The impact of the time to start radiation therapy on overall survival in newly diagnosed glioblastoma.

PURPOSE: The standard treatment for newly diagnosed glioblastoma includes maximal safe surgical resection followed by concurrent radiation therapy and temozolomide (TMZ) and maintenance TMZ. The impact of time to start radiation therapy (TRT) on overall survival (OS) in glioblastoma patients is controversial. The study aimed to evaluate the impact of TRT on OS in patients diagnosed with glioblastoma who received standard treatment. METHODS: In this retrospective study, we included patients with confirmed diagnosis of glioblastoma treated from 2011 to 2016. TRT was defined as the time between surgery (biopsy or resection) and the first day of radiation therapy. The endpoint was OS. The patients were divided according to the TRT in three categories: < 30 days, 30-60 days and ≥ 60 days. RESULTS: A total of 134 patients were included with a mean age of 51.82 years (range 19-78 years). Median TRT was 80 days. On univariate and multivariable analysis, we identified age as the only significant independent predictor for OS. There was no statistically significant negative impact of TRT on OS (p = 0.47). CONCLUSIONS: There was no clear evidence that delaying post-operative combined chemoradiotherapy negatively impacts OS, not even for TRT longer than 60 days.

Brazil-TNT: A Randomized Phase 2 Trial of Neoadjuvant Chemoradiation Followed by FOLFIRINOX Versus Chemoradiation for Stage II/III Rectal Cancer.

BACKGROUND: Neoadjuvant radiation and oxaliplatin-based systemic therapy (total neoadjuvant therapy-TNT) have been shown to increase response and organ-preservation rates in localized rectal cancer. However, trials have been heterogeneous regarding treatment protocols and few have used a watch-and-wait (WW) approach for complete responders. This trial evaluates if conventional long-term chemoradiation followed by consolidation of FOLFIRINOX increases complete response rates and the number of patients managed by WW. METHODS: This was a pragmatic randomized phase II trial conducted in 2 Cancer Centers in Brazil that included patients with T3+ or N+ rectal adenocarcinoma. After completing a long-course 54 Gy chemoradiation with capecitabine patients were randomized 1:1 to 4 cycles of mFOLFIRINOX (Oxaliplatin 85, irinotecan 150, 5-FU 2400)-TNT-arm-or to the control arm, that did not include further neoadjuvant treatment. All patients were re-staged with dedicated pelvic magnetic resonance imaging and sigmoidoscopy 12 weeks after the end of radiation. Patients with a clinical complete response were followed using a WW protocol. The primary endpoint was complete response: clinical complete response (cCR) or pathological response (pCR). RESULTS: Between April 2021 and June 2023, 55 patients were randomized to TNT and 53 to the control arm. Tumors were 74% stage 3, median distance from the anal verge was 6 cm, 63% had an at-risk circumferential margin, and 33% an involved sphincter. The rates of cCR + pCR were (31%) for TNT versus (17%) for controls (odds ratio 2.19, CI 95% 0.8-6.22 P = .091) and rates of WW were 16% and 9% (P = ns). Median follow-up was 8.1 months and recurrence rates were 16% versus 21% for TNT and controls (P = ns). CONCLUSIONS: TNT with consolidation FOLFIRINOX is feasible and has high response rates, consistent with the current literature for TNT. This trial was supported by a grant from the Brazilian Government (PROADI-SUS - NUP 25000.164382/2020-81).

The impact of metastatic sites in advanced pancreatic adenocarcinoma, systematic review and meta-analysis of prospective randomized studies.

The real impact of specific sites of metastasis on prognosis of metastatic pancreatic cancer (MPC) is unknown. To evaluate the association of specific metastatic sites and survival outcomes in MPC a systematic literature review was performed including prospective randomized trials of systemic treatments in metastatic pancreatic cancer indexed in PubMed, Embase and Web of Science. Data regarding systemic treatment regimens, progression free survival and overall survival were extracted. The outcomes were compared using a random effects model. The index I2 and the graphs of funnel plot were used for the interpretation of the data. Of 1,052 abstracts, 7 randomized trials were considered eligible with a combined sample size of 2,975 MPC patients. Combining the studies with meta-analysis, we could see that patients with liver metastasis had a HR for death of 1.53 with 95% CI of 1.15 to 2.02 (p-value 0.003) and HR for risk of progression of 1.96 with 95% CI of 1.28 to 2.99 (p-value 0.002), without significant heterogeneity. Having two or more sites of metastasis comparing to one site did not have impact on overall survival; RR of 1.05 with 95% CI 0.91 to 1.23 (p-value 0.493). In conclusion, liver metastasis confers worse outcomes among patients with MPC. Apparently, multiple metastatic sites do not present worse prognosis when compared with only one organ involved, therefore, demonstrating the severity of this disease. Prospective studies evaluating other treatments are necessary to address the impact of local treatments in liver metastasis in MPC.

Systematic review and meta-analysis of docetaxel perioperative chemotherapy regimens in gastric and esophagogastric tumors.

FLOT regimen became the standard perioperative treatment in several centers around the world for esophagogastric tumors despite concerns about toxicity. In addition, FLOT has never been compared with other docetaxel-based regimens. To address this question, we conducted a systematic review of PubMed, Embase and Web of Science including prospective or retrospective studies of docetaxel based perioperative regimen in gastric and esophagogastric tumors. Data regarding chemotherapy regimens, efficacy and toxicity were extracted. Outcomes were compared using a random effects model. Of 548 abstracts, 16 were considered eligible. Comparing the studies with meta-analysis we can see that the regimens are similar in terms of pathological complete response, resection rate, progression free survival and overall survival in one year, without significant heterogeneity. The meta-regression of docetaxel dose failed to show any association with dose ranging between 120-450 mg/m². Regarding the toxicity of the regimens it is noted that the regimens are quite toxic (up to 50-70% of grade 3-4 neutropenia). The results of this meta-analysis with a combined sample size of more than 1,000 patients suggest that docetaxel perioperative regimens are equivalent in outcomes. Prospective trials addressing modified regimens should be performed to provide less toxic strategies and be applicable to all patients.