Preoperative Chemoradiotherapy Group Research Articles

Preoperative Chemoradiotherapy for Resectable Gastric Cancer

BackgroundIn Western countries, the current standard of care for resectable gastric cancer is perioperative chemotherapy. Preoperative chemoradiotherapy has been considered, but data are limited regarding this treatment as compared with perioperative chemotherapy alone.MethodsWe conducted an international, phase 3 trial in which patients with resectable adenocarcinoma of the stomach or gastroesophageal junction were randomly assigned to receive preoperative chemoradiotherapy plus perioperative chemotherapy or perioperative chemotherapy alone (control). In both groups, patients received either epirubicin, cisplatin, and fluorouracil or fluorouracil, leucovorin, oxaliplatin, and docetaxel both before and after surgery; the preoperative-chemoradiotherapy group also received chemoradiotherapy (45 Gy in 25 fractions of radiation, plus fluorouracil infusion). The primary end point was overall survival, and secondary end points included progression-free survival, pathological complete response, toxic effects, and quality of life.ResultsA total of 574 patients underwent randomization at 70 sites in Australasia, Canada, and Europe: 286 to the preoperative-chemoradiotherapy group and 288 to the perioperative-chemotherapy group. A higher percentage of patients in the preoperative-chemoradiotherapy group than in the perioperative-chemotherapy group had a pathological complete response (17% vs. 8%) and greater tumor downstaging after resection. At a median follow-up of 67 months, no significant between-group differences in overall survival or progression-free survival were noted. The median overall survival was 46 months with preoperative chemoradiotherapy and 49 months with perioperative chemotherapy (hazard ratio for death, 1.05; 95% confidence interval, 0.83 to 1.31), and the median progression-free survival was 31 months and 32 months, respectively. Treatment-related toxic effects were similar in the two groups.ConclusionsThe addition of preoperative chemoradiotherapy to perioperative chemotherapy did not improve overall survival as compared with perioperative chemotherapy alone among patients with resectable gastric and gastroesophageal junction adenocarcinoma. (Funded by the National Health and Medical Research Council and others; TOPGEAR ClinicalTrials.gov number, NCT01924819.)

Differential clinical outcomes after 3 versus 5 years in a comparison of preoperative chemotherapy with and without radiotherapy in locally advanced rectal cancer: A national cohort propensity score-matched study

BackgroundPreoperative chemotherapy alone might be a good alternative to preoperative chemoradiotherapy for patients with locally advanced rectal cancer, yet long-term real-world data from the same cohort are lacking. MethodsPatients diagnosed with stage II-III rectal adenocarcinoma from 2011 to 2015 were randomly sampled from the SEER-Plus database to evaluate the superiority of preoperative chemoradiotherapy versus preoperative chemotherapy alone. FindingsA total of 1314 eligible patients were enrolled, with a median follow-up of 74.0 months. At 3-year follow-up, neither overall survival (OS) nor cancer-specific survival (CSS) was significantly different between the two treatment groups. At 5-year follow-up, CSS was similar across groups (HR 0.768, 95% CI 0.532–1.108; P = 0.156), but the 5-year OS was significantly better in the preoperative chemoradiotherapy group than in the preoperative chemotherapy group (HR 0.682, 95% CI 0.538–0.866; P = 0.002). Besides, the landmark analysis indicated a direct contrast in the CSS within 3 years (HR 1.101, 95% CI 0.598–2.029; P = 0.756) versus that at 3–5 years (HR 0.597, 95% CI 0.377–0.948; P = 0.027). The landmark analysis also showed directly contrasting OS outcomes within 3 years (HR 0.761, 95% CI 0.533–1.086; P = 0.130) versus those at 3–5 years (HR 0.621, 95% CI 0.451–0.857; P = 0.003). InterpretationIn patients with locally advanced rectal cancer under real-world treatment practices, the addition of preoperative radiotherapy to chemotherapy improves survival outcomes at 3–5 years’ follow-up but not at 3-year follow-up.

The safety of an MRI simulation-guided boost after short-course preoperative radiotherapy for unresectable rectal cancer (SUNRISE): interim analysis of a randomized phase II trial

PurposeThe safety of an MRI simulation-guided boost after short-course preoperative radiotherapy (SCPRT) for unresectable rectal cancer is assessed with a planned interim analysis.Methods and materialsPatients diagnosed with clinical stage T3-4 or regional lymph node-positive disease with positive mesorectal fascia or T4b disease evaluated by pelvic MRI were randomly assigned to the SCPRT-boost group (25 Gy in 5 fractions plus 4 Gy delivered to the gross tumor volume, followed by four cycles of chemotherapy) or preoperative chemoradiotherapy group (50 Gy in 25 fractions with concurrent chemotherapy). Then, patients received total mesorectal excision surgery after preoperative treatment. The primary endpoint was the R0 resection rate. The interim analysis was performed when 42 patients completed their assigned treatments.ResultsFrom October 2018 to November 2019, a total of 43 patients were enrolled, and 42 patients were included in the interim analysis. During preoperative therapy, grade 3 or above toxicities were observed in 10/21 (47.6%) patients in the experimental group, and 4/21 (19.0%) patients in the control group. A total of 17 (81.0%) and 13 (61.9%) patients in the experimental group and control group underwent surgery, respectively. Overall, 65.1% of the patients achieved R0 resection in the intention-to-treat analysis. Surgery-related adverse complications were observed in 2 patients (11.8%) in the experimental group and 1 patient (7.7%) in the control group.ConclusionOur results show that the toxicity of an MRI simulation-guided boost after SCPRT for unresectable rectal cancer is acceptable. Thus, this clinical trial will be continued as planned.

Efficacy of preoperative chemoradiotherapy in patients with cT2N0 distal rectal cancer.

This study was designed to determine the feasibility of preoperative chemoradiotherapy (PCRT) in patients with clinical T2N0 distal rectal cancer. Patients who underwent surgery for clinical T2N0 distal rectal cancer between January 2008 and December 2016 were included. Patients were divided into PCRT and non-PCRT groups. Non-PCRT patients underwent radical resection or local excision (LE) according to the surgeon's decision, and PCRT patients underwent surgery according to the response to PCRT. Patients received 50.0 to 50.4 gray of preoperative radiotherapy with concurrent chemotherapy. Of 127 patients enrolled, 46 underwent PCRT and 81 did not. The mean distance of lesions from the anal verge was lower in the PCRT group (P=0.004). The most frequent operation was transanal excision and ultralow anterior resection in the PCRT and non-PCRT groups, respectively. Of the 46 patients who underwent PCRT, 21 (45.7%) achieved pathologic complete response, including 15 of the 24 (62.5%) who underwent LE. Rectal sparing rate was significantly higher in the PCRT group (11.1% vs. 52.2%, P<0.001). There were no significant differences in 3- and 5-year overall survival and recurrence-free survival regardless of PCRT or surgical procedures. PCRT in clinical T2N0 distal rectal cancer patients increased the rectal sparing rate via LE and showed acceptable oncologic outcomes. PCRT may be a feasible therapeutic option to avoid abdominoperineal resection in clinical T2N0 distal rectal cancer.

Post-operative anastomotic leakage and collagen changes in patients with rectal cancer undergoing neoadjuvant chemotherapy vs chemoradiotherapy

A significant difference in the anastomotic leakage (AL) rate has been observed between patients with locally advanced rectal cancer who have undergone preoperative chemotherapy and those undergoing preoperative chemoradiotherapy. This study aimed to quantitatively analyse collagen structural changes caused by preoperative chemoradiotherapy and illuminate the relationship between collagen changes and AL. Anastomotic distal and proximal "doughnut" specimens from the Sixth Affiliated Hospital of Sun Yat-sen University (Guangzhou, China) were quantitatively assessed for collagen structural changes between patients with and without preoperative radiotherapy using multiphoton imaging. Then, patients treated with preoperative chemoradiotherapy were used as a training cohort to construct an AL-SVM classifier by the Mann-Whitney U test and support vector machine (SVM). An independent test cohort from the Fujian Province Cancer Hospital (Fuzhou, China) was used to validate the AL-SVM classifier. A total of 207 patients were included from the Sixth Affiliated Hospital of Sun Yat-sen University. The AL rate in the preoperative chemoradiotherapy group (n = 107) was significantly higher than that in the preoperative chemotherapy group (n = 100) (21.5% vs 7.0%, P = 0.003). A fully quantitative analysis showed notable morphological and spatial distribution feature changes in collagen in the preoperative chemoradiotherapy group. Then, the patients who received preoperative chemoradiotherapy were used as a training cohort to construct the AL-SVM classifier based on five collagen features and the tumor distance from the anus. The AL-SVM classifier showed satisfactory discrimination and calibration with areas under the curve of 0.907 and 0.856 in the training and test cohorts, respectively. The collagen structure may be notably altered by preoperative radiotherapy. The AL-SVM classifier was useful for the individualized prediction of AL in rectal cancer patients undergoing preoperative chemoradiotherapy.

Role of Preoperative Chemoradiotherapy in Clinical Stage II/III Rectal Cancer Patients Undergoing Total Mesorectal Excision: A Retrospective Propensity Score Analysis.

BackgroundAlthough the current standard preoperative chemoradiotherapy (PCRT) for stage II/III rectal cancer decreases the risk of local recurrence, it does not improve survival and increases the likelihood of preoperative overtreatment, especially in patients without circumferential resection margin (CRM) involvement.MethodsStage II/III rectal cancer without CRM involvement and lateral lymph node metastasis was radiologically defined by preoperative magnetic resonance imaging (MRI). Patients who received PCRT followed by total mesorectal excision (TME) (PCRT group) and upfront surgery (US) with TME (US group) between 2010 and 2016 were analyzed. We derived cohorts of PCRT group versus US group using propensity-score matching for stage, age, and distance from the anal verge. Three-year relapse-free survival rate, disease-free survival (DFS), and overall survival (OS) were compared between the two groups.ResultsA total of 202 patients were analyzed after propensity score matching. There were no differences in baseline characteristics. The median follow-up duration was 62 months (interquartile range, 46–87). There was no difference in the 3-year disease-free survival rate between the PCRT and US groups (83 vs. 88%, respectively; p=0.326). Likewise, there was no significant difference in the 3-year OS (89 vs. 91%, respectively; p=0.466). The 3-year locoregional recurrence rates (3 vs. 2% with US, p=0.667) and distant metastasis rates (16 vs. 11%, p=0.428) were not significantly different between the two groups. Time to completion of curative treatment was significantly shorter in the US group (132 days) than in the PCRT group (225 days) (p<0.001).ConclusionUsing MRI-guided selection for better risk stratification, US without neoadjuvant therapy can be considered in early stage patients with good prognosis. PCRT may not be required for all stage II/III rectal cancer patients, especially for the MRI-proven intermediate-risk group (cT1-2/N1, cT3N0) without CRM involvement and lateral lymph node metastasis. Further prospective studies are warranted.

Preoperative Chemoradiotherapy Versus Postoperative Chemoradiotherapy for Patients With Locally Advanced Gastric Cancer: A Retrospective Study Based on Propensity Score Analyses.

PurposeAlthough adjuvant chemoradiotherapy (CRT) used to be recommended as a standard of care for locally advanced gastric cancer, this suggestion has been strongly challenged recently. However, clear evidence regarding the optimization of radiotherapy is lacking. The purpose of this study was to compare the effectiveness of preoperative CRT versus that of postoperative CRT for resectable or potentially resectable gastric cancer.MethodsFrom January 2005 to December 2017, patients with clinical stage III/IVa (i.e., T3-4aN+M0 or T4bNxM0) locally advanced gastric cancer were retrospectively identified. Survival after preoperative CRT and postoperative CRT was assessed by unadjusted, propensity score matching (PSM) and inverse probability of treatment weight (IPTW) analyses. Moreover, exploratory subgroup analyses were performed, and toxicity and patterns of failure were also investigated.ResultsThe median follow-up time was 32.5 months. A total of 82 and 463 patients were enrolled in the preoperative and postoperative CRT groups, respectively. After propensity score matching, preoperative CRT was associated with improved overall survival (OS) and disease-free survival (DFS) compared with postoperative CRT (3-year OS: 72.6 vs. 54.4%, log-rank p = 0.0021; 3-year DFS: 61.7 vs. 44.7%, log-rank p = 0.002). The unadjusted and IPTW analyses yielded consistent results. A complete pathologic response was achieved in 13.4% of the preoperative CRT group. Although the incidence of grade 3 or 4 adverse effects and surgical complications were similar between the two groups, significantly fewer patients experienced treatment interruptions or dose reductions due to toxic effects in the preoperative CRT setting than in the postoperative CRT setting (3.7 vs. 10.6%, p = 0.049).ConclusionsCompared with postoperative CRT, preoperative CRT was associated with improved OS and DFS, superior treatment compliance and comparable surgical complications for patients with locally advanced gastric cancer. Our findings provide important evidence for the optimal combination modalities of surgery and CRT in the absence of randomized clinical data.

Beware of Early Relapse in Rectal Cancer Patients Treated With Preoperative Chemoradiotherapy.

Purpose Recurrence patterns in rectal cancer patients treated with preoperative chemoradiotherapy (PCRT) are needed to evaluate for establishing tailored surveillance protocol.Methods This study included 2,215 patients with locally-advanced mid and low rectal cancer treated with radical resection between January 2005 and December 2012. Recurrence was evaluated according to receipt of PCRT; PCRT group (n = 1,258) and no-PCRT group (n = 957). Early recurrence occurred within 1 year of surgery and late recurrence after 3 years. The median follow-up duration was 65.7 ± 29 months.Results The overall recurrence rate was similar between the PCRT and no-PCRT group (25.8% vs. 24.9%, P = 0.622). The most common initial recurrence site was the lungs in both groups (50.6% vs. 49.6%, P = 0.864), followed by the liver, which was more common in the no-PCRT group (22.5% vs. 33.6%, P = 0.004). Most of the recurrence occurred within 3 years after surgery in both groups (85.3% vs. 85.8%, P = 0.862). Early recurrence was more common in the PCRT group than in the no-PCRT group (43.1% vs. 32.4%, P = 0.020). Recurrence within the first 6 months after surgery was significantly higher in the PCRT group than in the no-PCRT group (18.8% vs. 7.6%, P = 0.003). Lung (n = 27, 44.3%) and liver (n = 22, 36.1%) were the frequent the first relapsed site within 6 months after surgery in PCRT group.Conclusion Early recurrence within the first 1 year after surgery was more common in patients treated with PCRT. This difference would be considered for surveillance protocols and need to be evaluated in further studies.

541P - Upfront radical surgery with total mesorectal excision (TME) versus preoperative chemoradiotherapy followed by TME in clinical stage II/III patients with rectal cancer: A propensity score analysis

BackgroundAlthough the current standard preoperative chemoradiotherapy (PCRT) for stage II/III rectal cancer decreases the risk of local recurrence, it does not improve overall survival and increase the likelihood of preoperative overtreatment, especially in patients without the circumferential resection margin (CRM) involvement. MethodsStage II/III rectal cancer without CRM involvement and lateral lymph node metastasis was radiologically defined by preoperative magnetic resonance imaging (MRI). Patients who received either PCRT followed by TME (PCRT group) or upfront surgery with TME (US group) between 2011 and 2016 were analyzed. We derived cohorts of PCRT group versus US group using propensity-score matching using staging, age, and distance from anal verge). Three-year relapse-free survival rate, disease-free survival (DFS), and overall survival (OS) were compared between two groups. ResultsA total of 221 patients were analyzed after propensity score matching. There were no differences in baseline characteristics. The median follow-up was 75 months (range, 28-101). No difference in 3-year relapse-free survival rate was noted between PCRT and US groups (89% vs 92% with US; P=0.657). Likewise, there was no statistically significant difference in DFS (7.7 years vs 8.0 years with US; P=0.162) and OS (8.1 years vs 8.3 years with US; P=0.431), respectively. The rates of locoregional recurrence (2.9% vs 0% with US, P=0.301) and distant metastasis (7.4% vs 7.1%, P=1.0) at 3-years were not significantly different between two groups. Interestingly, approximately half of patients had pathologic stage I cancer in both groups (56% with PCRT vs 45% with US; P=0.167) and 69% of patients in US group had not received adjuvant treatment, suggesting that upfront surgery without neoadjuvant therapy can be considered in early stage patients with good prognosis. ConclusionsPCRT may not be required for all stage II/III rectal cancer patients, especially for the MRI-based intermediate-risk group (cT1-2/N1, cT3N0) without CRM involvement and lateral lymph node metastasis. Further prospective studies are warranted. Legal entity responsible for the studyThe authors. FundingHas not received any funding. DisclosureAll authors have declared no conflicts of interest.

The effect of preoperative treatments on lymph node counts after total gastrectomy in esophagogastric adenocarcinoma.

This study aims to explore the effects of preoperative treatments on lymph nodes (LNs) counts after total gastrectomy with D2 lymphadenectomy in esophagogastric adenocarcinoma. A retrospective analysis was performed for 446 patients with locally advanced esophagogastric adenocarcinoma. The patients were divided into three groups: surgery first (SF), preoperative chemotherapy (PCT), and preoperative chemoradiotherapy (PCRT). Clinical-pathological data were analyzed. The case number in SF, PCT, and PCRT groups was 281, 109, and 56, respectively, and the median total LNs count was 32.0 (10.0-102.0), 31.0 (12.0-62.0), and 25.5 (10.0-50.0), respectively, (P < 0.001). Univariate and multivariate analyses demonstrated the total LNs count was lower in PCRT than SF/PCT (P < 0.001), and had no correlation with tumor regression grades (TRGs). Subgroup comparison showed radiation target LNs count was lower in PCRT than SF/PCT (P < 0.001), and peritarget LNs count was lower in PCRT than SF (P = 0.002). For esophagogastric adenocarcinoma, PCRT reduced total LNs count after total gastrectomy with D2 lymphadenectomy, whereas PCT did not. In the PCRT group, LNs count was lower in both radiation target and peritarget areas than in the SF group but only in radiation target area than in the PCT group. The correlation between TRGs and total LNs count remained unclear.

Preoperative chemoradiotherapy versus postoperative chemoradiotherapy for local advanced gastric or Siewert II/III GEJ cancer: A retrospective analysis.

115 Background: Radiation therapy has improved survival in gastric cancer in some randomized trials. However, post-operative fields have been difficult tolerate, and completion rates have been low. Preoperative therapy may afford the opportunity to radical therapy, and potentially improve the resectability in advanced patients. Methods: Patients with Siewert II/III GE junction or gastric cancer treated at Massachusetts General Hospital were evaluated with Institutional Review Board approval. Clinical parameters and prognostic factors including gender, age, clinical stage, pathological stage, radiation parameters, concurrent chemotherapy, non-radiation chemotherapy, toxicity and survival were included in the analysis. Results: From Jul 2005 to Jan 2017, we enrolled 88 patients had chemoradiotherapy (CRT) and surgery, 48 preoperative and 40 postoperative CRT patients. In the preoperative group, 16.7% (8/48) had nodes outside a standard D2 dissection range, and the pathologic complete regression (pCR) rate was 18.8% (9/48). Median preoperative and postoperative radiation dose was 50.4 Gy and 45 Gy. Two-drug regimen was the most commonly used preoperative concurrent chemotherapy: 60.5% and single drug was the most commonly used postoperative concurrent chemotherapy: 97.5%. Except concurrent chemotherapy, 25 preoperative CRT patients received induction FOLFOX (median 8 cycles); 9 postoperative CRT patients also received 5-FU and 23 received FOLFOX (or EOX) chemotherapy. The estimated 3-year relapse-free survival (RFS) and overall survival (OS) in the preoperative and postoperative group was 51% vs. 34.3% (p = 0.286), and 71.2% vs. 45.9% (p = 0.179), respectively. In preoperative CRT group, there was more hematological toxicity but less gastrointestinal toxicity than postoperative CRT group, more distant metastasis but less peritoneal recurrence rate. Conclusions: Compared to postoperative chemoradiotherapy, preoperative chemoradiotherapy option has the trend of better tolerance, higher RFS and OS in patients with local advanced gastric cancer. Different chemoradiotherapy strategy may lead to different recurrence patterns.

Matched case-control analysis comparing oncologic outcomes between preoperative and postoperative chemoradiotherapy for rectal cancer.

PurposeTo investigate patterns of recurrence and oncologic outcomes after recurrence between preoperative and postoperative chemoradiotherapy (CRT).MethodsRecords of patients with stage II or III locally advanced rectal cancer seen between January 2000 and December 2010 were analyzed. The outcomes for patients undergoing preoperative CRT followed by radical resection (n = 466) were compared with outcomes of patients matched for sex, age, and stage who had surgery and then postoperative CRT (n = 466). Recurrence rates and sites, treatment of recurrence, and oncologic outcomes after recurrence were investigated. The rate of sphincter preservation and permanent stoma formation were also evaluated.ResultsRecurrence occurred in 124 and 140 patients in the pre- and postoperative CRT groups, respectively. The local and systemic recurrence rates were 3.6% and 20.8%, respectively, in the preoperative CRT group and 3.0% and 25.3%, respectively, in the postoperative CRT group (P = 0.245). Time to recurrence was longer in the postoperative CRT group (19 months vs. 24.2 months, P = 0.029). The overall rates of sphincter preservation (sphincter preservation operation and postoperative permanent stoma formation) did not significantly different between the two groups (P = 0.381). The 5-year overall survival rate after recurrence did not differ between the two groups (25.6% vs. 18.6%, P = 0.051).ConclusionPreoperative and postoperative CRT are both safe and suitable treatment methods for rectal cancer, so the choice can be tailored to the patient's situation.

Clinical significance of preoperative chemoradiotherapy for advanced esophageal cancer patients using propensity score matching.

e15532Background: We introduced preoperative chemoradiotherapy(CRT) for advanced esophageal cancer in 1995 and have been reported it’s results. Although there were some reports compared preoperative CRT and surgery alone in Japan, it is known to be inferior to RCT. We evaluated the clinical significance of the preoperative CRT compared to surgery alone by calculating propensity score (PS) which make a pseudo-randomization. Methods: 112 resectable esophageal squamous cell carcinoma patients(StageII-IVA, preoperative CRT group 55, surgery alone group 57). We calculated PS by statistics software and make a matching by preoperative clinical factors of both groups. Additionally, we performed the matching between two groups using IPSW(Inverse Propensity Sore Matching). We analyzed a survival rate (Overall survival,OS ) and prognostic factors in Cox proportion hazard model. Results: 1,41 patients were selected by PS matching in each groups. OS of CRT group was better than that of surgery alone group (five years ...

Preoperative chemoradiotherapy for clinically diagnosed T3N0 rectal cancer.

This retrospective study compared the recurrence-free survival (RFS) and local recurrence rates of patients who received preoperative chemoradiotherapy (PCRT) for cT3N0 vs. those who did not. We analyzed the records of 593 patients with transrectal ultrasound (TUS) or magnetic resonance image (MRI)-staged cT3N0 mid and low locally advanced rectal cancer, including 255 who received PCRT and 338 who did not. The RFS and cumulative local recurrence rates were compared in the two groups. We also investigated the rates of pathologic complete response (pCR) and mesorectal lymph node (LN) involvement in the PCRT group. The overall pCR rate was 13.3%. Of the 338 non-PCRT patients, 125 (37.0%) had pathologically positive mesorectal LNs. Sphincter-preserving surgery was performed in 431 (72.7%) of the 593 patients, with similar rates in the two groups. However, the sphincter preservation rate in patients with low rectal cancer was higher among those who received PCRT than among those who did not (64.8 vs. 47%, P=0.002). The 5-year RFS (76.4 vs. 75.5%, P=0.92) and local recurrence (3.9 vs. 3.0%, P=0.97) rates were similar in the PCRT and non-PCRT groups. Although PCRT did not improve the RFS or local recurrence rates, it increased the chance of sphincter preservation in patients with low rectal cancer. The advantages of PCRT for patients with cT3N0 should be re-evaluated considering the limitation of pretreatment staging, oncologic benefits, and improved sphincter preservation.

Impression of prognosis regarding pathologic stage after preoperative chemoradiotherapy in rectal cancer.

To ascertain pathologic stage as a prognostic indicator for rectal cancer patients receiving preoperative chemoradiotherapy (PCRT). Patients with mid- and low rectal carcinoma (magnetic resonance imaging - based clinical stage II or III) between 2000 and 2009 and treated with curative radical resection were identified. Patients were divided into two groups: PCRT and No-PCRT. Recurrence-free survival (RFS) was examined according to pathologic stage and addition of adjuvant treatment. Overall, 894 patients were identified. Of these, 500 patients received PCRT. Adjuvant chemotherapy was delivered to 81.5% of the No-PCRT and 94.8% of the PCRT patients. Adjuvant radiotherapy was given to 29.4% of the patients in the No PCRT group. The 5-year RFS for the No-PCRT group was 92.6% for Stage I, 83.3% for Stage II, and 72.9% for Stage III. The 5-year RFS for the PCRT group was 95.2% for yp Stage 0, 91.7% for yp Stage I, 73.9% for yp Stage II, and 50.7% for yp Stage III. Pathologic stage can predict prognosis in PCRT patients. 5-year RFS is significantly lower among PCRT patients than No-PCRT patients in pathologic stage II and III. These results should be taken into account when considering adjuvant treatment for patients treated with PCRT.

Is preoperative chemoradiotherapy warranted in magnetic resonance imaging-based clinically T3N0 rectal cancer?

Purpose: Preoperative chemoradiotherapy (PCRT) has been widely adopted. However, benefit of PCRT for patients with clinically T3N0 (cT3N0) rectal cancer is doubtful. We analyzed oncologic outcome in patients with magnetic resonance image (MRI) staged cT3N0 rectal cancer according to receipt of PCRT. Methods: Between January 2006 and December 2010, one hundred twenty four patients were MRI-based T3N0 rectal cancer. In patients who received PCRT the median dose of given radiotherapy was 5,040 Gy, and either 5-fluorouracil/leucovorin, capecitabine or S-1/oxaliplatin was delivered. The 3-year disease free survival rate (DFS) and sphincter preservation were compared. Results: Sixty four patients received and sixty patients did not receive PCRT. Rate of complete remission was obtained in 17.2% of PCRT group. Sphincter-preserving surgery was performed in 79.7% of PCRT group and 88.3% of non-PCRT group (P=0.194). In patients with low-lying rectal cancer, sphincter-preservation was also not different; PCRT 70.5% and non-PCRT 66.7% (P=0.761). Overall recurrence occurred in 21.9% in PCRT group and 15.0% in non-PCRT group (P=0.327). Three-year DFS was comparable between PCRT (76.5%) and non-PCRT group (79.7%) (P=0.330). Conclusion: Preoperative chemoradiotherapy in MRI-based cT3N0 rectal cancer had no benefit on sphincter preservation and did not improve DFS. Therefore, the routine use of PCRT in cT3N0 rectal cancer should not be warranted. Keywords: Rectal neoplasm, Neoadjuvant chemoradiotherapy, Magnetic Resonance Imaging, Lymph nodes

Preoperative Chemoradiotherapy Effects on Anastomotic Leakage After Rectal Cancer Resection

To assess the effects of preoperative chemoradiotherapy (CRT) on anastomotic leakage (AL) after rectal cancer resection, using propensity score matching. Conflicting data have emerged over the last decade regarding the effect of preoperative CRT on AL. We reviewed 1437 consecutive patients with rectal cancer who underwent low anterior resection (LAR) at our institution between 2005 and 2012. AL evaluated as grade C was the primary endpoint, as proposed by the International Study Group of Rectal Cancer in 2010. The patients were treated with (n = 360) or without (n = 1077) preoperative CRT. The total radiation dose was 50.4 Gy in 28 fractions. Multivariate and propensity score matching analyses were used to compensate for the differences in some baseline characteristics. The preoperative CRT group contained more patients with the following characteristics, older age, male sex, smoker, advanced stage tumor, lower/mid rectal tumor location, ultra-LAR, and diverting stoma, than the non-preoperative CRT group (all Ps < 0.05). Postoperative AL occurred in 91 patients (6.3%). Before propensity score matching, the incidence of AL in patients with or without preoperative CRT was 7.5% and 5.9%, respectively (P = 0.293). After propensity score matching, the 2 groups were nearly balanced except for the initial stage and the length of the surgeon's career, and the incidence of AL in patients with or without preoperative CRT was 7.5% and 8.1%, respectively (P = 0.781). We did not observe that preoperative CRT increased the risk of postoperative AL after LAR in patients with rectal cancer, using propensity score matching analysis.

Patterns of failure in patients with locally advanced rectal cancer receiving pre-operative or post-operative chemoradiotherapy

BackgroundWe investigated patterns of failure in patients with locally advanced rectal cancer (LARC) according to chemoradiotherapy (CRT) timing: pre-operative versus post-operative. Also, patterns of failure, particularly distant metastasis (DM), were analyzed according to tumor location within the rectum.MethodsIn total, 872 patients with LARC who had undergone concurrent CRT and radical surgery between 2001 and 2007 were analyzed retrospectively. Concurrent CRT was administered pre-operatively (cT3–4) or post-operatively (pT3–4 or pN+) in 550 (63.1%) and 322 (36.9%) patients, respectively. Median follow-up period was 86 (range, 12–133) months for 673 living patients. Local recurrence (LR) was defined as any disease recurrence within the pelvis, and any failure outside the pelvis was classified as a DM. Only the first site of recurrence was scored.ResultsIn total, 226 (25.9%) patients developed disease recurrence. In the pre-operative CRT group, the incidences of isolated LR, combined LR and DM, and isolated DM were 17, 21, and 89 patients, respectively. In the post-operative CRT group, these incidences were 8, 15, and 76 patients, respectively. LR within 2 years constituted 44.7% and 60.9% of all LRs in the pre-operative and post-operative CRT groups, respectively. Late (> 5 years) LR comprised 13.2% and 4.3% of all LRs in the pre-operative and post-operative CRT groups, respectively. The lung was the most common DM site (108/249, 43.4%). Lung or para-aortic lymph node metastasis developed more commonly from low-to-mid rectal tumors while liver metastasis developed more commonly from upper rectal tumors. Lung metastasis occurred later than liver metastasis (n = 54; 22.6 ± 15.6 vs. 17.4 ± 12.1 months; P = 0.035).ConclusionsThis study showed that LARC patients receiving pre-operative CRT tended to develop late LR more often than those receiving post-operative CRT. Further extended follow-up than is conventional may be necessary in LARC patients who are managed with optimized multimodal treatments, and the follow-up strategy may need to be individualized according to tumor location within the rectum.

Effects of preoperative chemoradiotherapy on anal sphincter functions and quality of life in rectal cancer patients

Deterioration of anorectal function after long-course preoperative chemoradiotherapy combined with surgery for rectal cancer is poorly defined. We conducted a prospective study to evaluate the acute and long term effects of preoperative chemoradiotherapy on anorectal function and quality of life of the patients. There were 26 patients in surgery group and 31 patients in preoperative chemoradiotherapy group. Anorectal function and quality of life of the patients were assessed by anorectal manometry, incontinence score, quality of life questionnaire. Significant lower resting pressures in both groups and lower maximal squeeze pressures in the preoperative chemoradiotherapy group were observed after postsurgical evaluations compared with the paired pretreatment ones. In the surgery group, both the Wexner continence score, FIQL score, and the rectoscopy score were comparable before and after surgery, whereas significant worsening in the Wexner score was observed in the preoperative chemoradiotherapy group postoperatively (P < 0.01). Significant reduction in anal canal resting pressures and squeeze pressures, Wexner score, and FIQL score were observed immediately after the completion of preoperative chemoradiotherapy. Significant lower maximal squeeze pressures and worsening of the Wexner scores were observed in the preoperative chemoradiotherapy group compared to the surgery group during the postoperative assessments (P < 0.05 and P < 0.01, respectively). Both total mesorectal excision and preoperative chemoradiotherapy may adversely affect the anorectal function. Careful selection of the patients who will benefit from neoadjuvant therapy and identifying the patients with a high risk of developing functional problems may help to improve functional outcomes for the treatment of rectal cancer.

Influence of preoperative chemoradiotherapy, preoperative chemotherapy, and operation on immunity function in middle or lower rectal cancer patients

To study the influence of preoperative chemoradiotherapy, preoperative chemotherapy, and operation alone on the cellular immunity in patients with middle or lower rectal cancer. Ninety middle or lower rectal cancer patients were non-randomly divided into 3 equal groups: preoperative radiotherapy group, receiving conventional radiotherapy with a total dose of 30 Gy in 10 fractions completed within 2 weeks; preoperative chemoradiotherapy group, receiving 2 cycles of single-oral drug regimen (capecitabine 1000 mg/m(2) for 2 weeks as a cycle with an interval of 1 week) and then, i.e., 2 days later, receiving conventional radiotherapy as prescribed for the patients in the preoperative radiotherapy group; and operation alone group. Operation was performed on the patients of the former 2 groups 3 weeks after the completion of the relevant treatment. Blood samples were collected on the admission day, 1 day before operation, and 7 day and 1 month after operation. Flow cytometry was used to detect the levels of CD(3)(+), CD(4)(+), CD(8)(+), CD(4)(+)/CD(8)(+), and NK cells. There were no significant differences in the levels of CD(3)(+), CD(4)(+), CD(8)(+), CD(4)(+)/CD(8)(+), and NK cells before and after radiotherapy between the preoperative chemoradiotherapy group and preoperative chemotherapy group (all P > 0.05). 7 days after operation, the levels of CD(3)(+), CD(4)(+), CD(4)(+)/CD(8)(+), and NK cells were degraded and the CD(8)(+) level was increased significantly (all P < 0.05) in all 3 groups. One month after operation, the levels of CD(3)(+), CD(4)(+), CD(4)(+)/CD(8)(+), and NK cells were all significantly higher and the CD(8)(+) level was significantly lower than those before operation and 7 days after operation (all P < 0.05)in all 3 groups. There were no significant differences in the T cell number and the proportions of different categories of cells at different time points in these 3 group (all P < 0.05). Preoperative chemoradiotherapy and preoperative chemotherapy have no significant impact on the cellular immune function in the patients with rectal cancer.