Support Through Remote Observation and Nutrition Guidance (STRONG), a digital health intervention to reduce malnutrition among pancreatic cancer patients: A study protocol for a pilot randomized controlled trial.

Background: Malnutrition is a common and distressing condition among pancreatic cancer patients. Fewer than a quarter of pancreatic cancer patients receive medical nutrition therapy (MNT), important for improving nutritional status, weight maintenance, quality of life and survival. System, provider, and patient level barriers limit access to MNT. We propose to examine the feasibility of a 12-week multi-level, digital health intervention designed to expand MNT access among pancreatic cancer patients. Methods: Individuals with advanced pancreatic cancer starting chemotherapy (N = 80) will be 1:1 randomized to the intervention or usual care. The Support Through Remote Observation and Nutrition Guidance (STRONG) intervention includes system-level (e.g., routine malnutrition and screening), provider-level (e.g., dietitian training and web-based dashboard), and patient-level strategies (e.g., individualized nutrition plan, self-monitoring of dietary intake via Fitbit, ongoing goal monitoring and feedback). Individuals receiving usual care will be referred to dietitians based on their oncologists' discretion. Study assessments will be completed at baseline, 4-, 8-, 12-, and 16-weeks. Results: Primary outcomes will be feasibility (e.g., recruitment, retention, assessment completion) and acceptability. We will collect additional implementation outcomes, such as intervention adherence, perceived usability, and feedback on intervention quality via an exit interview. We will collect preliminary data on outcomes that may be associated with the intervention including malnutrition, quality of life, treatment outcomes, and survival. Conclusion: This study will advance our knowledge on the feasibility of a digital health intervention to reduce malnutrition among individuals with advanced pancreatic cancer. Trial registration: NCT05675059, registered on December 9, 2022.

Efficacy and safety of Zolbetuximab plus chemotherapy for advanced CLDN18.2-positive gastric or gastro-oesophageal adenocarcinoma: a meta-analysis of randomized clinical trials.

BACKGROUND: The benefit of adding Zolbetuximab to the treatment in patients with Claudin-18 isoform 2 (CLDN18.2)-positive, human epidermal growth factor receptor 2-negative, locally advanced unresectable or metastatic gastric or gastro-oesophageal junction adenocarcinoma (GC/GEJ) is not yet fully elucidated. METHODS: We searched PubMed, Embase and Cochrane databases for randomized controlled trials (RCTs) that investigated Zolbetuximab plus chemotherapy versus chemotherapy alone for GC or GEJ adenocarcinoma. We computed hazard-ratios (HRs) or odds-ratios (ORs) for binary endpoints, with 95% confidence intervals (CIs). RESULTS: Three studies and 1,233 patients were included. Comparing with Zolbetuximab plus chemotherapy versus chemotherapy alone, progression-free survival (PFS) rate (HR 0.64; 95% CI 0.49-0.84; p < 0.01) and overall survival (OS) rate (HR 0.72; 95% CI 0.62-0.83; p < 0.01) were significant in favor of the Zolbetuximab group. Regarding effectiveness, the Objective Response Rate (ORR) was (OR 1.15; 95% CI 0.87-1.53; p = 0.34). CONCLUSIONS: In this comprehensive systematic review and meta-analysis of RCTs, the incorporation of Zolbetuximab alongside chemotherapy offers a promising prospect for reshaping the established treatment paradigms for patients diagnosed with advanced CLDN18.2-positive GC/GEJ cancer.

Prognostic Impact of Primary Tumor Sidedness in Stage III Colorectal Cancer: Real-World Evidence from a Brazilian Cohort.

BACKGROUND: Primary tumor sidedness (PTS) is an independent prognostic factor in patients with metastatic colorectal cancer (CRC), with a worse prognosis for right-sided tumors. There are limited data on the prognostic impact of PTS in stage III CRC. The main objective of this study was to analyze the prognostic impact of PTS in stage III CRC. PATIENTS AND METHODS: A retrospective and uni-institutional cohort study was performed in an oncology reference center. Patients with stage III CRC treated with a 5-fluorouracil and oxaliplatin-based chemotherapy regimen (mFLOX regimen) from October 2007 to February 2013 were included. The primary outcome was the probability of overall survival (OS) at 5 years stratified by PTS. Secondary outcomes were the probability of disease-free survival (DFS) at 5 years and an analysis of the prognostic impact of clinical and molecular biomarkers. Kaplan‒Meier curves were used, and Cox models were used to evaluate prognostic factors associated with OS and DFS. RESULTS: Overall, 265 patients were evaluated. Transverse colon tumors, multicentric tumors, and undetermined primary subsites were excluded, resulting in 234 patients classified according to PTS: 95 with right sidedness (40.6%) and 139 with left sidedness (59.4%). The median follow-up time was 66 months [interquartile range (IQR): 39-81]. The 5-year OS probabilities for right-sided and left-sided tumors were 67% (95% CI: 58%-77%) and 82% (75%-89%), respectively [hazard ratio (HR): 2.02, 95% CI: 1.18-3.46; P = .010]. The 5-year probabilities of DFS for right-sided and left-sided tumors were 58% (49%-69%) and 65% (58%-74%), respectively (HR: 1.29, 0.84-1.97; P = 0.248). CONCLUSION: These data suggest that there may be a worse prognosis (inferior OS at 5 years) for resected right-sided stage III CRC patients treated in the real world. However, these data need to be confirmed by prospective studies with a larger number of participants.

A multi-center retrospective study on the efficacy and safety of regorafenib vs. regorafenib combined with PD-1 inhibitors as a second-line therapy in patients with advanced hepatocellular carcinoma.

Background: At present, there are no definitive optimal treatment options for patients with hepatocellular carcinoma (HCC) following first-line treatment failure. To maximize the survival benefit of patients, we compared the combination therapy of regorafenib and programmed death-1 (PD-1) inhibitors with regorafenib monotherapy as a second-line treatment for patients with advanced HCC. Methods: Our multicenter retrospective study evaluated consecutive patients with advanced HCC who received regorafenib plus PD-1 inhibitors or regorafenib alone as a later-line therapy from May 2019 to January 2022. The primary endpoint was progression-free survival (PFS), and the secondary endpoints included the objective response rate (ORR), disease control rate (DCR), overall survival (OS), and safety. Efficacy was evaluated using the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria, and safety was assessed by Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Results: A total of 133 patients were included in the study (regardless of first-line treatment), including 94 who received regorafenib plus PD-1 inhibitors and 39 who received regorafenib. The regorafenib plus PD-1 inhibitors group had a significantly higher ORR (25.53% vs. 10.26%, P=0.015), higher DCR (87.23% vs. 66.67%, P=0.006), and longer PFS (median 9.0 vs. 4.0 months, P<0.0001) than the regorafenib group. Meanwhile, the median OS (mOS) did not differ between the regorafenib plus PD-1 and regorafenib monotherapy groups {mOS, 14.0 months [95% confidence interval (CI), 14.0-16.0 months] vs. 12.0 months (95% CI, 10.0-22.0 months)}. There was no notable difference in the total incidence of treatment-related adverse effects (TRAEs) (71.79% vs. 78.72%, P=0.39) and the incidence of grade 3/4 serious adverse effects (5.13% vs. 18.09%, P=0.19) between the regorafenib monotherapy group and PD-1 inhibitors combination group. Conclusions: Compared with regorafenib alone, regorafenib combined with PD-1 inhibitors therapy increased PFS, ORR but did not improve OS, and can be used an option in second-line HCC therapy, regardless of first-line treatments. Regorafenib combined with PD-1 inhibitors is recommended as early as a second-line therapy to benefit patients. The combination regimen was as safe as regorafenib monotherapy for treatment of HCC in patients with compensated liver disease [Child-Turcotte-Pugh (CTP) A/B].

Advances in MRI-Based Assessment of Rectal Cancer Post-Neoadjuvant Therapy: A Comprehensive Review.

Rectal cancer presents significant diagnostic and therapeutic challenges, with neoadjuvant therapy playing a pivotal role in improving resectability and patient outcomes. MRI serves as a critical tool in assessing treatment response. However, differentiating viable tumor tissue from therapy-induced changes on MRI remains a complex task. In this comprehensive review, we explore treatment options for rectal cancer based on resectability status, focusing on the role of MRI in guiding therapeutic decisions. We delve into the nuances of MRI-based evaluation of treatment response following neoadjuvant therapy, paying particular attention to emerging techniques like radiomics. Drawing from our insights based on the literature, we provide essential recommendations for post-neoadjuvant therapy management of rectal cancer, all within the context of MRI-based findings.

Tremelimumab and durvalumab in the treatment of unresectable, advanced hepatocellular carcinoma.

Liver cancer is the third most common cause of cancer-related mortality worldwide, with over 780,000 deaths in 2018. About 90% of liver cancer cases are hepatocellular carcinoma (HCC), a prototype of inflammation-driven cancer, leading to a robust rationale for the exploration of immune therapy. Previously approved agents for first-line therapy, such as sorafenib, lenvatinib and bevacizumab combined with atezolizumab, have focused on angiogenesis. HIMALAYA was the first trial to demonstrate the benefit of dual immune checkpoint inhibitors, representing a new treatment option in this scenario.

Liver cancer is the third most common cause of cancer-related mortality worldwide, with over 780,000 deaths in 2018. About 90% of liver cancer cases originate in liver cells and are referred to as hepatocellular carcinoma (HCC). Systemic treatment (medications) is the mainstay for patients with advanced disease who are not suitable for resection or liver transplant and aims to improve survival and quality of life. HIMALAYA was the first study to demonstrate the benefit of using a combination of two immunotherapy medications for initial treatment.

The development and validation of a novel senescence-related long-chain non-coding RNA (lncRNA) signature that predicts prognosis and the tumor microenvironment of patients with hepatocellular carcinoma.

Background: The epigenetic regulators of cellular senescence, especially long non-coding RNAs (lncRNAs), remain unclear. The expression levels of lncRNA were previously known to be prognostic indicators for tumors. We hypothesized that lncRNAs regulating cellular senescence could also predict prognosis in patients with hepatocellular carcinoma (HCC) and developed a novel lncRNA predictive signature. Methods: Using RNA sequencing data from The Cancer Genome Atlas Liver Hepatocellular Carcinoma (TCGA-LIHC) database, a co-expression network of senescence-related messenger RNAs (mRNAs) and lncRNAs was constructed. Using univariate Cox regression analysis and a stepwise multiple Cox regression analysis, we constructed a prognostic HCC senescence-related lncRNA signature (HCCSenLncSig). Kaplan-Meier analysis was used to compare the overall survival (OS) of high- and low-risk groups stratified by the HCCSenLncSig. Furthermore, the HCCSenLncSig risk score and other clinical characteristics were included to develop an HCC prognostic nomogram. The accuracy of the model was evaluated by the time dependent receiver operating characteristic (ROC) and calibration curves, respectively. Results: We obtained a prognostic risk model consisting of 8 senescence-related lncRNAs: AL117336.3, AC103760.1, FOXD2-AS1, AC009283.1, AC026401.3, AC021491.4, AC124067.4, and RHPN1-AS1. The HCCSenLncSig high-risk group was associated with poor OS [hazard ratio (HR) =1.125, 95% confidence interval (CI): 1.082-1.169; P<0.001]. The accuracy of the model was further supported by ROC curves (the area under the curve is 0.783, sensitivity of 0.600, and specificity of 0.896 at the cut-off value of 1.447). The HCCSenLncSig was found to be an independent prognostic factor from other clinical factors in both univariate and multivariate Cox regression analyses. The prognostic nomogram shows HCCSenLncSig has a good prognostic effect for survival risk stratification. Finally, we found that a higher number of immunosuppressed Treg cells infiltrate in high-risk patients (P<0.001 compared to low-risk patients), possibly explaining why these patients have a poor prognosis. On the other hand, the expression of immunotherapy markers, such as CD276, PDCD1, and CTLA4, was also up-regulated in the high-risk patients, indicating potential immunotherapy response in these patients. Conclusions: The development of HCCSenLncSig allows us to better predict HCC patients' survival outcomes and disease risk, as well as contribute to the development of novel HCC anti-cancer therapeutic strategies.

Cytotoxic T-lymphocyte-associated protein 4 in gastric cancer: Prognosis and association with PD-L1 expression.

BACKGROUND: Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) is one of the most studied immune checkpoint in gastric cancer (GC). However, the prognostic role of CTLA-4 expression in GC is poorly described. This study aimed to evaluate CTLA-4 expression in GC and its impact on survival, including patients treated with standard platinum-based chemotherapy (CMT), and association with PD-L1 expression. METHODS: All GC patients who underwent D2-gastrectomy were investigated retrospectively. Tumor samples were examined for CTLA-4 and PD-L1 by immunohistochemistry. Tumor-infiltrating inflammatory cells, including CD4 + and CD8 + , were also examined. RESULTS: Among the 284 GC patients included, 159 (56%) were CTLA-4 positive and the remaining 125 (44%) were classified as negative. CTLA-4 positive GC was associated with increased inflammatory cell infiltration (p < 0.001), high CD8 + T cells (p = 0.016) and PD-L1 expression (p = 0.026). Considering GC referred for treatment, CTLA-4 negative patients who received CMT had a significant improvement in disease-free survival compared to untreated CLTA-4 negative (p = 0.028). In multivariate analysis, GC positive for both CTLA-4 and PD-L1 had a prognostic impact on survival. CONCLUSION: CTLA-4 positive was associated with PD-L1 expression and a high tumor-infiltrating CD8 + T cells. Accordingly, positivity for both CTLA-4 and PD-L1 was an independent factor associated to better survival in GC patients.

Scoring systems for PD-L1 expression and their prognostic impact in patients with resectable gastric cancer.

The combined positive score (CPS) and tumor proportion score (TPS) have been developed to evaluate programmed death ligand-1 (PD-L1) expression, especially due to the potential benefit of the targeted therapy. However, the prognostic value of PD-L1 scoring systems in gastric cancer (GC) remains unclear. This study aimed to evaluate PD-L1 expression according to CPS and TPS in curative resected GC patients and its correlation with prognosis. We retrospectively evaluated 284 GC patients who underwent D2-gastrectomy by tissue microarray. PD-L1 expression was analyzed by immunohistochemistry. PD-L1 positivity by CPS and TPS was observed in 45 (15.8%) and 34 (12%) patients, respectively. Larger tumor size (p = 0.028), undetermined Lauren type (p < 0.001), and heavy inflammatory infiltrate (p = 0.009) were associated with CPS-positive GC. TPS-positive were more frequent in patients with larger tumor size (p = 0.004), undetermined type (p < 0.001), moderate/severe inflammatory infiltrate (p = 0.001), total gastrectomy (p = 0.036), and poorly differentiated histology (p = 0.025). No differences were observed in the pT, pN, and pTNM status according to the PD-L1 scores. Both scores were associated with Epstein-Barr virus positivity, microsatellite instability and p53-normal expression. The disease-free survival (DFS) was worse for CPS-negative compared to CPS-positive group (p = 0.052). No difference was observed between TPS-positive and negative groups (p = 0.436). Total gastrectomy, advanced pT status, and CPS-negative were independent factor for worse survival in GC. CPS was an independent prognostic factor for survival and could be used as a prognostic biomarker in patients with resectable GC.

Hepatoid esophagogastric adenocarcinoma and tumoral heterogeneity: a case report.

Hepatoid adenocarcinoma of the stomach is an uncommon subtype of gastric cancer remarkably similar to hepatocellular carcinoma in histopathological analysis. It is also commonly associated with high serum alfa-fetoprotein and a poorer prognosis, despite the emergence of new therapeutic options. In recent years, next generation sequencing (NGS) technology has made it possible to identify and describe the genes and molecular alterations common to gastric cancer thereby contributing to the advancement of targeted therapies. A 62-year-old patient, with no prior risk factor for hepatocellular carcinoma (HCC), presented to the emergency room with dysphagia for solids, abdominal pain and weight loss of about 3 kilograms over 3 months. Histopathological analysis presented with disparities regarding HER2 and programmed death-ligand 1 (PD-L1) status in the primary and metastatic sites. We describe a case of a de novo metastatic, human epidermal growth factor receptor 2 (HER2) positive esophagogastric junction hepatoid adenocarcinoma. Although this is a rare subgroup of gastric cancer, treatment strategies were based in recent studies in immunotherapy and guided therapy, taking into consideration the molecular findings from the patient's tumor NGS analysis. Data about HER2 and PDL1 heterogeneity were also reviewed. Despite the aggressiveness and rarity of this histology, the patient had a good response to treatment.

RhoA, Claudin 18, and c-MET in Gastric Cancer: Clinicopathological Characteristics and Prognostic Significance in Curative Resected Patients.

Background: Recently, markers related to molecular classification were suggested as promising therapeutic targets for treatment and prediction of prognosis in gastric cancer (GC), including c-MET, RhoA, and Claudin-18 (CLDN18). This study aimed to investigate their expression in GC and its correlation with clinicopathological characteristics and survival. Methods: We retrospectively evaluated GC patients who underwent curative gastrectomy. c-MET, RhoA, and CLDN18 were analyzed through immunohistochemistry (IHC), and groups for analysis were determined according to the median values obtained for each marker. Results: Among the 349 GC evaluated, 180 (51.6%), 59 (16.9%), and 61 (17.5%) patients were completely negative for c-MET, RhoA, and CLDN18, respectively. Total gastrectomy, D1 lymphadenectomy, poorly differentiated histology, and greater inflammatory infiltrate were more frequent in the c-MET-negative group. Diffuse type, greater inflammatory infiltrate, and advanced pT and pTNM stage were associated with low-RhoA GC. The venous invasion was more frequent in the low-CLDN18 group. Furthermore, c-MET was positively correlated with RhoA and negatively with CLDN18. HER2 expression was associated with c-MET-positive and high-CLDN18 GC; and loss of E-cadherin expression in c-MET-negative and low-RhoA GC. c-MET-negative and Low-RhoA were significantly associated with worse disease-free survival. Conclusions: c-MET, RhoA, and CLD18 expression occurred frequently in GC. RhoA GC had distinct clinicopathological characteristics related to prognosis. c-MET and RhoA were associated with survival but were not independent predictors of prognosis.

Remnant gastric cancer: a neglected group with high potential for immunotherapy.

PURPOSE: The importance of targeted therapy and interest in the study of predictive markers in gastric cancer (GC) have increased in recent years with the use of anti-HER2 therapy and immunotherapy with anti-PD1/PD-L1 for microsatellite instability (MSI) and PD-L1 + tumors. However, the behavior of remnant GC (RGC) in this scenario is poorly reported. Thus, this study aims to evaluate the clinicopathological characteristics and prognosis of RGC and its association with the expression of current markers for targeted therapy. METHODS: All RGC resections performed in a single center from 2009 to 2019 were retrospectively reviewed. As a comparison group, 53 primary proximal GC (PGC) who underwent total D2-gastrectomy were selected. HER2, MSI status and PD-L1 expression were analyzed by immunohistochemistry. Combined Positive Score (CPS) was used to determine PD-L1 positivity. RESULTS: A total of 40 RGC were included. RGC patients were older (p = 0.001), had lower BMI (p = 0.001) and number of resected lymph nodes (p < 0.001) compared to the PGC. Regarding markers expression, MSI was higher in RGC than PGC (27.5% vs 9.4%, p = 0.022). The frequency of CPS-positive was 32.5% and 26.4% in RGC and PGC, respectively (p = 0.522). HER2 positivity was 17.5% and 22.6% for RGC and PGC, respectively (p = 0.543). In survival analysis, DFS was better for RGC CPS-positive than RGC CPS-negative (p = 0.039) patients. There was no difference in survival considering MSI status. CONCLUSION: RGC had higher incidence of MSI than PGC, and CPS-positive RGC was associated with better survival. The immunological profile of RGC patients suggests that they would be good candidates for immunotherapy.

Impact of neoadjuvant chemotherapy on surgical and pathological results of gastric cancer patients: A case-control study.

BACKGROUND AND OBJECTIVE: Neoadjuvant chemotherapy (NACT) followed by radical surgery represents a treatment option for patients with advanced gastric cancer (GC). This case-control study aimed to evaluate the clinicopathological characteristics and surgical outcomes of GC patients who received NACT, and its impact on survival. METHODS: We retrospectively reviewed all patients with GC who underwent gastrectomy. A total of 45 cases with NACT were matched with consecutive 45 patients who underwent upfront gastrectomy for the following characteristics: gender, age, gastrectomy type, lymphadenectomy extent, American Society of Anesthesiologists class, histological type, cT and cN. RESULTS: NACT group had smaller tumors (4.9 vs 6.8 cm P = .006), lower lymphatic invasion rate (40% vs 73.3%, P = .001), lower venous invasion rate (18% vs 46.7%, P = .003) and lower perineural invasion rate (35% vs 77.8%, P < .0001). The ypTNM stage was lower in patients treated with NACT (P < .001). The major postoperative complication (POC) rate was lower in NACT patients (6.7% vs 24.4%, P = .02), as was hospital length of stay (10.8 vs 17 days, P = .005). CONCLUSIONS: NACT allowed nodal and tumor downstaging. In addition, patients who underwent NACT had fewer POC and shorter length of hospital stay.

Induction Chemotherapy for Locally Advanced Esophageal Cancer.

BACKGROUND: Concurrent chemoradiotherapy followed by surgery is the standard treatment for locally advanced esophageal cancer (EC), and the role of induction chemotherapy (IC) remains unclear. We aimed to study if the addition of IC to standard treatment increases the rate of pathologic complete response (pCR). METHODS: We assembled a retrospective analysis of patients (pts) diagnosed with locally advanced EC and treated with preoperative chemoradiotherapy followed by esophagectomy (CRT+S), preceded or not by IC, between 2009 and 2017. Patients' characteristics, tumor variables, and treatment outcomes were evaluated. The Kaplan-Meier method was used to estimate overall survival and the Cox proportional hazard model to evaluate prognostic factors. RESULTS: One hundred and three patients were studied, with a median age of 62 years (range 37-84). Seventy-five patients (73%) were male, 67 (65%) had squamous cell carcinoma, and 31 (30%) had adenocarcinoma. Forty-three patients (41.7%) received IC followed by CRT+S (IC+CRT+S). The most frequent IC consisted of paclitaxel and platinum chemotherapy (90%), and the median number of cycles was 2. All patients received CRT+S. Concurrent chemotherapy was a combination of paclitaxel and platinum in 94 patients (91%). There was no statistically significant difference in pCR between the IC group and the standard CRT+S group. The pCR was 41.9% and 46.7% in the IC+CRT+S and CRT+S groups (p = 0.628), respectively. In the multivariate analysis, pCR was an independent prognostic factor for time to treatment failure (TTF) (HR 0.35, p = 0.021), but not for overall survival (OS) (p = 0.863). The factor that significantly affected OS in the multivariate analysis was positive lymph node (HR 5.9, 95%, p = 0.026). CONCLUSIONS: Our data suggest that the addition of IC to standard CRT + S does not increase the pCR rate in locally advanced EC. No difference in OS was observed between pts. that received or not IC. Regardless of the treatment received, pts. achieving a pCR presented improved TTF.

Lymph node regression after neoadjuvant chemotherapy: A predictor of survival in gastric cancer.

BACKGROUND AND OBJECTIVE: Neoadjuvant chemotherapy (nCMT) has been increasingly used in advanced gastric cancer (GC). However, the prognostic impact of tumor response remains unclear. This study aimed to evaluate if tumor response at the primary site and lymph nodes (LN) correlate with survival in GC patients after nCMT. METHODS: Patients with gastric adenocarcinoma treated with nCMT followed by gastrectomy were evaluated. Residual tumor was graded from 0% to 100%, defining two groups: poor (PR) and major response (MR). LN regression rate (LNRR) was determined based on tumor/fibrosis examination at each LN and a cutoff value established by receiver operating characteristic curve. RESULTS: Among 62 cases, 20 (32.2%) had MR and 42 (67.7%) PR. Smaller size, diffuse histology, lower ypT status and less advanced stage were associated with the MR group. Based on cutoff value of 57, 45.6% and 54.4% patients were classified as low-LNRR and high-LNRR. High-LNRR correlated with absence of venous, lymphatic and perineural invasion, and less advanced stage. Survival was equivalent between MR and PR (P = .956). High-LNRR had better disease-free survival (DFS) than low-LNRR (P < .001). In multivariate analysis, only LNRR associated with DFS. CONCLUSION: High-LNRR associates with DFS in GC treated with nCMT. Response at the primary site does not correlate with survival.

Return to Intended Oncologic Treatment (RIOT) in Resected Gastric Cancer Patients.

BACKGROUND: Postoperative chemotherapy (CMT) or chemoradiotherapy (CRT) is commonly recommended for gastric cancer (GC) patients in order to improve survival. However, some factors that prevent patients from return to intended oncologic treatment (RIOT) may increase the risk of recurrence and decrease the survival benefits achieved with curative resection. The aim of this study was to determine the frequency and factors associated with inability to RIOT and their impact on survival. METHODS: This retrospective study included stage II/III GC patients treated with potentially curative gastrectomy. Patients who could return to intended oncologic treatment (RIOT group) and those who could not (inability to RIOT group) were analyzed. RESULTS: Of the 313 eligible GC patients, 89 (28.4%) and 85 (27.2%) patients receive CRT and CMT, respectively, representing a RIOT rate of 55.6%. The main reason was attributed to general poor performance status (30.2%), followed by surgical postoperative complications (POC) (20.1%). Older age, higher ASA, D1 lymphadenectomy, and major POC were related to inability to RIOT. Older age, neutrophil-lymphocyte ratio (NLR), and major POC were independent risk factors for inability to RIOT. Five-year DFS and OS were worse for the inability to RIOT group than for the RIOT group (p = 0.008 and p = 0.004, respectively). In multivariate analyses, absence of neoadjuvant therapy, total gastrectomy, pT3/T4, pN+, and inability to RIOT were associated with worse DFS. Type of gastrectomy, lymphadenectomy, pN status, Rx resection, and RIOT group were associated with OS. CONCLUSION: Older age, high NLR, and major POC were risk factors for inability to RIOT. RIOT was an independent predictor of survival.

Expression Profile of Markers for Targeted Therapy in Gastric Cancer Patients: HER-2, Microsatellite Instability and PD-L1.

BACKGROUND: The assessment of human epidermal growth factor receptor 2 (HER2), microsatellite instability (MSI) and programmed cell death-ligand 1 (PD-L1) expression is relevant for the selection and effectiveness of targeted therapy in gastric cancer (GC). OBJECTIVE: We aimed to investigate the clinicopathological characteristics and prognosis of GC patients according to these profiles. METHODS: GC patients who underwent gastrectomy with D2 lymphadenectomy were eligible. HER2, MSI status and PD-L1 expression were analyzed by immunohistochemistry (IHC). Patients were grouped as follows: HER2+ group, immunotherapy (IT) group (MSI and/or PD-L1+), and non-targeted therapy (NTT) group (stable microsatellite and HER2/PD-L1-). RESULTS: Among 282 patients, 50 (17.7%) were HER2+ and 79 (28%) MSI/PD-L1+. Fifteen had HER2+ and MSI/PD-L1+, while 168 (59.6%) were in the NTT group. HER2+ GCs were related to male gender (p = 0.007), intestinal type (p = 0.001) and less advanced pTNM stage (p = 0.029). Older age (p = 0.003), subtotal gastrectomy (p = 0.025), intestinal type (p = 0.008), pN0 status (p = 0.002) and less advanced pTNM stage (p = 0.001) were associated with the IT group. IT GC had better disease-free survival (DFS) and overall survival than the NTT group (p = 0.015 and p = 0.027, respectively). Concerning patients eligible for the standard adjuvant therapy, the treatment impacted positively on DFS for HER2+ and NTT groups (p = 0.003 and p = 0.042, respectively). No difference in DFS was seen between IT patients who received perioperative/adjuvant therapy and those treated only with surgery (p = 0.160). CONCLUSIONS: GC patients who exhibited markers that can serve as an indication for known targeted therapy represent 40.4% of cases. The IT group was associated with a better prognosis. No benefit with standard adjuvant treatment appears to be achieved in MSI/PD-L1+ GCs.

Safety and Effectiveness of Chemotherapy for Metastatic Esophageal Cancer in a Community Hospital in Brazil.

PURPOSE: Despite epidemiologic and molecular differences between esophageal and stomach cancers, most published studies have included patients with either disease in a metastatic scenario. We evaluated the safety and effectiveness of chemotherapy in patients with metastatic esophageal cancer in the community setting. PATIENTS AND METHODS: We performed a retrospective cohort study of patients with synchronous metastatic esophageal cancer treated at a public hospital between 2008 and 2016. Patients were grouped according to a prescribed chemotherapy protocol: platinum and taxane (group A); platinum and irinotecan (group B); platinum and fluoropyrimidine (group C); and without platinum (group D). RESULTS: Of the 1,789 patients with esophageal cancer treated, we included 397 with metastatic disease at presentation. Squamous cell carcinoma was the most frequent histology (78.8%). Median overall survival (OS) was 7 months (95% CI, 6.15 to 7.85 months). Chemotherapy was administered to 285 patients, who reached a median OS of 9.0 months (95% CI, 8.0 to 9.9 months); for 112 patients who did not receive treatment, median OS was 3 months (95% CI, 2.3 to 3.7 months; P < .001). The most used combination was platinum plus irinotecan (A; 55.5%). Disease control with in groups A, B, C, and D was 39.2%, 30.1%, 53% and 14.3%, respectively. Patients in group C reached a median OS of 17 months (95% CI, 13.1 to 20.8 months; P = .034). No differences were observed in median OS obtained with other protocols (9 months). The toxicity profile was different according to chemotherapy, with more severe events (hematologic, diarrhea, and number of days hospitalized) occurring in group B. CONCLUSION: Platinum plus paclitaxel or platinum plus irinotecan provided similar OS in community patients, although patients receiving irinotecan experienced more severe events. In the adenocarcinoma population, a fluoropyrimidine plus platinum-based regimen, although less frequently used, had a more favorable toxicity profile, with superior median OS and disease control.