A Predictive Model to Evaluate Pathologic Complete Response in Rectal Adenocarcinoma.

Introduction: Neoadjuvant chemo-radiotherapy (nCRT) before surgery was a standard treatment strategy for locally advanced rectal cancer (LARC). The aim of this study was to assess the relationship between the predictive factors and pathological complete response (pCR) in rectal cancer patients, especially in ultra-low ones. Method: A total of 402 patients were involved in this retrospective study. The logistic regression analyses were used to compare the different subgroups in univariate analysis. Multivariate analysis was performed to determine the independent predictive factors of pCR by using a logistic regression model. Results: A total of 402 patients received preoperative CRT. In all patients, multivariate analysis revealed that circumferential tumor extent rate (CER) (≤ 2/3cycle vs >2/3 cycle, P < .001, OR = 4.834, 95% CI: 2.309-10.121), carcinoembryonic antigen (CEA) level (both ≤ 5 vs pre > 5 and post ≤ 5 vs both > 5, P = .033, OR = 1.537, 95% CI: 1.035-2.281), and interval time between the end of CRT and surgery (P = .031, OR = 2.412, 95% CI: 1.086-5.358) were predictive factors for pCR. The area under the curve (AUC) of the predictive model was 0.709 (95% CI: 0.649-0.769), which was significantly higher than the CER (0.646, 95% CI: 0.584-0.709), interval time (0.563, 95% CI: 0.495-0.631) and CEA level (0.586, 95% CI: 0.518-0.655). In ultra-low rectal patients, multivariate logistic regression analysis revealed that CER (≤ 2/3 cycle vs > 2/3 cycle, P = .003, OR = 7.203, 95% CI: 1.934-26.823) and mismatch repair (MMR) status (pMMR vs dMMR, P = .016, OR = 0.173, 95% CI: 0.041-0.720) were predictive factors for pCR. The AUC of the predictive model was 0.653 (95% CI: 0.474-0.832). Conclusion: New predictive models were varied by the histologic types and MMR statuses to evaluate the trend of tumor response to nCRT in all RC cases and ultra-low RC patients, which may be used to individualize stratify for selected LARC patients.

Neoadjuvant Chemo-Radiation Using IGRT in Patients with Locally Advanced Gastric Cancer.

The goal of this study was to see how effective and safe neoadjuvant chemoradiation with image-guided IMRT was in patients with locally advanced resectable gastric cancer. Between January 2013 and June 2019, patients with locally advanced (cT3/cT4 or N+) gastric cancer treated with neoadjuvant chemoradiotherapy at PUMCH (Peking Union Medical College Hospital) were retrospectively studied. Using concurrent chemotherapy (Capecitabine alone or XELOX*2 cycles), radiotherapy (IMRT (intensity-modulated radiation therapy) 45 Gy, 25#, 5 weeks) was delivered with IGRT (image-guided radiotherapy) before the start of each weeks therapy to ensure accuracy and repeatability. A total of 95 patients were enrolled in the study, 93 (97.9%) stage cT3/T4 and 85 (89.5%) stage N+. Of these, 85 patients (89.5%) had a tumor located in the upper 1/3 of the stomach, and 93/95 patients (97.9%) completed neoadjuvant chemoradiation, with 80 patients (84.2%) undergoing stomach resection (58 D2 and 22 D1 gastrostomies). Pathology downstaging was found in 68 patients (85.0%), with 66 patients (82.5%) receiving T downstaging and 56 patients (70.0%) receiving N downstaging. There were 11 individuals (13.8%) who had a pathological complete response (PCR). The average period of follow-up was 44.7 months (19-96 months). The 5-year OS (overall survival), LRFS (local recurrence-free survival), and DMFS (distant metastasis free survival) rates of patients were 47.0% (95% CI: 38.6-55.4), 86.55% (95% CI: 79.1-93.99) and 60.71% (95% CI: 51.49-69.93%), respectively. Thirteen (13.7%) patients had grade 3-4 leukopenia, anemia, and thrombocytopenia, while 9 (9.5%) patients had grade 3-4 anemia, and 5 (5.3%) patients had grade 3-4 thrombocytopenia. PCR was found to be a significant predictive factor for OS in multivariate analysis (HR = 11.211, 95% CI: 1.500-83.813, p = 0.024). The method of using IGRT image-guided IMRT (45 Gy, 25 fractions, 5 weeks) combined with concurrent chemotherapy in patients with locally advanced resectable gastric cancer was equally effective when compared to the clinical efficacy of neoadjuvant chemoradiotherapy, with clinical outcomes achieving equal efficacy, with similar PCR rates and high rates of OS, LRFS, and DMFS, as well as good tolerances of concurrent chemoradiotherapy with acceptable side effects.

Preoperative versus postoperative chemo-radiotherapy for locally advanced gastric cancer: a multicenter propensity score-matched analysis.

BACKGROUND: Peri-operative chemo-radiotherapyplayed important rolein locally advanced gastric cancer. Whether preoperative strategy can improve the long-term prognosis compared with postoperative treatment is unclear. The study purpose to compare oncologic outcomes in locally advanced gastric cancer patients treated with preoperative chemo-radiotherapy (pre-CRT) and postoperative chemo-radiotherapy (post-CRT). METHODS: From January 2009 to April 2019, 222 patients from 2 centers with stage T3/4 and/or N positive gastric cancer who received pre-CRT and post-CRT were included. After propensity score matching (PSM), comparisons of local regional control (LC), distant metastasis-free survival (DMFS), disease-free survival (DFS) and overall survival (OS) were performed using Kaplan-Meier analysis and log-rank test between pre- and post-CRT groups. RESULTS: The median follow-up period was 30 months. 120 matched cases were generated for analysis. Three-year LC, DMFS, DFS and OS for pre- vs. post-CRT groups were 93.8% vs. 97.2% (p = 0.244), 78.7% vs. 65.7% (p = 0.017), 74.9% vs. 65.3% (p = 0.042) and 74.4% vs. 61.2% (p = 0.055), respectively. Pre-CRT were significantly associated with DFS in uni- and multi-variate analysis. CONCLUSION: Preoperative CRT showed advantages of oncologic outcome compared with postoperative CRT. TRIAL REGISTRATION: ClinicalTrial.gov NCT01291407 , NCT03427684 and NCT04062058 , date of registration: Feb 8, 2011.

[Long-term outcome of patients with pyriform sinus squamous cell carcinoma treated with planned preoperative (chemo-) radiotherapy plus laryngeal function sparing surgery].

Objective: To analyze the long-term outcome of patients with pyriform sinus squamous cell carcinoma treated with planned preoperative (chemo-) radiotherapy plus laryngeal function sparing surgery. Methods: Patients with stage Ⅲ/Ⅳ pyriform sinus squamous cell carcinoma treated with planned preoperative (chemo-) radiotherapy plus laryngeal function sparing surgery during 1999 to 2000 were retrospectively analyzed. Data including concurrent chemotherapy or not, postoperative pathological diagnosis, postoperative complications, recurrence and survival were collected. Twenty patients were treated with preoperative radiotherapy while 14 patients with preoperative chemo-radiotherapy. Results: Among 31 cases of postoperative pathological diagnosed as pyriform sinus, 12 (38.7%) cases without tumor residue, 7 (22.5%) cases with severe radiation response and 12 (38.7%) cases with tumor residue. The 5-year cumulative local recurrence rate, regional recurrence rate and distant metastasis rate was 14.5%, 13.7% and 23.5%, respectively. Five-year cumulative overall survival rate and recurrence-free survival rate were 69.6% and 65.4%, respectively. Nine deaths were attributed to distant metastasis (8 cases) and regional recurrence (1 case). Conclusion: Most patients with pyriform sinus squamous cell carcinoma acquire long-term survival after treated with planned preoperative (chemo-) radiotherapy plus laryngeal function sparing surgery, and distant metastasis is the main cause of death.

Long-term outcome of patients with pyriform sinus squamous cell carcinoma treated with planned preoperative (chemo-) radiotherapy plus laryngeal function sparing surgery / 中华肿瘤杂志

Objective@#To analyze the long-term outcome of patients with pyriform sinus squamous cell carcinoma treated with planned preoperative (chemo-) radiotherapy plus laryngeal function sparing surgery.@*Methods@#Patients with stage Ⅲ/Ⅳ pyriform sinus squamous cell carcinoma treated with planned preoperative (chemo-) radiotherapy plus laryngeal function sparing surgery during 1999 to 2000 were retrospectively analyzed. Data including concurrent chemotherapy or not, postoperative pathological diagnosis, postoperative complications, recurrence and survival were collected. Twenty patients were treated with preoperative radiotherapy while 14 patients with preoperative chemo-radiotherapy.@*Results@#Among 31 cases of postoperative pathological diagnosed as pyriform sinus, 12 (38.7%) cases without tumor residue, 7 (22.5%) cases with severe radiation response and 12 (38.7%) cases with tumor residue. The 5-year cumulative local recurrence rate, regional recurrence rate and distant metastasis rate was 14.5%, 13.7% and 23.5%, respectively. Five-year cumulative overall survival rate and recurrence-free survival rate were 69.6% and 65.4%, respectively. Nine deaths were attributed to distant metastasis (8 cases) and regional recurrence (1 case).@*Conclusion@#Most patients with pyriform sinus squamous cell carcinoma acquire long-term survival after treated with planned preoperative (chemo-) radiotherapy plus laryngeal function sparing surgery, and distant metastasis is the main cause of death.

Critical role of bevacizumab scheduling in combination with pre-surgical chemo-radiotherapy in MRI-defined high-risk locally advanced rectal cancer: Results of the BRANCH trial.

BACKGROUND: We have previously shown that an intensified preoperative regimen including oxaliplatin plus raltitrexed and 5-fluorouracil/folinic acid (OXATOM/FUFA) during preoperative pelvic radiotherapy produced promising results in locally advanced rectal cancer (LARC). Preclinical evidence suggests that the scheduling of bevacizumab may be crucial to optimize its combination with chemo-radiotherapy. PATIENTS AND METHODS: This non-randomized, non-comparative, phase II study was conducted in MRI-defined high-risk LARC. Patients received three biweekly cycles of OXATOM/FUFA during RT. Bevacizumab was given 2 weeks before the start of chemo-radiotherapy, and on the same day of chemotherapy for 3 cycles (concomitant-schedule A) or 4 days prior to the first and second cycle of chemotherapy (sequential-schedule B). Primary end point was pathological complete tumor regression (TRG1) rate. RESULTS: The accrual for the concomitant-schedule was early terminated because the number of TRG1 (2 out of 16 patients) was statistically inconsistent with the hypothesis of activity (30%) to be tested. Conversely, the endpoint was reached with the sequential-schedule and the final TRG1 rate among 46 enrolled patients was 50% (95% CI 35%-65%). Neutropenia was the most common grade ≥ 3 toxicity with both schedules, but it was less pronounced with the sequential than concomitant-schedule (30% vs. 44%). Postoperative complications occurred in 8/15 (53%) and 13/46 (28%) patients in schedule A and B, respectively. At 5 year follow-up the probability of PFS and OS was 80% (95%CI, 66%-89%) and 85% (95%CI, 69%-93%), respectively, for the sequential-schedule. CONCLUSIONS: These results highlights the relevance of bevacizumab scheduling to optimize its combination with preoperative chemo-radiotherapy in the management of LARC.

A perspective on the current treatment strategies for locally advanced rectal cancer.

The introduction of total mesorectal excision (TME) and preoperative multimodality treatment have substantially improved the management of rectal cancer reducing local recurrence and increasing sphincter-saving surgery; distant metastases however remain a clinical challenge. Besides, although surgery remains the mainstay for cure of rectal cancer with the multimodality approach (chemotherapy, radiotherapy and surgery) being the standard of care for the majority of rectal cancer patients, there is a need of individualized risk-adapted treatment schemes based on clinico-pathological features because of treatment-induced morbidity and quality of life deterioration. This short viewpoint describes the emerging strategies addressing all these issues.