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.

Circulating tumor DNA (ctDNA) enables genomic profiling of colorectal cancer. We investigated therapeutic targets by performing ctDNA panel-captured sequencing of 152 blood samples from advanced stage patients, from which somatic mutations and potentially actionable targets were evaluated. An additional 11 matched tissue samples were retrospectively obtained to verify target validity. The mutation frequencies of 1,127 collective genetic variants identified in our study strongly correlated with those of multiple public databases (Pearson R2 = 0.92, P < 0.0001). The clonal fraction of driver genes was 90.3%, which was significantly higher than that of potential passenger genes (58.12%). Totally, 90 drug-sensitive genes from 56 patients (36.84%) were identified, including recurring targets PIK3CA, FBXW7, EGFR, BRAF, and NRAS. Various resistance mechanisms of anti-EGFR antibodies were revealed via ctDNA profiling, with 29 patients individually exhibiting multiple mechanisms, suggesting considerable resistance heterogeneity in our study population. Of the matched tissue/blood pairs, 88.14% of tissue-derived mutations were detected in ctDNA, and 88.9% of actionable targets were validated. The mutational landscape of ctDNA was highly consistent with tissue databases, and ctDNA profiling showed favorable concordance with tumor tissues in our matched analysis. Thus, comprehensive ctDNA genotyping is a promising noninvasive alternative to biopsy-derived analysis for determining targeted therapy in advanced colorectal cancer.

Background The UGT1A1*28 polymorphism, although closely linked with CPT-11-related adverse effects, cannot be used alone to guide individualized treatment decisions. However, CPT-11 dosage can be adjusted according to measured SN-38 pharmacokinetics. Our study is designed to investigate whether there is a relationship between SN-38 peak or valley concentrations and efficacy or adverse effects of CPT-11-based chemotherapy. We retrospectively studied 98 patients treated with advanced colorectal cancer in various UGT1A1*28 genotype groups (mainly (TA)₆/(TA)₆ and (TA)₆/(TA)₇ genotypes) treated with CPT-11 as first-line chemotherapy in Shanghai. Methods One hundred and sixty-four advanced colorectal cancer patients were enrolled. To understand differences in genotype expression, the frequency of UGT1A1*28 thymine–adenine (TA) repeats in TATA box arrangement was assessed by PCR with genomic DNA extracted from peripheral blood. For ninety-eight cases with the (TA)₆/(TA)₆ and (TA)₆/(TA)₇ genotypes treated with CPT-11 as first-line chemotherapy, the plasma concentration of SN-38 was detected by HPLC 1.5 and 49 h after CPT-11 infusion. Efficacy and adverse effects were observed subsequently, and the relationship between SN-38 plasma concentration and efficacy or adverse effects within genotype groups, as well as differences in efficacy and adverse effects between (TA)₆/(TA)₆ and (TA)₆/(TA)₇ genotypes were analyzed statistically. Results One hundred and fourteen patients (69.51 %) were identified with the (TA)₆/(TA)₆ genotype, forty-eight patients (29.27 %) with the (TA)₆/(TA)₇ genotype, and two patients (1.22 %) with the (TA)₇/(TA)₇ genotype. The average peak and valley concentrations of SN-38 after CPT-11 infusion and plasma bilirubin average levels before and after CPT-11 treatment in the (TA)₆/(TA)₇ genotype group were all higher than those in (TA)₆/(TA)₆ group, and the difference was statistically significant (p = 0.00). Stepwise regression analysis showed that SN-38 peak and valley concentration was correlated with PFS in the (TA)₆/(TA)₆ genotype. In the (TA)₆/(TA)₇ group, SN-38 peak concentration was correlated with CPT-11 starting dose and OS, valley concentration correlated with plasma bilirubin levels before CPT-11 treatment, delayed diarrhea, and OS. For the (TA)₆/(TA)₆ genotype, mPFS of the SN-38 peak concentration >43.2 ng/ml subgroup was significantly longer than that of ≤43.2 ng/ml subgroup (8.0 ± 0.35 vs. 6.5 ± 0.79 months, χ ² = 17.18, p = 0.00) with a relatively high incidence of Grade I/II° myelosuppression; for the (TA)₆/(TA)₇ genotype, there was no significant difference in mOS between the SN-38 valley concentration >16.83 ng/ml and ≤16.83 subgroups (17.3 ± 0.45 vs. 18.8 ± 0.50 months, χ ² = 1.38, p = 0.24), but the former had a higher incidence of Grade III/IV° mucositis and delayed diarrhea. For 2 (TA)₇/(TA)₇ cases, although 25 % dose reduction of CPT-11, which is calculated according to body surface area, Grade IV° bone marrow suppression and Grade III° delayed diarrhea still occurred after CPT-11 treatment, though both adverse effects resolved and did not recur again after a 50 % dose reduction. Conclusion The (TA)₆/(TA)₆ genotype and (TA)₆/(TA)₇ genotype accounted for the most, and (TA)₇/(TA)₇ genotype only account for a very small portion of advanced colorectal cancer patients in Shanghai. For the (TA)₆/(TA)₆ genotype, CPT-11 dosage can be increased gradually to improve efficacy for patients with SN-38 peak concentration ≤43.2 ng/ml after CPT-11 infusion; and for (TA)₆/(TA)₇ genotype patients, CPT-11 dosage may be lowered appropriately to reduce serious adverse effects such as bone marrow suppression and delayed diarrhea without affecting the efficacy for those with SN-38 valley concentration >16.83 ng/ml. For (TA)₇/(TA)₇ genotype patients, adverse effects should be closely observed after treatment even if CPT-11 dosage has been reduced.

Background: To evaluate the histological type, clinical presentation, treatment and prognosis of primary intestinal lymphoma (PIL). Methods: From 2003 to 2015, in a single institution in China, 82 patients with a diagnosis of PIL were enrolled in our study. According to World Health Organization (WHO) classification and Lugano staging system for gastrointestinal lymphoma, we divided patients into different subtypes and stages. Results: Male to female ratio was 1.8:1 and the median age was 59.5 years. Of the 82 patients, 68 patients (82.9%) suffered from intestinal B-cell lymphoma (IBCL) and 14 patients (17.1%) suffered from intestinal T-cell lymphoma (ITCL). Diffuse large B cell lymphoma (DLBCL) was the predominant histological subtype (59.8%) in all of the PIL cases. Mucosa-associated lymphoid tissue-type lymphoma (MALT) was the second most common subtype (15.9%). From the study we also concluded that PIL mostly occurred in the small intestine (45.1%), followed by colon and rectum (26.8%). The univariate prognosis analysis revealed that Lugano stage I/II, B-cell phenotype and treatment based on surgery plus chemotherapy were independent prognostic factors (P=0.003, 0.000 and 0.000, respectively). According to multivariate analysis, age of onset, Lugano stage, immunophenotype and the method of treatment were significant predictive factors for better survival (P=0.005, 0.005, 0.000 and 0.000, respectively). Conclusions: The patients with younger age of onset, B cell lymphoma, earlier stages, and treatment based on surgery plus chemotherapy have a better prognosis. To ensure the diagnosis of PIL to be made as soon as possible, we should make efforts to select the proper laboratory parameters and imaging findings of PIL.

The purpose of this study was to analyze the effects of all clinical characteristics on the overall survival time, in order to provide a basis for determining the prognostic factor of patients with pancreatic cancer. A total of 103 pancreatic cancer patients were admitted to the Department of Radiotherapy and Chemotherapy of the Ruijin Hospital, Shanghai Jiaotong University School of Medicine, between January 2002 and December 2012. There were 68 men and 35 women; the median age was 62 years. Diagnoses of pancreatic cancer in all patients were confirmed by histopathology, cytology, or clinical diagnosis. The Kaplan-Meier method was performed to calculate the overall survival rate. The log-rank method was used to examine the univariate analysis. The Cox regression model was performed for multivariate analysis. The median survival time was 293 days, the 1-, 2-, and 3-year survival rates were 27.18%, 5.83%, and 1.94%, respectively. Cox regression analysis revealed that age (P=0.015), Karnofsky performance status (PS) (P=0.002), surgical types (P<0.001), and platelet counts (P<0.001) were independent prognostic factors affecting the overall survival of patients with pancreatic cancer. Pancreatic cancer had a poor prognosis, the general physical condition, age, the availability of radical surgery, and platelet counts were factors influencing the overall survival of patients with pancreatic cancer.

Background: Radiotherapy (RT) is a modality of salvage therapy in relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL), but its efficacy is currently not well defined. This paper reports a retrospective review of patients who received salvage RT for R/R DLBCL in our hospital. Methods: We selected 32 patients who had relapsed and had progressive disease after chemotherapy or partial remission (PR) after chemotherapy. The patients had a median age of 47 years (range, 13–85 years) and were treated between January 1, 2009, and June 30, 2016. The histological type was DLBCL in all cases. Progression-free survival (PFS) and overall survival (OS) were estimated with the Kaplan-Meier method; predictors for adverse factors were evaluated using a Cox proportional hazards regression model. Results: Median age-adjusted International Prognostic Index (IPI) score was 3 (range, 0–4), and 20 (62.5%) patients had large tumors. Patients were irradiated with a median dose of 42.7 Gy (range, 30–54 Gy): 4 (12.5%) by conventional RT, 2 (6.3%) by conformal 3D technique and 26 (81.3%) by intensity-modulated RT (IMRT). Most toxicities were mild (CTCAE grade 1 or 2), including neutropenia, diarrhea, dermatitis, mucositis and dysphagia. With a median follow-up of 25.4 months (range, 0.4–98.9 months) after irradiation, the 5-year PFS and OS were 61.8% and 83.2%, respectively. In multivariate analysis, adverse factors associated with PFS in our cohort were multiple lesions. Conclusions: Due to its low toxicity and ease of use, RT should remain a salvage therapy option for patients with R/R DLBCL.