469 Background: The Gustave Roussy Immune Score (GRIm-S) considers a composite of neutrophil to lymphocyte ratio (> 6 = 1), albumin (< 35 = 1) and LDH (> ULN = 1) and has been established as a prognostic score and may in aid in the selection of patients for phase 1 trials of immune checkpoint inhibitors. Methods: We explored the prognostic impact of the GRIm-S (high > 1) in patients enrolled on the COMPASS trial and correlated the score with genomic and clinical characteristics. Patients in this trial had biopsies for whole genomic and RNA sequencing prior to standard chemotherapy regimens in the advanced setting. Results: 252 patients were included in the analyses with a median follow-up time of 28 months. 16% of patients had a high GRIm-S with significantly shorter median overall survival (OS) of 4.1 months versus 10.0 months in those with a low score (HR 2.18, 95% CI 1.4-3.4, p < 0.0001). In the GRIm-S-high cohort, early progression with non-evaluable disease and disease progression were more common than in the GRIm-S low cohort (56% vs 31%, p = 0.003). In a multivariable analysis, a high GRIm-S was poorly prognostic (HR 1.6 95% CI 1.3-1.9, p < 0.001), whereas the classical RNA subtype (vs. basal-like) (HR 0.41, 95% CI 0.3-0.6, p < 0.001) and a high HRDetect score (HR 0.47 95% CI 0.3-0.7, p < 0.001) associated with superior OS. The GRIm-S did not correlate with RNA subtypes or with specific KRAS mutations. There were no differences in structural variant load or tumour mutational burden between groups. However those with a high GRIm-S did have a higher total target lesion diameter at baseline (p < 0.001). Conclusions: The GRIm-S identifies a subset of patients who have aggressive pancreas cancer and short life expectancy. This information may help clinicians in treatment decision making and selection for clinical trials.
4057 Background: While several clinical scoring systems exist to aid prognostication and patient (pt) selection for clinical trials in oncology, none are standardly used. We compared the ability of four prognostic scores to predict overall survival (OS) in pts with advanced gastric and esophageal (GE) cancer. Methods: Pts with advanced (unresectable or metastatic) GE cancer receiving first-line palliative-intent systemic therapy at the Princess Margaret Cancer Centre from 2007 to 2020 were included. High prognostic risk pts were identified using four scoring systems: Royal Marsden Hospital (RMH), MD Anderson Cancer Centre (MDACC), Gustave Roussy Immune Score (GRIm-S) and MD Anderson Immune Checkpoint Inhibitor (MDA-ICI) score. OS was estimated using the Kaplan-Meier method and compared between risk groups (high vs. not-high) for each scoring system using the log-rank test. Cox proportional hazards models were used to analyze the association between each prognostic score and OS, adjusting for baseline clinical factors. Harrell’s c-index was used to evaluate predictive discrimination of the models. Time-dependent AUCs were used to measure predictive ability for early death (within 90 days). Results: In total, 451 pts with advanced GE cancer were included. The median age was 59 years, 68% were male, 51% had ECOG status 0-1, 63% presented with de novo metastatic disease. The proportion of pts categorized as high risk was: RMH 25% (N=113), MDACC 13% (N=95), GRIm-S 24% (N=109), MDA-ICI 26% (N=117). In all scoring systems, high risk pts had significantly shorter OS (median OS 7.9 versus 12.2 months for RMH high vs. low risk, p<0.001; 6.8 vs. 11.9 months p<0.001 for MDACC; 5.3 vs. 13 months p<0.001 for GRIm-S; 8.2 vs. 12.2 months p<0.001 for MDA-ICI). On multivariable analysis, each prognostic score was significantly associated with OS (Table). The GRIm-S had the highest predictive discrimination (c-index 0.645 [0.612-0.678]) and highest predictive ability for early death (AUC 0.754 [0.675-0.832]). Conclusions: All four prognostic scoring systems compared had reasonable accuracy in predicting OS for patients with advanced GE cancer. The higher accuracy for predicting early death may render the GRIm-S as preferable. These tools can aid oncologists in discussions about prognosis, therapeutic decision-making and patient selection for clinical trials.[Table: see text]
147 Background: Literature on recurrence and outcomes of HPGEC is scarce. The aim of this study was to determine pattern of recurrence and outcomes after curative intent surgery for locally advanced HPGEC. Methods: A retrospective database was used to identify consecutive patients with gastroesophageal adenocarcinomas undergoing curative intent resection between 2011 and 2016 at the Princess Margaret Cancer Centre. Clinico-demographic data were extracted from the electronic health record. Patterns of relapse are classified as nonvisceral (defined as recurrences in the bone, peritoneal or both), visceral (not nonvisceral, including the brain), or both. Time to relapse (TTR) and overall survival (OS) were calculated from date of histologic diagnosis. Results: Of 45 patients with HPGEC, 78% were male, and 91% were non-Asian. Median age was 64.4 years (interquartile range [IQR] 53, 70); 60% were gastroesophageal junction, 24% were gastric, and 16% were esophageal adenocarcinomas; 31% were poorly differentiated tumors while 68% had clinical or pathological node positive disease. Complete R0 resection occurred in 93%, and 84% had received perioperative therapy (31% with perioperative chemotherapy; 40% with pre-operative chemoradiation; 9% with post-operative chemoradiation). With a median follow-up time of 26.0 months. relapse rate of HPGEC at last follow-up was 78%. Among first relapses, 94% were distant, while 6% were local recurrences. Among distant relapses, visceral recurrences occurred in 85%, nonvisceral in 3%, and 12% patients had both visceral and nonvisceral recurrences. None had peritoneal only recurrence. Median TTR was 12.2 months (IQR 8.8, 23.5), while median post-recurrence survival was 9.7 months (IQR 4.7, 16.3). Of the entire cohort, 2-year OS was 53% and 3-year OS was 26%. Conclusions: More than three-quarters of patients with HPGEC experienced recurrence after curative intent multimodality therapy. Our results suggest that HPGEC rarely relapse with peritoneal only disease or local recurrence, thereby calling into question the utility for aggressive surveillance, pending verification from larger cohorts.
224 Background: Perioperative FLOT is standard-of-care for locally advanced resectable gastric and gastroesophageal (GEJ) adenocarcinoma. Completion of perioperative chemotherapy (8 cycles) is potentially jeopardised by significant toxicity and intolerance. Only 46% of patients completed all cycles in the initial phase 2/3 trial (FLOT-AIO). We sought to determine the rate of treatment completion in a real-world population and any subsequent impact on survival of incomplete treatment. Methods: A retrospective analysis of gastric and GEJ adenocarcinoma patients treated with perioperative FLOT at Princess Margaret Cancer Centre, Toronto between September 2017 and July 2020 was performed. The rate of perioperative FLOT administration, disease-free survival (DFS) and overall survival (OS) was analysed, with outcomes compared between patients that completed perioperative FLOT and those that didn’t. Results: 32 patients were identified as receiving neoadjuvant FLOT. Mean age was 61.5y, 26 (81%) were male and 29 (91%) were non-Asian. All patients were ECOG 0-1. The median number of neoadjuvant cycles was 4. 29 (91%) had surgery (2 = disease progression; 1 = declined surgery). 10 (34%) patients had minimal/nil response upon resection (College of American Pathologists Tumour Regression Grading (TRG) Score 3), 5 of whom received adjuvant FLOT whilst 5 did not (p0.28). 10 (34%) patients did not receive adjuvant FLOT, 18 (62%) did and 1 received 8 cycles of neoadjuvant chemotherapy. Nil demographic differences were observed between ‘yes’ and ‘no’ adjuvant FLOT groups. The reasons for not having adjuvant chemotherapy were: metastatic disease diagnosed post-operatively (n = 2), TRG Score 3 (n = 4), patient declined further chemotherapy (n = 1), reduced performance status and/or toxicity (n = 2), and the patient requiring treatment for a second malignancy (n = 2). 10 (34%) patients completed perioperative chemotherapy. Median DFS was 12.5m (95% CI 7.9-12.5) for ‘no’ FLOT’ and was not-reached for ‘yes’ FLOT (p = 0.29). 18m DFS was 50% (95% CI 27-93) v 81% (95% CI 64-100) respectively. The median OS for ‘no’ adjuvant FLOT was 16.7m (95% CI 11.5-16.7) with 5 deaths. Zero deaths due to malignancy had occurred at 23.3m in those who received adjuvant FLOT (p0.00164). 1 death in the ‘yes’ group occurred due to interstitial lung disease. Conclusions: In our small population size 34% of patients completed perioperative FLOT. Whilst nil statistically significant difference was observed in mDFS, an improved mOS was observed in those that received adjuvant FLOT suggesting an importance in receiving the maximum number of cycles of chemotherapy. Given the challenges of administering adjuvant FLOT future trials into the feasibility and efficacy of 8 cycles of neoadjuvant FLOT should be considered.
320 Background: Patient reported outcomes (PRO) measures are accurate self-reflections of an individual’s physical functioning and emotional well-being. The prognostic value is unknown in gastroesophageal (GE) cancer patients (pts). The Edmonton Symptom Assessment Scale (ESAS) is a simple and validated 10-item PRO tool which uses a 0 to 10 rating of ten common symptoms (total rating 0-100). In this study, we examined the association between the ESAS score and overall survival (OS) in pts with localized and metastatic GE adenocarcinoma (GEA). Methods: This study is based on the retrospective cohort database of pts with localized (stage I-III) and metastatic GEA. We included pts who were diagnosed with GEA between 2011 and 2021 and completed at least 1 baseline ESAS prior to the treatment. Pts were grouped into 3 cohorts based as follows: High symptom burden (SB) ESAS score ≥ 26, Moderate SB (11-25) or low SB (0-10). OS was defined as time from the first visit date to death. OS was assessed using the Kaplan-Meier method and significance was set at 2-sided P < 0.05. Univariate statistical analyses were used to examine the relationships between OS and multiple variables in the presentation. Results: 233 pts met the inclusion criteria: median age was 60.8y [51.4, 69.4]; 58% of pts were ECOG PS 1; 81% were non-Asian and 18.9% Asian; 67.4% of pts were male and 32.6% female. In terms of tumor location, gastric represented 47.2% of pts, GEJ 40.8% and esophageal 12.0% primaries; 43.7% pts were stage I-III, while 56.3% were de-novo metastatic pts. Median OS in Low, Mod, High SB pts cohorts were 22.7m, 17.6mm, & 14.6m, respectively (p < 0.036). Although worse OS and worse ESAS levels were not statistically significant in the localized pts (p, 505) and metastatic subgroup (p 0,092), there was a numerical tendency, especially in the metastatic pts. In the univariate analysis, there was a significant association between OS and high-symptom burden (Hazard ratio [HR] = 1.64 (95% CI, 1.12-2.38; p = 0.0104), ECOG ≥2 (HR= 2.79 (95% CI, 1.62-4.79; p = 0.0002) and metastatic pts (HR= 3.50 (95% CI, 2.51-4.86, p<0.0001). Conclusions: Higher SB based on ESAS was associated with poorer OS among GEA pts. ESAS is a reliable tool that carries a prognostic significance that could be used in practice.[Table: see text]
131 Background: The landmark ToGA trial established trastuzumab (T) based therapy as the standard of care for advanced HER2+ gastric and gastroesophageal junction cancer. However, outcomes for T based therapy for HER2+ esophageal cancer have not been well characterized. Methods: We conducted a retrospective analysis of patients (pts) with HER2+ gastroesophageal cancer receiving T based therapy at our institution from 2011-2016. Distal esophagus ( < 35 cm) and Siewert type I/II tumours were defined as esophageal (E). Siewert type III and stomach tumours were defined as gastric (G). Trained abstractors collected pt demographics and treatment details. Overall survival (OS) and progression-free survival (PFS) were calculated from the date of first T treatment. Chi-square tests, t-tests and Cox proportional hazards models were applied where appropriate. Results: We identified 87 pts with advanced HER2+ disease. 62% (n = 54) had de novo metastatic (M1) disease. 57 patients were treated with T based therapy, with median age 57 years (IQR 48-67), 91% baseline performance status 0-1, 19% female, and 7% Asian. 63% (n = 36) had E and 37% (n = 21) had G primary tumours. 67% (n = 38) presented with M1 disease. 33% (n = 19) underwent surgery with curative intent and received T based therapy at recurrence. Baseline characteristics were balanced between the E and G groups. Survival data were available for 51 patients. The E and G groups did not have significant differences in PFS (median 9.5 vs. 9.1 months, HR 0.89 (95% CI 0.44-1.80), p = 0.74) or in OS (median 15.8 vs. 14.2 months, HR 0.88 (95% CI 0.42-1.82), p = 0.73). 63% (n = 36) were treated with subsequent systemic therapy after progression on T, with 23 receiving one line, 9 receiving two lines and 4 receiving three additional lines of treatment. The number subsequent therapies received was similar between E and G groups. Conclusions: Although patients with distal esophagus tumours were not included in the ToGA trial, our analysis suggests that patients with E and G tumours had similar outcomes. Our contemporary cohort had comparable survival outcomes relative to patients receiving T in the ToGA trial (median PFS = 6.7 months, median OS = 13.8 months).
4149 Background: Systemic inflammatory scores have been developed as tools to aid clinicians in prognostication and patient (pt) selection for clinical trials. We compared the accuracy of five prognostic scores to predict overall survival (OS) in pts with advanced pancreatic adenocarcinoma (PDAC). Methods: Pts with advanced PDAC enrolled on the COMPASS trial (NCT02750657) from 2015 to 2020 were included. All pts had biopsies for whole genome and RNA sequencing prior to standard first-line chemotherapy in the advanced setting. Prognostic risk was calculated using: neutrophil-to-lymphocyte ratio (NLR; >5 = high), platelet-to-lymphocyte ratio (PLR; > 150 = high), Prognostic Nutritional Index (PNI = albumin + 5 x lymphocytes. PNI < 45 = high risk), Gustave Roussy Immune Score (GRIm-S; NLR>6 = 1 point, albumin <35 = 1 point, LDH > upper limit of normal [ULN] = 1 point. GRIm-S ≥2 = high risk), and Memorial Sloan Kettering Prognostic Score (MPS; NLR >4 and albumin < 40 = high risk). OS was estimated using the Kaplan-Meier method and compared between risk groups (high vs. not-high) for each scoring system using the log-rank test. Cox proportional hazards models were used to analyze the association between each prognostic score and OS, adjusting for baseline clinical and genomic factors. Results: In total, 263 pts with advanced PDAC cancer were included, with median follow up of 32.9 (95% CI 15.9-64.2) months. Median OS in the intention to treat population was 9.3 months (95% CI 8-10.2). PLR and PNI were not prognostic. High risk NLR (N=85, 32%), GRIm-S (N=47, 18%) and MPS (N=46, 17%) identified pts with poor prognosis. The GRIm-S and MPS were most significant: median OS in high vs low risk pts 6.4 vs. 10 months p<0.001 (GRIm-S) and 6.3 vs. 10 months p=0.002 (MPS). On multivariable analyses, high risk NLR, GRIm-Score and MPS were each associated with poor OS after adjusting for baseline clinical and genomic factors (Table). For all models, ECOG ≥1 (N=165, 63%); the basal-like Moffitt RNA subtype (N=49, 20% vs 80% classical) and low HRDetect scores (N=31, 13%) were significantly associated with poor OS. However these scores did not associate with RNA based classifiers or HRD scores and can therefore provide additional prognostic information. Conclusions: Both the GRIm-S and MPS are highly prognostic in PDAC and are scores easily used in the clinical setting and may help in clinical trial selection. Genotypic correlates are being explored.[Table: see text]
357 Background: Radiomic characterisation of tumour phenotypes can generate image-driven biomarkers that potentially aid in clinical decision-making. We sought to identify radiomic features in metastatic GEA that may be predictive for survival outcomes. Methods: A retrospective analysis between 2009-20 identified patients (pts) with metastatic GEA. All pts received chemotherapy (CTx), with a ‘baseline’ and 8-12 week ‘on-treatment’ contrast-enhanced CT chest/abdomen/pelvis performed. Radiomic analysis was performed with LIFEx (livexsoft.org). Population demographics and clinical outcomes were recorded. Univariable Cox proportional hazards model (UVA) assessed clinical variables (n=26) predictive of overall survival (OS) and progression-free survival (PFS) with p=0.05 indicating significance. Multivariable Cox model (MVA) was used to assess radiomic features (n=78) in the presence of clinical variables. Concordance index (C-index) was calculated to assess model performance (≥0.7 = high predictive accuracy). A ‘validation’ cohort analysis was performed to validate the model. Results: 166 pts were identified (primary cohort n=143; validation cohort n=23). 123 had de-novo metastatic disease, 43 recurrence following curative-intent therapy. In the primary cohort the median age was 58.1y, 101 (71%) were male, 120 (84%) were non-Asian and 131 (92%) were ECOG 0-1. Similar demographics were observed in the validation cohort. Both ‘baseline’ and ‘on-treatment’ scans UVA identified Her2 status, ethnicity, and the number of CTx cycles as predictive of PFS, while ECOG, brain metastases, neutrophil count (ANC), albumin and number of CTx cycles were predictive of OS. ‘Baseline’ model analysis for PFS and OS identified consistent radiomic features (HUskewness; HUpeakSphere), with an observed C-index 0.6 and 0.657 respectively. No radiomic features were identified on ‘on-treatment’ PFS analysis. ‘On-treatment’ OS analysis is shown in the table with 3 radiomic features (SHAPE Surface; SHAPE Compacity; PARAMS ZSpatial-Resampling) predictive for OS. The C-index is 0.76. Analysis of the validation cohort supported the model (C-index 0.815) for ‘on-treatment’ OS. Conclusions: Radiomic analysis identified a number of features associated with PFS and OS. The features specifically identified on ‘on-treatment’ scans were highly predictive for OS. Our analysis suggests radiomic features in addition to clinical variables can be predictive of outcome in patients with metastatic GEA receiving CTx.[Table: see text]
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