Citations

e14711 Background: Postoperative adjuvant chemotherapy has been historically limited to single agent 5FU in stage II/III rectal cancer pts. This phase III trial evaluated differences between pts treated with adjuvant FOLFOX versus FOLFIRI versus FU alone in stage II/III rectal cancer. Methods: Eligibility: resectable (T3-4 N0,Tany N1-3) adenocarcinoma rectum ≤12cm from anal verge. Pts had the option to receive FU with pre or postoperative XRT (50.4Gy). Preoperative FU/XRT pts were randomized to adjuvant FOLFIRI (arm A), FOLFOX (arm B), FU/LV(arm C). Postoperative FU/XRT pts were randomized to adjuvant FOLFIRI (arm D), FOLFOX (arm E), FU/LV (arm F). Pts received 8 cycles. Overall survival (OS) was the primary endpoint. Secondary endpoints included toxicity, sphincter preservation and patterns of failure. Results: 225pts out of planned 3150 were enrolled (10/03 to 10/05). Data Monitoring Committee closed E3201 when the GI Intergroup developed an alternative trial with bevacizumab (E5204). 179 pts were randomized; (A:28, B:25, C:30, D:31, E:33, F:32). There was increased grade 3/4 toxicity, mainly diarrhea,in postoperative FU/XRT arms (D:39%), (E:28%), (F:48%). Twenty-two (12%) pts did not receive adjuvant therapy. At a median follow up of 7.4yrs, the five-year recurrence free rate was 69%. Median OS was 8.3 yrs. There was no statistical difference in OS between all randomized groups. Five-year OS in arms (A:B:C:D:E:F) were (73%, 83%, 83%, 73%, 78%, 73%) respectively. Conclusions: FOLFOX can be safely administered to rectal cancer pts following chemo radiation. Given limitations of early trial closure and small sample size, there was no difference in OS between pts who received FU alone, oxaliplatin based or irinotecan based adjuvant therapy. Clinical trial information: NCT00068692.

4022 Background: While the overall incidence of gastric cancer has declined in the United States, the incidence of proximal gastric cancers has increased. Understanding the differences between proximal and distal gastric cancer, may enable us to identify important risk factors and treatment patterns. Methods: Data on 6099 patients diagnosed with gastric adenocarcinoma were collected as a Patient Care Evaluation under the auspices of the American College of Surgeons Commission on Cancer. Clearly defined proximal and distal cancers were compared using the Pearson chi-square test and logistic regression. Results: The proximal cancer group included 1924 patients (87% cardia; 13% fundus) and the distal cancer group included 1312 patients (85% antrum; 15% pylorus). Proximal gastric cancers occurred more often in men (p<0.0001), whites (compared to Black, Hispanic, Native American and Asian races) (p<0.0001), and at younger age (p<0.0001) compared to distal cancers. Risk factors for proximal presentation included tobacco use (Hazard ratio (HR) 1.9, p= 0.002) alchohol use (HR 1.5, p= 0.038) and Barretts (HR 2.7, p<0.0001). Risk factors for distal presentation included H. Pylori (HR 2.3, p= 0.001). Despite increased use of multi-modality therapy, fewer proximal gastric cancers underwent resection compared to distal cancers (p<0.0001). Conclusions: Different risk factors can be identified for proximal and distal gastric cancers, which can impact on risk reduction, screening efforts and help define the pathogenesis of gastric cancer. While proximal cancer patients receive more aggressive multimodality treatments, including adjuvant and neoadjuvant therapy, fewer undergo surgical resection. Long term survival based upon proximal and distal tumor differences will be explored when follow-up data become available.Key Words: gastric adenocarcinoma, proximal gastric cancer, distal gastric cancer, risk factors, treatment. [Table: see text] No significant financial relationships to disclose.

3526 Background: In the US pts with stage II/III rectal cancer routinely receive pre or postoperative RT/FU. To date, in addition to chemoradiation, standard adjuvant chemotherapy has been limited to single agent FU. Improved survival with irinotecan and oxaliplatin in pts with metastatic colorectal cancer led to exploration of combination chemotherapy in the adjuvant setting in pts with rectal cancer. Methods: Pts on E3201 (T3–4 Nany M0, T1- 2 N + M0) had the option to receive FU with either pre- or postoperative RT (50.4 Gy). Pts were randomized to postoperative chemotherapy: FU (500mg/m2) + LV (500mg/m2) weekly x 6/8 wks x 3 cycles or irinotecan (FOLFIRI) (180mg/m2) vs oxaliplatin (FOLFOX) (85mg/m2) both administered with LV (400 mg/m2) FU (400mg/m2 bolus) + continuous FU (2.4 gm/m2/46 hours) q 2 wks x 8 cycles. Results: 225 pts of 3150 planned were recruited. 178 pts were randomized and 126 pts submitted treatment completion forms (accrual period 10/03–4/05). The Data Monitoring Committee closed E3201 when the GI Intergroup developed an alternative trial with bevacizumab (E5204). Toxicity information is reported for 93% of pts (165/178) ( Table ). There were no significant differences in toxicity between those pts treated with pre- vs postoperative RT/FU, although, for the subset of pts who received adjuvant FOLFIRI after postoperative RT/FU, there was a trend towards more diarrhea. Conclusion: FOLFOX as rectal adjuvant therapy is a common platform for new clinical trials, although there have been limited toxicity data reported. E3201 provides important comparative toxicity information demonstrating that FOLFOX can be safely administered to rectal cancer pts following chemoradiation. [Table: see text] [Table: see text]

3515 Background: Patients with metastatic colorectal cancer (mCRC) treated with 5Fluorouracil plus leucovorin (5FU/LV) have a median life expectancy (LE) of approximately12 months. The addition of irinotecan, oxaliplatin, bevacizumab and cetuximab has increased LE significantly. Although they have been widely adopted, little is known about the financial impact of these new drugs. Methods: Using published reports and aggregate data from NCCTG 9741, we developed a Markov Model which assumes forward progression through up to three lines of therapy compared to 5FU/LV alone. Patients who do not die of toxicity (tox) transition through supportive care prior to death. State changes are based on progression and dose-limiting toxicity. Drug costs are based on Average Sales Price. No other direct or indirect costs are included. Dose modifications for toxicity are defined as 80% of standard doses. Sensitivity analyses (SA) were performed on key variables. Results: LE, total drug costs, and cost-effectiveness (CE) ratios compared to single line-5FU/LV and FOLFOX for 9 commonly used treatement sequences are presented below. SA show that results are sensitive to progression rates,drug costs and length of time on supportive care. Changes in 1st line tox rates have a greater impact on final results than changes in 2nd or 3rd line therapy tox rates. Conclusions: Using drug costs alone, this model shows sequential combination therapy including all available agents to cost $2000-$2800K/week life gained ($100-$145K/year) compared to both 5FU/LV and FOLFOX. For clarity only 9 strategies are presented, but the model presented will contain multiple sequences consisting of 1–3 lines of therapy. Refined tox data, associated costs and quality of life adjustments are needed for realistic comparisons among specific combinations. Combination therapy may have CE ratios similar to other currently accepted intensive medical interventions. These data can help inform discussions of how the cost of care impacts patients, providers, and societies. [Table: see text] [Table: see text]

4020 Background: Adjuvant chemotherapy (AC) presents a substantial patient education challenge to medical oncologists (MOs). Findings from our 2005 pilot survey suggest that a significant fraction of colorectal cancer (CRC) survivors are willing to undergo AC for modest treatment benefits, but their understanding of risks and benefits may be suboptimal. This project attempted to validate these findings by surveying patients with CRC (Pts) who previously received AC. Methods: 150 Pts who received AC for CRC in the last 5 years were recruited to listen to an audio program on AC featuring interviews with clinical investigators (CIs) and Pts who received AC. Based on this input, Pts were asked whether they would undergo the same AC again for varying absolute treatment benefits. A corresponding survey asked 24 CRC CIs and 150 MOs to predict how patients would respond. The survey also queried Pts about their expectations of and experiences with AC side effects. Results: About 1/3 of Pts would be treated again with AC for a 1% absolute reduction in recurrence risk (ARRR), and about 2/3 believed a 5% ARRR would justify treatment. There were no statistically significant differences between responses of males and females or between Pts receiving oxaliplatin (OX) and those receiving other regimens. ( Table 1 ) The corresponding estimates of CIs and MOs were lower. Additionally, AC side effects were different than expected: 57% and 66% of Pts experienced less GI toxicity and alopecia, respectively, while 38% and 46% of Pts receiving OX experienced greater cold intolerance and numbness. Conclusions: Many potential obstacles exist in communicating with Pts about AC including heterogeneity in Pts’ attitudes towards risk/benefit trade-offs and preconceptions about treatment side effects. The next step in this initiative will be to examine these issues prospectively by evaluating the impact of an audio/web education supplement on the decision-making process. [Table: see text] No significant financial relationships to disclose.

Background Social determinants of health are relevant to cardiovascular outcomes but have had limited examination in atrial fibrillation (AF). Objectives The purpose of this study was to examine the association of annual household income and cardiovascular outcomes in individuals with AF. Methods We analysed administrative claims for individuals with AF from 2009 to 2015 captured by a health claims database. We categorised estimates of annual household income as <$40 000; $40–$59 999; $60–$74 999; $75–$99 999; and ≥$100 000. Covariates included demographics, education, cardiovascular disease risk factors, comorbid conditions and anticoagulation. We examined event rates by income category and in multivariable-adjusted models in reference to the highest income category (≥$100 000). Results Our analysis included 336 736 individuals (age 72.7±11.9 years; 44.5% women; 82.6% white, 8.4% black, 7.0% Hispanic and 2.1% Asian) with AF followed for median (25th and 75th percentile) of 1.5 (95% CI 0.6 to 3.0) years. We observed an inverse association between income and heart failure and myocardial infarction (MI) with evidence of progressive risk across decreased income categories. Individuals with household income <$40 000 had the greatest risk for heart failure (HR 1.17; 95% CI 1.05 to 1.30) and MI (HR 1.18; 95% CI 0.98 to 1.41) compared with those with income ≥$100 000. Conclusions We identified an association between lower household income and adverse outcomes in a large cohort of individuals with AF. Our findings support consideration of income in the evaluation of cardiovascular risk in individuals with AF.

Although oncology care has evolved, outcome assessment remains a key challenge. Outcome measurement requires identification and adoption of a succinct list of metrics indicative of high-quality cancer care for use within and across healthcare systems. NCCN established an advisory committee, the NCCN Quality and Outcomes Committee, consisting of provider experts from NCCN Member Institutions and other stakeholders, including payers and patient advocacy, community oncology, and health information technology representatives, to review the existing quality landscape and identify contemporary, relevant cancer quality and outcomes measures by reevaluating validated measures for endorsement and proposing new measure concepts to fill crucial gaps. This manuscript reports on 22 measures and concepts; 15 that align with existing measures and 7 that are new.

PURPOSE To determine the sensitivity and specificity of genetic testing criteria for the detection of germline pathogenic variants in women with breast cancer. MATERIALS AND METHODS Women with breast cancer enrolled in a breast cancer registry at a tertiary cancer center between 2000 and 2016 were evaluated for germline pathogenic variants in 9 breast cancer predisposition genes ( ATM , BRCA1, BRCA2, CDH1, CHEK2, NF1, PALB2, PTEN, and TP53). The performance of the National Comprehensive Cancer Network (NCCN) hereditary cancer testing criteria was evaluated relative to testing of all women as recommended by the American Society of Breast Surgeons. RESULTS Of 3,907 women, 1,872 (47.9%) meeting NCCN criteria were more likely to carry a pathogenic variant in 9 predisposition genes compared with women not meeting criteria (9.0% v 3.5%; P < .001). Of those not meeting criteria (n = 2,035), 14 (0.7%) had pathogenic variants in BRCA1 or BRCA2. The sensitivity of NCCN criteria was 70% for 9 predisposition genes and 87% for BRCA1 and BRCA2, with a specificity of 53%. Expansion of the NCCN criteria to include all women diagnosed with breast cancer at ≤ 65 years of age achieved > 90% sensitivity for the 9 predisposition genes and > 98% sensitivity for BRCA1 and BRCA2. CONCLUSION A substantial proportion of women with breast cancer carrying germline pathogenic variants in predisposition genes do not qualify for testing by NCCN criteria. Expansion of NCCN criteria to include all women diagnosed at ≤ 65 years of age improves the sensitivity of the selection criteria without requiring testing of all women with breast cancer.

Abstract For over 150 years, bronchoscopy, especially flexible bronchoscopy, has been a mainstay for airway inspection, the diagnosis of airway lesions, therapeutic aspiration of airway secretions, and transbronchial biopsy to diagnose parenchymal lung disorders. Its utility for the diagnosis of peripheral pulmonary nodules and therapeutic treatments besides aspiration of airway secretions, however, has been limited. Challenges to the wider use of flexible bronchoscopy have included difficulty in navigating to the lung periphery, the avoidance of vasculature structures when performing diagnostic biopsies, and the ability to biopsy a lesion under direct visualization. The last 10–15 years have seen major advances in thoracic imaging, navigational platforms to direct the bronchoscopist to lung lesions, and the ability to visualize lesions during biopsy. Moreover, multiple new techniques have either become recently available or are currently being investigated to treat a broad range of airway and lung parenchymal diseases, such as asthma, emphysema, and chronic bronchitis, or to alleviate recurrent exacerbations. New bronchoscopic therapies are also being investigated to not only diagnose, but possibly treat, malignant peripheral lung nodules. As a result, flexible bronchoscopy is now able to provide a new and expanding armamentarium of diagnostic and therapeutic tools to treat patients with a variety of lung diseases. This State-of-the-Art review succinctly reviews these techniques and provides clinicians an organized approach to their role in the diagnosis and treatment of a range of lung diseases.

Introduction In 2016, individual training programs in regional anesthesiology and acute pain medicine (RA/APM) became eligible for accreditation by the Accreditation Council for Graduate Medical Education (ACGME), thereby culminating a process that began 15 years earlier. Herein, we review the origins of regional anesthesia training in the USA, the events leading up to accreditation and the current state of the fellowship. Methods We reviewed pertinent literature on the historical aspects of RA/APM in the USA, related subspecialty training and the formation and current state of RA/APM fellowship training programs. Additionally, a survey was distributed to the directors of the 74 RA/APM fellowships that existed as of 1 January 2017 to gather up-to-date, program-specific information. Results The survey yielded a 76% response rate. Mayo Clinic Rochester and Virginia Mason Medical Center likely had the first structured RA/APM fellowships with formalized curriculums and stated objectives, both starting in 1982. Most programs (86%), including ACGME and non-ACGME fellowships, came into existence after the year 2000. Six responding programs have or previously had RA/APM comingled with another subspecialty. Eight current programs originally offered unofficial or part-time fellowships in RA/APM, with fellows also practicing as attending physicians. Discussion The history of RA/APM training in the USA is a tortuous one. It began with short ‘apprenticeships’ under the tutelage of the early proponents of regional anesthesia and continues today with 84 official RA/APM programs and a robust fellowship directors’ group. RA/APM programs teach skills essential to the practice and improvement of anesthesiology as a specialty.