PURPOSE:This study aimed to evaluate the locoregional control in patients with early-stage natural killer/T-cell lymphoma (NKTCL) treated with sandwich chemoradiation therapy. METHODS AND MATERIALS:We performed a post hoc analysis of 87 consecutive patients with early-stage NKTCL enrolled in a prospective, multicenter, randomized phase 3 trial. All participants received standardized treatment comprising 4 cycles of asparaginase-based chemotherapy with integrated radiation therapy. RESULTS:With a median follow-up of 37.9 months, the 3-year survival outcomes of the cohort were overall survival (OS) 87.1%, progression-free survival 84.6%, and locoregional recurrence-free survival 90.8%. Six patients experienced locoregional recurrence, with 4 in the nasal cavity (4.6%), 4 in the nasopharynx (4.6%), and 1 in the cervical lymph node. Recurrence is typically in the radiation field (5 of 6), often in the initial high-standardized uptake value (SUV) region (4 of 6). Radiation therapy-chemotherapy interval (RCI) between 32 and 35 days was associated with improved prognosis, including OS (P = .043), progression-free survival (P = .013), and locoregional recurrence-free survival (P = .007) versus shorter RCI (21-31 days). Quantitative imaging analysis demonstrated that higher mean baseline apparent diffusion coefficient values (≥0.1125 × 10-3 mm²/s) were associated with an improved OS (95.2% vs 71.6%, P = .049). CONCLUSIONS:Asparaginase-based sandwich chemoradiation therapy shows favorable efficacy in early-stage NKTCL, with distinct locoregional recurrence patterns. RCI and apparent diffusion coefficient values emerge as critical prognostic factors, potentially informing treatment optimization.

BACKGROUND:CD19 chimeric antigen receptor (CAR) T-cell therapy is a potential treatment for relapsed/refractory (R/R) large B-cell lymphoma (LBCL). The combination of targeted therapeutic strategies, particularly bruton tyrosine kinase inhibitor zanubrutinib and programmed death-1 inhibitor tislelizumab, may improve clinical outcomes and modulate the tumour microenvironment (TME). METHODS:We studied patients with R/R LBCL who received response-adapted zanubrutinib plus tislelizumab upon CD19 CAR T-cell therapy between June 2021 and March 2023. Patients were treated with zanubrutinib daily from leukapheresis to day 28 post-infusion; those achieving complete response continued zanubrutinib monotherapy for 3 months, while partial responders received combined zanubrutinib for 3 months and tislelizumab for up to 2 years. We evaluated the overall response rate (ORR), complete response rate (CRR), progression-free survival (PFS), overall survival (OS), and safety. DNA sequencing and RNA sequencing were performed on available tumour samples to analyse genetic aberrations and TME characteristics. RESULTS:A total of 54 patients with LBCL were included, with a median follow-up of 23.6 months. The ORR at day 28, month 3, and month 6 were 94% (CRR 66%), 87% (CRR 80%), and 80% (CRR 76%), respectively. The 2-year PFS and 2-year OS rates were 68% and 76%, respectively. Median PFS and median OS were not reached. Grade ≥ 3 cytokine release syndrome occurred in 9% of patients, with no grade ≥ 3 neurotoxicity observed. Genomic and transcriptomic data indicated that this regimen was effective across genetic subtypes and abrogated T-cell exhaustion within the TME. However, tumour-infiltrating M2 macrophages with dysregulated lipid metabolism were associated with poor clinical outcome. CONCLUSIONS:Response-adapted zanubrutinib and tislelizumab potentially enhances the efficacy of CAR T-cell therapy with a favourable safety profile in R/R LBCL, effectively counteracting T-cell exhaustion. Future studies should focus on targeting M2 macrophages by reprogramming lipid metabolism to further attenuate the immunosuppressive TME. HIGHLIGHTS:Response-adapted zanubrutinib plus tislelizumab potentially enhances the efficacy of CAR T-cell therapy for R/R LBCL with acceptable safety profile. This regimen functions independently of genetic subtypes, rendering it more applicable for clinical practice with CAR T-cell therapy. This regimen effectively abrogates T-cell exhaustion, but fails to overcome the immunosuppressive effects of M2 macrophages, providing a rationale for remodelling TME to optimise CAR T-cell therapy.

Natural killer T cell lymphoma (NKTCL) is highly aggressive, with advanced stage patients poorly responding to intensive chemotherapy. To explore effective and safe treatment for newly diagnosed advanced stage NKTCL, we conducted a phase II study of anti-metabolic agent pegaspargase plus PD-1 antibody sintilimab (NCT04096690). Twenty-two patients with a median age of 51 years (range, 24–74) were enrolled and treated with induction treatment of pegaspargase 2500 IU/m2 intramuscularly on day 1 and sintilimab 200 mg intravenously on day 2 for 6 cycles of 21 days, followed by maintenance treatment of sintilimab 200 mg for 28 cycles of 21 days. The complete response and overall response rate after induction treatment were 59% (95%CI, 43–79%) and 68% (95%CI, 47–84%), respectively. With a median follow-up of 30 months, the 2 year progression-free and overall survival rates were 68% (95%CI, 45–83%) and 86% (95%CI, 63–95%), respectively. The most frequently grade 3/4 adverse events were neutropenia (32%, n = 7) and hypofibrinogenemia (18%, n = 4), which were manageable and led to no discontinuation of treatment. Tumor proportion score of PD-L1, peripheral blood high-density lipoprotein cholesterol, and apolipoprotein A-I correlated with good response, while PD-1 on tumor infiltrating lymphocytes and peripheral Treg cells with poor response to pegaspargase plus sintilimab treatment. In conclusion, the chemo-free regimen pegaspargase plus sintilimab was effective and safe in newly diagnosed, advanced stage NKTCL. Dysregulated lipid profile and immunosuppressive signature contributed to treatment resistance, providing an alternative therapeutic approach dual targeting fatty acid metabolism and CTLA-4 in NKTCL.

Introduction Despite the improvements in relapsed or refractory B-cell non-Hodgkin lymphoma (R/R B-NHL) therapies, more than 60% of patients (pts) with diffuse large B cell lymphoma (DLBCL) eventually progress or relapse following CD19-CAR-T therapy, especially those with a heavy tumor burden. Novel approaches are critically needed for R/R B-NHL pts. LY007 is a novel CD20-targeting CAR-T cell therapy, in which inclusion of OX40 co-stimulation for enhancing CAR proliferation, persistence and anti-tumor response, showed promising safety and efficacy in dose-escalation part of on-going phase 1 study in 9 pts with R/R B-NHL. Here, we present updated data from the finished dose-escalation and dose-expansion parts of 12 pts in the study. Methods In this phase 1 study, eligible pts with CD20-positive R/R B-NHL received lymphodepletion with fludarabine (30 mg/m2 Day -5 to -3) and cyclophosphamide (300 mg/m2 Day -5 to -3) before a single CAR-T cell infusion. Pts were allowed bridging radiotherapy, if needed, prior to lymphodepletion. LY007 was infused at doses of 0.5, 1.5, and 5.0 × 106 cells/ kg in the dose-escalation part in “3+3” module and additional pts received 5.0 × 106 cells/ kg in the dose-expansion part. The primary objectives were to determine the maximum tolerated dose and/or recommended phase 2 dose (RP2D), safety and tolerability, pharmacokinetics (PK), and preliminary clinical efficacy of LY007. Results As of June 25, 2024, 12 pts received a single infusion of LY007 at doses of 0.5 (n = 3), 1.5 (n = 4), 5.0 (n = 5) × 106 cells/ kg with a median age of 65 years (range, 37 to 69), of which 5 (42%) were ≥65 years. 10 pts (83%) had extranodal involvement, 8 pts (67%) had an International Prognostic Index (IPI) score of ≥2, 5 pts (42%) had a maximum tumor length of ≥ 5 cm, including 2 pts (17%) had a maximum tumor length of >8 cm. Among all, 5 pts (42%) had received three prior lines of therapy and 3 pts (25%) were refractory to prior lines of therapy, including 1 pt (8%) who received prior CD19-directed CAR T-cell therapy and autologous stem-cell transplantation (ASCT). Ten pts (87%) had ≥50% Ki67 expression, and 1 pts (8%) had MYC, BCL2 and/or BCL6 rearrangements. The best overall response rate (ORR) was 92% (11/12) among all enrolled study participants, with 100% (5/5) in 5.0 × 106 cells/ kg and pts aged ≥ 65 years, respectively. Best complete response (CR) rate was 67% (8/12). The ORR was 75% (9/12) at day 28 and 73% (8/11) at month 3, with 100% (5/5) and 75% (3/4) in 5.0 × 106 cells/ kg at day 28 and month 3, respectively. The CR rate was 42% (5/12) at day 28 and 55% (6/11) at month 3. Encouragingly, 1 pt treated with prior CD19-directed CAR T-cell therapy and ASCT, and 1 pt with MYC, BCL2 and/or BCL6 rearrangements achieved CR at month 3. Median duration of response (DoR), median progression-free survival (PFS) and median overall survival (OS) had not been reached with a median follow-up of 7.2 months (range, 2.8-11.6). By the data cutoff, 58% of responses (7/12) were ongoing, with 58% of responses (7/12) lasting > 3 months and 1 pt still CR at 24 months. Pts at all 3 dose levels had good CAR-T expansion and long-term persistence, especially in the DL3 cohort, with a median peak of CAR-T cells in the peripheral blood of 43,200 copies/μg (range, 25,000-173,000) DNA and a median peak time of day 11 (range 11-18 day). The highest mean cell copy number was achieved on day 11 and was still detectable at day 264 in the DL2 cohort. No dose-limiting toxicities (DLTs) were observed, no immune effector cell-associated neurotoxicity syndrome (ICANS) or Grade (G) 3+ cytokine release syndrome (CRS) was reported even with increasing dose levels. G3+ treatment-emergent adverse events (TEAEs) occurred in 12 (100%) pts without severe infectious events and G1/2 CRS occurred in 9 (75%) pts. No Grade 3+ hypogammaglobulinemia was observed and 3 pts (25%) experienced Grade 1/2 hypogammaglobulinemia related to LY007. Conclusions In this phase 1 study, LY007 was well tolerated at the dose levels up to 5.0 × 106 cells/kg with no DLTs or ICANS observed and the RP2D was recommended as 5.0 × 106 cells/kg. LY007 showed a favorable safety profile, promising efficacy and good PK characteristics at all tested dose levels with 92% best ORR including pts with a high tumor burden, such as extranodal involvement, maximum tumor length of ≥5 cm, aged ≥ 65 years and prior CD19-directed CAR T therapy and ASCT. Follow-up of enrolled pts is on-going and the planned phase 2 study will start for enrollment shortly.

This phase I/II trial (ChiCTR2000032879) assessed the safety and efficacy of toripalimab combined with chemoradiotherapy for locally advanced cervical squamous cell carcinoma. Twenty-two patients, regardless of their programmed death ligand-1 (PD-L1) status, received toripalimab combined with concurrent chemoradiotherapy (CCRT). CCRT included cisplatin (40 mg/m2, once weekly for 5 weeks), radiotherapy (45–50.4 Gy/25–28 Fx, 5 fractions weekly), followed by brachytherapy (24–30 Gy/3–5 Fx) and toripalimab (240 mg, intravenous) on days 1, 22 and 43 during CCRT. The primary endpoints were safety and 2-year progression-free survival (PFS). The secondary endpoints included 2-year local control (LC), local regional control and overall survival (OS). All patients successfully completed CCRT and toripalimab treatment. Grade III and higher adverse events (AEs) were observed in 11 patients (11/22, 50

Not all patients with glioblastoma multiforme (GBM) eligible for systemic chemotherapy after upfront surgery and radiotherapy finally receive it. The information on patients with GBM was retrieved from the surveillance, epidemiology, and end results database. Patients who underwent upfront surgery or biopsy and external beam radiotherapy between 2010 and 2019 were eligible for systemic chemotherapy. The available patient and tumor characteristics were assessed using multivariable logistic regression and chi-squared test. Out of the 16,682 patients eligible, 92.1% underwent systemic chemotherapy. The characteristics linked to the lowest systemic chemotherapy utilization included tumors of the brain stem/cerebellum (P = 0.01), former years of diagnosis (P = 0.001), ≥ 80 years of age (P < 0.001), Hispanic, Non-Hispanic Asian, Pacific Islander, or Black race (P < 0.001), non-partnered status (P < 0.001), and low median household income (P = 0.006). Primary tumor site, year of diagnosis, age, race, partnered status, and median household income correlated with the omission of systemic chemotherapy in GBM in adult patients.

Purpose: This study aimed to assess the treatment outcomes, toxicity, and potential prognostic factors in patients with early-stage extranodal natural killer/T-cell lymphoma treated with radiation therapy combined with chemotherapy. Methods and Materials: One hundred eighteen patients with stage I/II extranodal natural killer/T-cell lymphoma who were treated with radiation therapy combined with chemotherapy were retrospectively analyzed between July 2003 and January 2019. The median dose was 50 Gy (Range, 45-61.2 Gy). The Kaplan-Meier method was used to calculate progression-free survival and overall survival. The patients were scored according to their prognostic indices. Results: The overall and complete response rates were 93.2% and 82.2%, respectively. At a median follow-up of 43 months, the 5-year overall survival and progression-free survival rates were 73.9% and 68.4%, respectively. Adverse events of grade 3 or higher were observed in 20 patients (16.9%). Patients with primary disease in the Waldeyer's ring had poorer survival (P = .015). Compared with anthracycline-based regimens, non-anthracycline-based regimens significantly improved the 5-year overall survival (76.6% vs 54.8%, P = .027) and progression-free survival (72.4% vs 53.1%, P = .013). After treatment, the 5-year overall survival rate was 78.6% in complete response patients versus 44.9% in noncomplete response patients (P = .003). For patients with low- and intermediate-low- risk according to the nomogram-revised risk index model, the complete response rate was 100%. When primary lesion data were added to the nomogram-revised risk index as the basis for another prognostic index (modified nomogram-revised risk index), the low- risk (0 to 2 risk factors) and high-risk (3 or more risk factors) categories were noted (84.2% vs 62.2%, P = .036). Conclusions: Patients with early-stage extranodal natural killer/T-cell lymphoma had high response rates and favorable survival rates with radiation therapy and non-anthracycline-based chemotherapy regimens. Patients who achieved complete response had better survival than those who did not. The extranodal natural killer/T-cell lymphoma-specific prognostic models may require further optimization. (c) 2024 The Authors. Published by Elsevier Inc. on behalf of American Society for Radiation Oncology. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

7027 Background: Approved chimeric antigen receptor (CAR) T cell therapies targeting CD19 with a single co-stimulatory domain in the treatment of relapsed/refractory B-cell non-Hodgkin lymphoma (r/r B-NHL) may face challenges including drug resistance and disease recurrence. This Phase 1 study was conducted to evaluate the safety and tolerability of LY007, a novel CD20-targeting CAR-T cell containing both OX40 and 4-1BB co-stimulatory domains to enhance CAR-T cell proliferation and anti-cancer cytotoxicity, for the treatment of r/r B-NHL pts. Methods: In this open-label, single-arm phase 1 trial, r/r B-NHL pts were infused with LY007 in 3 dose levels (DLs) (DL1, 0.5 x 106 cells/ kg; DL2, 1.5 x 106 cells/ kg; DL3, 5.0 x 106 cells/ kg) based on a standard 3+3 dose escalation design after cyclophosphamide/fludarabine lymphodepletion. The main objectives were to determine the safety and tolerability, pharmacokinetics, and preliminary efficacy of LY007. The key eligibility criteria included pts with cytologically or histologically confirmed CD20 positive r/r B-NHL according to WHO 2016 including diffuse large B cell lymphoma (DLBCL) and transformed follicular lymphoma (TFL). Results: As of December 25th, 2023, 9 pts were treated with single LY007 infusions at 3 dose levels with a median follow-up of 5.09 (range 0.92-18.10) months. The median age of treated pts was 65 years (range, 44 to 69), and 44% (4/9) of pts had received three prior lines of therapy. Their B-NHL subtypes were all DLBCL. Among the treated pts, 78% (7/9) relapsed after prior lines of treatment, 89% (8/9) had extranodal involvement, 78% (7/9) had an International Prognostic Index (IPI) score of ≥ 2, and 44% (4/9) had a maximum tumor length of ≥ 5 cm. The overall response rate (ORR) and complete response (CR) were 67% (6/9) and 33% (3/9) at day28, 83% (5/6), and 67% (4/6) at month 3 of the pts evaluable for efficacy. Among all study participants, the best reported ORR was 89% (8/9). The longest duration of remission was 12.3 months to date. The overall survival (OS) and progression-free survival (PFS) were 100% and 88.9% at 6 months, respectively. The LY007 was generally well tolerated. No dose-limiting toxicities (DLTs) were observed. And no immune effector cell-associated neurotoxicity syndrome (ICANS) or G3+ cytokine release syndrome (CRS) was reported. The most common G3+ AEs were lymphopenia (9/9), leukopenia (9/9), and neutropenia (7/9). No pts discontinued, withdrew, or died due to AE. 6 pts experienced G1/2 CRS. Pts at all 3 dose levels had good CAR-T expansion and long-term persistence, particularly in the LD3 cohort, where the highest mean cell copy number of 93,750 copies/μg DNA was achieved at day 11 and was still detectable to date. Conclusions: This phase 1 trial demonstrated that LY007 was well tolerated at the dose levels up to 5.0 x 106 cells/ kg and showed a favorable dose-response relationship for the treatment of r/r B-NHL. Clinical trial information: NCT06279611.

Neoadjuvant chemotherapy (nCT) appears in a few clinical studies as an alternative to neoadjuvant chemoradiation (nCRT) in selected patients with locally advanced rectal cancer (LARC). We aimed to compare the clinical outcomes of nCT with or without nCRT in patients with LARC and to identify patients who may be suitable for nCT alone.

Background: In light of the growing evidence suggesting the impact of inflammatory parameters on the survival of individuals with cancer, this research assessed the prognostic significance of the neutrophil-tolymphocyte ratio (NLR) in individuals diagnosed with locally advanced nasopharyngeal carcinoma (NPC) prior to undergoing intensity-modulated radiation therapy (IMRT).Methods: A total of 163 individuals diagnosed with locally advanced NPC treated with IMRT at our hospital between January 2012 and December 2017 were included in this research. For each patient, the absolute counts of neutrophils and lymphocytes were recorded, and the NLR was calculated at the first diagnosis. To determine the optimal cut-off values for NLR, receiver operating characteristic (ROC) curve analysis was conducted. The effects of the determined cut-off value on local failure-free survival (LFFS), overall survival (OS), progression-free survival (PFS), and distant failure-free survival (DFFS) were evaluated employing the Cox regression model.Results: The median follow-up duration for the individuals in this study was 15 months (ranging from 6 to 79 months). According to the determined NLR cut-off value of 3.27, individuals were classified into two groups (high NLR and low NLR). Individuals in the high-NLR group had remarkably poorer 3-year OS (62.8% vs. 91.7%), PFS (51.4% vs. 82.4%), and DFFS (70.7% vs. 89.6%) compared to the low-NLR group. Furthermore, the outcomes of univariate and multivariate survival analyses revealed that NLR served as an independent predictor of DFFS (HR: 2.81, 95% CI: 1.195-6.608, P=0.018), OS (HR: 3.1, 95% CI: 1.211- 7.935, P=0.018), and PFS (HR: 2.21, 95% CI: 1.133-4.292, P=0.02).Conclusions: Elevated NLR exhibited a significant correlation with reduced OS, DFFS, and PFS. These findings suggest that NLR holds promise as a cost-effective and reliable marker for the prediction of clinical outcomes among patients with locoregionally advanced nasopharyngeal carcinoma (LANPC). Furthermore, incorporating NLR into clinical decision-making regarding LANPC treatment strategies may contribute to a more targeted approach aimed at reducing the risk of distant failure.

Radiotherapy combined with chemotherapy reported promising response rate and a favorable survival for patients with stage I-II nasal ENKTL. Anthracycline-based chemotherapy regimen and no remission after RT and CT were adverse factors of OS.

Anti-CD19 chimeric antigen receptor (CAR)-T cells not only target CD19-positive malignant lymphoma cells but also normal B cells. The utility of CAR-T cell therapy has been reported in rheumatoid arthritis and systemic lupus erythematosus; however, its use in Sjögren’s disease (SjD) remains unknown. In this study, we describe the case of a 76-year-old woman with active SjD for 10 years who was diagnosed with diffuse large B-cell lymphoma. After receiving anti-CD19 CAR-T cell therapy, she achieved complete remission (CR) on day 28. Since the onset of her 10-year history with SjD, she was negative for antinuclear antibodies and anti-Ro-52 for the first time on day 90 after CAR-T cell therapy. Six months after CAR-T cell therapy, the CR status was maintained, serum cytokine levels returned to their normal levels, and dry mouth symptoms improved. The EULAR Sjögren’s Syndrome Disease Activity Index score decreased from 5 to 2, indicating a partial remission of SjD activity compared with that before CAR-T cell treatment. In the early stage of treatment, she presented with grade 2 cytokine release syndrome and grade 1 neurotoxicity, which were completely controlled after an active intervention. This case highlights the potential application of CAR-T cells in treating autoimmune diseases, such as SjD.

Background SETD2 protects against genomic instability via maintenance of homologous recombination repair (HRR) and mismatch repair (MMR) in neoplastic cells. However, it remains unclear whether SETD2 dysfunction is a complementary or independent factor to microsatellite instability-high (MSI-H) and tumor mutational burden-high (TMB-H) for immunocheckpoint inhibitor (ICI) treatment, and little is known regarding whether this type of dysfunction acts differently in various types of cancer. Methods This cohort study used multidimensional genomic data of 6726 sequencing samples from our cooperative and non-public GenePlus institute from April 1 through April 10, 2020. MSIsensor score, HRD score, RNAseq, mutational data, and corresponding clinical data were obtained from the TCGA and MSKCC cohort for seven solid tumor types. Results A total of 1021 genes underwent target panel sequencing reveal that SETD2 mutations were associated with a higher TMB. SETD2 deleterious mutation dysfunction affected ICI treatment prognosis independently of TMB-H ( p < 0.01) and had a lower death hazard than TMB-H in pancancer patients (0.511 vs 0.757). Significantly higher MSI and lower homologous recombination deficiency were observed in the SETD2 deleterious mutation group. Improved survival rate was found in the MSKCC-IO cohort ( P < 0.0001) and was further confirmed in our Chinese cohort. Conclusion We found that SETD2 dysfunction affects ICI treatment prognosis independently of TMB-H and has a lower death hazard than TMB-H in pancancer patients. Therefore, SETD2 has the potential to serve as a candidate biomarker for ICI treatment. Additionally, SETD2 should be considered when dMMR is detected by immunohistochemistry.

BackgroundMany studies have shown that the peripheral blood inflammatory index and nutritional index, such as the platelet lymphocyte ratio (PLR), neutrophil lymphocyte ratio (NLR), lymphocyte monocyte ratio (LMR), systemic inflammation response index (SIRI), pan-immune-inflammation value (PIV), systemic immune-inflammation index (SII), and prognostic nutrition index (PNI), are independent prognostic factors for tumors. The present study aimed to investigate the prognostic role of these peripheral blood indexes before treatment in locally advanced gastric cancer (LAGC) treated with adjuvant chemoradiotherapy after D2 dissection.MethodsA total of 89 patients with LAGC who underwent D2 gastrectomy and adjuvant chemoradiotherapy at our hospital from 2010–2018 were eligible. Systemic inflammatory indicators before treatment were evaluated. Receiver operating characteristic curve (ROC), Kaplan–Meier analysis, and Cox regression were utilized for prognosis evaluation.ResultsThe median follow-up time was 29.1 (4.1–115.8) months. The overall survival at 3 years (OS) and the disease-free survival (DFS) were 78.9% and 59.1%, respectively. According to the ROC curve for 3-year DFS, the best cut-off values of pre-treatment NLR, PLR, LMR, SII, SIRI, PIV and PNI were 1.7, 109.3, 2.9, 369.2, 0.58, 218.7, and 48, respectively. Multivariate Cox regression analysis showed that NLR was an independent prognostic factor for DFS (HR 2.991, 95%CI 1.085–8.248, P = 0.034). Kaplan-Meier analysis showed that a higher NLR (>1.70) was significantly associated with a poorer OS (3-year OS: 68.8% vs 92.9%, P = 0.045) and DFS (3-year DFS: 47.5% vs 80.9%, P = 0.005). In terms of the free locoregional recurrence rate (LRR), the prognosis of patients with high NLR was also significantly worse than those with low NLR (70.2% vs 96.0%, P = 0.017). Paraaortic lymph nodes were the most common site of LRR (7/14 patients). The seven cases of paraaortic lymph node metastasis occurred in patients with high NLR.ConclusionsIn our retrospective analysis, we found that pretreatment NLR could serve as a prognostic factor for survival in LAGC treated with adjuvant chemoradiotherapy after D2 dissection, especially for the prediction of LRR and paraaortic lymph node metastasis. Prospective studies are needed to confirm our findings.

Background One of the most controversial areas in gastrointestinal oncology is the benefit of postoperative chemoradiotherapy (CRT) over chemotherapy (CT) alone after D2 dissection of locally advanced gastric cancer (LAGC). We aimed to identify the LAGC patients who may benefit from adjuvant CRT. Methods We analyzed retrospectively 188 patients receiving radical gastrectomy with D2 dissection for LAGC in our hospital. Patients were divided into two balanced groups by using propensity score matching: CRT group (n = 94) received adjuvant CRT, and CT group received adjuvant CT alone. Results At a median follow-up of 27.10 months, 188 patients developed 79 first recurrence events (36 in CRT group and 43 in CT group). Our results showed that adjuvant CRT significantly decreased the risk of developing local regional recurrence (LRR) when compared to CT alone (14.9% vs. 25.5%, p = 0.044), while the estimated 3-year disease-free survival (DFS) was comparable between the CRT and CT groups (59.3% vs. 50.9%, p = 0.239). In the subgroup analysis, a significantly decreased LRR rate was also observed in LAGC patients with N1-3a stage after adjuvant CRT (p = 0.046), but not for N3b. Para-aortic lymph nodes (station No. 16) were the most frequent sites of LRR. After receiving radiotherapy, recurrence of 16 a2 region and 16 b1 region were significantly deceased (p = 0.026 and p = 0.044, respectively). Patients who received irradiation more than 4 months after surgery showed an increased risk of LRR (p = 0.022). Conclusions This study showed that adjuvant CRT significantly reduced LRR after D2 dissection of LAGC. Early initiation of adjuvant RT with clinical target volume encompassing a2 and b1 regions of para-aortic lymph nodes is recommended for pN1-3a patients after D2 dissection.

Background The lesion of primary gastric non-Hodgkin’s lymphoma (PGL) originates from the submucosa, so conventional gastroscopy has limited diagnostic potential. This study evaluated the diagnosis and follow-up value of endoscopic ultrasonography (EUS) in PGL. Methods Seventy-nine patients diagnosed with PGL either by EUS and biopsy pathology or by postoperative pathology were included in the study. All subjects underwent EUS with deep targeted biopsy and regular follow-up. Results We found sensitivity and specificity of EUS combined with deep targeted biopsy for PGL as 87.3% (69/79) and 80.0% (20/25) respectively, and the diagnostic accuracy as 85.6% (89/104). EUS combined with deep targeted biopsy had significantly greater diagnostic accuracy than gastroscopy [85.6% (89/104) vs. 57.7% (60/104); (P<0.001)]. The diagnostic accuracy of T tumor staging and N tumor staging of EUS were 13/13 and 11/13 respectively compared with postoperative staging. The mean time of complete remission of lymphoma after eradication treatment in the H. pylori-negative (successful eradication) group (3.2±0.7 months) was shorter than that in H. pylori-positive patients (failed eradication) group (4.5±0.8 months), there was statistically significant difference between the two groups (t=4.3, P<0.001). Conclusions This study demonstrated that EUS combined with deep targeted biopsy was associated with increased detection of Primary gastric non-Hodgkin’s lymphoma (PGL), in terms of depth and extent of the lesion to guide treatment selection and to evaluate treatment efficacy.

BACKGROUND:To investigate the prognostic value of pretreatment primary gross tumor with (GTVp) and without retropharyngeal lymph nodes (GTVnx) for predicting survival outcomes in patients with local-regional advanced nasopharyngeal carcinoma (NPC) after intensity-modulated radiation therapy (IMRT). METHODS:From Jan 2012 to Dec 2017, 148 patients with local-regional advanced NPC who had undergone definitive radiotherapy were identified. GTVnx volume and retropharyngeal lymph nodes (GTVrLNs) volume were measured based on registration of MRI with contrast-enhanced CT images. The Kaplan-Meier method was used for survival analysis. Univariate and multivariate prognostic analyses was performed by using the Cox proportional hazard model. Receiver operating characteristic (ROC) curves were used to identify the cut-off point and assess the prognostic value for GTVnx, GTVp and GTVrLNs. RESULTS:The median follow-up time for the entire group was 27 months (ranging 7 to 80 months). The 3-year overall survival (OS) rate was 85%, and the 3-year local failure-free rate (LFFR), distant failure-free rate (DFFR) and disease-free survival (DFS) rates were 93%, 81%, and 73%, respectively. A positive correlation between GTVnx or GTVp volume and T stage was observed (both P<0.001). The 3-year LFFR, OS, and DFS rate, but not for DMFS, in NPC patients with GTVnx ≤42.7 cm3 was significantly better than those with >42.7 cm3 (all P<0.05). Multivariate analysis indicated that GTVnx volume (P=0.041) was the only independent prognostic factor for LFFR, while age and AJCC stage were two independent prognostic factors for OS. CONCLUSIONS:The GTVnx is an independent prognostic factor for local control, while the prognostic value of GTVrLNs is limited. Physicians are recommended to distinguish between GTVnx and retropharyngeal lymph nodes (RLN) involvement when assessing the risk for local recurrence in advanced NPC.

e16057 Background: Patients (pts) with peritoneal metastatic (PM) colorectal cancer (CRC) have significantly poorer prognosis than those with other metastases. In this study, we aim to investigate genomic profiles of PM-CRC and metastatic CRC without peritoneal involvement (non-PM-CRC) and PM-CRC with other organ involvement (PM-CRC+) using circulating tumor DNA (ctDNA)-based sequencing. Methods: A total of 169 pts with metastatic CRC were enrolled irrespective of treatment history, including 53 pts with non-PM-CRC, 47 pts with PM-CRC, and 69 pts with PM-CRC+. Matched tumor-normal next-generation sequencing of 1021 cancer-related genes was performed on ctDNA and white blood cells derived from plasma samples. The differences of mutation number were examined with student t test, and the differences of mutation detection rate were examined with two tailed Fisher’s exact test. p≤0.05 was considered statistically significant. Results: Somatic mutations were identified in 96% of pts with non-PM-CRC, 77% of pts with PM-CRC, and 97% of pts with PM-CRC+. The number of somatic mutations observed in the PM-CRC cohort was significantly lower than that in the other cohorts with the median value of 2 in the PM-CRC cohort, 9 in the non-PM-CRC cohort, and 7 in the PM-CRC+ cohort (p = 0.0002 and p < 0.0001, respectively). The most frequently mutated genes in these cohorts was listed in Table. The detection rate of APC and TP53 mutations in the PM-CRC cohort was significantly lower than the other cohorts. Significant differences were also observed when comparing TCF7L2 mutations in the non-PM-CRC and the other cohorts, LRP1B mutations in the PM-CRC cohort and PM-CRC+ cohort, and NOTCH4 and PCK1 mutations in the non-PM-CRC and PM-CRC+ cohorts. In addition, BRAF mutations were more commonly observed in the PM-CRC cohort (13%) than the other cohorts (8% for non-PM-CRC cohort, 4% for PM-CRC+ cohort) (p = 0.51 and 0.16, respectively). Conclusions: Pts with PM-CRC exhibit a distinct molecular profile compared with non-PM-CRC and PM-CRC+, which may be helpful to explain their relatively poor prognosis and potentially be used in the early diagnosis of PM. [Table: see text]

Lacking quantitative evaluations of clinicopathological features and the risk factors for loco-regional recurrence (LRR) in gastric cancer after D2 gastrectomy, we aimed to develop a competing risk nomogram to identify the risk predictors for initial LRR. We retrospectively analysed 1105 patients who underwent radical gastrectomy with D2 resection for stage I-III gastric cancer. A nomogram predicting initial LRR of gastric cancer was conducted based on Fine and Grey’s competing risk analysis. The predictive accuracy and discriminative ability of the model were determined using the concordance index (C-index) and calibration curve. Decision tree analysis was performed for patient grouping. At a median follow-up of 28.4 months, 274 patients developed 373 first recurrence events (local, regional, and distant disease). The median recurrence-free survival (RFS) was 16.7 months. Multivariate competing risk analysis showed that age (SHR, 1.72; 95% CI, 1.10–2.83, p = 0.031), CEA (SHR, 1.94; 95% CI, 1.09–3.46, p = 0.024), pT4 (SHR, 2.77; 95% CI, 1.01–7.57, p = 0.047), lymph node metastasis (SHR 1.92, 95% CI: 1.09–3.38, p = 0.024) and LVI (SHR, 1.84; 95% CI, 1.06–3.20, p = 0.028) were independent risk factors for LRR (all p < 0.05). The nomogram incorporating these factors achieved good agreement between prediction and actual observation with a concordance index of 0.738 (95% CI, 0.767 to 0.709). In a subgroup analysis of node-positive patients, pN3b was associated with increased peritoneal and distant metastasis (p = 0.048). The para-aortic lymph nodes were the most frequent sites (n = 71) of LRR, and among them, the 16a2 and 16b1 nodes exhibited even more prevalence (90.1 and 81.7%). Adjuvant radiotherapy might be recommended in gastric cancer patients ≥65 years old or those with pN+, pT4, LVI, or increased CEA levels, particularly in high-risk or pN1-3a patients. The competing risk nomograms may be considered as convenient and individualized predictive tools for LRR in gastric cancer after D2 gastrectomy. It is also recommended that the clinical target volume (CTV) include 16a2 and 16b1 regions of para-aortic lymph nodes.

Background: Cervical lymph node metastasis was an important prognostic factor. However, the prognosis of the maximum diameter of cervical lymph nodes before treatment has always been controversial. The aim of this study was to analyze the relationship between treatment outcomes and the maximum diameter of lymph nodes (Dmax) in loco-regional advanced nasopharyngeal carcinoma (NPC) after intensity modified radiotherapy. Methods: From Jan. 2012 to Dec. 2017, 163 patients with locally advanced NPC treated with intensity modified radiotherapy were retrospectively analyzed. The T-stage distribution was 6.7% in T1, 23.3% in T2, 38.7% in T3, and 31.3% in T4. The N-classifications were 6.1% in NO, 23.3% in N1, 47.9% in N2, and 22.7% in N3. TNM stages were III 51.5% and IVa 48.5%. All patients received intensity modified radiotherapy to the nasopharynx and neck. The dose was 66-70.4 Gy, 2-2.2 Gy per fraction over 6-7 weeks to the primary tumor and lymph nodes and 54-60 Gy to clinical target volumes (CTVs). One hundred fifty patients were received induction chemotherapy and/or concurrent chemotherapy. The maximum diameter of the lymph node is measured on the axial or coronal MRI image. Results: The median follow-up time was 31 months (range, 6.1-79.3 months). Six cases developed neck recurrence and 9 cases developed nasopharynx recurrence. The lymph nodes diameter was 0-12 cm, median 2.9 cm. Three-year overall survival (OS) rate was 77.8%. Three-year local failure-free rate (L-FFR), distant failure-free rate (D-FFR) and disease-free survival (DFS) rate were 88.1%, 77.6% and 63.9% respectively. Multivariate analysis showed Dmax was not a prognostic factor for OS, L-FFR, D-FFR, DFS. Both uni-and multivariate analyses demonstrated that N-classification and age is the significant prognostic factor for predicting OS while the maximum diameter of lymph nodes, T-classification, N-classification and AJCC-classification are the significant prognostic factor for predicting OS in univariate analyses in local-regional advanced NPC. Conclusions: The maximum diameter of the lymph nodes was not a prognostic factor for local-regional advanced NPC treated with intensity modulated radiotherapy.