Liping Liang

Phase II trial of first-line chemoradiotherapy with intensity-modulated radiation therapy followed by chemotherapy for synchronous unresectable distant metastases rectal adenocarcinoma.

AimsBased on the hypothesis that first-line chemoradiation followed by chemotherapy was superior for primary tumor and non-inferior for distant lesions compared to chemotherapy alone in synchronous unresectable distant metastases rectal adenocarcinoma, this study was designed to assess the efficacy and safety of this strategy.Materials and methodsThirty two eligible patients received intensity modulated radiation therapy (45 Gy to the pelvis and a concomitant 10 Gy boost to the gross tumor), along with concurrent weekly capecitabine and oxaliplatin. Patients underwent radical surgery if all lesions were visually evaluated as resectable and received chemotherapy for a total of 6 months, whether pre- or post-operatively (definitive therapy group). The remaining patients received 6 months of consolidation chemotherapy followed by maintenance chemotherapy (non-definitive therapy group).ResultsThe toxicities were acceptable, with radiation-induced dermatitis around the anal verge being the most common (18.8%). Fourteen patients underwent surgical resection of the rectal tumor, with 5 (35.7%) experiencing a pathological complete response. Nine out of 14 received definitive treatment, defined as R0 resections of all visible tumors. At a median follow-up of 12 months (range, 4–23 months), 2 cases were evaluated as local failure, and the median overall survival (OS) and progression free survival (PFS) for all 32 patients were 17.5 and 12 months, respectively. OS differed significantly in the definitive and non-definitive therapy groups (p=0.045), and PFS tended to differ (p=0.274).ConclusionIt was demonstrated that the strategy of first-line chemoradiation followed by chemotherapy was effective and tolerable, especially for local control. OS and PFS were superior in patients who did than did not undergo curative therapy.

TNF rs1799964 as a Predictive Factor of Acute Toxicities in Chinese Rectal Cancer Patients Treated With Chemoradiotherapy

AbstractAcute toxicity is the main dose-limiting factor in the chemoradiotherapy of rectal cancer patients and depends on several pro-inflammatory factors, including interleukin-1 (IL-1), IL-6, and tumor necrosis factor-alpha (TNF-&agr;). It is unknown whether genetic factors, such as single-nucleotide polymorphisms (SNPs) in the IL-1, IL-6, and TNF genes, are also associated with acute toxicity in the process.We genotyped 5 potentially functional SNPs in these 3 genes (TNF rs1799964, TNF rs1800629, IL-6 rs1800796, and IL-1 rs1143623, IL-1 rs1143627) and estimated their associations with severe acute radiation injury (grade ≥2) in 356 rectal cancer patients.We found a predictive role of the TNF rs1799964 T variant allele in the development of acute injury (for CT vs CC: adjusted odds ratio [OR] = 4.718, 95% confidence interval [CI] = 1.152–19.328, P = 0.031; for TT vs CC: adjusted OR = 4.443, 95% CI = 1.123–17.581, P = 0.034). In the dominant model, for CT/TT vs CC, the adjusted OR = 4.132, 95% CI = 1.069–15.966, and P = 0.04.Our results suggested that genetic variants in the TNF gene may influence acute injury in rectal cancer patients treated with chemoradiotherapy and may be a predictor for personalized treatment. Additional larger and independent studies are needed to confirm our findings.

Identification of patients with lymph node metastasis from gastric cancer who may benefit from adjuvant chemoradiotherapy after D2 dissection—do N3 patients benefit from additional radiation?

OBJECTIVE The role of adjuvant chemoradiotherapy (CRT) in locally advanced gastric cancer (LAGC) after D2 dissection is controversial. Subgroup analysis of the ARTIST trial indicated that patients with lymph node metastasis might benefit from additional radiation. The present study compared adjuvant CRT with adjuvant chemotherapy (CT) for the treatment of lymph node metastasis and suggested patient-selection guidelines. METHODS Patients with LAGC and positive lymph nodes who underwent D2, R0 gastrectomy in our hospital were retrospectively investigated. Patients were divided into two balanced groups by the use of propensity-score matching: CRT group (n = 138) received adjuvant CRT with fluorouracil-based regimens and radiation (45-50.4 Gy), and the CT group (n = 138) received adjuvant CT alone. RESULTS Of the 276 patients, 147 patients died (69 patients in the CRT group and 78 patients in the CT group), and 151 patients experienced recurrence (65 patients in the CRT group and 86 patients in the CT group). The estimated 3-year disease-free survival (DFS) and overall survival in the CRT and CT groups were 51.5% vs 41.3% (p = 0.05) and 52.0% vs 50.1% (p = 0.35), respectively. The risk of local regional recurrence was increased in the CT group compared with the CRT group (16.7% vs 8.7%, p = 0.04, respectively). In the subgroup analysis, patients with N1-2 stage were associated with better survival from CRT (hazard ratio = 0.44, p = 0.01). CONCLUSION Adjuvant CRT may improve the 3-year DFS and local control in patients with LAGC after D2 dissection. Investigation of stratification factors for patient selection is warranted. ADVANCES IN KNOWLEDGE Patients with N1-2 stage rather than those with N3 stage benefit most from additional radiation after D2 dissection.

Genetic polymorphisms of PAI-1 and PAR-1 are associated with acute normal tissue toxicity in Chinese rectal cancer patients treated with pelvic radiotherapy

Plasminogen activator inhibitor type 1 (PAI-1) and protease-activated receptor-1 (PAR-1) are crucial mediators of the intestinal microenvironment and are involved in radiation-induced acute and chronic injury. To evaluate whether genetic polymorphisms of PAI-1 and PAR-1 were predictors of radiation-induced injury in patients with rectal cancer, we retrospectively evaluated 356 rectal cancer patients who had received pelvic radiotherapy and analyzed the association of genetic polymorphisms of PAI-1 and PAR-1 with acute toxicities after radiotherapy. Acute adverse events were scored, including dermatitis, fecal incontinence (anal toxicity), hematological toxicity, diarrhea, and vomiting. The patients were grouped into grade ≥2 and grade 0–1 toxicity groups to analyze the acute toxicities. Genotyping of six single nucleotide polymorphisms (SNPs) of PAI-1 and PAR-1 was performed using TaqMan assays. A logistic regression model was used to estimate the odds ratios and 95% confidence intervals. Of the 356 individuals, 264 (72.5%) had grade ≥2 total toxicities; within this group, there were 65 (18.3%) individuals who reached grade ≥3 toxicities. There were 19.5% (69/354) and 36.9% (130/352) patients that developed grade ≥2 toxicities for diarrhea and fecal incontinence, respectively. The variant genotype GG of rs1050955 in PAI-1 was found to be negatively associated with the risk of diarrhea and incontinence (P<0.05), whereas the AG and GG genotypes of rs2227631 in PAI-1 were associated with an increased risk of incontinence. The CT genotype of PAR-1 rs32934 was associated with an increased risk of total toxicity compared with the CC allele. Our results demonstrated that SNPs in the PAI-1 and PAR-1 genes were associated with acute injury in rectal cancer patients treated with pelvic irradiation. These SNPs may be useful biomarkers for predicting acute radiotoxicity in patients with rectal cancer if validated in future studies.

Disparities in survival for right-sided vs. left-sided colon cancers in young patients: a study based on the Surveillance, Epidemiology, and End Results database (1990–2014)

Purpose To investigate whether young patients exhibit different characteristics and survival according to tumor location and stage using data from the Surveillance, Epidemiology, and End Results (SEER) database. Patients and methods Young patients (20–49 years old) with stage I–III colon cancers were identified from the SEER program from 1990 to 2014. Kaplan–Meier survival analysis and Cox proportional hazards regression were used to analyze the data. Subset analyses were also done among different age and stage subgroups. Results Of 8197 patients, 3709 (45.2%) had right-sided colon cancers (RCCs). Patients with RCCs were more likely to be male, to be younger, and to have more poorly differentiated and more advanced tumors. The Kaplan–Meier survival curves and univariate survival models revealed that left-sided colon cancers (LCCs) had lower mortality for all stages combined and stage III, but higher mortality for stage II, compared with right-sided tumors. However, multivariate Cox regression models showed no significant survival differences by location for all patients (adjusted hazard ratio [HR], 0.95; 95% confidence interval [CI], 0.86–1.05; P=0.34) or for stage I (adjusted HR, 1.47; 95% CI, 0.82–2.63; P=0.20). Stage II left-sided cancers had higher mortality (adjusted HR, 1.24; 95% CI, 1.00–1.54; P=0.048), whereas stage III left-sided cancers had lower mortality (adjusted HR, 0.86; 95% CI, 0.77–0.97; P=0.01). For 20- to 39-year-old patients, a significant difference was only found in stage II disease, with a higher mortality for left-sided tumors (adjusted HR, 1.82; 95% CI, 1.12–2.97; P=0.02). However, for 40- to 49-year-old patients, a significant difference was only found in stage III disease, with a lower mortality for left-sided tumors (adjusted HR, 0.83; 95% CI, 0.72–0.95; P=0.008). Conclusion In patients younger than 50 years, there were no significant differences in mortality between RCCs and LCCs for all stages combined after adjusting for multiple clinicopathological features. However, RCCs had lower mortality in stage II (especially in 20- to 39-year-old patients) and higher mortality in stage III (especially in 40- to 49-year-old patients).