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Neoadjuvant chemotherapy and radiotherapy followed by resection/ablation in stage IV rectal cancer patients with potentially resectable metastases.

ABSTRACT: BACKGROUND:The optimal treatment of stage IV rectal cancer remains controversial. The purpose of this study was to assess the treatment outcomes and toxicity of neoadjuvant chemotherapy and radiotherapy followed by local treatment of all tumor sites and subsequent adjuvant chemotherapy in stage IV rectal cancer patients with potentially resectable metastases. METHODS:Adult patients diagnosed with locally advanced rectal adenocarcinoma with potentially resectable metastases, who received neoadjuvant chemotherapy and radiotherapy from July 2013 and September 2019 at Sun Yat-sen University cancer center, were included. Completion of the whole treatment schedule, pathological response, treatment-related toxicity and survival were evaluated. RESULTS:A total of 228 patients were analyzed with a median follow-up of 33 (range 3.3 to 93.4) months. Eventually, 112 (49.1%) patients finished the whole treatment schedule, of which complete response of all tumor sites and pathological downstaging of the rectal tumor were observed in three (2.7%) and 90 (80.4%) patients. The three-year overall survival (OS) and progression-free survival (PFS) of all patients were 56.6% (50.2 to 63.9%) and 38.6% (95% CI 32.5 to 45.8%), respectively. For patients who finished the treatment schedule, 3-year OS (74.4% vs 39.2%, P < 0.001) and 3-year PFS (45.5% vs 30.5%, P = 0.004) were significantly improved compared those who did not finish the treatment. Grade 3-4 chem-radiotherapy treatment toxicities were observed in 51 (22.4%) of all patients and surgical complications occurred in 22 (9.6%) of 142 patients who underwent surgery, respectively. CONCLUSIONS:Neoadjuvant chemotherapy and radiotherapy followed by resection/ablation and subsequent adjuvant chemotherapy offered chances of long-term survival with tolerable toxicities for selected patients with potentially resectable stage IV rectal cancer, and could be considered as an option in clinical practice.

SUBMITTER: Li R

PROVIDER: S-EPMC8672531 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundThe purpose of this study was to develop a large population-based nomogram incorporating the log odds of positive nodes (LODDS) for predicting the overall survival (OS) of stage II/III rectal cancer patients treated with neoadjuvant chemoradiotherapy (NCRT) followed by surgical resection.MethodsThe Surveillance, Epidemiology, and End Results database was used to collect information on patients diagnosed with stage II/III rectal cancer between 2010 and 2015 and treated with NCRT followed by surgical resection. The Cox regression analyses were performed to determine the independent prognostic factors. In this study, LODDS was employed instead of American Joint Committee on Cancer (AJCC) 7th N stage to determine lymph node status. Then a nomogram integrating independent prognostic factors was developed to predict the 24-, 36-, and 60-month overall survival. The receiver operating characteristic (ROC) curves and calibration curves were used to validate the nomogram. Furthermore, patients were stratified into three risk groups (high-, middle-, and low-risk) based on the total points obtained from the nomogram. And Kaplan-Meier curves were plotted to compare the OS of the three groups.ResultsA total of 3829 patients were included in the study. Race, sex, age, marital status, T stage, tumor grade, tumor size, LODDS, CEA level, and postoperative chemotherapy were identified as independent prognostic factors, based on which the prognostic nomogram was developed. The area under curve values of the nomogram for the 24-, 36-, and 60-month OS in the training cohort were 0.736, 0.720, and 0.688, respectively; and 0.691, 0.696, and 0.694 in the validation cohort, respectively. In both the validation and training cohorts, the calibration curves showed a high degree of consistency between actual and nomogram-predicted survival rates. The Kaplan-Meier curves showed that the three risk groups had significant differences in overall survival (P < 0.001).ConclusionA large population-based nomogram incorporating LODDS was developed to assist in evaluating the prognosis of stage II/III rectal cancer patients treated with NCRT followed by surgical resection. The nomogram showed a satisfactorily discriminative and stable ability to predict the OS for those patients.

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.

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Neoadjuvant chemotherapy and radiotherapy followed by resection/ablation in stage IV rectal cancer patients with potentially resectable metastases.

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