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Purpose The US National Cancer Institute (NCI) Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) was developed to enable patient reporting of symptomatic adverse events in oncology clinical research. This study was designed to assess the feasibility and resource requirements associated with implementing PRO-CTCAE in a multicenter trial. Methods Patients with locally advanced rectal cancer enrolled in the National Cancer Institute–sponsored North Central Cancer Treatment Group (Alliance) Preoperative Radiation or Selective Preoperative Radiation and Evaluation before Chemotherapy and Total Mesorectal Excision trial were asked to self-report 30 PRO-CTCAE items weekly from home during preoperative therapy, and every 6 months after surgery, via either the Web or an automated telephone system. If participants did not self-report within 3 days, a central coordinator called them to complete the items. Compliance was defined as the proportion of participants who completed PRO-CTCAE assessments at expected time points. Results The prespecified PRO-CTCAE analysis was conducted after the 500th patient completed the 6-month follow-up (median age, 56 years; 33% female; 12% nonwhite; 43% high school education or less; 5% Spanish speaking), across 165 sites. PRO-CTCAE was reported by participants at 4,491 of 4,882 expected preoperative time points (92.0% compliance), of which 3,771 (77.2%) were self-reported by participants and 720 (14.7%) were collected via central coordinator backup. Compliance at 6-month post-treatment follow-up was 333 of 468 (71.2%), with 122 (26.1%) via backup. Site research associates spent a median of 15 minutes on PRO-CTCAE work for each patient visit. Work by a central coordinator required a 50% time commitment. Conclusion Home-based reporting of PRO-CTCAE in a multicenter trial is feasible, with high patient compliance and low site administrative requirements. PRO-CTCAE data capture is improved through centralized backup calls.

Older adults with cognitive impairment face many healthcare challenges, chief among them participating in medical decision‐making about their own health care. Advance care planning (ACP) is the process whereby individuals communicate their wishes for future care with their clinicians and surrogate decision‐makers while they are still able to do so. ACP has been shown to improve important outcomes for individuals with cognitive impairment, but rates of ACP for these individuals are low because of individual‐, clinician‐, and system‐related factors. Addressing ACP early in the illness trajectory can maximize the chances that people can participate meaningfully. This article recommends best practices for approaching ACP for older adults with cognitive impairment. The importance of providing anticipatory guidance and eliciting values to guide future care to create a shared framework between clinicians, individuals, and surrogate decision‐makers is emphasized. It is recommended that ACP be approached as an iterative process to continue to honor and support people's wishes as cognitive impairment progresses and increasingly threatens independence and function. The article describes effective strategies for assessing decision‐making capacity, identifying surrogate decision‐makers, and using structured communication tools for ACP. It also provides guidelines for documentation and billing. Finally, special considerations for individuals with advanced dementia are described, including the use of artificial hydration and nutrition, decisions about site of care, and the role of hospice care.

AbstractAnaplasia may be identified in a subset of tumors with a presumed pilocytic astrocytoma (PA) component or piloid features, which may be associated with aggressive behavior, but the biologic basis of this change remains unclear. Fifty‐seven resections from 36 patients (23 M, 13 F, mean age 32 years, range 3–75) were included. A clinical diagnosis of NF1 was present in 8 (22%). Alternative lengthening of telomeres (ALT) was assessed by telomere‐specific FISH and/or CISH. A combination of immunohistochemistry, DNA sequencing and FISH were used to study BRAF, ATRX, CDKN2A/p16, mutant IDH1 p.R132H and H3‐K27M proteins. ALT was present in 25 (69%) cases and ATRX loss in 20 (57%), mostly in the expected association of ALT+/ATRX‐ (20/24, 83%) or ALT‐/ATRX+ (11/11, 100%). BRAF duplication was present in 8 (of 26) (31%). H3‐K27M was present in 5 of 32 (16%) cases, all with concurrent ATRX loss and ALT. ALT was also present in 9 (of 11) cases in the benign PA precursor, 7 of which also had ATRX loss in both the precursor and the anaplastic tumor. In a single pediatric case, ALT and ATRX loss developed in the anaplastic component only, and in another adult case, ALT was present in the PA‐A component only, but ATRX was not tested. Features associated with worse prognosis included subtotal resection, adult vs. pediatric, presence of a PA precursor preceding a diagnosis of anaplasia, necrosis, presence of ALT and ATRX expression loss. ALT and ATRX loss, as well as alterations involving the MAPK pathway, are frequent in PA with anaplasia at the time of development of anaplasia or in their precursors. Additionally, a small subset of PA with anaplasia have H3‐K27M mutations. These findings further support the concept that PA with anaplasia is a neoplasm with heterogeneous genetic features and alterations typical of both PA and diffuse gliomas.

11008 Background: SARC028 is the first multicenter Phase II study of P monotherapy in patients (pts) with STS and BS. Designed to detect clinical efficacy signals in multiple histologies, the study collected blood & tissue samples on all pts. We report extended clinical follow-up and in-depth biomarker correlates of response. Methods: The primary endpoint was objective response rate (ORR) by RECIST 1.1. Secondary endpoints were safety, 12 wk progression-free survival (PFS), and overall survival (OS). The STS arm had 10 pts in each of 4 cohorts: undifferentiated pleomorphic sarcoma (UPS), dedifferentiated liposarcoma (DDLPS), synovial sarcoma (SS) and leiomyosarcoma (LMS). The BS arm included 40 pts with osteosarcoma (OS), Ewing sarcoma (ES) or dedifferentiated chondrosarcoma (CS). Pre- and on-P biopsies were required as well as blood at multiple time points. Tumor was assessed for PD-L1 expression (clone 22C3) and immune infiltrates by multi-color IHC (Vectra). Ongoing analyses include circulating cytokine and checkpoint levels and exome (DNA), transcriptome (RNA), and T-cell receptor (TCR) sequencing. Results: 86 pts were enrolled, 80 were evaluable for response. For STS, median follow-up was 14.5 months. The ORR in the overall STS cohort was 18% and the 12-wk PFS 55% [95% CI, 42-71]). Clinical activity was variable by histologic subtype with 40% ORR in UPS (1 CR and 3PR out of 10 evaluable pts), 2 PR/10 were seen in DDLPS, 1PR/10 in SS and 0/10 in LMS. For BS, median follow-up was 12.3 months (ORR 5%; 12-wk PFS 28% [95% CI, 14-41]), with 1PR/22 OS, 1PR/5 CS and 0/13 ES. 70 pre-P tissues were analyzed (11 excluded for insufficiency), with PD-L1+ in 3/70 (4%); all 3 were UPS. Of the 2 evaluable pts, 1 had CR and 1 PR. 2 OS were PD-L1+ on multi-color IHC, 1 had PR. All PD-L1+ samples had CD8+ T-cell infiltration. There were no post-P PD-L1+ samples. Conclusions: P has clinical activity in UPS and LPS, and expansion cohorts in those subtypes are planned. Pre-treatment PD-L1 expression was infrequent, but correlated with T-cell infiltration and response in UPS & OS. Ongoing biomarker analyses that may guide combination strategies are ongoing and will be presented at the meeting. Clinical trial information: NCT02301039.

11007 Background: Patients (pts) with metastatic sarcoma (SAR) have limited options. Nivolumab(N), a fully human anti-PD-1 mAb and ipilimumab (I), a humanized anti-CTLA-4 mAb, have favorable safety & efficacy in other tumors. Pembrolizumab demonstrated a response rate (RR) of 12% in SAR pts. We evaluated N, independently from N+I, in SAR pts. Methods: This open-label multi-center phase II study enrolled pts failing prior regimens. Randomized (non-comparative) pts received either N3 [N (3 mg/kg q2W)] or N3+I1 [N(3 mg/kg Q3W x4, then Q2W) & [I(1 mg/kg q3W x4)]. Treatment continued beyond progressive disease (PD) in 1st12 weeks. 5 confirmed responses in 38 evaluable pts yielded 90% power (0.05 1-sided alpha) to detect a 20% (vs 5%) confirmed RR. Other endpoints: adverse events (AEs), progression-free, overall survival (PFS, OS), and correlative studies including PD-L1 expression by IHC, mutational burden/neoantigen analysis, TCR clonality and TIL characterization. Results: 85 pts (43 - N3; 42 - N3+I1) were enrolled [mean age 54 yrs (21–81), 52% female). No significant differences in histological subtypes across cohorts: 36% LMS, 4% LPS, 10% UPS/MFH, 6% synovial, 5% bone, 5% Ewing’s, and 34% other. Pts were refractory to 1(20%), 2(22%), and ≥3 (58%) regimens. Grade 3-4 treatment related adverse events (TRAE) occurred in 7% (N3) and 14% (N3+I1) and 0 Gr 5 TRAEs. 8% of pts stopped due to AEs (2% N3, 14% N3+I1). 2/3 confirmed responses on N3, with 2 ongoing (range 1.1-3.2 months). 6/7 confirmed responses (2 complete) on N3+N1, with 5 ongoing (range 6-13 months). Responses occurred in 7 histologies. See Table for pt outcomes. Conclusions: N + I showed acceptable safety and encouraging antitumor activity with most responses ongoing across multiple SAR histologies, passing efficacy criteria. There was minimal activity observed with N alone. Increased TRAEs were observed in N3+I1. Correlative analyses ongoing. NCT02500797. Support: U10CA180821, U10CA180882, Conquer Cancer Foundation, BMS. Clinical trial information: NCT02500797. [Table: see text]

4109 Background: Prognostic nomograms have been developed in various cancers, including ovarian, breast, and gastrointestinal; however, there is limited information on nomograms in MPC. The large, phase 3 MPACT study of nab-P + Gem vs Gem alone for the treatment of MPC provides a robust database for the development of a nomogram to predict OS using baseline patient variables. Methods: A multivariable Cox model was created from MPACT data using factors that were significantly predictive of OS in univariable analysis or considered clinically important (stepwise selection to remain in model). From the Cox model, a nomogram was derived that assigned points equal to the weighted sum of relative significance of each variable. The nomogram was internally validated using bootstrapping, a concordance index (c-index), and calibration plots. Results: Data from all 861 pts were used. Seven of the 34 considered variables were retained in the multivariable analysis (Table; all factors significant at the P < 0.01 level, except for analgesic use [ P = 0.07]). The resulting nomogram was able to distinguish low (n = 216), medium (n = 430), and high (n = 215) risk groups (c-index: 0.69; CI: 0.67-0.71) with median OS values of 12.9, 8.2, and 3.7 months, respectively. Calibration curves showed that the nomogram’s predicted probabilities were mostly consistent with observed probabilities for 6-, 9-, and 12-month OS. Conclusions: Treatment arm, Karnofsky performance status (KPS), neutrophil-to-lymphocyte ratio (NLR), albumin level, sum of longest tumor diameters (SLD), and presence of liver metastasis were the key predictors of OS. This nomogram, which will be presented in visual format in the final presentation, may help physicians and pts make informed treatment decisions. Clinical trial information: NCT00844649. [Table: see text]