Comparison of preoperative chemoradiation with radiation or chemotherapy alone in patients with non-metastatic, resectable retroperitoneal sarcoma

Aim: Optimal preoperative therapy regimen in the treatment of resectable retroperitoneal sarcoma (RPS) remains unclear. This study compares the impact of preoperative radiation, chemoradiation and chemotherapy on overall survival (OS) in RPS patients. Materials and Methods: The National Cancer Database (NCDB) was queried for patients with non-metastatic, resectable RPS (2006–15). The primary endpoint was OS, evaluated by Kaplan–Meier method, log-rank test, Cox multivariable analysis and propensity score matching. Results: A total of 1,253 patients met the inclusion criteria, with 210 patients (17%) receiving chemoradiation, 850 patients (68%) receiving radiation and 193 patients (15%) receiving chemotherapy. On Cox multivariable analysis, when compared to preoperative chemoradiation, preoperative radiation was not associated with improved OS (hazards ratio [HR] 0·98, 95% CI 0·76–1·25, p = 0·84), while preoperative chemotherapy was associated with worse OS (HR 1·64, 95% CI 1·24–2·18, p < 0·001). Similar findings were observed in 199 and 128 matched pairs for preoperative radiation and chemotherapy, respectively, when compared to preoperative chemoradiation. Findings: Our study suggested an OS benefit in using preoperative chemoradiation compared to chemotherapy alone, but OS outcomes were comparable between preoperative chemoradiation and radiation alone.

Overexpression of MLPH in Rectal Cancer Patients Correlates with a Poorer Response to Preoperative Chemoradiotherapy and Reduced Patient Survival

Data mining of a public transcriptomic rectal cancer dataset (GSE35452) from the Gene Expression Omnibus, National Center for Biotechnology Information identified the melanophilin (MLPH) gene as the most significant intracellular protein transport-related gene (GO:0006886) associated with a poor response to preoperative chemoradiation. An MLPH immunostain was performed on biopsy specimens from 172 rectal cancer patients receiving preoperative chemoradiation; samples were divided into high- and low-expression groups by H-scores. Subsequently, the correlations between MLPH expression and clinicopathologic features, tumor regression grade, disease-specific survival (DSS), local recurrence-free survival (LRFS), and metastasis-free survival (MeFS) were analyzed. MLPH expression was significantly associated with CEA level (p = 0.001), pre-treatment tumor status (p = 0.022), post-treatment tumor status (p < 0.001), post-treatment nodal status (p < 0.001), vascular invasion (p = 0.028), and tumor regression grade (p < 0.001). After uni- and multi-variable analysis of five-year survival, MLPH expression was still associated with lower DSS (hazard ratio (HR), 10.110; 95% confidence interval (CI), 2.178–46.920; p = 0.003) and MeFS (HR, 5.621; 95% CI, 1.762–17.931; p = 0.004). In conclusion, identifying MLPH expression could help to predict the response to chemoradiation and survival, and aid in personal therapeutic modification.

The efficiency of 18F-FDG-PET/CT in the assessment of tumor response to preoperative chemoradiation therapy for locally recurrent rectal cancer

Background Locally recurrent rectal cancer (LRRC) remains a major problem after curative resection of primary rectal cancer. A noninvasive, prognostic biomarker with which to accurately evaluate disease status and assess the treatment response is critically needed to optimize treatment plans. This study assesses the effectiveness of PET/CT evaluation of preoperative chemoradiation therapy (CRT) in patients with LRRC. Methods Since 2004, we have been performing preoperative CRT to improve local tumor control and survival. Between 2004 and 2013, 40 patients with LRRC underwent preoperative CRT (radiation: 50 Gy/25 fractions; chemotherapy: irinotecan plus UFT [tegafur and uracil]/leucovorin) and radical surgery, and underwent 18F-FDG-PET/CT before and 3 weeks after the completion of CRT. The maximum standardized uptake values (SUVmax) of the pre-CRT scan (Pre-SUV) and the post-CRT scan (Post-SUV) were measured. The predictive value of the 18F-FDG-PET and CT/MRI response assessments was evaluated. Results The mean Pre-SUV was significantly higher than the Post-SUV (8.2 ± 6.1, vs. 3.8 ± 4.0; P < 0.0001). Following CRT, 17/40 patients (42.5%) were classified as responders according to the Mandard tumor regression grade (TRG1–2). The mean Post-SUV was significantly lower in responders than in nonresponders (2.0 ± 1.7 vs. 5.1 ± 3.9; P = 0.0038). Pathological response was not correlated with the response as evaluated by CT (P > 0.9999) or MRI (P > 0.9999). Multivariate regression analysis identified Post-SUV as an independent predictor of local re-recurrence-free survival (P = 0.0383) and for overall survival (P = 0.0195). Conclusions PET/CT is useful in assessing tumor response to preoperative CRT for LRRC and predicting prognosis after surgery.

Preoperative Chemoradiation With Image-guided IMRT in Patients With Locally Advanced Gastric Cancer

PurposeTo evaluate the efficacy and toxicity of preoperative chemoradiation with image-guided IMRT in locally advanced resectable gastric cancer patients.Patients and methodsPatients with locally advanced (T3/T4 or N+) gastric cancer treated with neoadjuvant chemoradiotherapy followed by surgery between Jan 2013 and June 2019 in PUMCH were retrospectively analyzed. Radiotherapy(IMRT 45Gy/25#/5weeks) were delivered with megavolt computed tomography performed before every delivery to ensure the accuracy repeatability of gastric filling during treatment, with concurrent chemoctherapy(Capecitabine alone or XELOX*2 cycles). ResultsA total of 95 patients were included in the study with 93 patients (97.9%) had stage cT3/T4, 85 patients (89.5%) had stage N+.The location of the tumors was in the upper 1/3 in 85 patients (89.5%). Alltogether 93/95(97.9%) patients finished the neoadjuvant chemoradiation, 80 patients (84.2%) underwent gastric resection(58 D2 and 22 D1 gastrectomy). Pathology downstaging was observed in 68 patients (85.0%), including 66 patients (82.5%) with T downstaging and 56 patients (70.0%) with N downstaging. 11 patients (13.75%) obtained pathological complete response (pCR). The median follow-up was 44.7 months (19-96 months). Compared with the clinical efficacy of neoadjuvant chemotherapy in the previous literature, the clinical efficacy of image-guided IMRT combined with concurrent chemotherapy in patients with locally advanced resectable gastric cancer was improved, the 5-year OS, LRFS, and DMFS rates of patients were 46.98% (95% CI: 38.60%-55.36%), 86.55% (95% CI: 79.11%-93.99%), and 60.71% (95% CI: 51.49%-69.93%), respectively.Grades 3-4 leukopenia, anemia,and thrombocytopenia were observed in 13 (13.68%) patients, 9 (9.47%) patients, and 5 (5.26%) patients, respectively. Multivariate analysis demonstrated that pCR was significant prognostic factor for OS (HR =11.211, 95% CI: 1.500–83.813, P = 0.024).ConclusionCompared with the previous literature results of preoperative neoadjuvant chemotherapy for patients with gastric cancer, the application of image-guided IMRT(45Gy/25#/5weeks) combined with chemotherapy in preoperative neoadjuvant therapy for patients with locally advanced gastric cancer can achieve improved clinical efficacy, with higher rates of OS, LRFS, and DMFS, good tolerance of concurrent chemoradiotherapy with acceptable side effects.

Relation between body composition and severe diarrhea in patients treated with preoperative chemoradiation with capecitabine for rectal cancer: a single-centre cohort study

Background Chemoradiation with capecitabine followed by surgery is standard care for locally advanced rectal cancer (LARC). Severe diarrhea is considered a dose-limiting toxicity of adding capecitabine to radiation therapy. The aim of this study was to describe the risk factors and the impact of body composition on severe diarrhea in patients with LARC during preoperative chemoradiation with capecitabine. Methods A single centre retrospective cohort study was conducted in a tertiary referral centre. All patients treated with preoperative chemoradiation with capecitabine for LARC from 2009 to 2015 were included. Patients with locally recurrent rectal cancer who received chemoradiation for the first time were included as well. Logistic regression analyses were performed to identify risk factors for severe diarrhea. Results A total of 746 patients were included. Median age was 64 years (interquartile range 57–71) and 477 patients (64%) were male. All patients received a radiation dosage of 25 × 2 Gy during a period of five weeks with either concomitant capecitabine administered on radiation days or continuously during radiotherapy. In this cohort 70 patients (9%) developed severe diarrhea. In multivariable logistic regression analyses female sex (OR: 4.42, 95% CI 2.54–7.91) and age ≥ 65 (OR: 3.25, 95% CI 1.85–5.87) were the only risk factors for severe diarrhea. Conclusions Female patients and patients aged sixty-five or older had an increased risk of developing severe diarrhea during preoperative chemoradiation therapy with capecitabine. No relation was found between body composition and severe diarrhea.