Search

This review article explores advanced surgical approaches and anatomical insights for tailoring rectal cancer surgery, particularly focusing on low‐lying rectal cancer. With the evolution of imaging technologies, precise preoperative planning has become possible, enhancing the visualization of anatomy surrounding the rectum and enabling more accurate assessments of circumferential resection margin (CRM) involvement. The article emphasizes the dynamic nature of rectal cancer treatment, advocating for individualized surgical planning based on comprehensive preoperative imaging and intraoperative assessment. This approach aims to optimize patient care by integrating recent advancements and anatomical insights into clinical practice for the management of low‐lying rectal cancer. Particularly, the article discusses the importance of customizing the excision of Denonvilliers' fascia (DVF) based on tumor characteristics for optimal oncologic and functional outcomes, especially for anteriorly located tumors. It highlights the need for precise dissection techniques to ensure a negative CRM while preserving critical anatomical structures. Additionally, the review addresses the surgical management of tumors at the anorectal ring and introduces the Gate Approach for deep anterolateral pelvic dissection. Special attention is given to tumors impacting the membranous and prostate urethra, emphasizing tailored surgical approaches to balance complete tumor resection with the preservation of urogenital functions. [ABSTRACT FROM AUTHOR]

Objectives: This study evaluated pretreatment magnetic resonance imaging (MRI)–detected extramural venous invasion (pmrEMVI) as a predictor of survival after neoadjuvant chemoradiotherapy (nCRT) in patients with locally advanced rectal cancer (LARC). Materials and methods: Medical records of 1184 patients with rectal adenocarcinoma who underwent TME between January 2011 and December 2016 were reviewed. MRI data were collected from a computerized radiologic database. Cox proportional hazards analysis was used to assess local, systemic recurrence, and disease-free survival risk based on pretreatment MRI-assessed tumor characteristics. After propensity score matching (PSM) for pretreatment MRI features, nCRT therapeutic outcomes according to pmrEMVI status were evaluated. Cox proportional hazards analysis was used to identify risk factors for early recurrence in patients receiving nCRT. Results: Median follow-up was 62.8 months. Among all patients, the presence of pmrEMVI was significantly associated with worse disease-free survival (DFS; HR 1.827, 95% CI 1.285–2.597, p = 0.001) and systemic recurrence (HR 2.080, 95% CI 1.400–3.090, p < 0.001) but not local recurrence. Among patients with pmrEMVI, nCRT provided no benefit for oncological outcomes before or after PSM. Furthermore, pmrEMVI(+) was the only factor associated with early recurrence on multivariate analysis in patients receiving nCRT. Conclusions: pmrEMVI is a poor prognostic factor for DFS and SR in patients with non-metastatic rectal cancer and also serves as a predictive biomarker of poor DFS and SR following nCRT in LARC. Therefore, for patients who are positive for pmrEMVI, consideration of alternative treatment strategies may be warranted. Clinical relevance statement: This study demonstrated the usefulness of pmrEMVI as a predictive biomarker for nCRT, which may assist in initial treatment decision-making in patients with non-metastatic rectal cancer. Key Points: • Pretreatment MRI-detected extramural venous invasion (pmrEMVI) was significantly associated with worse disease-free survival and systemic recurrence in patients with non-metastatic rectal cancer. • pmrEMVI is a predictive biomarker of poor DFS following nCRT in patients with LARC. • The presence of pmrEMVI was the only factor associated with early recurrence on multivariate analysis in patients receiving nCRT. [ABSTRACT FROM AUTHOR]

Objective: To evaluate whether robotic for middle or low rectal cancer produces an improvement in surgical outcomes compared with laparoscopic surgery in a randomized controlled trial (RCT). Background: There is a lack of proven clinical benefit of robotic total mesorectal excision (TME) compared with a laparoscopic approach in the setting of multicenter RCTs. Methods: Between July 2011 and February 2016, patients diagnosed with an adenocarcinoma located <10 cm from the anal verge and clinically rated T1-4aNxM0 were enrolled. The primary outcome was the completeness of TME assessed by a surgeon and a pathologist. Results: The RCT was terminated prematurely because of poor accrual of data. In all, 295 patients were assigned randomly to a robot-assisted TME group (151 in R-TME) or a laparoscopy-assisted TME group (144 in L-TME). The rates of complete TME were not different between groups (80.7% in R-TME, 77.1% in L-TME). Pathologic outcomes including the circumferential resection margin and the numbers of retrieved lymph nodes were not different between groups. In a subanalysis, the positive circumferential resection margin rate was lower in the R-TME group (0% vs 6.1% for L-TME; P =0.031). Among the recovery parameters, the length of opioid use was shorter in the R-TME group (P =0.028). There was no difference in the postoperative complication rate between the groups (12.0% for R-TME vs 8.3% for L-TME). Conclusions: In patients with middle or low rectal cancer, robotic-assisted surgery did not significantly improve the TME quality compared with conventional laparoscopic surgery (ClinicalTrial.gov ID: NCT01042743). [ABSTRACT FROM AUTHOR]

The optimal treatment of locally advanced rectal cancer with synchronous liver metastases remains controversial. In this study, we aimed to evaluate the safety, efficacy, and oncologic outcomes of upfront chemotherapy and short-course radiotherapy with delayed surgery in patients with locally advanced rectal cancer and synchronous liver metastases. Forty-four patients who underwent upfront chemotherapy and short-course radiotherapy with delayed surgery for locally advanced rectal cancer (cT3/4, <2.0 mm from the mesorectal fascia) with synchronous liver metastases between January 2010 and June 2017 were reviewed retrospectively. Primary and metastatic liver lesions were resected with curative intent. Upfront chemotherapy and short-course radiotherapy were administered. Thereafter, restaging, surgery only, or additional chemotherapy followed by surgery was performed. At the time of initial diagnosis, 20 patients had <3 liver metastases; 24 patients had ≥3 liver metastases. Twenty-three patients had hemi-liver metastases; 21 patients had bilobar liver metastases. R0 resection of rectal lesions was achieved in 43 patients. Synchronous R0 resection of liver metastases was achieved in 41 patients. Postoperative complications (Clavien–Dindo Grade ≥ III) were noted in 5 patients. Grade 3/4 adverse events were observed in 26 patients. All adverse events were managed effectively with medication and supportive care. The 3-year overall survival and progression-free survival rates were 65.3% and 26.9%, respectively. Upfront chemotherapy and short-course radiotherapy with delayed surgery appear to be safe and effective in patients with locally advanced rectal cancer and synchronous liver metastases without substantially increasing treatment induced morbidity. [ABSTRACT FROM AUTHOR]

Background: Although 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. Methods: Stage 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. Results: A 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). Conclusion: Using 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. [ABSTRACT FROM AUTHOR]

Some locally advanced rectal cancer (LARC) patients treated with neoadjuvant chemoradiotherapy (CRT) prior to total mesorectal excision (TME) show early recurrence with a short disease-free interval. This is unacceptable for patients and their families, necessitating re-evaluation of the treatment process. We aimed to evaluate the risk factors and prognostic impact of early recurrence in patients who received preoperative CRT (pCRT) followed by TME for LARC. Of 714 patients who underwent curative resection after pCRT for LARC from January 2010 to December 2016, we included 139 who developed recurrence after resection. Patients were divided into an early recurrence group, diagnosed <12 months after primary surgery, and a late recurrence group, diagnosed ≥12 months after primary surgery. Forty-nine patients experienced early recurrence and 90 experienced late recurrence. Multivariate analysis revealed that tumor regression grade (hazard ratio [HR] 2.962, 95% confidence interval [CI] 1.434–6.119, P = 0.003) and positive ypN stage (HR 2.110, 95% CI 1.144–3.892, P = 0.017) correlated with early recurrence. The 5-year overall survival rates for early and late recurrences were not significantly different (P = 0.121). In patients with early recurrence after pCRT followed by TME, tumor regression grade and ypN stage positivity were independent predictors of the early recurrence. [ABSTRACT FROM AUTHOR]

Background: The incidence of lymph node metastasis (LNM) in colorectal cancer is known to be 2–6%, but little data are available regarding metachronous metastasis confined to isolated LN. The aim of this study is to determine the distribution of isolated LNM and the risk factors for survival of isolated LNM in colorectal cancer. Methods: We retrospectively reviewed consecutive patients with colorectal adenocarcinoma between January 2008 and December 2015 at a tertiary referral center. A total of 5902 patients with biopsy-proven colorectal adenocarcinoma treated via surgery were included. Multivariate Cox proportional hazards analysis was used to identify prognostic factors for overall survival. Results: Of the 5902 patients, recurrent cases were 1326. Among the relapsed patients, 301 patients had isolated LNM (22.69%). Para-aortic (48.8%), pelvic (29.9%), and Lung hilum (10.0%) were the most common sites of isolated LNM; there were statistically significant differences in the distribution of isolated LNM between the colon and rectal cancer (p = 0.02). Approximately 80% of isolated LNM were diagnosed within 3 years. Multidisciplinary therapy for LNM, diagnosis time to LNM, the T-stage, and histological type of primary cancer were identified as independent prognostic factors for overall survival. Conclusion: This study suggests that multidisciplinary management is a potentially effective treatment strategy for isolated LNM. Since time to LNM, the T-stage, and histological type are prognostic factors, an active follow-up program for colorectal cancer is required. [ABSTRACT FROM AUTHOR]

Background: Preoperative chemoradiotherapy (PCRT) followed by surgery and adjuvant chemotherapy is the current standard treatment for stage II/III rectal cancer. However, radiotherapy in the pelvic area is commonly associated with complications such as anastomotic leakage, sexual dysfunction, and fecal incontinence. Recently, the MERCURY study showed that preoperative high-resolution magnetic resonance imaging (MRI) helped to selectively avoid PCRT. It remains unclear whether PCRT is necessary in patients who can achieve a negative circumferential resection margin (CRM) with surgery alone and in patients with cT1-2N1 or cT3N0 without CRM involvement and lateral lymph node metastasis. This study aims to evaluate the efficacy of upfront radical surgery with total mesorectal excision (TME) followed by adjuvant chemotherapy with folinic acid (or leucovorin), fluorouracil, and oxaliplatin (FOLFOX) versus the current standard treatment in patients with surgically resectable, locally advanced rectal cancer.Methods: This study, named TME-FOLFOX, is a prospective, open-label, multicenter, phase II randomized trial. Patients with locally advanced rectal cancer will be randomized to receive PCRT followed by TME and adjuvant chemotherapy (arm A) or upfront radical surgery with TME followed by adjuvant FOLFOX chemotherapy (arm B). Clinical stage II/III rectal cancer without CRM involvement and lateral lymph node metastasis will be defined using preoperative MRI. The primary endpoint is 3-year disease-free survival (DFS). Secondary endpoints include 5-year DFS, local recurrence rate, systemic recurrence rate, cost-effectiveness, and overall survival. We hypothesized that our experimental group (arm B) will have a 3-year DFS of 75% and a non-inferiority margin of 15%.Discussion: Identifying whether patients require PCRT is one of the critical issues in locally advanced rectal cancer. This study aims to elucidate whether PCRT may not be required for all patients with stage II/III rectal cancer, especially for the MRI-based intermediate-risk group (with cT1-2N1 or cT3N0) without CRM involvement and lateral lymph node metastasis. If the findings indicate that our proposed treatment, which omits PCRT, is non-inferior to the standard treatment, then patients may avoid unnecessary radiation-related toxicity, have a shorter treatment duration, and save on medical costs.Trial Registration: ClinicalTrials.gov, NCT02167321. Registered on 19 June 2014. [ABSTRACT FROM AUTHOR]

Purposes: Although adjuvant chemotherapy (AC) has been established as a standard of treatment for advanced rectal cancer, there is no guideline regarding the timing of AC initiation. In this study, we aimed to evaluate the oncologic outcome of early AC initiation and clarify the ideal time to AC among rectal cancer patients receiving preoperative chemo-radiotherapy (preCRT). Methods: The medical records of 719 patients who underwent curative resection followed by AC for rectal cancer were analyzed retrospectively. Data distributions were compared according to the calculated cut-off for AC initiation, survival results, and chemotherapy-induced toxicity. Additionally, patients were divided into two groups according to preCRT status and compared with respect to differences in the optimal time to AC. Results: Overall, a cut-off time point of 20 days after surgery for AC initiation was identified as the optimal interval; this yielded a significant difference in disease-free survival but no significant difference in AC toxicity. In the cut-off analysis of patients treated without preCRT, 19 days was identified as the optimal time to AC. However, for patients treated with preCRT, no significant value affected the survival outcome. Conclusions: Earlier initiation of AC (within approximately 3 weeks) was associated with better oncological outcomes among patients with rectal cancer. Additionally, the optimal timing of AC was unclear among patients who received preCRT; this might be attributable to an undetermined role of AC after preCRT or the effects of complications such as anastomotic leakage. [ABSTRACT FROM AUTHOR]

The aim of the present study was to investigate the utility of 3D cell culture and in vitro cytotoxicity assays, performed using cells derived from biopsies obtained prior to the initiation of preoperative chemoradiotherapy (preop-CRT), in predicting tumor response to chemoradiotherapy following preop-CRT in rectal cancer. Biopsies were obtained from 49 patients with locally advanced rectal cancer that underwent preop-CRT between August 2015 and March 2017. Tumor tissue was obtained before initiating preop-CRT. The response to chemoradiation was assessed by in vitro cytotoxicity assay following 3D cell culture and radiation treatment. The associations between the results from the cytotoxicity assay, and tumor regression grade (TRG) and yp node (ypN) positivity were investigated. Among 49 patients, 26 patients were available for analysis. Cytotoxicity ranged from 25.5–72.6% (median, 47.6%). There was no difference in cytotoxicity according to the TRGs 1–5 (P=0.940), or good tumor response (TRGs 1–2 vs. TRGs 3–5; P=0.729). However, there was a significant difference in cytotoxicity between the ypN-negative and -positive groups (53.2±14.1 and 38.7±10.1, respectively; P=0.021). Following dichotomization of patients with 45% cut-off value, the cytotoxicity assay was the only factor that predicted ypN positivity in multivariate analysis (odds ratio, 13; 95% confidence interval, 1.2–133.2; P=0.031). In conclusion, the cytotoxicity assay using the 3D cell culture method can be used to predict tumor response, particularly ypN positivity, in patients with rectal cancer who are scheduled for preop-CRT. [ABSTRACT FROM AUTHOR]

Background and Purpose: Majority of patients with locoregionally recurrent rectal cancer will require re-irradation (reRT). This study aimed to analyze the treatment outcomes, particularly infield progression, and severe late toxicity rates after reRT for recurrent rectal cancer and further identify a subgroup of patients who may optimally benefit from reRT. Materials and Methods: Patients with rectal cancer who underwent reRT to the pelvis between January 2000 and December 2017 were included for analysis. Results: The records of 41 patients were retrospectively reviewed. The median follow-up period after reRT was 53.7 months (range 3.5–130.3 months). The 2-year infield progression-free rate (IPFR) was 49.4%. The 2-year overall survival (OS) and progression-free survival (PFS) rates were 55.3 and 28.5%, respectively. Severe late toxicity events occurred in 17 patients, and the median time from reRT to severe late toxicity event was 10.5 months (range 2.3–33.3 months). The 2-year severe late toxicity free-rate (SLTFR) was 55.5%, and the median SLTFR was 33.3 months. Patients who did not experience severe late toxicity events showed a significantly higher number of recurred tumors at the posterior or lateral location compared to axial or anterior location. The selected subgroup with recurrent tumor size <3.3 cm and treated with total reRT dose of >50 Gyab10 (n = 13) showed superior IPFR, OS, and PFS to the other patients. Conclusion: ReRT was a reasonable treatment option for patients with locoregionally recurrent rectal cancer. However, severe late toxicity rates were substantially high. Thus, patients indicated for ReRT with curative dose should be selected properly according to tumor size and location. [ABSTRACT FROM AUTHOR]

Background: Anastomotic leakage can be classified by free and contained leakage according to clinical manifestations. The risk factors and their comparison between these leakage subtypes are uncertain. This study aims to evaluate anastomotic leakage patterns and to compare clinical features between free and contained leakages after low anterior resection for rectal cancer. Materials and methods: Between January 2005 and December 2012, a total of 2035 consecutive patients who underwent low anterior resection for primary rectal cancer were evaluated retrospectively at two-tertiary referral centers. The primary end points of this study were to assess detailed clinical features among leakage subtypes. The secondary end point was to compare risk factors between free and contained leakages. Results: Patients were subdivided into a no leakage group (n = 1890), free leakage group (n = 73), and contained leakage group (n = 72). Free leakage occurred more frequently in laparoscopic and robotic surgeries than open surgery (p = 0.015). On the other hand, contained leakage was developed in a higher rate of patients who received preoperative chemoradiotherapy (p<0.001). The mean development time was 4.6 days in the free leakage group, and 23.6 days in the contained leakage group. Patients with free leakage had a lower rate of a defunctioning stoma than contained leakage (5.5% vs. 29.2%, p<0.001). Risk factors for free leakage were smoking, tumor location, and laparoscopic surgery. However, tumor location and preoperative chemoradiotherapy increased the risk for contained leakage. Conclusions: Contained leakage in rectal cancer surgery showed different clinical manifestations and risk factors compared to free leakage. It is necessary to pay more attention to patients with particular risk factors for anastomotic leakage subtypes. [ABSTRACT FROM AUTHOR]

Purpose/Objective(s): Optimal treatment for locally advanced rectal cancer (LARC) with distant metastasis remains elusive. We aimed to evaluate upfront systemic chemotherapy and short-course radiotherapy (RT) followed by delayed surgery for such patients, and to identify favorable prognostic factors. Materials/Methods: We retrospectively reviewed 50 LARC patients (cT4 or cT3, <2 mm from the mesorectal fascia) with synchronous metastatic disease. The primary endpoint was progression-free survival (PFS). The secondary endpoints were overall survival, treatment-related toxicity, and compliance. We considered P values <0.05 significant. Results: At 22 months median follow-up, the median PFS time was 16 months and the 2-year PFS rate was 34.8%. Thirty-five patients who received radical surgery for primary and metastatic tumors were designated the curable group. Six patients with clinical complete response (ypCR) of metastases who underwent radical surgery for only the primary tumor were classified as potentially curable. Nine patients who received no radical surgery (3 received palliative surgery) were deemed the palliative group. The ypCR rate among surgery patients was 13.6%. PFS rates for the curable or potentially curable groups were significantly longer than that of the palliative group (P<0.001). On multivariate analysis, solitary organ metastasis and R0 status were independent prognostic factors for PFS. Conclusions: These findings demonstrated that a strong possibility that upfront chemotherapy and short-course RT with delayed surgery are an effective alternative treatment for LARC with potentially resectable distant metastasis, owing to achievement of pathologic down-staging, R0 resection, and favorable compliance and toxicity, despite the long treatment duration. [ABSTRACT FROM AUTHOR]

BACKGROUND The purpose of the current study was to examine the effect of an oncologist's exercise recommendation with and without an exercise motivation package on the amount of exercise participation and quality of life (QOL) in survivors of breast and colorectal cancer. METHODS A total of 162 survivors of early-stage breast and colorectal cancer who completed primary and adjuvant treatments were recruited for the current study. Participants were randomly assigned into 1 of 3 groups: 1) control (59 patients); 2) those receiving an oncologist's exercise recommendation (53 patients); and 3) those receiving an oncologist's exercise recommendation with an exercise motivation package (50 patients). At baseline and after 4 weeks, the level of exercise participation and QOL were assessed. RESULTS Of the 162 participants, 130 (80.2%) completed the trial. Intention-to-treat analysis indicated that participants who received an oncologist's exercise recommendation with an exercise motivation package significantly increased their level of exercise participation in terms of minutes (47.57 added minutes per week; 95% confidence interval, 9.62-85.52 minutes [ P =.022] vs control) and in Metabolic Equivalent of Task (MET)-hours per week (4.14 additional MET-hours per week; 95% confidence interval, 1.70-6.58 MET-hours [ P =.004] vs control) compared with the control group. Participants who received only their oncologist's exercise recommendation did not increase their exercise participation level. Further analysis demonstrated that role functioning was significantly improved among participants who received an oncologist's exercise recommendation with an exercise motivation package. CONCLUSIONS Providing an exercise motivation package in addition to the oncologist's exercise recommendation to increase the level of exercise among survivors of breast and colorectal cancer should be considered. Cancer 2015;121:2740-2748. © 2015 American Cancer Society [ABSTRACT FROM AUTHOR]

Background: Obesity is a known risk factor for colorectal cancer (CRC), and emerging data suggest that this association is mediated by visceral fat rather than total body fat. However, there is a lack of studies evaluating the association between visceral fat area and the prevalence of CRC. Methods: To investigate the relationship between visceral adiposity and prevalence of CRC, data of 497 women diagnosed with CRC and 318 apparently healthy women were analysed and data of well-balanced 191 pairs of women with CRC and healthy women matched based on propensity scores were additionally analysed. Diagnosis of CRC was confirmed by colonoscopy and histology. Metabolic parameters were assessed, along with body composition, using computed tomography. Results: The median visceral fat area was significantly higher in the CRC group compared with the control group before and after matching. The prevalence of CRC increased significantly with increasing visceral fat tertiles after matching (p for trend <0.01). A multivariate analysis showed that mean visceral fat area of individuals in the 67th percentile or greater group was associated with an increased prevalence of CRC (adjusted odds ratio: 1.80; 95% confidence interval: 1.12–2.91 before matching and adjusted odds ratio: 2.96; 95% confidence interval: 1.38–6.33) compared with that of individuals in the 33th percentile or lower group. Conclusion: Thus, we conclude that visceral fat area is positively associated with the prevalence of CRC. Although we could not determine the causality, visceral adiposity may be associated with the risk of CRC. Further prospective studies are required to determine the benefits of controlling visceral obesity for reducing CRC risk. [ABSTRACT FROM AUTHOR]

Background: To evaluate the impact of diabetes on outcomes in colorectal cancer patients and to examine whether this association varies by the location of tumor (colon vs. rectum). Patients and methods: This study includes 4,131 stage I-III colorectal cancer patients, treated between 1995 and 2007 (12.5% diabetic, 53% colon, 47% rectal) in South Korea. Cox proportional hazards modeling was used to determine the prognostic influence of DM on survival endpoints. Results: Colorectal cancer patients with DM had significantly worse disease-free survival (DFS) [hazard ratio (HR) 1.17, 95% confidence interval (CI): 1.00–1.37] compared with patients without DM. When considering colon and rectal cancer independently, DM was significantly associated with worse overall survival (OS) (HR: 1.46, 95% CI: 1.11–1.92), DFS (HR: 1.45, 95% CI: 1.15–1.84) and recurrence-free survival (RFS) (HR: 1.32, 95% CI: 0.98–1.76) in colon cancer patients. No association for OS, DFS or RFS was observed in rectal cancer patients. There was significant interaction of location of tumor (colon vs. rectal cancer) with DM on OS (P = 0.009) and DFS (P = 0.007). Conclusions: This study suggests that DM negatively impacts survival outcomes of patients with colon cancer but not rectal cancer. [ABSTRACT FROM AUTHOR]

Abstract: Background and purpose: The aim of this study is to evaluate the efficacy and safety of preoperative radiation therapy combined with S-1 and irinotecan (SI) in LARC. Materials and methods: Patients were considered LARC if they had a T3/T4 lesion or node positive. Weekly doses of 40mg/m2 irinotecan were intravenously administered once per week during weeks 1–5 of radiotherapy. S-1 (70mg/m2) was given from Monday to Friday in all weeks of radiotherapy. 3-D conformal radiotherapy was given at daily fractions of 1.8Gy for 5days for a total dose of 50.4 (45+5.4)Gy. Surgery was performed 4–6weeks following the completion of chemoradiation. Results: Between June 2006 and November 2007, 43 pts were enrolled. The stage was: cT3 24 patients, cT4 6 patients; 28 patients were cN+. Forty-one patients completed the chemoradiation and 42 patients underwent operation: a low anterior resection was performed in 36 patients, a total colectomy in 1 patient, and an abdominal perineal resection in 5 patients. T downstaging was observed in 50%; 23 N+ patients became N− (55%). The complete pathological response was observed in 9 patients (21%). The 3-year locoregional failure rate, distant failure rate, disease-free survival, and overall survival were 9.5%, 18.6%, 72.1%, and 94.3%, respectively. Only three patients experienced G3 diarrhea; one had G3 sepsis and two had septic shock. Hematological toxicity (G3–G4) was observed in five patients. Conclusions: This study demonstrated the efficacy of preoperative CRT with S-1 and irinotecan with 21% of complete response. However, prompt recognition and management of infection is needed to use it in patients with locally advanced rectal cancer. [Copyright &y& Elsevier]

Abstract: S-1 is a novel, oral fluoropyrimidine and a known radiosensitizer. We conducted a phase I trial to establish a schedule of S-1/irinotecan with standard pelvic radiotherapy as a preoperative treatment of locally advanced rectal cancer. Our findings suggest that this new combination is feasible and well tolerable. [Copyright &y& Elsevier]

Purpose: To compare tumor volume reduction rate, histopathologic downstaging, and tumor regression grade (TRG) among tumor responses in rectal cancer after preoperative chemoradiotherapy (CRT). Patients and Methods: Between 2002 and 2004, 30 patients with locally advanced rectal cancer underwent preoperative CRT, followed by surgical resection. Magnetic resonance volumetry was performed before and after CRT. Histopathologic tumor staging and tumor regression were reviewed. We compared pre- and post-CRT tumor volume and percent of volume reduction, according to histopathologic downstaging and TRG. Results: The tumor volume reduction rates ranged from 14.6% to 100%. Mean pre- and post-CRT tumor volumes were significantly smaller in patients who showed T downstaging than in those who did not (p = 0.040, 0.014). The mean tumor volume reduction was 66.4% vs. 55.2% (p = 0.361). However, the mean pre- and post-CRT tumor volume and mean tumor volume reduction rate between patients who showed N downstaging and those who did not were not statistically different (p = 0.176, 0.767, and 0.899). With respect to TRG, the mean pre- and post-CRT tumor volumes were not statistically significant (p = 0.108, 0.708, and 0.120). Conclusion: Tumor volume reduction rate does not correlate with histopathologic downstaging and TRG. It might be hazardous to evaluate tumor response with respect to volume reduction and to select the surgical method on this basis. [Copyright &y& Elsevier]

Purpose: This study aims to correlate thymidylate synthase (TS) gene polymorphisms with the tumor response to preoperative 5-fluorouracil (5-FU)–based chemoradiation therapy (CRT) in patients with rectal cancer. Methods and Materials: Forty-four patients with rectal cancer treated with 5-FU–based preoperative CRT were prospectively enrolled in this study. Thymidylate synthase expression and TS gene polymorphisms were evaluated in tumor obtained before preoperative CRT and were correlated with the pathologic response, as assessed by histopathologic staging (pTNM) and tumor regression grade. Results: Patients exhibited 2R/3R and 3R/3R tandem repeat polymorphisms in the TS gene. With regard to TS expression in these genotypes, 2R/3RC and 3RC/3RC were defined as the low-expression group and 2R/3RG, 3RC/3RG, and 3RG/3RG as the high-expression group. There was no significant correlation between TS expression and tumor response. There was no significant difference in the tumor response between patients homozygous for 3R/3R and patients heterozygous for 2R/3R. However, 13 of 14 patients in the low-expression group with a G>C single-nucleotide polymorphism (SNP) (2R/3RC [n = 5] or 3RC/3RC [n = 9]) exhibited a significantly greater tumor downstaging rate, as compared with only 12 of 30 patients in the high-expression group without the SNP (2R/3RG [n = 10], 3RC/3RG [n = 9], or 3RG/3RG [n = 11]) (p = 0.001). The nodal downstaging rate was also significantly greater in this low-expression group, as compared with the high-expression group (12 of 14 vs. 14 of 30, p = 0.014). However, there was no significant difference in the tumor regression grade between these groups. Conclusions: This study suggests that SNPs within the TS enhancer region affect the tumor response to preoperative 5-FU–based CRT in rectal cancer. [ABSTRACT FROM AUTHOR]