Effects of Neoadjuvant Radiotherapy on Postoperative Complications in Rectal Cancer: A Meta-Analysis.
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ABSTRACT: Objective
Neoadjuvant radiotherapy (nRT) is an important treatment approach for rectal cancer. The relationship, however, between nRT and postoperative complications is still controversial. Here, we conducted a meta-analysis to evaluate such concerns.Methods
The electronic literature from 1983 to 2021 was searched in PubMed, Embase, and Web of Science. Postoperative complications after nRT were included in the meta-analysis. The pooled odds ratio (OR) was calculated by the random-effects model. Statistical analysis was conducted by Review Manager 5.3 and STATA 14.Results
A total of 23,723 patients from 49 studies were included in the meta-analysis. The pooled results showed that nRT increased the risk of anastomotic leakage (AL) compared to upfront surgery (OR = 1.23; 95% CI, 1.07-1.41; p=0.004). Subgroup analysis suggested that both long-course (OR = 1.20, 95% CI 1.03-1.40; p=0.02) and short-course radiotherapy (OR = 1.25, 95% CI, 1.02-1.53; p=0.04) increased the incidence of AL. In addition, nRT was the main risk factor for wound infection and pelvic abscess. The pooled data in randomized controlled trials, however, indicated that nRT was not associated with AL (OR = 1.01; 95% CI 0.82-1.26; p=0.91).Conclusions
nRT may increase the risk of AL, wound infection, and pelvic abscess compared to upfront surgery among patients with rectal cancer.
SUBMITTER: Yang J
PROVIDER: S-EPMC8754670 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Background and purposeWith the advent of more intensive chemotherapy regimens, neoadjuvant chemoradiotherapy (NACRT) for patients with locally advanced rectal cancer (LARC) has always been questioned due to its inevitable radiation toxicity. Hence, we conducted a meta-analysis to compare the clinical efficacy of neoadjuvant chemotherapy (NAC) and NACRT.Materials and methodsEligible studies were searched using PubMed, MEDLINE, Embase, the Cochrane Library, and Web of Science up to 31 July 2020, comparing the clinical efficacy of NAC versus NACRT for LARC. Short- and long-term outcomes were determined using the odds ratio (OR) with 95% confidence interval (CI).ResultsSix studies with 12,812 patients were eligible for this meta-analysis, including 677 patients in the NAC group and 12,135 patients in the NACRT group. There were no significant differences between the two groups in terms of pathological complete response rate (OR=0.62, 95%CI=0.27~1.41), N down-staging rate (OR=1.20, 95%CI=0.25~5.79), R0 resection rate (OR=1.24, 95%CI=0.78~1.98), and local relapse rate (OR=1.12, 95%CI=0.58~2.14). The pooled OR for the total response rate and T down-staging were in favor of NACRT (OR=0.41, 95%CI=0.22~0.76 versus OR=0.67 95%CI=0.52~0.87). However, the pooled OR for the sphincter preservation rate favored NAC compared with NACRT (OR=1.87, 95%CI=1.24~2.81). Moreover, NAC was found to be superior to NACRT in terms of distant metastasis (14.3% vs. 20.4%), but the difference was not significant (OR=0.84, 95%CI=0.31~2.27).ConclusionWe concluded that NAC was superior to NACRT in terms of the sphincter preservation rate, and non-inferior to NACRT in terms of pCR, N down-staging, R0 resection, local relapse, and distant metastasis. However, the conclusion warrants further validation.
| S-EPMC8101236 | biostudies-literature
Project description:Different neoadjuvant therapy regimens are available for rectal cancer, but the relative effects are controversial. The aim of the present network meta-analysis (NMA) was to estimate the relative efficacy and safety of neoadjuvant therapies for resectable rectal cancer. MEDLINE, EMBASE and Cochrane Central Registry of Controlled Trials were searched for publications dated from 1946 up to June 2018. The present study included randomized clinical trials that compared treatments for resected rectal cancer: Surgery alone, surgery preceded by neoadjuvant radiotherapy (RT), neoadjuvant chemotherapy (CT) or neoadjuvant chemoradiotherapy (CRT). Direct pairwise comparisons and NMA were conducted. A total of 23 randomized controlled trials were included in the present study. RT had an overall survival (OS) benefit when compared with surgery alone [HR (hazard ratio), 0.89; 95% confidence interval (CI), 0.82-0.97; quality of evidence, high]. All three neoadjuvant regimens were associated with lower local recurrence (LR) when compared with surgery alone [RT: odds ratio (OR), 0.44; 95% CI, 0.35-0.65; quality of evidence, high; CRT: OR, 0.34; 95% CI, 0.23-0.56; quality of evidence, low and CT: OR, 0.32; 95% CI, 0.11-1.00; quality of evidence, low]. There were no significant differences in OS and LR between CRT and RT (OS: OR, 1.10); 95% CI, 0.93-1.20; LR: OR, 0.81; 95% CI, 0.61-1.10). Ranking probabilities indicated that CRT was the best strategy for local control, with a surface under the cumulative ranking curve (SUCRA) of 78.78%. Patients treated with RT had improved disease-free survival compared with those treated with surgery alone (HR, 0.82; 95% CI, 0.64-1.00; quality of evidence, low). Neoadjuvant RT or CRT did not significantly improve distant metastases compared with surgery alone (RT: OR, 0.87; 95% CI, 0.69-1.10 and CRT: OR, 0.75; 95% CI, 0.47-1.10). CRT had an improved pathological complete response rate compared with RT (OR, 4.90; 95% CI, 21.80-17.00; quality of evidence, low). No significant difference for the risk of anastomotic leak between each treatment was observed in the NMA. In conclusion, RT decreased the LR and improved OS compared with surgery alone for resected rectal cancer. CRT was the best neoadjuvant therapy analyzed and CT was likely the second best for all outcomes based on SUCRA. However, these findings were limited by overall low quality of evidence.
| S-EPMC7086160 | biostudies-literature
Project description:ObjectiveRobotic surgery (RS) has been increasingly used for the resection of rectal cancer, and its advantages over laparoscopic surgery (LS) have been demonstrated. However, few studies focused on the severity of postoperative complications. This study aimed to compared the postoperative complications within 30 days after RS over LS according to the Clavien-Dindo (C-D) classification.MethodsA literature research of PubMed, Embase, Cochrane Library and Web of Science were systematically performed. The studies comparing the complications of RS and LS for rectal cancer based on the C-D classification were enrolled. Primary outcomes were C-D grade III, IV, V, III-V (severe complications).ResultsSeventeen studies (3193 patients) were included in the final analysis: 1554 underwent RS and 1639 underwent LS. The RS group was associated with significantly lower rates of severe complications (OR = 0.69, 95% CI 0.53-0.90, P = 0.005), C-D grade IV (OR = 0.69, 95% CI 0.53-0.90, P = 0.005), and anastomotic leak (OR = 0.66, 95% CI 0.48-0.91, P = 0.01). There was no significant difference in C-D grade III, C-D grade I, II, I-II (minor complications), overall complications, bleeding, wound complications, postoperative ileus, urinary retention, readmission, reoperation between two groups.ConclusionsRobotic surgery is safe for rectal cancer and may be an effective alternative to laparoscopic surgery, with lower rates of severe complications, C-D grade IV, and anastomotic leak. Further large randomized controlled trials are necessary to confirm this conclusion.
| S-EPMC7529204 | biostudies-literature
Project description:Neoadjuvant chemoradiotherapy (nCRT) followed by total mesorectal excision and adjuvant chemotherapy is the standard regimen for patients with locally advanced rectal cancer (LARC). However, whether and to which extent neoadjuvant radiotherapy could be removed from nCRT for patients with LARC is still unclear. This was a multicenter, retrospectively recruited, prospectively maintained cohort study. A propensity score matching model was employed to minimize potential confounding factors between subgroup patients treated with neoadjuvant chemotherapy (nCT) or nCRT. Overall survival (OS), disease-free survival (DFS), local recurrence-free survival (LRFS), and distant metastasis-free survival (DMFS) were assessed between subgroup patients by Kaplan-Meier analysis, log-rank test, and Cox regression model. In total, 3233 consecutive patients, consist of 571 nCT and 2662 nCRT-treated cases, were included. After propensity score matching (1:4), 565 nCT-treated patients were matched to 1852 nCRT-treated patients. Compared with nCT, nCRT treatment indeed decreased 3-y local recurrence (10.0% vs 6.6%, P = .026), but had no impact on OS, DFS and DMFS (all P > .05) for LARC. Stratified analysis further confirmed that nCRT treatment was associated with higher 3-y LRFS and 3-y DFS than nCT treatment for baseline high-risk subgroup (cT4, cN+, and cIII stage) patients (all P < .05). Conversely, for the baseline low-risk subgroup patients (cT3, cN0, and cII stage), nCRT and nCT treatment had similar 3-y OS, LRFS, DFS, and DMFS (all P > .05). The administration of neoadjuvant radiotherapy for LARC patients might be determined by baseline risk classification, the high-risk individuals could be delivered while low-risk patients might be omitted.
| S-EPMC7648035 | biostudies-literature
Project description:ObjectiveInvestigate the association between neoadjuvant treatment strategy and perioperative complications in patients undergoing proctectomy for nonmetastatic rectal cancer.Summary of background dataNeoadjuvant SC-TNT is an alternative to neoadjuvant CRT for rectal cancer. Some have argued that short-course radiation and extended radiation-to-surgery intervals increase operative difficulty and complication risk. However, the association between SC-TNT and surgical complications has not been previously investigated.MethodsThis single-center retrospective cohort study included patients undergoing total mesorectal excision for nonmetastatic rectal cancer after SC-TNT or CRT between 2010 and 2018. Univariate analysis of severe POM and multiple secondary outcomes, including overall POM, intraoperative complications, and resection margins, was performed. Logistic regression of severe POM was also performed.ResultsOf 415 included patients, 156 (38%) received SC-TNT and 259 (62%) received CRT. The cohorts were largely similar, though patients with higher tumors (69.9% vs 47.5%, P < 0.0001) or node-positive disease (76.9% vs 62.6%, P = 0.004) were more likely to receive SC-TNT. We found no difference in incidence of severe POM (9.6% SC-TNT vs 12.0% CRT, P = 0.46) or overall POM (39.7% SC-TNT vs 37.5% CRT, P = 0.64) between cohorts. Neoadjuvant regimen was also not associated with a difference in severe POM (odds ratio 0.42, 95% confidence interval 0.04-4.70, P = 0.48) in multivariate analysis. There was no significant association between neoadjuvant regimen and any secondary outcome.ConclusionIn rectal cancer patients treated with SC-TNT and proctectomy, we found no significant association with POM compared to patients undergoing CRT. SC-TNT does not significantly increase the risk of POM compared to CRT.
| S-EPMC8245013 | biostudies-literature
Project description:Although neoadjuvant treatment has become the established approach for women with large primary tumors or locally advanced breast cancer for which immediate surgery is not the best approach, it may also stimulate cancer stem cell self-renewal and facilitate recurrence. We sought to determine the survival outcomes of preoperative radiotherapy (PRRT) compared with postoperative radiotherapy (PORT).The Surveillance, Epidemiology, and End Results (SEER) registry was queried for patients who were diagnosed with breast cancer and underwent cancer-directed surgery. Survival analyses were performed with Cox proportional hazard regression for both overall survival (OS) and disease-specific survival (DSS), and 1:1 propensity score (PS) matching-adjusted competing risk analyses were conducted for DSS.We first identified 1,111,218 eligible patients in 18 registries from 1973 to 2013 and found that, outside of the Utah registry, sequence patterns other than PORT were rarely used. Thus, we next identified eligible patients registered in Utah (n = 7,042) from 1988 to 2007. The treatment trends shifted abruptly in 1988. Compared with the PORT group, the PRRT group showed significantly higher risks of overall mortality (absolute difference, 22.4%; P < 0.001), breast cancer-specific mortality (absolute difference, 8.6%; P < 0.001), and cardiovascular disease-specific mortality (absolute difference, 11.5%; P = 0.021). Survival differences in treatment sequences were correlated with stage.Substantial shifts in treatment patterns for malignant breast cancer were identified in Utah. Compared with PORT, PRRT showed significantly worse outcomes. These results could inform future standardized options for radiation sequence with surgery and further clinical trials.
| S-EPMC5966264 | biostudies-literature
Project description:BackgroundNeoadjuvant (chemo) radiotherapy is used as a standard treatment for locally advanced rectal cancer (LARC), but there is no general consensus on either the efficacy of postoperative adjuvant chemotherapy in patients with LARC after neoadjuvant treatment and surgery, or whether the addition of oxaliplatin to adjuvant chemotherapy provides survival benefits.MethodsWe performed a meta-analysis of data from the PubMed and Embase databases. We included patients with LARC who received neoadjuvant (chemo) radiotherapy and curative surgery. Overall survival (OS), disease-free survival (DFS), toxicity, and compliance were analyzed in the oxaliplatin/fluorouracil- (OX/FU-) based group compared with the FU-based group, and in the chemotherapy group compared with the observation group.ResultsTwenty studies were included in the analysis. Our results indicated that adjuvant chemotherapy prolonged OS (hazard ratio [HR] = 0.78, 95%CI = 0.67-0.91) in patients with LARC treated with neoadjuvant (chemo) radiotherapy and surgery compared with those in the observation group. Subgroup analysis showed the same results in both the ypStage II and ypStage III groups. Compared with those in the observation group, patients in the chemotherapy group also showed an increase in DFS (HR = 0.75, 95%CI = 0.60-0.93). No significant increase was observed in OS (HR = 1.04, 95%CI = 0.87-1.24) or DFS (HR = 0.98, 95%CI = 0.76-1.27) when oxaliplatin was added to FU-based adjuvant chemotherapy, as compared with the FU-based treatment, and subgroup analysis also indicated no survival benefits in the clinical stage II, clinical stage III, ypStage II, and ypStage III groups.ConclusionsFor patients with LARC who have already received neoadjuvant (chemo) radiotherapy and curative surgery, adjuvant chemotherapy improves OS over that in the observation group. Adding oxaliplatin to FU-based adjuvant chemotherapy does not confer survival benefits beyond those from FU-based adjuvant chemotherapy.
| S-EPMC8319733 | biostudies-literature
Project description:IntroductionIn locally advanced rectal cancer, longer delay to surgery after neoadjuvant radiotherapy increases the likelihood of histopathological tumour response. Chronomodulated radiotherapy in rectal cancer has recently been reported as a factor increasing tumour response to neoadjuvant treatment in patients having earlier surgery, with patients receiving a larger proportion of afternoon treatments showing improved response. This paper aims to replicate this work by exploring the impact of these two temporal factors, independently and in combination, on histopathological tumour response in rectal cancer patients.MethodsA retrospective review of all patients with rectal adenocarcinoma who received long course (≥24 fractions) neoadjuvant radiotherapy with or without chemotherapy at a tertiary referral centre was conducted. Delay to surgery and radiotherapy treatment time were correlated to clinicopathologic characteristics with a particular focus on tumour regression grade. A review of the literature and meta-analysis were also conducted to ascertain the impact of time to surgery from preoperative radiotherapy on tumour regression.ResultsFrom a cohort of 367 patients, 197 patients met the inclusion criteria. Complete pathologic response (AJCC regression grade 0) was seen in 46 (23%) patients with a further 44 patients (22%) having at most small groups of residual cells (AJCC regression grade 1). Median time to surgery was 63 days, and no statistically significant difference was seen in tumour regression between patients having early or late surgery. There was a non-significant trend towards a larger proportion of morning treatments in patients with grade 0 or 1 regression (p = 0.077). There was no difference in tumour regression when composite groups of the two temporal variables were analysed. Visualisation of data from 39 reviewed papers (describing 27379 patients) demonstrated a plateau of response to neoadjuvant radiotherapy after approximately 60 days, and a meta-analysis found improved complete pathologic response in patients having later surgery.ConclusionsThere was no observed benefit of chronomodulated radiotherapy in our cohort of rectal cancer patients. Review of the literature and meta-analysis confirms the benefit of delayed surgery, with a plateau in complete response rates at approximately 60-days between completion of radiotherapy and surgery. In our cohort, time to surgery for the majority of our patients lay along this plateau and this may be a more dominant factor in determining response to neoadjuvant therapy, obscuring any effects of chronomodulation on tumour response. We would recommend surgery be performed between 8 and 11 weeks after completion of neoadjuvant radiotherapy in patients with locally advanced rectal cancer.
| S-EPMC8244879 | biostudies-literature
Project description:BackgroundComplications after esophagectomy are common and the possible increase in postoperative complications associated with neoadjuvant chemoradiotherapy is of concern. The aim of our study was to analyze if the addition of radiotherapy to neoadjuvant chemotherapy increases the incidence and severity of postoperative complications, including evaluation of the relation between radiation doses to the heart and lungs and postoperative complications.MethodsThe study was based on an institutional surgical database for esophageal cancer. The study period was October 2008 to March 2020. Patients treated with neoadjuvant chemoradiotherapy were compared to patients treated with neoadjuvant chemotherapy and dose/volume parameters for the lungs and heart considered. The primary outcome was 30-day postoperative complications.ResultsDuring the study period, 274 patients underwent surgery for esophageal cancer, 93 patients after neoadjuvant chemotherapy and 181 patients after neoadjuvant chemoradiotherapy. The median prescribed radiation dose to the planning target volume was 41.4 Gy, the median of the mean lung dose was 6.2 Gy, and the median of the mean heart dose was 20.3 Gy. The addition of radiotherapy to neoadjuvant chemotherapy did not increase the incidence of postoperative complications. Neither were radiation doses to the lungs and heart associated with postoperative complications. Taxane-based chemotherapy regimens were however associated with an increased incidence of postoperative complications.ConclusionsIn our cohort, the addition of neoadjuvant radiotherapy to chemotherapy was not associated with postoperative complications. However, taxane-based chemotherapy regimens, with or without concomitant radiotherapy, were associated with postoperative complications.
| S-EPMC10018434 | biostudies-literature
Project description:BackgroundTotal neoadjuvant therapy (TNT) is a novel approach for locally advanced rectal cancer (LARC), which attempts to deliver both systemic chemotherapy and neoadjuvant chemoradiotherapy prior to surgery. However, its efficacy and safety remain controversial in randomized controlled trials (RCTs). We conducted this meta-analysis to assess such concerns.Materials and methodsHead-to-head phase II/III RCTs were searched in Embase, PubMed, Web of Science, and the Cochrane Library, as well as other sources. The primary endpoint was pathologic complete response (pCR). Secondary endpoints were disease-free survival (DFS), overall survival (OS), local recurrence-free survival, distant metastasis-free survival, and the R0 resection rate.ResultsEight phase II/III RCTs involving 2,196 patients with LARC were assessed. The primary analysis demonstrated a statistically significant improvement in the pCR rate for TNT treatment (odds ratio, 1.77; 95% confidence interval [CI], 1.28-2.45; p = .0005). TNT treatment also showed improvements in DFS and OS outcomes compared with standard chemoradiotherapy (hazard ratio [HR], 0.83; 95% CI, 0.72-0.96; p = .03 and HR, 0.88; 95% CI, 0.74-1.05; p = .15). In addition, TNT treatment showed significant efficacy in reducing the risk of distant metastasis (HR, 0.81; 95% CI, 0.68-0.95; p = .012).ConclusionThe overall pCR rate may be improved with TNT compared with standard treatment. The TNT strategy may also improve DFS and OS and reduce the risk of distant metastasis.Implications for practiceLocally advanced rectal cancer (LARC) is a relatively common disease, with a poor prognosis because of its high metastatic potential. The role of total neoadjuvant therapy (TNT) has always been controversial. This meta-analysis found that TNT in LARC is associated with a significant improvement in overall pathologic complete response rate, disease-free survival, overall survival, and distant metastasis-free survival compared with standard treatment. TNT is a promising strategy for LARC, especially for patients who have little desire for surgery.
| S-EPMC8417863 | biostudies-literature