Hamid Nasrolahi, Sepideh Mirzaei, Mohammad Mohammadianpanah, Ali Mohammad Bananzadeh, Maral Mokhtari, Mohammad Reza Sasani, Ahmad Mosalaei, Shapour Omidvari, Mansour Ansari, Niloofar Ahmadloo, Seyed Hasan Hamedi, Nezhat Khanjani
Ann Coloproctol. 2019;35(5):242-248. Published online October 31, 2019
Purpose Currently, neoadjuvant chemoradiation (CRT) followed by total mesorectal resection is considered the standard of care for treating locally advanced rectal cancer. This study aimed to investigate the efficacy and feasibility of adding induction chemotherapy to neoadjuvant CRT in locally advanced rectal cancer.
Methods This phase-II clinical trial included 54 patients with newly diagnosed, locally advanced (clinical T3–4 and/or N1–2, M0) rectal cancer. All patients were treated with 3 cycles of preoperative chemotherapy using the XELOX (capecitabine + oxaliplatin) regimen before and after a concurrent standard long course of CRT (45–50.4 Gy) followed by standard radical surgery. Pathologic complete response (PCR) rate and toxicity were the primary and secondary endpoints, respectively.
Results The study participants included 37 males and 17 females, with a median age of 59 years (range, 20–80 years). Twenty-nine patients (54%) had clinical stage-II disease, and 25 patients (46%) had clinical stage-III disease. Larger tumor size (P = 0.006) and distal rectal location (P = 0.009) showed lower PCR compared to smaller tumor size and upper rectal location. Pathologic examinations showed significant tumor regression (6.1 ± 2.7 cm vs. 1.9 ± 1.8 cm, P < 0.001) with 10 PCRs (18.5%) compared to before the intervention. The surgical margin was free of cancer in 52 patients (96.3%). Treatment-related toxicities were easily tolerated, and all patients completed their planned treatment without interruption. Grade III and IV toxicities were infrequent.
Conclusion The addition of induction chemotherapy to neoadjuvant CRT is an effective and well-tolerated treatment approach in patients with rectal cancer.
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Purpose This study evaluated the oncologic outcomes of locally advanced rectal cancer patients who underwent preoperative neoadjuvant chemoradiotherapy (CRT) followed by surgery and determined the prognostic significance of pathologic complete response (pCR).
Methods Between January 2002 and December 2015, 580 patients with rectal cancer who underwent surgery after neoadjuvant CRT were identified. Survival according to tumor response to CRT and pathologic stage was analyzed using the Kaplan-Meier method, and the Cox proportional hazard model was used to identify factors associated with survival outcomes.
Results A total of 111 patients (23.7%) achieved pCR while the other 469 patients showed residual disease. Patients with pCR had a lower pretreatment carcinoembryonic antigen level and earlier cT classification than those with residual disease. With a median follow-up of 78 months, disease-free survival (DFS) and overall survival (OS) were significantly better in the pCR group than in the residual disease group. The 5-year DFS and 5-year OS for patients with ypStage 0, I, II, or III were 92.5%, 85.1%, 72.2%, 54.3% (P < 0.001) and 94.5%, 91.0%, 83.1%, 69.3%, respectively (P < 0.001). Pathologic AJCC stage after CRT was the most statistically significant independent predictor of OS (HR, 6.97 [95% confidence interval, 3.16–15.39] for stage III vs. stage 0) and DFS (HR, 7.30 [95% confidence interval, 3.63–14.67] for stage III vs. stage 0).
Conclusion Rectal cancer patients who achieved pCR showed improved survival compared to those with residual disease after preoperative CRT. Moreover, pCR was an independent indicator of OS and DFS, and pathologic AJCC stage was correlated with survival after preoperative CRT.
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The current standard of care for treating patients with locally advanced rectal cancer includes preoperative chemoradiation therapy (PCRT) followed by a total mesorectal excision and postoperative adjuvant chemotherapy. A subset of these patients has achieved a pathologic complete response (pCR) and they have shown improved disease-free and overall survival compared to non-pCR patients. Thus, many efforts have been made to achieve a higher pCR through PCRT. In this review, results from various ongoing and recently completed clinical trials that are being or have been conducted with an aim to improve tumor response by modifying therapy will be discussed.
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