Esophageal Cancer Radiotherapy Dose Escalation Meta Regression Commentary: "High vs. Low Radiation Dose of Concurrent Chemoradiotherapy for Esophageal Carcinoma With Modern Radiotherapy Techniques: A Meta-Analysis".
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SUBMITTER: Chow R
PROVIDER: S-EPMC8317968 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Purpose: The aim of this study was to evaluate the clinical benefit of different radiation doses in concurrent chemoradiotherapy (CCRT) for esophageal carcinoma using modern radiotherapy techniques. Methods: A systematic review was conducted by screening PubMed, EMBASE, Cochrane Central Register of Controlled Trials, SCOPUS, Wanfang, and Chinese National Knowledge Infrastructure (CNKI) databases with prespecified searching strategy. Studies which compared high radiation dose group with low-dose radiation group using modern radiotherapy techniques for esophageal cancer patients in CCRT were identified. The hazard ratios (HR) for overall survival (OS) and the odds ratios (OR) for local-regional failure (LRF), distant metastasis (DM), and toxicities were considered as the outcomes of interest. R 3.6.2 software was used for statistical analysis. Results: Twelve studies involving 10,896 patients were included for analyses. The results showed that the high-dose group had better OS (HR = 0.79, 95% CI = 0.70-0.90, P = 0.0004) and the local-regional control (OR = 0.59, 95% CI = 0.46-0.76, P < 0.0001), especially for patients who were diagnosed with squamous cell carcinoma (SCC). The subgroup analyses further indicated that ≥ circa 60 Gy can significantly improve the OS (HR = 0.73, 95% CI = 0.68-0.80, P < 0.0001) as well as the local-regional control (OR = 0.54, 95% CI = 0.40-0.74, P < 0.0001) as compared with < circa 60 Gy. Another subgroup analysis comparing ≤ 50.4 Gy with > 50.4 Gy showed no substantial difference in OS (HR = 0.98, 95% CI = 0.93-1.03, P = 0.43). In addition, there are no significant differences between the two groups in grade 3-5 radiation pneumonitis (OR = 1.05, 95% CI = 0.54-2.05, P = 0.89), grade 3-5 radiation esophagitis (OR = 1.40, 95% CI = 0.93-2.11, P = 0.11), treatment-related death (OR = 1.60, 95% CI = 0.70-3.66, P = 0.27), and DM (OR = 1.21, 95% CI = 0.92-1.59, P = 0.17). Conclusions: For esophageal carcinoma receiving CCRT with modern radiation techniques, evidence suggested that high-dose radiotherapy, especially ≥circa 60 Gy, had potentials to improve the OS and local-regional control without increase in severe toxicities when compared with low-dose radiotherapy. The result needs to be confirmed by randomized clinical trials.
| S-EPMC7418493 | biostudies-literature
Project description:BACKGROUND AND OBJECTIVES:Radiation Therapy Oncology Group (RTOG) 94-05 has demonstrated that higher dose radiation didn't improve outcome of patients with esophageal cancer (EC). However, several retrospective studies showed that a higher dose radiation based on modern radiotherapy techniques could improve overall survival (OS) and local control rate (LCR) of patients with EC, especially esophageal squamous cell cancer (ESCC). As trials have provided updated and controversial data, we performed this updated meta-analysis to investigate whether high-dose (> = 60 Gy) radiotherapy in definitive concurrent chemo-radiotherapy (CCRT) could yield benefit compared to standard dose radiotherapy. METHODS:A systematic literature search was carried out in the database of MEDLINE, PubMed and Embase. All studies published between 1 January 1990 and 31 December 2018 on the association between radiation dose and curative efficiency in EC were included in this meta-analysis. The hazard ratio (HR) was used to evaluate the time-to-event data employing RevMan version 5.3. RESULTS:Eight articles with a total of 3736 patients were finally included. Results indicated that there was a significant benefit in favor of high dose radiotherapy (HD-RT) regarding OS (HR = 0.78, 95%CI: 0.72-0.84, p < 0.001; 2-year OS risk ratio (RR) = 1.25, 95%CI: 1.14-1.37, p < 0.001), progression-free survival (PFS) (P = 0.001, HR = 0.7, 95%CI: 0.57-0.87) and LRFS (P < 0.001, HR = 0.52, 95%CI: 0.36-0.74) . CONCLUSIONS:HD-RT (> = 60 Gy) based on modern radiotherapy techniques in definitive CCRT appears to improve OS, PFS amd LRFS compared to the SD-RT in patients with ESCC.
| S-EPMC6798457 | biostudies-literature
Project description:BackgroundConcurrent chemoradiotherapy (CRT) with 5-fluorouracil (5-FU) and cisplatin (CDDP) are often associated with significant incidence of toxic effects in elderly patients with esophageal cancer. This phase I trial was designed to determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of S-1, an oral 5-FU derivative, when given with radiotherapy in elderly patients.MethodsPatients who were age of 70 years or older with histologically confirmed esophageal cancer, and had an Eastern Cooperative Oncology Group (ECOG) score of 0-2 were eligible for this study. Radiotherapy was administered in 1.8 Gy fractions 5 times weekly to a total dose of 54 Gy. S-1 was administered on days 1-14 and 29-42 at the following dosages: 60, 70, and 80 mg/m(2)/day.Trial registrationNCT01175447 (ClinicalTrials.gov).ResultsTwelve previously untreated patients were enrolled in this study. No grade 3 or 4 toxicity was observed in six patients treated at the 60 and 70 mg/m(2) dose levels. DLT was observed in four of six patients treated at the 80 mg/m(2) dose level. Two patients developed grade 3 esophagitis, one patient developed grade 3 esophagitis and pneumonitis, and one patient developed grade 3 thrombocytopaenia. Endoscopic complete response (CR) was observed in eight patients (66.7%). The median progression free survival (PFS) was 20 months and median overall survival was 29 months.ConclusionsThe MTD of S-1 was 80 mg/m(2), and the recommended dose (RD) for phase II studies was 70 mg/m(2). This regimen was well tolerated and active in elderly patients with esophageal cancer, meriting further investigation in phase II studies.
| S-EPMC4805812 | biostudies-literature
Project description:BackgroundThe optimal radiotherapy dose for locally advanced cervical esophageal squamous cell carcinoma (C-ESqCC) treated with definitive concurrent chemoradiotherapy (dCCRT) is unclear. Here, we aimed to compare the survival of those treated with high dose versus standard dose via a population based approach.MethodsEligible C-ESqCC patients diagnosed between 2011 and 2017 were identified via the Taiwan Cancer Registry. We used propensity score (PS) weighting to balance observable potential confounders between groups. The hazard ratio (HR) of death and incidence of esophageal cancer mortality (IECM) were compared between high (60-70 Gy) and standard dose (50-50.4 Gy). We also evaluated the outcome in supplementary analyses via alternative approaches.ResultsOur primary analysis consisted of 141 patients in whom covariates were well balanced after PS weighting. The HR of death when high dose was compared with standard dose was 0.65 (95% confidence interval [CI]: 0.4-1.03, p = 0.07). The HR of IECM was 0.74 (p = 0.45). The HR of OS remained similarly insignificant in supplementary analyses.ConclusionsWe observed a trend in favor of high radiotherapy dose versus standard dose for C-ESqCC treated with dCCRT in this population-based nonrandomized study. Further studies are needed to confirm the findings of the study.
| S-EPMC8287021 | biostudies-literature
Project description:BACKGROUND:Concurrent chemoradiotherapy is a standard treatment for local advanced esophageal cancer, but the outcomes are controversial. Our goals were to compare the therapeutic effects of concurrent chemoradiotherapy and radiotherapy alone in local advanced esophageal cancer using meta-analysis. METHODS:MEDLINE, EMBASE and the Cochrane library were searched for studies comparing chemoradiotherapy with radiotherapy alone for advanced esophageal cancer. Only randomized controlled trials were included, and extracted data were analyzed with Review Manager Version 5.2. The pooled relative risks (RR) and their 95% confidence intervals (CI) were calculated for statistical analysis. RESULTS:Nine studies were included. Of 1,135 cases, 612 received concurrent chemoradiotherapy and 523 were treated with radiotherapy alone. The overall response rate (complete remission and partial remission) was 93.4% for concurrent chemoradiotherapy and 83.7% for radiotherapy alone (P = 0.05). The RR values of 1-year, 3-year, and 5-year survival rates were 1.14 (95% CI: 1.04 - 1.24, P = 0.006), 1.66 (95% CI: 1.34 - 2.06, P < 0.001), and 2.43 (95% CI: 1.63 - 3.63, P < 0.001), respectively. The RR value of the merged occurrence rate of acute toxic effects was 2.34 (95% CI: 1.90 - 2.90, P <0.001). There was no difference in the incidence of late toxic effects, which had an RR value of 1.21 (95% CI: 0.96 - 1.54, P = 0.11). The RR level of persistence and recurrence was 0.71 (95% CI: 0.62 - 0.81, P <0.001), and for the distant metastasis rate, the RR value was 0.79 (95% CI: 0.61 - 1.02, P = 0.07). CONCLUSIONS:Concurrent chemoradiotherapy significantly improved overall survival rate, reduced the risk of persistence and recurrence, but had little effect on the primary tumor response, and increased the occurrence of acute toxic effects.
| S-EPMC4457836 | biostudies-literature
Project description:BackgroundTo date, intensity-modulated radiation therapy (IMRT) with concurrent chemoradiotherapy (CCRT) and CCRT with standard fractionation three-dimensional conformal radiation therapy (3D-CRT) have not been compared. In this study, the outcomes of IMRT-based concurrent CCRT and those of 3D-CRT-based CCRT were compared in patients with thoracic esophageal squamous cell carcinoma (TESCC).MethodsWe enrolled 2062 patients with TESCC who had received CCRT and categorized them into two groups on the basis of their treatment modality: Group 1 (3D-CRT-based CCRT) and Group 2 (IMRT-based CCRT).ResultsMultivariate Cox regression analysis indicated that the American Joint Committee on Cancer advanced stages (?IIIA) and 3D-CRT were significant independent predictors of poor outcomes in patients with TESCC who received definitive CCRT. Moreover, receiving IMRT-based CCRT (adjusted hazard ratio [aHR]: 0.88, 95% confidence interval [CI]: 0.78-0.98) was a significant independent prognostic factor for overall survival (p = 0.0223). In Group 2, aHRs (95% CIs) for overall mortality at early (IA-IIB) and advanced clinical stages were 0.91 (0.67-1.25, p = 0.5746) and 0.88 (0.77-0.99, p = 0.0368), respectively.ConclusionIMRT-based CCRT resulted in higher survival rates in patients with advanced clinical stages of TESCC (i.e., IIIA-IIIC), namely, clinical T3, clinical T4, or lymph node involvement.
| S-EPMC6826542 | biostudies-literature
Project description:Purpose: This meta-analysis was aimed to evaluate the role of postoperative concurrent chemoradiotherapy (post-CCRT) for esophageal cancer patients after surgery. Methods: We systematically searched PubMed, PMC, EMBASE, Cochrane Central Register of Controlled Trials, Chinese National Knowledge Infrastructure and Wanfang databases. Studies which compared CCRT with non-CCRT treatment for esophageal cancer patients after surgery were eligible. Outcomes of interest were odds ratios (OR) for overall survival (OS), local-regional recurrence rate, distant metastasis rate and adverse-event rate. Results: Thirteen studies with 2165 patients were included in this meta-analysis. Post-CCRT significantly improved OS for esophageal cancer patients. Comparing the CCRT group with the non-CCRT one, the OR and 95% confidence interval (CI) for 1-year, 3-year and 5-year OS were 1.66 [1.30-2.11], 1.50 [1.24-1.81] and 1.54 [1.22-1.94], respectively. The local-regional recurrence rate was significantly reduced in the CCRT group (OR=0.58, 95% CI=0.46-0.72), but no significant difference was observed in the distant metastasis rate between the CCRT and non-CCRT groups (OR=0.94, 95% CI=0.68-1.30). Post-CCRT didn't increase the risk of pneumonitis, anastomotic stenosis or severe hematologic toxicities. Mild esophagitis in the CCRT group was increased but could be well tolerated. Conclusions: This meta-analysis based on the largest-scale of published literature confirms that post-CCRT yields significant survival benefit and improves local-regional control with tolerable toxicity for patients with esophageal carcinoma.
| S-EPMC5820926 | biostudies-literature
Project description:ObjectiveTo evaluate the efficacy and safety of cisplatin-based concurrent chemoradiotherapy (DDP-CCRT) in patients with high-risk cervical carcinoma (CC) compared with exclusive radiotherapy (RT).Materials and methodsDatabases were searched for randomized controlled trials (RCTs) and cohort studies comparing DDP-CCRT with RT alone. Risk of bias assessment for RCTs was performed using the Cochrane Collaboration's tool, and the Newcastle-Ottawa quality scale was used to perform quality assessment for cohort studies. Meta-analysis was conducted using Review Manager 5 and Stata 12.0 software.ResultsFinally, eight RCTs and three cohort studies containing 2,130 subjects were included. Analysis on total failures revealed a statistically significant difference in favor of DDP-CCRT (risk ratio =0.77, 95% confidence intervals [CIs]: 0.67-0.89). No significant heterogeneity was detected for pooled analysis concerning overall survival; the result of which demonstrated the superiority of DDP-CCRT over RT alone (hazard ratio =0.68, 95% CI: 0.57-0.80), and stable and established accumulative effects were observed in cumulative meta-analysis. Similar results were observed for progression-free survival (hazard ratio =0.63, 95% CI: 0.50-0.76). In terms of treatment-related Grade 3 and 4 adverse events, our pooled analysis with a fixed-effects model showed significantly enhanced toxicity in the DDP-CCRT group compared with that in the RT group (odds ratio =3.13, 95% CI: 2.37-4.13).ConclusionSolid and stable beneficial effects are associated with DDP-CCRT, and its superiority over comparative RT in patients with high-risk CC is confirmed. DDP-CCRT should be considered one of the frontline treatment options for high-risk CC patients without contraindications. However, enhanced toxicity associated with DDP-CCRT should never be ignored.
| S-EPMC4821385 | biostudies-literature
Project description:We hypothesised that gastric cancer outcome could be improved with more effective and intensified postoperative chemoradiotherapy. This phase I/II study was performed to determine the maximal tolerated dose (MTD) and toxicity profile of postoperative radiotherapy with concurrent daily cisplatin and capecitabine. Patients were treated with capecitabine 1000 mg m(-2) twice a day (b.i.d.) for 2 weeks. Subsequently, patients received capecitabine (250-650 mg m(-2) orally b.i.d., 5 days week(-1)) and cisplatin (3-6 mg m(-2) i.v., 5 days week(-1)) according to an alternating dose-escalation schedule. Radiotherapy was given to a total dose of 45 Gy in 25 fractions. Thirty-one patients completed treatment. During chemoradiotherapy, eight patients developed nine items of grade III and one episode of grade IV (mainly haematological) toxicity. The MTD was determined to be cisplatin 5 mg m(-2) i.v. and capecitabine 650 mg m(-2) b.i.d. orally. This phase I/II study demonstrated that chemoradiotherapy with daily cisplatin and capecitabine is feasible in postoperative gastric cancer at the defined dose level and is currently being tested in a phase III multicenter study.
| S-EPMC2360378 | biostudies-literature
Project description:PURPOSE:To evaluate the effect of escalated dose radiation therapy (EDR, defined as doses >50.4 Gy in 28 fractions [59.5 Gy BED]) on overall survival (OS), freedom from local progression (FFLP), and freedom from distant progression (FFDP) of patients with unresectable extrahepatic cholangiocarcinoma (EHCC). METHODS:A consecutive cohort of 80 patients who underwent radiotherapy for unresectable EHCC from 2001 to 2015 was identified. Demographic, tumor, treatment, toxicity, and laboratory variables were collected. The maximal RT doses ranged from 30 to 75 Gy (median 50.4 Gy, at 1.8-4.5 Gy/fraction). Gross tumor volume (GTV) coverage by maximal dose in EDR group ranged from 38% to 100%. Kaplan-Meier method was used to estimate OS, FFLP, and FFDP. Univariate and multivariate Cox regression models were analyzed. RESULTS:After radiotherapy, median OS, FFLP, and FFDP were 18.7, 22.6, and 24.3 months, respectively. There was no significant difference in OS or FFLP between patients who received EDR to portions of the GTV and patients who did not. On multivariate analysis, bigger GTV, age, and ECOG performance status were independently associated with shorter OS. Local progression on chemotherapy prior to RT was independently associated with shorter FFLP. High baseline neutrophil/lymphocyte ratio (>5.3) was independently associated with shorter FFDP. Toxicity grades were similar in EDR and lower doses except lymphopenia which was higher in EDR (P = 0.053). CONCLUSIONS:EDR to selective portions of the GTV may not benefit patients with unresectable EHCC despite having acceptable toxicity. New methods to improve local control and survival for unresectable EHCC are needed.
| S-EPMC6198206 | biostudies-other