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Background Pancreatic cancer (PC) remains a highly fatal disease. There is a gap in the literature on the of quality care on survival in a real-world population. Objectives This study: (1) assessed compliance with a consensus set of quality indicators (QIs); and (2) evaluated the association between compliance with these QIs and survival. Methods Data were collected on a core set of quality indicators by the Upper Gastrointestinal Cancer Registry (UGICR) for patients diagnosed with PC between 1 January 2016 and 31 December 2019. Univariable and multivariable Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% CIs for the association between survival and patient characteristics, hospital characteristics and QIs, stratified by resectability. A multivariable analysis tested the relationship between significant patient and hospital characteristics, patient cluster effects within hospitals and survival. Results 1061 patients were eligible for this study with 52% male, 71% over the age of 65, 23% potentially resectable and 51% with metastatic disease at diagnosis. 52% received some form of cancer directed treatment. Significant association with improved survival were: (1) in the potentially resectable group having adjuvant chemotherapy administered following surgery or a reason documented (HR, 0.29; 95 CI, 0.19-0.46); (2) in the locally advanced group included having chemotherapy ± chemoradiation, or a reason documented for not undergoing treatment (HR, 0.38; 95 CI, 0.25-0.58) and (3) in the metastatic disease group included having documented ECOG at presentation and/or American society of Anaesthesiologists (ASA) performance status at a diagnostic procedure (HR, 0.65; 95 CI, 0.47-0.89), being seen by a medical oncologist and/or a radiation oncologist in the absence of treatment (HR, 0.48; 95 CI, 0.31-0.77), and having disease management discussed at an MDT meeting (HR, 0.79; 95 CI, 0.64-0.96). Conclusion Capture of a concise data set has enabled quality of care to be assessed and an analysis of factors associated with improved survival identified.

9069 Background: Most patients with extensive SCLC develop drug resistance to platinum-based 1L therapy or discontinue for other reasons, and second-line (2L) therapies are limited. RESILIENT (NCT03088813) is a two-part phase 2/3 study assessing the safety, tolerability and efficacy of 2L liposomal irinotecan monotherapy in adults with SCLC who progressed with platinum-based 1L therapy. Preliminary data from RESILIENT part 1 (cut-off May 8 2019; ≥ 12 weeks follow-up) showed that liposomal irinotecan 70 mg/m2 free base every 2 weeks was generally well tolerated and had encouraging antitumor activity (Paz-Ares et al. WCLC 2019 OA03.03). Objective response rate (ORR; secondary endpoint) was 44% (11/25). Here we report efficacy analyses in post hoc subgroups by platinum sensitivity. Methods: RESILIENT part 1 was an open-label, single-arm study comprising dose-finding and dose-expansion phases. Eligible patients were aged ≥ 18 y, with an ECOG performance status score of 0/1 and adequate organ function; a single line of prior immunotherapy was allowed. Participants received liposomal irinotecan 70 mg/m2 or 85 mg/m2 free base every 2 weeks, with tumor assessments every 6 weeks (RECIST v1.1). Analyses were undertaken for the dose-finding phase recommended dose (RD) in subgroups of platinum-resistant/sensitive patients (with/without progression within 90 days from completion of 1L therapy). Results: During dose finding, 5 patients received liposomal irinotecan 85 mg/m2 (deemed not tolerable; dose-limiting toxicity) and 12 received 70 mg/m2 (deemed tolerable; RD for dose-expansion phase in which 13 more patients were included). Analyses included all 25 patients receiving the RD (mean exposure, 13.95 weeks [median 14.86; SD 7.222]). In the platinum-sensitive subgroup (33.3% men; median age 62.0 y) ORR was 53.3% (8/15) and 12-week disease control rate (DCR12wks) was 60% (9/15); in the platinum-resistant subgroup (50% men, median age 58.0 y) both ORR and DCR12wks were 30% (3/10). Overall and progression-free survival (secondary endpoints) are not yet mature. Conclusions: ORR and DCR12wks were numerically higher in platinum-sensitive than in platinum-resistant patients with SCLC who had progressed with platinum-based 1L therapy before receiving 2L liposomal irinotecan 70 mg/m2 in this phase 2 study. RESILIENT part 2, an ongoing, phase 3, randomized controlled trial vs topotecan, will provide further data. Clinical trial information: NCT03088813.

TPS9081 Background: Although small cell lung cancer (SCLC) is often sensitive to established first-line therapies, many patients relapse and develop drug resistance, and second-line therapies are limited. RESILIENT (NCT03088813) is a two-part phase 2/3 study assessing the safety, tolerability, and efficacy of liposomal irinotecan monotherapy in patients with SCLC who progressed with platinum-based first-line therapy. Preliminary data from the dose-ranging part of the study (part 1) showed that liposomal irinotecan 70 mg/m2 administered every 2 weeks was well tolerated and had promising antitumor activity (Paz-Ares et al. ASCO 2019; poster 318). Here, we present the design of the second, larger part of the study, which will evaluate the efficacy and safety of liposomal irinotecan versus topotecan in the same patient population. Methods: Part 2 of RESILIENT is a phase 3, open-label study with a planned sample size of 450. Patients are randomly allocated 1:1 to intravenous liposomal irinotecan or intravenous topotecan. Liposomal irinotecan is administered every 2 weeks at 70 mg/m2 (free-base equivalent) and topotecan is administered for 5 consecutive days every 3 weeks at 1.5 mg/m2. As of January 2020, 80 patients have been enrolled in part 2 of the trial. Tumor assessments are performed using the Response Evaluation Criteria in Solid Tumors version 1.1 and the Response Assessment in Neuro-oncology criteria for CNS lesions; symptom improvement is measured using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30. Safety assessments include monitoring for adverse events. The primary endpoint is overall survival (OS) and secondary endpoints are progression-free survival (PFS), objective response rate, and proportion of patients reporting symptom improvement. Patients will continue study treatment until disease progression, unacceptable toxicity or study withdrawal and will then be followed for survival until death or study end (when all patients have died, withdrawn consent or are lost to follow-up). Clinical trial information: NCT03088813.

8562 Background: Nal-IRI is investigated as monotherapy in patients with SCLC who progressed on or after platinum regimen. The RESILIENT study is a Part 1 study of a Phase 2/3 trial to assess safety, tolerability, and efficacy of Irinotecan Liposome Injection in patients with SCLC. Methods: Nal-IRI is evaluated in patients ≥18 yrs with advanced SCLC with an ECOG performance status ≤1 and adequate organ function; prior exposure to immunotherapy is allowed. Safety and tolerability at dose levels of 85 mg/m2 and 70 mg/m2 are the primary endpoints, with assessment of exploratory efficacy signal. Results: At 24 Dec 2018 safety cutoff 12 patients in Part 1 received ≥1 dose of nal-IRI (Cohort 1 [C-1] at 85 mg/m2 dose n=4; Cohort 2 [C-2] at 70 mg/m2 dose n=8; median age 60.0 yrs; range 49–73 yrs). Three patients experienced ≥1 DLT (Cohort 1 n=3/4; Cohort 2 n=0/8). Most frequent treatment-emergent adverse events (TEAE) were gastrointestinal (GI) disorders (any grade): diarrhea (91.7%), nausea (58.3%), vomiting (41.7%), decreased appetite (58%), abdominal pain (33%) manageable by antidiarrheal regimen and antiemetics; as well as fatigue (50%) and asthenia (37.5%). Overall, hematologic toxicity was neutropenia (any grade) at 16.7% and anemia (any grade) at 16.7%. At 11 Dec 2018 efficacy cutoff the best objective response was partial response (PR) at 33.3% in 4/12 patients (C-1 n=1/4; C-2 n=3/8), median time to response was 6 wks. Overall disease control rate (DCR) was 58.3%; progressive disease (PD) was observed in 2 patients (16.7%), and 3 patients were non-evaluable (25%). Conclusions: Initial assessment suggests that nal-IRI at 70 mg/m2 dose given bi-weekly is well-tolerated and has promising antitumor activity in patients with SCLC who progressed on or after platinum regimen. Part 1 dose expansion is ongoing. Clinical trial information: NCTN03088813. [Table: see text]

Detection of circulating tumor DNA (ctDNA) after resection of stage II colon cancer may identify patients at the highest risk of recurrence and help inform adjuvant treatment decisions. We used massively parallel sequencing–based assays to evaluate the ability of ctDNA to detect minimal residual disease in 1046 plasma samples from a prospective cohort of 230 patients with resected stage II colon cancer. In patients not treated with adjuvant chemotherapy, ctDNA was detected postoperatively in 14 of 178 (7.9%) patients, 11 (79%) of whom had recurred at a median follow-up of 27 months; recurrence occurred in only 16 (9.8 %) of 164 patients with negative ctDNA [hazard ratio (HR), 18; 95% confidence interval (CI), 7.9 to 40; P < 0.001]. In patients treated with chemotherapy, the presence of ctDNA after completion of chemotherapy was also associated with an inferior recurrence-free survival (HR, 11; 95% CI, 1.8 to 68; P = 0.001). ctDNA detection after stage II colon cancer resection provides direct evidence of residual disease and identifies patients at very high risk of recurrence.

3511Background: The conventional approach to testing the benefit of adjuvant therapies in patients (pts) with relatively favorable prognoses is to follow a large number of pts for long periods of t...

TPS1135 Background: Neoadjuvant chemotherapy for breast cancer allows response to be assessed depending on subtype, and to judge impact of response to therapy on progression-free survival (PFS). Me...

The testis is one of the most abundant sources of microtubule networks. These networks include mitotic and meiotic spindles, the spermatid manchette and axoneme, and the Sertoli cell cytoskeleton. Microtubules are composed of alpha- and beta-tubulin subunits that are polymerized and stabilized by a variety of microtubule-associated proteins (MAPs). One of these, MAP2, has been extensively characterized as a brain-specific protein with the capacity to bind tubulin, cAMP-dependent kinase, and calmodulin. MAP2 mRNA is processed into at least two variants encoding proteins designated MAP2a, MAP2b, and MAP2c. Of the 5.7 kb of coding sequence in the 9-kb mRNA that encodes MAP2a and MAP2b, a deletion of approximately 4 kb produces mRNA encoding MAP2c, which consists of only the N- and C- terminal regions of MAP2b. To determine whether MAP2 was present in the rat testis, microtubule preparations were isolated from adult rat testis and brain by means of taxol-mediated polymerization and analyzed by gel filtration, ELISA, and Western blotting using polyclonal and monoclonal antibodies reactive with MAP2. A 74-kDa protein corresponding to MAP2c was detected in the testis. These results were confirmed by Northern blot analysis of total RNA from adult rat brain and testis with cDNA probes that distinguish between the known MAP2 splice variants. The predominant mRNAs in testis of 6 kb and 2.5-3.5 kb corresponded to MAP2c. A single 6-kb mRNA with the potential to encode MAP2c was detected in enriched preparations of immature Sertoli cells and adult Leydig cells. Round spermatids contained at least two MAP2 mRNAs between approximately 2.5 and 3.5 kb in size that displayed a stage-specific pattern of expression. Immunohistochemistry showed a MAP2-like protein in both somatic and germ cells, with a particularly distinct localization within the cytoplasm of primary and secondary spermatocytes at stage XIV of the seminiferous cycle during meiotic metaphase. In addition to cytoplasmic staining, a novel localization of this protein was observed in the nucleus of many testicular cells.