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58 Background: In the phase 2 CheckMate 142 trial, NIVO + low-dose IPI had robust, durable clinical benefit and was well tolerated as 1L therapy for MSI-H/dMMR mCRC (median follow-up, 29.0 months [range, 24.2–33.7]) (Lenz et al. J Clin Oncol 2020;38:Abstract 4040; NCT02060188). Objective response rate (ORR) per investigator (INV) was achieved in 69% of pts (95% CI, 53–82); progressive disease rate was 13%. Median progression-free survival (PFS) and overall survival (OS) were not reached. Median duration of treatment was 19.1 months (95% CI, 11.1–29.0). Grade 3–4 treatment-related adverse events (TRAEs) occurred in 22% of pts. We present the post hoc subgroup analyses of efficacy and safety outcomes in pts from the same follow-up based on demographics and baseline disease characteristics. Methods: Pts with MSI-H/dMMR mCRC and no prior treatment for metastatic disease received NIVO 3 mg/kg Q2W + low-dose IPI 1 mg/kg Q6W until disease progression or discontinuation. ORR (primary endpoint, RECIST v1.1) and PFS were assessed per INV. Post hoc subgroup analyses of efficacy (by ECOG performance status [PS], stage at initial diagnosis, primary tumor location, and BRAF/KRAS mutation status) and safety (by age and ECOG PS) are presented. Results: Among 45 treated pts, efficacy (Table) and safety were generally consistent across evaluated subgroups. ORR was similar in pt subgroups by BRAF/ KRAS mutation status, stage at initial diagnosis, primary tumor location, and ECOG PS (Table). Median PFS and OS were not reached (NR) in evaluated subgroups after a minimum follow-up of 24.2 months (Table). Incidence of grade 3–4 TRAEs for subgroups by age and ECOG PS were consistent with the overall population. Conclusions: NIVO + low-dose IPI demonstrated robust, durable clinical benefit; was well tolerated with 2-year follow-up; and was consistent in evaluated subgroups in 1L MSI-H/dMMR mCRC. Clinical trial information: NCT02060188. [Table: see text]

Background Despite recent improvements, management of locally advanced rectal cancer (LARC) remains challenging, and many patients (pts) still experience recurrence. In preclinical models, combining Rego with an anti-PD-1 inhibitor led to superior tumour growth suppression as compared with either treatment alone. In a phase I clinical trial, remarkable results were reported for the combination of Rego and Nivo in advanced MSS colorectal cancer. This synergistic effect is thought to be secondary to the anti-angiogenic effects of Rego and its potential to reduce TAMs, promote M1 macrophage conversion, and downregulate expression of immunosuppressive factors. Building on these data, we designed a trial of Rego-Nivo with standard SCRT in the neoadjuvant setting of RC. Trial design REGINA is an academic, multicentre, single-arm, phase II trial sponsored by Institut Jules Bordet. Eligible patients are treated according to the following plan: induction phase (Nivo 240 mg IV D1&15, and Rego 80 mg PO D1-14), SCRT (D22-26), consolidation phase (Nivo 240 mg IV D29,43&57, and Rego 80 mg PO D29-49), and surgery (7-8 weeks after SCRT). Key eligibility criteria include age ≥18 years, ECOG PS ≤1, adenocarcinomas below the peritoneal reflection, intermediate-risk, stage II-III tumour (ie, cT3/T4aNany or cT1-2N+, no involvement/threatening of the mesorectal fascia, no involvement of lateral pelvic lymph nodes). The primary endpoint is pathological complete response (pCR). Secondary endpoints include, among others, toxicity, compliance to treatment, pTRG, event-free survival, and overall survival. The study follows a Simon’s two-stage design (null hypothesis pCR=12%, alternative hypothesis pCR=24%; α=5%, β=20%) with a maximum of 60 pts to be enrolled. A safety interim analysis is planned after the first 6 pts have completed treatment. Serial collection of tumour, blood, and stool samples is mandatory at pre-specified time points for exploratory correlative biomarker analyses. The trial is planned to be run at 8-10 centres across Belgium. Study recruitment started in Q1 2021 and is anticipated to complete in Q3 2023. Clinical trial information: NCT04503694.

Supplemental material, sj-docx-1-tam-10.1177_17588359211045860 for Isotoxic high-dose stereotactic body radiotherapy integrated in a total multimodal neoadjuvant strategy for the treatment of localized pancreatic ductal adenocarcinoma by Christelle Bouchart, Jean-Luc Engelholm, Jean Closset, Julie Navez, Patrizia Loi, Yeter Gökburun, Thierry De Grez, Laura Mans, Alain Hendlisz, Maria Antonietta Bali, Pierre Eisendrath, Dirk Van Gestel, Matthieu Hein, Luigi Moretti and Jean-Luc Van Laethem in Therapeutic Advances in Medical Oncology

Background and Objectives The histological growth pattern (HGP) represents a strong prognostic factor in patients undergoing surgery for colorectal liver metastases (CRLM). We evaluated whether the combination of HGP with clinico-metabolic parameters could improve its prognostic value. Methods In a series of 108 patients undergoing resection of CRLM, the HGP of CRLM was scored according to international guidelines. Baseline clinico-metabolic clinical status was evaluated using a metabolic-Clinical Risk Score (mCRS), combining traditional Memorial Sloan Kettering-CRS parameters with the tumor-to-liver glucose uptake ratio as measured with (18)Fluorodeoxyglucose/positron emission tomography. Results In patients with desmoplastic HGP (DHGP) CRLM (20% of all patients), 5- and 10-years overall survival (OS) and disease free survival (DFS) were 66% and 43% and 37% and 24.5%, as compared with 35% and 21% and 11% and 11% in the non-DHGP group (p = 0.07 and 0.054). Among DHGP patients, those with a low-risk mCRS had improved postoperative outcomes, 5- and 10-years OS and DFS reaching 83.3% and 62.5% and 50% and 33%, as compared with 18% and 0% and 0% and 0% in high-risk mCRS patients (p = 0.007 and 0.003). In contrast, mCRS did not influence postoperative survivals in non-DHGP patients. Conclusions Combining the clinico-metabolic characteristics with the HGP may improve prognostication in patients undergoing surgery for CRLM.

SCOPUS: le.j, info:eu-repo/semantics/published

Protocol tittle: Study of BO-112 with pembrolizumab for colorectal or gastric/GEJ cancer with liver metastasis.Background: Gastric (GC), oesophagogastric junction (EGJC) and colorectal tumors (CRC) with microsatellite stability (MSS) are poorly responders to PD(L)-1 inhibition, due to low CD8+ T cell infiltration and PD-L1 expression. Therefore, modulation of the tumor microenvironment (TME) could increase disease control. In these tumors the presence of liver lesions is difficult to control because of the hepatic immune tolerance. Control of the hepatic disease could increase survival.BO-112 is a non-coding dsRNA agonist of TLR3, MDA5 and RIG-I which activates the innate and adaptative immune response, inducing apoptosis and immunogenic cell death, with a local and a systemic effect. A prior Phase I trial showed that the combination of pembrolizumab and intratumoral (IT) BO-112 has a good safety profile and encouraging activity. Study design: This is a single arm phase IIa trial to assess the efficacy of intrahepatic IT BO-112 and iv pembrolizumab in 3W cycles in patients with MSS CRC, GC or EGJ tumors. Up to 69 patients with at least one liver lesion and 2 prior lines for CRC and 1 for GC/EGJC will be enrolled. Primary endpoints: ORR and related TEAEs ≥ grade 3. Secondary endpoints: ORR (iRECIST), PFS, 6-months OS and safety. Exploratory endpoint: Changes in TME (PD-L1 expression and CD8+ T cell infiltration) from baseline to C2D1.Results: A total of 11 CRC and 7 GC/EGJC patients were enrolled since July 2020. This abstract focuses on the CRC patients´ biomarker expression. These patients had low PD-L1 CPS (combined positive score) expression and CD8+ T cell infiltration with a median value of 5 and 4%, respectively, in the TME at baseline. Following two IT BO-112 injections, an important increase in PD-L1 expression and CD8+ T cell infiltration was observed in 5 and 7 patients, respectively. PD-L1 CPS median value increased to 37.9 while CD8+ T cell infiltration median values raised to 12.9%.Conclusions: A meaningful increase in PD-L1 expression and CD8+ T cell infiltration was achieved in MSS CRC patients after one cycle of BO-112-pembrolizumab. Table 1.Baseline characteristics and TME changesBaseline characteristicsCRC N=11Demographics-Sex-Male-Female-Age (mean, range)7 (63.6%)4 (36.4%)55 (38-74)Location of primary tumor-Right colon-Left colon2 (36.4%)7 (63.6%)Presence of extrahepatic disease-No-YesLocation of the extrahepatic disease-Lungs-Lymph nodes-Ohers (bone, adrenal gland, peritoneum, pancreas)2 (18.2%)9 (81.8%)6 (54.5%)5 (45.5%)1 (9.1%)Molecular characteristics:-MMR status-MSS-KRAS-Wild type-Mutant -PD-L1-CPS Citation Format: Mariano Ponz-Sarvisé, Elena Élez, Andrés Muñoz, Marc Van den Eynde, Antonio Gaetano Rampoldi, Alain Hendlisz, Hans Prenen, Mercedes Rodríguez, María Teresa Cano, Marya Chaney, Helena Escuin, Vanesa Pons, Marisol Quintero, Andrés Cervantes. Phase IIa open-label clinical study of intratumoural administration of BO-112 in combination with pembrolizumab in subjects with liver metastasis from colorectal cancer or gastric/gastro-oesophageal junction cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr CT192.

Currently, there are no markers to identify patients with liver-only or liver-dominant metastases that would benefit from hepatic surgery. Here we characterized histopathological growth patterns (HGPs) of liver metastases in a consecutive series of 36 breast cancer patients who underwent hepatic surgery. Survival analyses showed that the presence of a desmoplastic HGP in the liver metastases (a rim of fibrous tissue separating cancer cells from the liver parenchyma, present in 20 (56%) patients) is independently associated with favorable progression-free and overall survival when compared with the replacement HGP (cancer cells growing into the liver parenchyma, present in 16 (44%) patients)., SCOPUS: ar.j, info:eu-repo/semantics/published

Background: Relatively high morbidity rates are reported after cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC). However, early predictors of complications after CRS plus HIPEC have not been identified. The aim of this study was to evaluate the predictive role of early postoperative serum C-reactive protein (CRP) level (Day 2–4) for the detection of post-operative complications. Patients and methods: We performed a retrospective study including 94 patients treated with complete CRS (R1) and HIPEC for PC from various primary origins (2011–2016). Post-operative complications were recorded. The values for postoperative inflammatory markers (white blood cells [WBC] and platelet counts, CRP) were compared between the different groups. Results: CRP on post-operative days 2–4 was significantly higher in patients with than without complications (124 mg/L vs 46 mg/L; p < 0.0001) and higher in those with more major complications (162 mg/L vs 80 mg/L; p < 0.0012). WBC and platelet counts showed no difference within 5 days postoperatively. Conclusion: CRP levels, and kinetics mainly, between post-operative day 2 and 4, are decisive predictive markers of early and late post-operative complications after CRS plus HIPEC. The presence of post-operative complications should be suspected in patients with a high CRP mean, and a plateau level (days 2–4)., SCOPUS: ar.j, info:eu-repo/semantics/published

info:eu-repo/semantics/published

Oesophageal cancer (OEC) is an aggressive disease with a poor survival rate. Prognostic markers are thus urgently needed. Due to the demonstrated prognostic value of histopathological growth pattern (HGP) in other cancers, we performed a retrospective assessment of HGP in patients suffering from invasive OEC., info:eu-repo/semantics/published

TPS226 Background: Despite recent improvements, management of locally advanced rectal cancer (LARC) remains challenging, and many patients (pts) still experience recurrence. In preclinical models, combining Rego with an anti-PD-1 inhibitor led to superior tumour growth suppression as compared with either treatment alone. In a phase I clinical trial, remarkable results were reported for the combination of Rego and Nivo in advanced MSS colorectal cancer. This synergistic effect is thought to be secondary to the anti-angiogenic effects of Rego and its potential to reduce TAMs, promote M1 macrophage conversion, and down-regulate expression of immunosuppressive factors. Building on these data, we designed a trial of Rego-Nivo with standard SCRT in the neoadjuvant setting of RC. Methods: REGINA is an academic, multicentre, single-arm, phase II trial sponsored by Institut Jules Bordet. Eligible patients are treated according to the following plan: induction phase (Nivo 240 mg IV D1&15, and Rego 80 mg PO D1-14), SCRT (D22-26), consolidation phase (Nivo 240 mg IV D29,43&57, and Rego 80 mg PO D29-49), and surgery (7-8 weeks after SCRT). Key eligibility criteria include age ≥18 years, ECOG PS ≤1, adenocarcinomas below the peritoneal reflection, intermediate-risk, stage II-III tumour (ie, cT3/T4aNany or cT1-2N+, no involvement/threatening of the mesorectal fascia, no involvement of lateral pelvic lymph nodes) irrespective of microsatellite instability status. The primary endpoint is pathological complete response (pCR). Secondary endpoints include, among others, toxicity, compliance to treatment, pathological tumour regression grade, event-free survival, and overall survival. Subjects will be followed for recurrence and survival for 5 years after end of treatment visit. The study follows a Simon’s two-stage design (null hypothesis pCR = 12%, alternative hypothesis pCR = 24%; α= 5%, β= 20%) with a maximum of 60 pts to be enrolled. A safety interim analysis is planned after the first 6 pts have completed treatment. Serial collection of tumour, blood, and stool samples is mandatory at pre-specified time points for exploratory correlative biomarker analyses. The trial is planned to be run at 8-10 centres across Belgium. Study recruitment started in Q1 2021 and is anticipated to complete in Q3 2023. The study is funded by Bayer. Clinical trial information: NCT04503694.

Introduction: Decision making in refractory colorectal cancer (rCRC) is challenging, with limited data available to predict patient outcome. We conducted a study to assess the pace of cancer progression as a potential prognostic and decision tool. Methods: CORIOLAN was a prospective, single-center, single-arm trial recruiting refractory CRC patients with an ECOG performance status of &le, 1 and an estimated life expectancy of &ge, 12 weeks. 18 fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) scan and blood sample collection were carried out at baseline and after 2 weeks with no cancer treatment given between these timepoints. The primary objective was to evaluate the association between pace of cancer progression as defined by changes of the whole-body metabolically active tumor volume (WB-MATV) and overall survival (OS). Exploratory objectives included evaluation of the prognostic value of circulating cell-free DNA (cfDNA), circulating tumor cells (CTCs) and carcinoembryonic antigen (CEA). Results: 47 eligible patients who had received a median number of 5 (range 2&ndash, 8) prior treatments were enrolled. At the time of analysis, 45 deaths had occurred, with 26% of patients dying within 12 weeks. The median OS was 6.3 months (range 0.4&ndash, 14.3). The median relative delta between WB-MATV at baseline and 2 weeks was +21%. Changes of WB-MATV, however, failed to predict OS (hazard ratio (HR) 1.3, p = 0.383). Similarly, no association was observed between changes of any of the circulating biomarkers investigated and prognosis. By contrast, high WB-MATV (4.2 versus 9.4 months, HR 3.1, p = 0.003), high CEA (4.4 versus 7.0 months, HR 1.9, p = 0.053), high cfDNA (4.7 versus 7.0 months, HR 2.2, p = 0.015) and high CTC count (3.3 versus 7.5 months, HR 6.5, p &lt, 0.001) at baseline were associated with worse OS. Conclusions: In this study, approximately 1 out of 4 refractory CRC patients who were judged to have a life expectancy &gt, 12 weeks actually died within 12 weeks. Baseline assessment of WB-MATV, cfDNA, CTCs and CEA, but not early change evaluation of the same, may help to refine patient prognostication and guide management decisions.

ObjectivesAlthough systemic chemotherapy is often administered to patients with malignant bowel obstruction (MBO), its benefit remains unknown. This study assessed the outcomes of patients who received systemic chemotherapy as part of MBO treatment.MethodsFor this retrospective cohort study, data were extracted from records of patients hospitalised due to MBO in a tertiary cancer centre from 2008 to 2020. Eligible patients were not candidates for surgery and received systemic chemotherapy targeting the underlying malignancy causing MBO. Primary objective was to assess patient outcomes after chemotherapy; secondary objectives were rates of intestinal function recovery, hospital discharge and grade ≥3 toxicities. The primary endpoint was overall survival (OS).ResultsA total of 167 patients were included: median age was 55 (18–81) years, 91% had an Eastern Cooperative Oncology Group (ECOG) performance status ≥2, 75.5% had gastrointestinal tumours and 70% were treatment-naive. The median OS after chemotherapy was 4.4 weeks (95% CI 3.4 to 5.5) in the overall population. No OS difference was observed according to treatment line (p=0.24) or primary tumour (p=0.13). Intestinal function recovery occurred in 87 patients (52%), out of whom 21 (24.1%) had a reobstruction. Hospital discharge was possible in 74 patients (44.3%). Grade≥3 adverse events occurred in 26.9% of the patients, and a total of 12 deaths (7%) attributed to toxicities were observed after chemotherapy.ConclusionsMBO was associated with a dismal prognosis in this mostly treatment-naive population. The administration of chemotherapy yielded a significant risk of toxicities, whereas it did not appear to provide any relevant survival benefit in this scenario.

High-throughput sequencing technologies are increasingly used in research but limited data are available on the feasibility and value of these when routinely adopted in clinical practice.We analyzed all consecutive cancer patients for whom genomic testing by a 48-gene next-generation sequencing (NGS) panel (Truseq Amplicon Cancer Panel, Illumina) was requested as part of standard care in one of the largest Belgian cancer networks between 2014 and 2019. Feasibility of NGS was assessed in all study patients, while the impact of NGS on the decision making was analyzed in the group of gastrointestinal cancer patients.Tumor samples from 1064 patients with varying tumor types were tested, the number of NGS requests increasing over time (Our findings confirm that NGS is feasible in the clinical setting with acceptably low failure rates and rapid turnaround time. In gastrointestinal cancers, however, NGS-based multiple-gene testing adds very little to standard targeted sequencing, and in routine practice the clinical impact of NGS panels including genes which are not routinely recommended by international guidelines remains limited.

Pancreatic ductal adenocarcinoma (PDAC) remains one of the most aggressive solid tumours with an estimated 5-year overall survival rate of 7% for all stages combined. In this highly resistant disease that is located in the vicinity of many radiosensitive organs, the role of radiotherapy (RT) and indications for its use in this setting have been debated for a long time and are still under investigation. Although a survival benefit has yet to be clearly demonstrated for RT, it is the only technique, other than surgery, that has been demonstrated to lead to local control improvement. The adjuvant approach is now strongly challenged by neoadjuvant treatments that could spare patients with rapidly progressive systemic disease from unnecessary surgery and may increase free margin (R0) resection rates for those eligible for surgery. Recently developed dose-escalated RT treatments, designed either to maintain full-dose chemotherapy or to deliver a high biologically effective dose, particularly to areas of contact between the tumour and blood vessels, such as hypofractionated ablative RT (HFA-RT) or stereotactic body RT (SBRT), are progressively changing the treatment landscape. These modern strategies are currently being tested in prospective clinical trials with encouraging preliminary results, paving the way for more effective treatment combinations using novel targeted therapies. This review summarizes the current literature regarding the use of RT for the treatment of primary PDAC, describes the limitations of conventional RT, and discusses the emerging role of dose-escalated RT and heavy-particle RT., SCOPUS: re.j, info:eu-repo/semantics/published

Background: The benefit of surgery in patients with non-colorectal non-neuroendocrine liver metastases (NCRNNELM) remains controversial. At the population level, several statistical prognostic factors and scores have been proposed but inconsistently verified. At the patient level, no selection criteria have been demonstrated to guide individual therapeutic decision making. We aimed to evaluate potential individual selection criteria to predict the benefit of surgery in patients undergoing treatment for NCRNNELM. Methods: Data for 114 patients undergoing surgery for NCRNNELM were reviewed. In this population, we identified an early relapse group (ER), defined as patients with unresectable recurrence < 1 year postoperatively who did not benefit from surgery (N = 28), and a long-term survival group (LTS), defined as patients who were recurrence-free ≥ 5 years postoperatively and benefited from surgery (N = 20). Clinicopathologic parameters, the Association Française de Chirurgie (AFC) score, and a modified 4-point Clinical Risk Score (mCRS) (excluding CEA level) were analyzed and compared between LTS and ER groups. Results: The majority of patients were female and a majority had an ASA score ≤ 2 at the time of liver surgery. The median age was 55 years. Almost half of the patients (46%) presented with a single-liver metastasis. Intermediate- and low-risk AFC scores represented 40% and 60% of the population, respectively. Five- and 10-year overall survival (OS) and disease-free survival (DFS) rates were 56% and 27%, and 30% and 12%, respectively. Negative prognostic factors were the size of liver metastases > 50 mm and delay between primary and NCRNNELM, SCOPUS: ar.j, info:eu-repo/semantics/published

Background: In the phase 2 CheckMate 142 trial, NIVO + low-dose IPI had robust, durable clinical benefit and was well tolerated as 1L therapy for MSI-H/dMMR mCRC (median follow-up 13.8 months [mo; range, 9–19]; Lenz et al. Ann Oncol 2018;29:LBA18). Longer follow-up is presented here. Methods: Patients (pts) with MSI-H/dMMR mCRC and no prior treatment for metastatic disease received NIVO 3 mg/kg Q2W + low-dose IPI 1 mg/kg Q6W until disease progression or discontinuation. The primary endpoint was investigator-assessed (INV) objective response rate (ORR) per RECIST v1.1. Results: In 45 pts with median follow-up of 29.0 mo, ORR (95% CI) increased to 69% (53–82) (Table) from 60% (44.3–74.3); complete response (CR) rate increased to 13% from 7%. The concordance rate of INV and blinded independent central review was 89%. Median duration of response (DOR) was not reached (Table). Median progression-free survival (PFS) and overall survival (OS) were not reached, and 24-mo rates were 74% and 79%, respectively (Table). Nineteen pts discontinued study treatment without subsequent therapy. An analysis of tumor response post discontinuation will be presented. Ten (22%) pts had grade 3–4 treatment-related adverse events (TRAEs); 3 (7%) had grade 3–4 TRAEs leading to discontinuation. Conclusions: NIVO + low-dose IPI continued to show robust, durable clinical benefit with a deepening of response, and was well tolerated with no new safety signals identified with longer follow-up. NIVO + low-dose IPI may represent a new 1L therapy option for pts with MSI-H/dMMR mCRC.

Background Although data from preclinical and clinical studies provide a strong rationale for combining capecitabine with anti-angiogenic agents, clinical development of this fluoropyrimidine in combination with aflibercept has lagged behind other treatments. We conducted a nonrandomized, noncomparative, 2-arm, phase I trial to address this unmet need. Patients and Methods Patients with chemorefractory gastrointestinal and breast cancer were sequentially recruited into a continuous (Arm A, starting dose 1100 mg/m2/day) or intermittent (Arm B, 2 weeks on/1 week off, starting dose 1700 mg/m2/day) capecitabine dosing arm. Aflibercept was administered at a flat dose of 6 mg/kg every 3 weeks in both arms. A classical 3 + 3, dose-escalation design was used. The primary objective was to establish the maximum tolerated dose, dose-limiting toxicities (DLTs), and recommended dose for phase II trials. Results Thirty-eight eligible patients were recruited of whom 33 were assessable for DLTs (15 in arm A and 18 in arm B). Fourteen had colorectal cancer, 8 gastric cancer, and 11 breast cancer. DLTs included grade 2 hand-foot syndrome, grade 2 anorexia considered unacceptable by the patient, and grade 3 hypertension. The recommended dose for phase II trials for capecitabine was established at 1300 mg/m2/day in Arm A and 2500 mg/m2/day in Arm B with treatment-related grade ≥ 3 adverse events occurring in 47% and 50% of patients, respectively. Among 26 assessable patients, the objective response rate was 15.4% in Arm A and 7.7% in Arm B. Conclusion Combining capecitabine with aflibercept is feasible and associated with a manageable safety profile and some anti-tumor activity in patients with chemorefractory gastrointestinal and breast cancer.

Background & aims: While long-term obesity is a well-known risk factor for esophageal adenocarcinoma (ADC), recent weight loss represents a significant concern in esophageal cancer (EC), in relation with dysphagia and disease aggressiveness. These phenomenons may diversely impact the adipose tissue density, suggested in other cancer settings as an important prognostic biomarker. The analysis of body mass composition (BMC) parameters, including adipose tissue attenuation is studied here in a population of EC operated with curative intent. Methods: BMC was retrospectively evaluated on Computed-Tomography (CT)-scan images from fluorodeoxyglucose (FDG)-positron-emitting (PET)/CT scans performed as a diagnostic procedure in a cohort of 145 EC patients operated with curative intent The mean subcutaneous (SFD) and visceral fat (VFD) density along with the index (area/height2) (SF index (SFI), VF index (VFI)) were assessed on two adjacent slides at the third lumbar vertebra level by two independent investigators. Overall survival (OS) was calculated from the date of the baseline FDG-PET/CT scan. Results: Inter-observer correlations are excellent for all BMC parameters (r = 0.94–0.99). As expected, weight loss is associated with worse outcome. We show that low SFD (HR 0.5 (95% CI: 0.3–0.7), p < 0.001) and low VFD (HR 0.6 (95% CI: 0.4–0.9), p = 0.04) at diagnosis are associated with better OS. In contrast, body mass index (BMI) fails to show any relevance in predicting survival. Conclusions: Adipose tissue density is an important prognostic factor in EC., SCOPUS: ar.j, info:eu-repo/semantics/published

11 Background: In the phase 2 CheckMate 142 trial, nivolumab plus low-dose ipilimumab provided robust and durable clinical benefit and was well tolerated as first-line therapy for microsatellite instability-high/DNA mismatch repair deficient (MSI-H/dMMR) metastatic colorectal cancer (mCRC) (Lenz et al. Ann Oncol 2018;29:LBA18). Longer follow-up data will be presented. Methods: Patients with MSI-H/dMMR mCRC and no prior treatment for metastatic disease received nivolumab 3 mg/kg every 2 weeks plus low-dose ipilimumab 1 mg/kg every 6 weeks until disease progression or discontinuation. The primary endpoint was investigator-assessed objective response rate (ORR). Results: For all 45 patients (median follow-up was 13.8 months), ORR was 60% (95% CI 44.3–74.3). Responses were consistent with the overall population across subgroups including age, Eastern Cooperative Oncology Group (ECOG) performance status, prior adjuvant/neoadjuvant therapy, and mutation status (Table). Seven patients (16%) had grade 3–4 treatment-related adverse events; 3 (7%) had any grade treatment-related adverse events leading to discontinuation. Updated response, survival, and safety data after a longer follow-up (median 19.9 months) will be presented. Conclusions: Nivolumab plus low-dose ipilimumab demonstrated robust and durable clinical benefit and was well tolerated. Evaluated subgroups had responses consistent with the overall population. Nivolumab plus low-dose ipilimumab may represent a new first-line treatment option for patients with MSI-H/dMMR mCRC. Clinical trial information: NCT02060188. [Table: see text]