of 29 eligible patients completed AD, compared to 0% of eligible controls (p < 0.01). At 3 mo, patients in the PN arm were significantly less likely to report moderate/severe pain than controls (10 vs 33%, p = 0.006). There were no significant differences in other symptoms or in FACT-G scores (76 vs 76.3, p = 0.46) between PN and control arms at 3 mo. Conclusions: PN can lead to significant improvements in early access to SC, AD completion, and pain control among patients with metastatic cancer treated in a resource-limited setting. Clinical trial information: NCT03293849.

Early case ascertainment and prospective multidisciplinary review for management of new melanoma diagnoses within an integrated healthcare system: The Kaiser Permanente Northern California experience.

6523 Background: Appropriate surgical treatment of early-stage melanoma yields a high cure rate, but this management can be nuanced. In particular, surgical management, including sentinel lymph node biopsy (SLNB), of thin melanoma (≤1.0mm) is not well-defined. Methods: Biopsies with new melanoma diagnoses were identified electronically and manually reviewed. In a community oncology setting, we organized a review panel of physicians specialized in melanoma from dermatology, medical oncology, nuclear medicine, radiation oncology, and surgical subspecialties (oncology, plastics, head and neck). Patients were assigned to care pathways based on NCCN and ASCO guidelines, including guidance on SLNB for thin melanomas with high-risk features like lymphovascular invasion, high mitotic rate, positive deep margin, and ulceration. These recommendations were documented in the chart and communicated directly to the patient’s care team. Results: From 11/2016 through 10/2018, our multidisciplinary committee reviewed 3626 patients with new melanoma from 22 sites in our integrated, regional hospital system. Median age was 66 (range 19-99); 60% were male. cT2N0 tumors comprised 7%, cT3 3%, and cT4 2%. Thin melanomas ≤1.0mm represented 71% of cases, of which 34% were ≤0.5mm. SLNB was performed in 9.8% of thin melanomas, and 18% were positive, much higher than historical positive rates of 3-4%. Conclusions: Early case ascertainment and prospective multidisciplinary review in a community oncology setting resulted in increased identification of high-risk thin melanoma, and consequently increased identification of nodal disease through SLNB. Positive SLNB triggers important clinical decision-making regarding need for node dissection versus clinical surveillance, and need for adjuvant therapy, which have been shown to improve survival. This clinical practice structure improved risk-stratification and adherence to national guidelines. We plan to further study the impact of these improvements to melanoma care on disease-free survival and overall survival.

Real-world efficacy of bone modifying agents (BMAs) in patients with breast cancer (BC) treated in an academic health system: Use of the “green button.

e18054 Background: BC patients (pts) have a high incidence of bone metastases (mets) and associated morbidity. BMAs – zoledronic acid (ZA) and denosumab (Den) – reduce bone met related skeletal related events (SREs). ASCO guidelines do not recommend one over another, and survival and real-world outcome data to guide point-of-care decision-making is lacking. We used the previously developed “Green Button” informatics consult service, designed to rapidly test hypotheses when no applicable published data is available to guide treatment choices (Longhurst et al Health Affairs 2014), to compare BMA efficacy in BC patients. Methods: Patients treated for BC at Stanford HealthCare between 2009 - 2018, receiving standard of care cancer and BMA therapy, as determined by their oncologists, were identified who had > 2 electronic health records (EHRs) documenting BMA administration, and had either ICD9 174 or ICD10 C50 diagnostic codes. Pts were grouped into Den only, ZA only, or both. Two outcomes were analyzed: 1) SREs as a composite outcome of pathologic fracture (1st ICD10 M84.5); spinal cord compression (1st ICD10 M47.1 or G95.2), radiation therapy (1st CPT 77300) or hypercalcemia (calcium ≥10.5); and 2) death. Effects were compared relative to baseline treatment with ZA; we show results of log rank tests for differences in survival outcomes. Three analyses were performed: 1) Unadjusted analysis; 2) Basic matching analysis accounting for length of medical record, age, sex and year of treatment; 3) Propensity score matching using all available data; all prior to index treatment with either Den or ZA. Results: 802 patients had ≥ 2 records of BMA administration. Comparison of Den only and ZA only pts is shown in the table below. Median ages and length of medical record were balanced in all groups. Conclusions: This preliminary retrospective analysis of unsupervised BMA use suggests that Den is superior to ZA for the outcomes of interest; confirmatory analyses are underway.[Table: see text]

Improving time to initiation of bone modifying agents in patients with newly diagnosed multiple myeloma.

6528 Background: Current ASCO and IMWG guidelines recommend that all patients (pts) on active anti-myeloma therapy receive concurrent supportive care treatment with a bone modifying agent (BMA) to decrease the risk of skeletal related events (SRE). Unfortunately, recent data shows only 51% of Medicare pts with myeloma received a BMA within 90 days of first chemotherapy. We implemented a quality improvement project to identify the average time to BMA initiation at all Cleveland Clinic affiliated sites, with the primary goal to improve time to initiation of BMA in newly diagnosed multiple myeloma (NDMM) pts by 4 weeks at Cleveland Clinic Main Campus (MC). Methods: Barriers with BMA initiation were identified using quality improvement tools developed at the ASCO Quality Training Program. The first PDSA cycle was implemented between September 2018 – January 2019 with an emphasis on education. This included review of updated guidelines, literature review of risks and toxicities associated with BMAs, and strategies for choosing BMA based on pt factors. Baseline data on time to start BMA and data to evaluate impact of PDSA intervention was completed via chart review. Results: 161 NDMM pts were evaluated between 2015 to 2018 at all sites. The average time difference between the start of anti-myeloma therapy and the start date of a BMA in NDMM pts was 10.5 weeks. Subset analysis based on whether pts were treated at MC vs affiliate sites was 10.6 weeks vs 9.1 weeks, respectively. During the first PDSA cycle, 14 NDMM pts were treated at MC. 86% (12/14) pts were treated with a BMA. The average time between cycle 1 day 1 of first line treatment and first dose BMA was 4.3 weeks (range 4-12 weeks). Conclusions: With increased physician education and awareness of internal baseline data, we achieved our initial goal and observed a significant improvement in time to initiation of BMA from 10.5 weeks to 4.3 weeks. Obstacles regarding effective communication with patients on the benefit of BMAs as well as need for dental clearance were barriers identified early on. We plan to incorporate BMA guidelines in our institutional care path with the goal to decrease time to initiation at all affiliated practices. Further mechanisms to ensure reinforcement of BMA initiation in NDMM patients is warranted to maintain therapeutic benefit.

Survivorship care: Improving delivery of care plans for hematology patients at the Washington Cancer Institute (WCI).

6605 Background: Cancer and long-term sequalae of its treatment impact the future health and psychosocial wellness of these survivors. ASCO guidelines recommend providing survivorship care to cancer patients who have completed treatment with curative intent. The Commission on Cancer (COC) recommends that survivorship care including treatment summaries be delivered to 50% of eligible patients. In our ASCO Quality Training Program project, we aimed to achieve this COC goal of 50% for the year 2018. Methods: Baseline data collected from Jan 1, 2016 to June 30, 2018 indicated that 33% of hematologic malignancy survivors at WCI received treatment summaries and survivorship care. For the year 2018, there were 11 survivors of hematologic malignancy, and 4 of them (36%) had received survivorship care prior to initiation of the project. We surveyed 12 providers to obtain data for perceived challenges to deliver survivorship care. Large volume of patients, lack of resources, no standardized process and high no-show rates were identified as the most important barriers. A bi-monthly survivorship clinic run by hematology/oncology fellows was initiated in September 2018 to address some of these barriers. Patient referral forms were mounted in the clinic work rooms to assist providers with identifying patients that qualify for survivorship; a pathway for referrals to the survivorship clinic was created and providers were informed about the clinic. Information flyers regarding survivorship care and the clinic were placed in the waiting room to increase awareness amongst patients. Results: By November 30, 2018, 63% of hematological cancer survivors received survivorship care and treatment summaries. Compared to the average from the preceding two years, survivorship care delivery increased by 30%. Conclusions: Our institution was able to meet the COC requirement by delivering survivorship care to 63% of survivors of hematological malignancies through the intervention from this quality improvement study. We intend to extend this process to other tumor types to increase the delivery of consolidated survivorship care at the WCI.

Physician concordance with update to ASCO guidelines for antiemetic use with carboplatin AUC ≥ 4.

11595 Background: In 2017, NCCN (2/2017) and ASCO (8/2017) each amended antiemetic guidelines to classify carboplatin AUC ≥4 as highly emetogenic chemotherapy (HEC), recommending upfront triple prophylaxis with an NK1 receptor antagonist (RA) + 5HT3 RA + dexamethasone. Physician concordance with the new recommendations, and the consequences for avoidable post-chemotherapy acute care, merit study. Methods: In a large electronic health record database (IBM Explorys), we identified carboplatin courses of therapy (≥14-day cycles as a proxy for AUC ≥4) and courses with ≥7-day cycles of other HEC and non-HEC therapy from 4Q 2012 through August 2018. Guideline concordance, defined as triple prophylaxis at HEC initiation, was evaluated. We also assessed 30-day post-chemotherapy acute care (inpatient or emergency department) associated with nausea or vomiting (NV) or eight other toxicities deemed avoidable in the US Centers for Medicare & Medicaid’s new oncology outcome measure OP-35. Results: 11,554 carboplatin courses were identified. Before the guideline change, rates of upfront triple prophylaxis grew from 14% in 2013 to 16% in mid-2017. Rates then rose to 26% by 1Q 2018 before dropping to 21% by 3Q 2018; quarterly rates averaged 20% (range 15%-26%) following the guideline change. In 31% of carboplatin courses we noted 30-day acute care use, of which 75% involved ≥1 of the ten OP-35 toxicities. NV (with or without acute care use) was reported in 24% of courses, and 27% of total OP-35 acute care events involved NV. Rates for NV, and for OP-35-related and NV-related acute care after carboplatin, were similar to rates after other HEC chemotherapy, and higher than rates after other non-HEC IV chemotherapy or oral HEC/MEC agents. Conclusions: Use of upfront triple antiemetic prophylaxis has increased only marginally for carboplatin AUC ≥ 4 since its 2017 re-classification as HEC in national guidelines, perhaps due to low awareness of the change. Patients receiving carboplatin had similar rates of NV and related 30-day acute care events as seen for other HEC, confirming that the new HEC definition fits clinical experience. More triple prophylaxis use is needed to reduce NV and NV-related avoidable acute care seen with carboplatin AUC ≥ 4.

Treatment of Multiple Myeloma: ASCO and CCO Joint Clinical Practice Guideline.

To provide evidence-based recommendations on the treatment of multiple myeloma to practicing physicians and others. ASCO and Cancer Care Ontario convened an Expert Panel of medical oncology, surgery, radiation oncology, and advocacy experts to conduct a literature search, which included systematic reviews, meta-analyses, randomized controlled trials, and some phase II studies published from 2005 through 2018. Outcomes of interest included survival, progression-free survival, response rate, and quality of life. Expert Panel members used available evidence and informal consensus to develop evidence-based guideline recommendations. The literature search identified 124 relevant studies to inform the evidence base for this guideline. Evidence-based recommendations were developed for patients with multiple myeloma who are transplantation eligible and those who are ineligible and for patients with relapsed or refractory disease.

Treatment of Multiple Myeloma: ASCO and CCO Joint Clinical Practice Guideline Summary

Treatment of Multiple Myeloma: ASCO and CCO Joint Clinical Practice Guideline Summary

Hypofractionated Radiation Therapy for Localized Prostate Cancer: Executive Summary of an ASTRO, ASCO and AUA Evidence-Based Guideline.

The aim of this guideline is to present recommendations regarding moderately hypofractionated (240-340 cGy per fraction) and ultrahypofractionated (500 cGy or more per fraction) radiation therapy for localized prostate cancer. The American Society for Radiation Oncology convened a task force to address 8 key questions on appropriate indications and dose-fractionation for moderately and ultrahypofractionated radiation therapy, as well as technical issues, including normal tissue dose constraints, treatment volumes, and use of image guided and intensity modulated radiation therapy. Recommendations were based on a systematic literature review and created using a predefined consensus-building methodology and Society-approved tools for grading evidence quality and recommendation strength. Based on high-quality evidence, strong consensus was reached for offering moderate hypofractionation across risk groups to patients choosing external beam radiation therapy. The task force conditionally recommends ultrahypofractionated radiation may be offered for low- and intermediate-risk prostate cancer but strongly encourages treatment of intermediate-risk patients on a clinical trial or multi-institutional registry. For high-risk patients, the task force conditionally recommends against routine use of ultrahypofractionated external beam radiation therapy. With any hypofractionated approach, the task force strongly recommends image guided radiation therapy and avoidance of nonmodulated 3-dimensional conformal techniques. Hypofractionated radiation therapy provides important potential advantages in cost and convenience for patients, and these recommendations are intended to provide guidance on moderate hypofractionation and ultrahypofractionation for localized prostate cancer. The limits in the current evidentiary base-especially for ultrahypofractionation-highlight the imperative to support large-scale randomized clinical trials and underscore the importance of shared decision making between clinicians and patients.

Abstract P1-12-03: Prevalence, predictive factors, and clinical outcomes of anthracycline induced cardiac dysfunction among patients with breast cancer in Japan, where the normal body weight (BMI < 25) is dominant

Abstract Objective: Cardiac dysfunction (CD) is a major clinical problem for survivors of breast cancer. ASCO released a guideline for prevention and monitoring CD in survivors of adult cancer in 2017. Exposure to anthracycline (A) and trastuzumab are both risk factor for CD, as well as obesity is a part of multiple risk factors in the guideline. Meta-analysis shown obesity itself increases risk of A induced CD (A-CD). Prevalence of obesity and CD among non-oncology patients vary in countries, as many Western countries have obesity dominant population. Then little is known about clinical characteristics of A-CD in survivors of adult cancer among normal weight dominant countries, especially in Asia. This study was conducted to understand characteristics of A-CD among patients with breast cancer in Japan. Method: This study used electrical charts, breast oncology database, and cardiology database to find prevalence, predictive factors, and clinical outcomes of A-CD in Hyogo Cancer Center. The definition of CD is based on diagnosis by the cardiologist. Major Cardiac Events (MACE) is defined as cardiac death or emergency admission due to CD. Obesity is defined as BMI > 30, normal body weight is defined as BMI < 25, and elderly is defined as age > 60 years old, same as in ASCO guideline. Patients gave written informed consent. IRB approved this study. Result: From Apr. 2006, to Mar. 2017, 855 patients received A for the treatment of breast cancer. Median body weight was 55 Kg, median BMI was 23, and 93.4 % of patients are non-obese. Half of patients (46.9 %) are elderly. Almost a quarter (24 %) of patients received trastuzumab. At the median follow up 60 months, 20 patients (2.3 %) experienced CD, one patient (0.11 %) passed away due to CD, and four patients were admitted as emergency, then five patients (0.58 %) experienced MACE. Median time to onset of CD after the last dose of A is seven months. Among patients with CD, 18 patients (90 %) recovered their ejection fraction (EF), and the median time to recover of EF was two months. Predictive factors for CD include usage of trastuzumab (15 patients), elderly (eight patients), high dose anthracycline (four patients), and multiple cardiac risk factors at base line (four patients). Among patients treated without trastuzumab, only five (0.76 %) patients experienced CD, but four of them experienced MACE. Conclusion: Prevalence of A-CD in the normal weight dominant population was lower than reported in obesity dominant population, especially in patients treated without trastuzumab. In this population, clinical outcome such as prevalence of MACE may vary depending on the usage of trastuzumab. Further study is warranted to set an optimal strategy for the prevention and monitoring of A-CD in non-obese dominant population. Citation Format: Matsumoto K, Nonaka A, Ogata T, Ogata M, Sakai H, Nishimura M, Onoe T, Soyama M, Hashimoto K, Tane K, Hirokaga K, Takao S. Prevalence, predictive factors, and clinical outcomes of anthracycline induced cardiac dysfunction among patients with breast cancer in Japan, where the normal body weight (BMI < 25) is dominant [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-12-03.

Abstract P4-01-05: Cell free DNA analysis identifies actionable ERBB2 amplifications in patients with HER2 equivocal breast cancer

Abstract Background: Determination of ERBB2 (HER2) expression or amplification informs eligibility of HER2-targeted therapies. ASCO and NCCN guidelines recommend evaluation of HER2 status on primary invasive breast cancers and on a metastatic site if stage IV, where possible, as treatment is based on the status of the metastasis. Reassessment of HER2 status should also be considered in patients with disease recurrence as initially HER2-negative tumors may acquire HER2 amplification at progression. HER2 status can be complicated by equivocal results from in situ hybridization (ISH) and/or immunohistochemistry (IHC). Clarification requires reflex testing on the same tissue specimen or repeat testing on a new specimen, however some patients' tissue status remains equivocal. Furthermore, metastases to bone, lung, or brain may be difficult to re-biopsy or of low DNA quality. Rapid and non-invasive blood-based cell-free DNA (cfDNA) NGS may facilitate identification of HER2 targetable disease in advanced breast cancer. Methods: We assessed the frequency of ERBB2 amplification detectable by a blood-based cell-free DNA (cfDNA) assay among patients with metastatic breast cancer with equivocal HER2 results in tissue. cfDNA samples were ordered as part of routine clinical care using an assay validated for the detection of copy number amplification in ERBB2 (tests run between 03/2014-04/2017 by Guardant Health, Redwood City, CA). Submitted pathology reports were reviewed for HER2 status which was categorized as positive, negative, or equivocal based on the interpretation issued by the reading pathologist at the time the test was ordered. Patients were included if they had an equivocal result on IHC and/or ISH unless both assays were performed on the same specimen and one provided a definitive negative or positive HER2 result. Additionally, 4 patients with equivocal IHC or ISH results were excluded as biopsy of another tumor site revealed a positive HER2 result around the same time as the equivocal test. For the 349 patients with multiple cfDNA samples, the earliest pathology report was referenced. Results: Tissue HER2 status was available for 1,853 unique patients (98.8% female, median age at testing was 58y, range 26-91y). 141 patients (7.6%) had equivocal HER2 results in tissue; 99 by IHC alone, 14 by ISH alone, and 28 were equivocal by both assays. Among these, 126 patients (89.4%) had at least one sample with ctDNA detected. 12/126 (9.5%) had amplification of ERBB2 detected in at least one cfDNA sample. Samples were drawn a median of 267 days after tissue collection (range 4 days – 11.5 years). Frequency of ERBB2 amplification was similar regardless of time between tissue and blood collection but was higher among patients with ISH results alone (4/14, 36.4%) compared to those with IHC alone (6/89, 6.7%) or both assays (6/26, 7.6%; p=0.006). Conclusion: cfDNA testing identifies a significant number of patients with HER2-targetable advanced breast cancer whose tissue was HER2 equivocal. cfDNA testing may supplement tissue-based methods to help clarify HER2 status in metastatic disease as well as identify patients who may acquire HER2 amplification subsequent to their initial biopsy. Citation Format: Rich TA, Raymond VM, Ahn ER, Banks KC, Brufsky A, Lee C, Lippman M, Pluard TJ, Schwab RB, Lanman RB. Cell free DNA analysis identifies actionable ERBB2 amplifications in patients with HER2 equivocal breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-01-05.

Improving clinician confidence and practice behavior on the therapeutic management of microsatellite-instability high (MSI-H) gastrointestinal (GI) cancers.

641 Background: With recent advances of immunotherapy and updates to practice guidelines, clinicians may be challenged in applying and managing the outcomes of new treatment standards for their patients with MSI-H GI cancers. To address this need, a one-hour education session was provided to clinicians and learner responses were evaluated to determine the areas of improvement in the therapeutic management of MSI-H GI cancers. Methods: PlatformQ Health developed and executed a 1-hour online CME program on MSI-H GI cancers, which was broadcast live in March 2018 and offered online for 6 months. The program attracted a total of 439* learners. Survey-based evaluations before (n = 338) and after education (n = 147) targeted self-reported clinician data on confidence, practice behaviors, knowledge, and competence. Results: A self-reported survey (n = 56) conducted 8-12 weeks after education reported that 50% of learners were more confident in managing patients with MSI-H GI cancers, 41% in following NCCN practice guidelines for MMR/MSI testing, and 34% in utilizing checkpoint inhibitors for MSI-H GI tumors. Competence on selecting an appropriate treatment for a patient with MSI-H colon cancer significantly improved between pre- and post-education (52% and 63%, respectively; p < 0.001). Significant improvements in knowledge regarding the latest immunotherapy data (33% at baseline to 54% post-education; p < 0.001) and available methods for determining MMR/MSI-H status (18% at baseline to 41% post-education; p < 0.001) were also observed. Conclusions: Outcomes results from education demonstrate learner improvements on facets of management of MSI-H GI cancers. Based on the analysis, further education is needed, particularly in areas of management of immune-related side effects in line with recent ASCO and NCCN guidelines, tools for determining dMMR/MSI-H status, and deciding on optimal treatment based on tumor status. *As of September 10, 2018, data collection is ongoing.

The Discrepancy Between Palliative and Oncology Providers in Palliative Referrals (QI704)

1.Justify the need for palliative care consultation to outpatient oncologists by meeting with them on a regular basis in order to increase the rate of referrals.2.Identify other patient-centered outcomes as a result of proactive palliative care consultation, including rate of completion of advance directives, rate of state-authorized portable orders (SAPO) completion, and rates of in-hospital and community deaths. According to NCCN and ASCO guidelines, there is evidence that early palliative care consultation in patients with advanced cancer led to significant improvement in quality of life, mood and longer survival as compared to patients receiving standard care. To improve the rate of palliative care consultation by 20% in patients with advanced cancer over a 15 month period at Buffalo Veterans Affairs Medical Center (VAMC). Buffalo VAMC is an academic center affiliated with the University at Buffalo. We provide both outpatient palliative and oncology services. In 2017, we decided to seek proactive palliative care consultations (PPCC) with advanced cancer patients; defined as stage 4 lung cancer, any pancreatic cancer, or any cancer with more than 1 emergency, hospital or ICU admissions. Based on our root analysis our intervention was a meeting between palliative and oncology services once a week since 01/01/2017 to 3/30/2018 at the VA and reviewing the oncology cases on weekly basis with average 80-100 patients per week. From 163 patients requested to be seen by palliative team, oncologists approved 63 proactive palliative consults with denial rate of 60%. PPCC resulted in an increase of referrals by 33% over a 15 month period. Of those patients seen by outpatient palliative care, 92% died in a community setting (hospice or home) while those identified but denied PPCC died in the community setting only 50% of the time. Interestingly, patients whose PPCC were denied but were later seen by the palliative care team during a hospital admission died in the community 91% of the time. In addition, advanced directives and SAPO increased by 30% and 65% respectively. Seeking proactive palliative care consultation in patients with advanced cancer led to an increased outpatient referral rate with a simultaneous decrease in in-hospital mortality.

Hypofractionated Radiation Therapy for Localized Prostate Cancer: An ASTRO, ASCO, and AUA Evidence-Based Guideline Summary

Hypofractionated Radiation Therapy for Localized Prostate Cancer: An ASTRO, ASCO, and AUA Evidence-Based Guideline Summary

Обзор рекомендаций Американского общества клинической онкологии (ASCO) и Американского общества по инфекционным болезням (IDSA) по антимикробной профилактике у иммунокомпрометированных взрослых пациентов, получающих терапию в связи со злокачественными новообразованиями

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