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The Role of Consolidation Chemoradiotherapy in Locally Advanced Pancreatic Cancer Receiving Chemotherapy: An Updated Systematic Review and Meta-Analysis.

ABSTRACT: The role of consolidation chemoradiation (CCRT) after systemic chemotherapy in locally advanced pancreatic cancer (LAPC) is still controversial. We aim to evaluate the effectiveness of CCRT in LAPC using systematic review and meta-analysis of prospective studies.Prospective clinical trials of LAPC receiving chemotherapy with or without subsequent CCRT were included in the analysis. We systematically searched in PubMed, MEDLINE, Embase, and Web of Science. The primary outcome of interest was 1-year survival. Secondary endpoints were median overall survival, progression-free survival, toxicity, and resection rate.Forty-one studies with 49 study arms were included with a total of 1,018 patients receiving CCRT after induction chemotherapy (ICT) and 954 patients receiving chemotherapy alone. CCRT after ICT did not improve 1-year survival significantly in LAPC patients compared with chemotherapy alone (58% vs. 52%). ICT lasted for at least 3 months revealed significantly improved survival of additional CCRT to LAPC patients compared to chemotherapy alone (65% vs. 52%). A marginal survival benefit of consolidation CCRT was noted in studies using maintenance chemotherapy (59% vs. 52%), and fluorouracil-based CCRT (64% vs. 52%), as well as in studies conducted after the 2010 (64% vs. 55%).The survival benefit of ICT+CCRT over chemotherapy alone in treating LAPC was noted when ICT lasted for at least 3 months. Fluorouracil-based CCRT, and maintenance chemotherapy were associated with improved clinical outcomes.

SUBMITTER: Chang JS

PROVIDER: S-EPMC5912129 | biostudies-other | 2018 Apr

REPOSITORIES: biostudies-other

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The Role of Consolidation Chemoradiotherapy in Locally Advanced Pancreatic Cancer Receiving Chemotherapy: An Updated Systematic Review and Meta-Analysis.

Chang Jeffrey S JS Chiu Yen-Feng YF Yu Jih-Chang JC Chen Li-Tzong LT Ch'ang Hui-Ju HJ

Cancer research and treatment 20170609 2

<h4>Purpose</h4>The role of consolidation chemoradiation (CCRT) after systemic chemotherapy in locally advanced pancreatic cancer (LAPC) is still controversial. We aim to evaluate the effectiveness of CCRT in LAPC using systematic review and meta-analysis of prospective studies.<h4>Materials and methods</h4>Prospective clinical trials of LAPC receiving chemotherapy with or without subsequent CCRT were included in the analysis. We systematically searched in PubMed, MEDLINE, Embase, and Web of Sci ...[more]

PMID: 28602054

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Project description:The benefit of adjuvant hysterectomy after definitive concurrent chemoradiotherapy (CCRT) for locally-advanced cervical cancer (LACC) is controversial. The purpose of the present study was to systematically search the literature and perform a meta-analysis to compare overall survival (OS) and disease-free survival (DFS) between patients subjected to CCRT with hysterectomy and those who underwent CCRT alone. The PubMed, Scopus, Embase and Google scholar databases were searched. A meta-analysis to determine hazard ratios (HRs) and odds ratios (ORs) with meta-regression was performed for the following moderators: Disease stage, histology and proportion of radical hysterectomy. Data from 14 studies were included. The results indicated that patients who received CCRT with hysterectomy had significantly better OS (HR, 0.72; 95% CI, 0.56 to 0.91; I2=19%; P=0.007) and DFS (HR, 0.72; 95% CI, 0.56 to 0.93; I2=27%; P=0.01) than those treated with CCRT alone. However, in a subgroup analysis by study type, the results were significant only for retrospective studies but not for randomized controlled trials (RCTs). However, only 2 RCTs were included with small sample size, heterogeneity and low overall quality. Subgroup analyses based on the use of brachytherapy in the CCRT with hysterectomy group demonstrated no difference in OS and DFS between the two groups. Regarding the absolute numbers of death and recurrence events, no significant difference in mortality (OR, 0.91; 95% CI, 0.62 to 1.33; I2=0%; P=0.64) was determined between the two groups, but a significantly reduced incidence of recurrence was observed in the CCRT with hysterectomy group (OR, 0.61; 95% CI, 0.47-0.79; I2=29%; P=0.0002). The meta-regression results point to a significant influence of the proportion of stage II patients on OS. Despite the overall analysis indicating improved OS and DFS with the use of adjuvant hysterectomy after CCRT, subgroup analysis based on similar treatment protocols failed to demonstrate any significant benefit of hysterectomy in LACC. However, the results indicated that the recurrence rate may be higher in patients undergoing CCRT without hysterectomy. The limited quality of the studies included and selection bias from retrospective studies restrict the possibility to draw strong conclusions.

Project description:BackgroundPatients with locally advanced rectal cancer (LARC) have an improved prognosis if achieved a pathological complete response (pCR) on account of neoadjuvant chemoradiation therapy (nCRT). However, the proportion of patients achieving pCR is only 8-24%. The purpose of this study was to explore whether the addition of consolidation chemotherapy to nCRT could improve pCR rate in patients with LARC.Materials and methodsThe subjects were 144 individuals with clinical stage II (T3-4, N0) or III (any T, N1-2) LARC who had received neoadjuvant CRT followed by total mesorectal excision (TME). Eighty-three patients in the consolidation chemotherapy group received two cycles XELOX between CRT and TME, while 61 patients in the standard treatment group without consolidation chemotherapy. The pCR (ypT0N0), tumor downstaging (ypT0-2N0) after TME and adverse events (AEs) during and post treatment were compared between the treatment groups using multivariable logistic regression analysis. To adjust the unbalanced variables for the primary endpoint, logistic regression analysis and stratified analysis were performed.ResultsThe consolidation chemotherapy group improved pCR rate (19.3% vs 4.9%, p = 0.01) and tumor downstaging rate (45.8% vs 24.6%, p = 0.009) compared to the standard treatment group. After adjustment for clinical tumor stage, clinical nodal stage and time interval to surgery, patients with consolidation chemotherapy were more likely to reach pCR (adjusted odds ratio 4.91, 95% CI [1.01-23.79], p = 0.048). AEs during and post treatment in the two groups were 54.1% vs 49.3% (p = 0.57), respectively. In addition, the incidence of any grade 1-2 AEs in the two groups was 93.4% vs 95.1% (p = 0.93), while the incidence of grade 3 AEs was 1.6% versus 2.4% (p = 0.74), respectively. No grade 4 AEs occurred in two groups.ConclusionsThe addition of neoadjuvant consolidation chemotherapy after CRT significantly increased the pCR rate and did not increase the AEs during and post treatment and in patients with LARC.

Project description:BackgroundThere is no consensus on the indication for salvage chemoradiotherapy (CRT) after failure of primary chemotherapy for locally advanced pancreatic cancer (LAPC). Here we report on the retrospective analysis of patients who received salvage CRT after primary chemotherapy for LAPC. The primary objective of this study was to evaluate the efficacy and safety of salvage CRT after primary chemotherapy for LAPC.MethodsThirty patients who underwent salvage CRT, after the failure of primary chemotherapy for LAPC, were retrospectively enrolled from 2004 to 2011 at the authors' institution. All the patients had histologically confirmed pancreatic adenocarcinoma.ResultsPrimary chemotherapy was continued until progression or emergence of unacceptable toxicity. Eventually, 26 patients (87%) discontinued primary chemotherapy because of local tumor progression, whereas four patients (13%) discontinued chemotherapy because of interstitial pneumonitis caused by gemcitabine. After a median period of 7.9 months from starting chemotherapy, 30 patients underwent salvage CRT combined with either S-1 or 5-FU. Toxicities were generally mild and self-limiting. Median survival time (MST) from the start of salvage CRT was 8.8 months. The 6 month, 1-year and 2-year survival rates from the start of CRT were 77%, 33% and 26%, respectively. Multivariate analysis revealed that a lower pre-CRT serum CA 19-9 level (≤ 1000 U/ml; p = 0.009) and a single regimen of primary chemotherapy (p = 0.004) were independent prognostic factors for survival after salvage CRT. The MST for the entire patient population from the start of primary chemotherapy was 17.8 months, with 2- and 3-year overall survival rates of 39% and 22%, respectively.ConclusionsCRT had moderate anti-tumor activity and an acceptable toxicity profile in patients with LAPC, even after failure of gemcitabine-based primary chemotherapy. If there are any signs of failure of primary chemotherapy without distant metastasis, salvage CRT could be a treatment of choice as a second-line therapy. Patients with relatively low serum CA19-9 levels after primary chemotherapy may achieve higher survival rates after salvage CRT. The strategy of using chemotherapy alone as a primary treatment for LAPC, followed-by CRT with salvage intent should be further investigated in prospective clinical trials.Trial registration2011-136

Project description:IntroductionConcurrent chemoradiotherapy (CCRT) is the standard of care for inoperable locally advanced non-small cell lung cancer. To further improve prognosis, the use of consolidation treatments after CCRT has been explored extensively. Although durvalumab is the only consolidation treatment recommended by national clinical practice guidelines, there have been many studies exploring the effectiveness of other agents. However, until now, no studies have compared all agents systematically, and no studies have provided evidence for the optimal combination of different CCRTs and consolidation treatments regimens. This systematic review will evaluate the comparative clinical efficacy of consolidation therapies after CCRT as well as various combinations of CCRTs and consolidation therapies.Methods and analysisPubMed, the Cochrane Controlled Register of Trials (CENTRAL), EMBASE and ClinicalTrials.gov will be searched for relevant information. The estimated end date for the search will be 3 February 2022. Each stage of the review, including the study section, data extraction and risk of bias and quality of evidence assessments, will be performed in duplicate. We will include randomised controlled trials that included participants who received CCRT and consolidation treatment in at least one treatment arm. The primary endpoints will be overall survival and progression-free survival. Tumour response, health-related quality of life, disease-free survival and treatment-related toxicity will be presented as secondary outcomes. Both traditional meta-analysis and network meta-analysis (NMA) with the Bayesian approach will be conducted. Subgroup analyses and meta-regression will be completed to investigate heterogeneity, and sensitivity analyses will be conducted to assess the robustness of the findings.Ethics and disseminationEthical approval and patient consent are not required as this study is a meta-analysis based on published studies. The results of this study will be submitted to a peer-reviewed journal for publication. In case of any changes in the protocol, protocol amendments will be updated in PROSPERO and explanations of these modifications will be described in the final report of this review. The results of this systematic review and NMA will be published in a peer-reviewed journal.Prospero registration numberCRD42021239433.

Project description:BackgroundConcurrent chemoradiotherapy followed by adjuvant chemotherapy (CCRT-AC) is currently recommended as the standard treatment for locally advanced nasopharyngeal carcinoma (LA-NPC). Neoadjuvant chemotherapy followed by concurrent chemoradiotherapy (NAC-CCRT) is an alternative strategy for decreasing tumor size and controlling micrometastases before main treatment. The aim of this study was to investigate and compare survival outcomes between LA-NPC patients treated with CCRT-AC and those treated with NAC-CCRT.MethodsThis retrospective cohort study included consecutive histologically confirmed LA-NPC patients that were treated with NAC-CCRT or CCRT-AC at Siriraj Hospital during the March 2010 to October 2014 study period. CCRT in both protocols consisted of 3-week cycles of cisplatin 100 mg/m2 with concurrent radiotherapy. Either NAC or AC consisted of 3-week cycles of cisplatin on day 1 and fluorouracil/leucovorin on days 1-4 for a maximum three cycles. The primary endpoint was 5-year overall survival (OS). Flexible parametric survival analysis was used, because the proportional hazards assumption of Cox regression was violated.ResultsOf the 266 LA-NPC patients that received treatment during the study period, 79 received NAC-CCRT and 187 received CCRT-AC. Median follow-up was 37 months. Significantly more patients with advanced clinical stage (stage IVA-IVB) received NAC-CCRT (86% in NAC-CCRT vs. 29% in CCRT-AC; p < 0.001). Compared to CCRT-AC in crude analysis, 3-year and 5-year OS of NAC-CCRT were 72% vs. 86% and 62% vs. 75% respectively (p = 0.059). Interestingly, the 3-year and 5-year post-estimation adjusted OS was 84% and 74% for NAC-CCRT and 81% and 70% for CCRT-AC, respectively (HR: 0.83, 95% confidence interval (CI): 0.45-1.56; p = 0.571). Also, adjusted analysis of distant-metastasis survival, NAC-CCRT showed HR was 0.79 (95% CI:0.37-1.72, p = 0.557). Conversely, adjusted analysis of locoregional relapse (LLR)-free survival revealed NAC-CCRT to have a significantly higher risk of LRR (HR: 2.18, 95% CI: 0.98-4.87; p = 0.057).ConclusionsThe results suggested that prognosis in the NAC-CCRT treated patients was not superior to that of the CCRT-AC treated individuals. In patients that receive neoadjuvant chemotherapy, locoregional relapse should be of concern. High-risk distant metastasis patients (N3 stage) that could achieve survival advantage from NAC-CCRT is an interesting and important topic for further study.

Project description:BackgroundAdding modified FOLFOX6 (folinic acid, fluorouracil, and oxaliplatin) after chemoradiotherapy and lengthening the chemoradiotherapy-to-surgery interval is associated with an increase in the proportion of rectal cancer patients with a pathological complete response.ObjectiveThe purpose of this study was to analyze disease-free and overall survival.DesignThis was a nonrandomized phase II trial.SettingsThe study was conducted at multiple institutions.PatientsFour sequential study groups with stage II or III rectal cancer were included.InterventionAll of the patients received 50 Gy of radiation with concurrent continuous infusion of fluorouracil for 5 weeks. Patients in each group received 0, 2, 4, or 6 cycles of modified FOLFOX6 after chemoradiation and before total mesorectal excision. Patients were recommended to receive adjuvant chemotherapy after surgery to complete a total of 8 cycles of modified FOLFOX6.Main outcome measuresThe trial was powered to detect differences in pathological complete response, which was reported previously. Disease-free and overall survival are the main outcomes for the current study.ResultsOf 259 patients, 211 had a complete follow-up. Median follow-up was 59 months (range, 9-125 mo). The mean number of total chemotherapy cycles differed among the 4 groups (p = 0.002), because one third of patients in the group assigned to no preoperative FOLFOX did not receive any adjuvant chemotherapy. Disease-free survival was significantly associated with study group, ypTNM stage, and pathological complete response (p = 0.004, <0.001, and 0.001). A secondary analysis including only patients who received ≥1 cycle of FOLFOX still showed differences in survival between study groups (p = 0.03).LimitationsThe trial was not randomized and was not powered to show differences in survival. Survival data were not available for 19% of the patients.ConclusionsAdding modified FOLFOX6 after chemoradiotherapy and before total mesorectal excision increases compliance with systemic chemotherapy and disease-free survival in patients with locally advanced rectal cancer. Neoadjuvant consolidation chemotherapy may have benefits beyond increasing pathological complete response rates. See Video Abstract at http://links.lww.com/DCR/A739.

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The Role of Consolidation Chemoradiotherapy in Locally Advanced Pancreatic Cancer Receiving Chemotherapy: An Updated Systematic Review and Meta-Analysis.

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The Role of Consolidation Chemoradiotherapy in Locally Advanced Pancreatic Cancer Receiving Chemotherapy: An Updated Systematic Review and Meta-Analysis.

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