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Purpose: Neoadjuvant therapy is routinely used in the management of locally advanced rectal cancer. This study aimed to evaluate the predictive value of pathological parameters in tumor response after treatment. Methods: We reviewed the hematoxylin–eosin slides from pretreatment biopsies of 150 rectal cancer patients who received preoperative chemoradiotherapy (PCRT) at Sun Yat-sen University Cancer Center between May 2013 and June 2016. Pathological and clinical parameters were both studied. The tumor response after chemoradiotherapy was evaluated using the tumor regression grade (TRG). Logistic regression was used to evaluate the relevance between these parameters and tumor response. Results: Complete tumor response (TRG0 and pCR) to PCRT was identified in 40 (26.7%) patients. The pCR rate was 93.33% (14 of 15) in cases with signet ring cell component versus 19.26% (26 of 135) in those without signet ring cell component (p < 0.001). Four cases with signet ring cell component were evaluated as clinical complete response (cCR), all of whom also achieved pCR; in contrast, only 9 of 15 (60%) cCR cases without signet ring cell achieved pCR. Conclusion: Our data suggest that the signet ring cell component in pretreatment biopsies may be a potential predictor of tumor response to PCRT in rectal cancer. This suggests patients with clinical complete response are more suitable for a wait-and-watch approach. [ABSTRACT FROM AUTHOR]

Preoperative radiotherapy improves local disease control and disease-free survival in patients with advanced rectal cancer; however, a reliable predictive biomarker for the effectiveness of irradiation has yet to be elucidated. Phosphorylation of H2A histone family member X (H2AX) to γ-H2AX is induced by DNA double-strand breaks and is associated with the development of colorectal cancer (CRC). The current study aimed to clarify the relationship between γ-H2AX expression and CRC radiosensitivity in vitro and in vivo. H2AX levels were analyzed in datasets obtained from cohort studies and γ-H2AX expression was investigated by performing immunohistochemistry and western blotting using clinical CRC samples from patients without any preoperative therapy. In addition, the CRC cell lines WiDr and DLD-1 were subjected to irradiation and/or small interfering RNA-H2AX, after which the protein levels of γ-H2AX were examined in samples obtained from patients undergoing preoperative chemoradiotherapy. To quantify the observable effect of treatment on cancer cells, outcomes were graded as follows: 1, mild; 2, moderate; and 3, marked, with defined signatures of cellular response. Datasets obtained from cohort studies demonstrated that H2AX mRNA levels were significantly upregulated and associated with distal metastasis and microsatellite instability in CRC tissues, in contrast to that of normal tissues. In addition, γ-H2AX was overexpressed in clinical samples. In vitro, following irradiation, γ-H2AX expression levels increased and cell viability decreased in a time-dependent manner. Combined irradiation and γ-H2AX knockdown reduced the viability of each cell line when compared with irradiation or γ-H2AX knockdown alone. Furthermore, among clinical CRC samples from patients undergoing preoperative chemoradiotherapy, levels of γ-H2AX in the grade 1 group were significantly higher than those in grade 2 or grade 3. In conclusion, γ-H2AX may serve as a novel predictive marker and target for preoperative radiotherapy effectiveness in patients with CRC. [ABSTRACT FROM AUTHOR]

Perianal Paget's disease is a rare condition, which is not usually accompanied by cancer. Here, a case of anal canal carcinoma with pagetoid spread and inguinal lymph node metastasis, which exhibited a significant response to preoperative chemoradiotherapy (CRT), is presented. A 58-year-old woman was admitted to The University of Tokyo Hospital with a complaint of discomfort around the anus. Physical examination revealed an erythematous inflamed skin lesion in the perianal region and a tumor of 15 mm in diameter detected on palpation in the left inguinal region, which was diagnosed as metastatic adenocarcinoma by excisional biopsy. Colonoscopy revealed moderately differentiated adenocarcinoma of 15 mm in diameter in the anal canal. Skin biopsy of the perianal region revealed an infiltration of pagetoid cells, which were positive for cytokeratin 7, and negative for cytokeratin 20 and gross cystic disease fluid protein 15. Based on these results, the patient was diagnosed as having anal canal adenocarcinoma with pagetoid spread. The patient received preoperative CRT including the bilateral inguinal region. After CRT, robotic-assisted laparoscopic abdominoperineal resection was performed. The macroscopic findings of the surgical specimen confirmed the formation of a scar as a result of the preoperative CRT. Microscopic examination of the anal tumor revealed no residual carcinoma or lymph node metastasis. In conclusion, this case may suggest the potential applicability of preoperative CRT for the local control of anal canal carcinoma with pagetoid spread. [ABSTRACT FROM AUTHOR]

Purpose: Preoperative chemoradiotherapy (CRT) can be a promising treatment for pancreatic ductal adenocarcinoma (PDAC). However, its administration for patients with impaired renal function has not been well investigated, let alone its clinical effect. We previously reported preliminary feasibility of CRT in PDAC patients with renal impairment. Herein, we aimed to investigate the clinical effects of preoperative CRT including safety and long-term prognosis in more PDAC patients with renal impairment as an extension to our previous work.Methods: This study enrolled twenty patients harboring resectable PDAC with creatinine clearance level less than 60 ml/min. Patients underwent preoperative CRT with gemcitabine, followed by surgery. The clinical effects of the therapy were evaluated in terms of safety and long-term prognosis.Results: Preoperative CRT was completed in all 20 patients. Grade 4 leukopenia/neutropenia was identified as an observed toxicity in four cases (20.0%). Renal function was not worsened after CRT. After CRT, 17 cases were judged resectable and underwent laparotomy. Pancreatic resection was performed in 15 of the 17 patients; it was not performed in two patients because of peritoneal dissemination. The 1-/3-/5-year cumulative survival rate from the initiation of CRT for the 20 patients was 88.8%/45.5%/22.8%. In the 15 patients, renal function was not worsened after surgery.Conclusion: Our findings suggest that the clinical effects of preoperative CRT would be favorable in PDAC patients with renal impairment. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the prognostic impact of sarcopenia and skeletal muscle change in rectal cancer patients who underwent preoperative chemoradiotherapy (preop-CRT). From April 2004 to June 2013, we identified non-metastatic rectal cancer patients who underwent preop-CRT. Sarcopenia was evaluated according to previous cut-off value by computed tomography measured before starting preop-CRT (sarcopenia_pre) and 4–6 weeks after cessation of preop-CRT (sarcopenia_post). The severe muscle loss was defined as change in muscle mass < −4.2%/100 days. The hazard ratio (HR) and 95% confidence interval (CI) of sarcopenia and muscle change were estimated using a Cox proportional hazards model adjusted for potential confounders. Among 93 patients who underwent both pre and post-CRT CTs, 48 (51.6%) and 51 (54.8%) were identified as sarcopenia_pre and sarcopenia_post respectively. Twenty-three patients (24.7%) were included in the severe muscle loss group. Multivariable analysis identified sarcopenia_post (HR 2.6, 95% CI 1–6.2, p = 0.023), and severe muscle loss (HR 2.8, 95% CI 1.2–6.2, p = 0.011) along with age and ypStage as independent risk factors for overall survival. Clinical T4 stage was the only factor that can predict severe muscle loss (OR 3.4, 95% CI 1.2–9.4, p = 0.016). Sarcopenia identified after the completion of preop-CRT and change in muscle mass < −4.2%/100 days during preop-CRT are promising parameters to predict overall survival in patents with locally advanced rectal cancer and should be investigated more rigorously. [ABSTRACT FROM AUTHOR]

Background/Aim: Neutrophil-to-lymphocyte ratio (NLR) is an indicator of systemic inflammation and could be a predictive factor in malignant tumors. The aim of this study was to investigate the impact of NLR in patients with lower rectal cancer who received preoperative chemo-radiotherapy (CRT). Patients and Methods: Forty-eight patients with lower rectal cancer who underwent preoperative CRT and curative resection were enrolled. Blood samples were obtained before and after CRT. The relationship of NLR with clinical outcome was investigated. Results: Post-CRT NLR was higher compared to pre-CRT NLR. The patients with higher post-CRT NLR tended to have worse pathological response to CRT compared to those with low post-CRT NLR. The patients with high post-CRT NLR showed poorer 5-year overall survival and 3-year disease free survival while there was no correlation according to pre-CRT NLR. The univariate analysis showed that post-CRT stage and post-CRT NLR were associated with a poorer 5-year overall survival. Conclusion: NLR after preoperative CRT could be a potential prognostic indicator for patients with lower rectal cancer . [ABSTRACT FROM AUTHOR]

Abstract Background Various types of preoperative chemoradiotherapy (CRT) have been established for rectal cancer; thus,Physicians will need to refine the selection of appropriate preoperative CRT for different patients since there are various treatment regimens. Oral tegafur-uracil (UFT) plus leucovorin (LV) is commonly used to treat rectal cancer in Japan. Oral chemotherapy offers patients many potential advantages. Since 2008, we have been performing preoperative CRT with intermittent oral UFT plus LV in locally advanced rectal cancer patients to prevent postoperative local recurrence. Here, in a retrospective analysis, we evaluated the efficacy and short-term outcomes of preoperative CRT with intermittent oral UFT plus LV. Methods We analyzed data from 62 patients with locally advanced rectal cancer, including 31 patients who underwent preoperative CRT between 2009 and 2013 (the CRT group) and 31 patients who were treated with surgery alone between 2001 and 2008 (the non-CRT group). Clinicopathologically, both groups included patients with rectal cancer at clinical tumor stages 3-4 or clinical node stages 0-3. In the CRT group, curative operations were performed ≥8 weeks after CRT. Patients were concomitantly treated with 2 cycles of oral UFT (300 mg/m2/day, days 1–14 and 29–42) plus LV (75 mg/day, days 1–14 and 29–42) and 45 Gy of radiotherapy. Chemotherapy was repeated every 28 days, followed by a 2-week break. Results The completion rate of CRT was high at 94% (n = 29/31). The downstaging rate of CRT was 61% (n = 19/31). The pathological complete response rate was 6.5% (n = 2/31). Significant differences were observed in the 3-year local recurrence rate between the two groups (P < 0.05). Conclusions Preoperative CRT with intermittent oral UFT plus LV appears to be a tolerable and effective treatment for Japanese patients with rectal cancer. A further investigation of a diversification of preoperative CRT for Japanese rectal cancer patients is required.

• A complex preoperative staging was adopted for high-risk GC. • We adopted an intensive, weekly-split, triplet regimen with favorable toxicities. • Induction chemotherapy and chemoradiotherapy indicate a promising outcome. To evaluate the safety and efficacy of preoperative chemotherapy (CTx) followed by chemoradiotherapy (CCRT) for high-risk gastric cancer (GC). The inclusion criteria were as follows: (1) Borrmann type 4; (2) large Borrmann type 3 (≥8 cm); (3) single bulky (≥3 cm × 1) or multiple lymph nodes (≥1.5 cm × 3). Patients received two 21-day courses of induction CTx of TS-1 (35 mg/m2, p.o, twice daily on days 1–14), docetaxel (30 mg/m2, i.v., days 1 and 8), and cisplatin (30 mg/m2, i.v., days 1 and 8) followed by CCRT (two courses of TS-1 and cisplatin in combination with 45 Gy radiation). Forty-two patients were enrolled between March 2014 and February 2016, and 39 of these completed sequential CTx and CCRT. Among the 33 patients who underwent R0 resection, the pathologic response rate was 39.4% [no residual carcinoma (n = 5, 15.2%), with 1–10% residual carcinoma (n = 8, 24.2%)]. Overall, 4 patients (12.1%) were pathologic stage 0, 7 (21.2%) were stage I, 10 (30.3%) were stage II, and 12 (36.4%) were stage III. The overall survival rate at 3 years was 77.9% for stages 0 and I, 66.8% for stages II–III, and 33.3% for unresectable cases (P = 0.001). Toxicity was mild to moderate with grade 4 neutropenia (n = 1) and neutropenic fever (n = 1) as the most prominent side-effects. Sequential CTx and CCRT prior to surgery are feasible and effective for high-risk GC. Trial registration number: NCT02495493. [ABSTRACT FROM AUTHOR]

The number of elderly patients who receive surgical treatment for rectal cancer has gradually increased with aging of the population. In recent years, preoperative chemoradiotherapy, followed by surgical treatment, has been widely used for treating patients with locally advanced rectal adenocarcinoma. The aim of the present study was to evaluate if preoperative chemoradiotherapy is efficacious and safe for the treatment of rectal cancer in patients older than 80 years. A total of 293 patients with rectal cancer, who received preoperative chemoradiotherapy from 2007 to 2017, were studied. Comorbidities and the short- and long-term outcomes in elderly patients (aged ≥80 years old) were investigated and compared to younger patients. The elderly group comprised of 17 patients (5.8%). Pulmonary disease was the most common comorbidity (23.5%). No significant difference between the two groups regarding the rate of completeness of chemoradiotherapy was detected (P=0.26). Curative resection was performed in 14 patients in the elderly group and 252 patients in the younger group. Among 7 patients from both groups who could not receive curative resection due to their poor general condition, 4 patients had decreased lower respiratory function due to pneumonia (3 patients) or chronic obstructive pulmonary disease (1 patient). Morbidity and mortality rates were similar in elderly and younger groups (35.7% vs. 27.0%, 0% vs. 0%, respectively; P=0.54, P=1.00). No significant difference was found regarding recurrence between the two groups (P=1.00). To conclude, preoperative chemoradiotherapy in elderly patients with rectal cancer is safe and well tolerated. [ABSTRACT FROM AUTHOR]

Highlights • Addition of oxaliplatin to preoperative CRT with S-1 in patients with LARC might be feasible and lead to better local control than standard treatment. • We adopted a chemotherapy gap and S-1 in the regimen, and these may have been factors in the excellent results. • This trial showed that CRT with S-1 plus oxaliplatin and the incorporation of a chemotherapy gap in the third week of radiotherapy was feasible and resulted in a high pCR rate without severe toxicity and excellent loco-regional control. Abstract Purpose The study was designed to evaluate the safety and efficacy of adding oxaliplatin to py (CRT) with S-1 in patients with locally advanced rectal carcinoma (LARC). We report here the final results of the study. Patients and methods Patients with histopathologically confirmed LARC (cT3-T4, any N) were eligible. They received oral S-1 (80 mg/m2/day on days 1–5, 8–12, 22–26, and 29–33) and infusional oxaliplatin (60 mg/m2/day on days 1, 8, 22, 29) plus radiotherapy (1.8 Gy/day, total dose of 50.4 Gy in 28 fractions), with a chemotherapy gap in the third week of radiotherapy. Primary endpoint of the study was pathological complete response (pCR) rate. Secondary endpoints were rates of R0 resection, down-staging, cumulative 3-year local recurrence, 3-year disease-free survival (DFS), and toxicity. Results Forty-five patients were enrolled at six centers in Japan. All patients received CRT, and 44 underwent operation. The pCR rate was 27.3% (12/44). The R0 resection rate was 95.5% (42/44). T-down-staging rate was 59.1% (26/44), and N-down staging rate was 65.9% (29/44); the combined pathological down-staging rate was 79.5% (35/44). There were no grade 4 adverse events, but 11.1% of the patients had grade 3 adverse events. Cumulative 3-year local recurrence rate was 0%. However, 13 (30.0%) patients suffered from distant metastasis, and one patient suffered from secondary esophageal cancer that was unrelated to rectal cancer. Eight patients had lung metastasis, 4 had liver metastasis, and 3 patients died of the metastatic disease. The 3-year DFS rate of the 44 patients was 67.5% (median follow-up 36.3 months), and the 3-year overall survival (OS) rate was 93.0% (median follow-up 39.6 months). The patients were then divided into the pCR (12 patients) group and non pCR (32 patients) group. The 3-year rate of DFS for each group was 91.7% and 58.1% and that of OS was 100% and 90.3%, respectively. Conclusions The study showed a high pCR rate with no severe toxicity, good follow-up results, and good loco-regional control. Therefore, addition of oxaliplatin to preoperative CRT with S-1 in patients with LARC might be feasible and lead to better local control than standard treatment. [ABSTRACT FROM AUTHOR]

Background: Preoperative chemoradiotherapy (pre-CRT) followed by total mesorectal excision (TME) is currently a standard therapy for locally advanced mid-to-low rectal cancer. Less aggressive, organ-preserving option such as local excision (LE) or watchful wait can alternatively be used for patients who respond well to pre-CRT. High-resolution rectal magnetic resonance imaging (MRI) is one of the most useful methods to assess pre-CRT response, and the MERCURY group has shown that the MR tumor regression grade (mrTRG) correlated with the pathologic TRG. The aim of this study is to compare postoperative complication and oncologic outcomes between LE and TME in mid-to-low rectal cancer patients whose tumors are mrTRG grade 1 (radiological complete remission) or 2 (predominant fibrosis; near-complete remission) after pre-CRT.Methods: A prospective, double-arm, randomized, open-labeled, single center, clinical trial will be conducted in patients with mid-to-low rectal cancer whose tumors are mrTRG 1/2 after pre-CRT at the Asan Medical Center, Seoul, Korea, after approval from the Institution Review Board. Patient medical records will be de-identified using a serial number to protect personal information. Inclusion criteria will include rectal adenocarcinoma with an inferior border < 8 cm from the anal verge, mrTRG 1/2, age > 20, and provision of informed consent. Postoperative complications will be assessed by Clavien-Dindo Classification Grade. Oncologic and functional outcomes will be collected and risk factors related to these outcomes will be investigated.Discussion: We believed that the rate of postoperative complication of LE will be comparable to that of TME in mid-to-low advanced rectal cancer patients with a favorable response after pre-CRT.Trial Registration: KCT0002579 ( https://cris.nih.go.kr ) Dec-2017. [ABSTRACT FROM AUTHOR]

Background: Currently, preoperative chemoradiotherapy, perioperative chemotherapy and preoperative chemotherapy are recommended by NCCN, ESMO and Japanese guidelines respectively for resectable esophageal and junctional cancer. However, these recommendations are mainly based on esophageal cancer research. Therefore, specific for esophagogastric junction cancer, we conducted the first systematic review and network meta-analysis to rank all potential treatments simultaneously and hierarchically. Methods: Record retrieval was conducted in PubMed, Web of Science, Cochrane Central Register of Controlled Trials, Embase, ASCO and ESMO Meeting Library from inception to September 2018. Regarding time-to-event survival data, randomized controlled trials featuring comparisons between different multimodal treatments against resectable esophagogastric junction cancer were eligible. Overall survival was the endpoint. Network calculation was based on a random-effects model and the relative ranking of each node was numerically indicated by P-score (CRD42018110369, registration identifier of the meta-analysis in PROSPERO.). Results: Eight studies were included in our systematic review, corresponding to 1218 patients. Regarding overall survival, 'PreCRT' (preoperative chemoradiotherapy) topped the hierarchy (HR 1.00, P-score = 0.823), better than 'PeriCT' (perioperative chemotherapy; HR 1.32, P-score = 0.591) and 'PreCT' (preoperative chemotherapy; HR 1.54, P-score = 0.428). In sensitivity analyses, irrespective of interchanging to fixed-effects model or removing potentially heterogeneous studies, relative rankings remained stable and 'PreCRT' was still the optimal node. Conclusion: Preoperative chemoradiotherapy could potentially be the optimal multimodal treatment, which displayed more overall survival benefits than perioperative chemotherapy and preoperative chemotherapy among resectable esophagogastric junction cancer patients. To further verify our pooled results, more randomized trials will be needed to compare preoperative chemoradiotherapy with perioperative chemotherapy (especially FLOT-based regimens). [ABSTRACT FROM AUTHOR]

OBJECTIVE The aim of the present study is the dosimetric comparison of intensity-modulated radiation therapy and volumetric arc therapy (VMAT) that are currently applied in the preoperative radiotherapy of locally advanced rectal cancer. METHODS Ten patients with locally advanced rectal cancer were recontoured according to defined protocol on computed tomography simulation that was previously scanned. Dosimetric comparison was performed for each patient with 7 and 9 fields intensity-modulated radiation therapy and VMAT. Compared dosimetric parameters were determined as doses of organs at risk, the total duration of treatment, target coverage, conformity index, homogeneity index, and the total monitor unit (MU). RESULTS All plans provided comparable dosimetric parameters for target volumes. Arc plans demonstrated a statistically significant benefit with lower doses on V15 and Dmean of the small bowel than intensity-modulated radiation therapy. Arc plans were obviously superior relating to measured volumes of the whole body, and plans with 7 field had the worst results. In addition, the reduction in total treatment time by approximately 60% was achieved in arc plans. CONCLUSION VMAT with short treatment duration and low MUs can be considered as providing a more comfortable and qualified treatment. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to evaluate the relationship of anastomotic leakage, local recurrence, and overall survival in rectal cancer patients treated with preoperative chemoradiotherapy (CRT) and curative resection. Background: Little is known about the association between anastomotic leakage and oncologic outcomes after preoperative CRT. Methods: A total of 698 consecutive primary rectal cancer patients after preoperative CRT between April 19, 2000, and December 27, 2013, were retrospectively reviewed. Forty-seven patients who had anastomotic leakage were compared with 651 patients who had no anastomotic leakage. Results: Of 698 patients, 47 (6.7%) patients had anastomotic leakage. Among these 47 patients, 39 (83.0%) had grade C leak that required urgent operation, while 8 (17.0%) had grade B leak that was managed expectantly or by percutaneous drainage. The median follow-up period was 47.6 months (range, 27.1 to 68.9 months). One hundred twenty (17.2%) recurrences were identified among all patients. The median overall disease-free survival was 43 months (range, 22.4 to 66.7 months). Five-year disease-free survival did not differ significantly between the 2 groups (80.5% vs 80.4%, P = 0.839). Five-year local recurrence-free survival did not differ significantly either between the 2 groups (93.7% vs 94.9%, P = 0.653). Five-year overall survival rates of patients with or without leakage were 90.9% and 86.3%, respectively (P = 0.242). Five-year cancer-specific survival rates of patients with or without leakage were 92.2% and 86.3%, respectively (P = 0.248). Conclusion: After preoperative CRT, an anastomotic leak is not associated with a significant increase in local recurrence or long-term survival in rectal cancer. [ABSTRACT FROM AUTHOR]

OBJECTIVE The aim of the present study was to evaluate the efficacy and safety of preoperative hypofractionated chemoradiotherapy in our patients with locally advanced rectum cancer, which was previously observed in the Far East (KROG 11-02). METHODS Twenty-seven patients with locally advanced rectal cancer (cT3-4N0-2M0) between November 2014 and August 2016 were included in the study. A 2-week schedule of hypofractionated radiotherapy, 33 Gy/10 fractions, with concurrent 1 cycle of oral capecitabine (1650 mg/m2/day) was applied. Patients were planned to undergo surgery 6-8 weeks after the completion of chemoradiotherapy. End points were tumor responses and toxicity. RESULTS All patients underwent total mesorectal excision except for only 1 patient, and statistical analysis was performed on 26 patients. Of the 27 patients, 10 (38.4%) were downstaged, and 3 (11.5%) had a pathologically complete response. No grade 3-4 toxicity was observed in the patient group. Grade 1-2 hematologic toxicity developed in 2 (8%) patients, and no biochemical abnormality was observed. Gastrointestinal toxicity was observed in 17 (65%), genitourinary toxicity in 8 (30%), and radiodermatitis in 3 (11%) patients. One patient had permanent anastomosis and wound dehiscence, and presacral abscess was also seen in one patient. Enterocutaneous fistula developed in only one patient. CONCLUSION A 2-week schedule of radiotherapy with oral capecitabine in patients with locally advanced rectal cancer resulted in similar toxicity levels and tumor response rate in comparison with previous results. [ABSTRACT FROM AUTHOR]

Abstract Introduction In measuring tumor height for rectal cancer, rigid sigmoidoscopy (RS) is a standard modality, and the accuracy of magnetic resonance imaging(MRI) in patients with/without preoperative chemoradiotherapy (CRT) has not been fully investigated. The aim of this study was to investigate the accuracy of MRI for measuring tumor height. Materials and methods Among rectal cancer patients seen between July 2006 and May 2012, the initial group (RS and MRI available at initial diagnosis) and the post-CRT group (RS and MRI available after the completion of preoperative CRT) were selected. Intra-class correlation coefficient (ICC) comparison tests were performed between RS and MRI results for each group. Results Ninety-nine and 29 patients were allocated into the initial group and the post-CRT group, respectively. The tumor heights measured by RS and MRI demonstrated a positive relationship in the scatter plot (linear regression; R2 = 0.898; p < 0.001 in the initial group, R2 = 0.696; p < 0.001 in the post-CRT group). With respect to difference of absolute value (DAV) between RS and MRI, the overall mean and standard deviation of DAV were 10.9 ± 10 mm in the initial group and 8 ± 6 mm in the post-CRT group. ICC comparison analysis revealed that inter-rater agreement of RS and MRI in the initial group was significantly better than that of the post-CRT group [ICC (95% CI) 0.946 (0.919–0.963) vs. 0.823 (0.621–0.917); p = 0.004)]. Conclusions MRI can be used as a viable option to measure tumor height in rectal cancer even in patients who have undergone preoperative CRT. [ABSTRACT FROM AUTHOR]

Background: Preoperative chemoradiotherapy (CRT) is a standard treatment for stage II/III esophageal cancer. Preoperative chemotherapy is also considered a standard treatment for stage II/III esophageal squamous cell carcinoma (ESCC) in patients who undergo radical lymph node dissection. We conducted a feasibility study of preoperative CRT with cisplatin plus 5-fluorouracil (CF) and elective lymph node irradiation followed by esophagectomy with radical lymph node dissection in patients with stage II/III ESCC.Methods: Patients with clinical stage II/III, excluding T4, ESCC (International Union Against Cancer TNM classification system, 6th edition) were eligible. Chemotherapy comprised two courses of CF infusion repeated after 4-weeks. Radiation therapy was concurrently administered to the primary tumor, metastatic lymph nodes, and regional lymph nodes at a dose of 41.4 Gy. After the completion of CRT, transthoracic esophagectomy with 2-3 fields lymphadenectomy was performed. The primary endpoint was the completion rate of protocol treatment with R0 resection.Results: Thirty-one eligible patients were enrolled. During CRT, the most common grade 3 or 4 toxicities were leukopenia (65%), neutropenia (65%), anemia (13%), thrombocytopenia (13%), febrile neutropenia (13%), anorexia (16%), esophagitis (16%) and hyponatremia (16%). Thirty patients (96.8%) underwent surgery. One patient received palliative chemotherapy because of appearance of lung metastasis during CRT. The completion rate of protocol treatment was 93.5% (29/31). There was one treatment-related death after surgery. Pathological complete response was achieved in 42% (13/30).Conclusion: Preoperative CRT with CF and elective lymph node irradiation showed an acceptable toxicity and promising activity especially in ESCC. [ABSTRACT FROM AUTHOR]

The purpose of the study was to assess the immediate response to combination therapy including prolonged preoperative concurrent chemoradiotherapy with capecitabine as a radiosensitizer and local hyperthermia for patients with rectal cancer.Materials and methods. A total of 25 patients received combined modality treatment. The proportions of patients with stages II (T3–4N0 M0 ), III (T1–4N1–2M0 ) and IVa (T1–4N0–2M1 ) were 3 (12 %), 13 (52 %) and 9 (36 %), respectively. The rectal ampulla was diagnosed most frequently (68 %). The patients received preoperative radiation therapy (1.3 Gy twice daily for 5 days per week to a total dose of 54 Gy) concurrently with capecitabine (825 мg/m2 , twice a day for 5 days a week) and local hyperthermia (3 times a week, 3 hours before irradiation session, at temperatures between 42–44°С, for 45–60 minutes, to a maximum of 10 sessions).Results. Grade 1-2 radiation-induced skin reactions were observed in 3 (12 %) patients. By assessing immediate tumor response 6 months after completing radiotherapy, histologically confirmed complete regression was registered in 2 (8%) patients and partial regression in 23 (92%) patients. Rectal extirpation was performed on 8 (32%) patients and sphincter-preserving surgeries on 15 (68%) patients. Patients with complete regression were followed up. Postoperative complications were observed in 3(12%) patients. None of the patients died. No local recurrence and distant metastases were registered at the 12–18 month follow-up.Conclusion. Short-and long-term outcomes of combined modality treatment including preoperative concurrent chemoradiotherapy with capecitabine as a radiosensitizer and local hyperthermia indicate that this treatment protocol is effective and safe for patients with stage II–IVа rectal cancer. Concurrent chemoradiotherapy results in a significant tumor regression, thus extending the indications for sphincter-preserving surgery.

Combination of neoadjuvant chemoradiotherapy and surgery is the basic treatment for locally advanced rectal tumors. Despite that, a subgroup of patients does not benefit from combined treatment. A wide search of biological markers predicting neoadjuvant chemoradiotherapy efficacy is currently conducted. Tumor cell signal pathways are investigated (EGFR, Wnt), cell cycle and apoptosis, tumor stroma. Several studies with DNA microarray analysis were conducted. Predictive value of these biological markers is reviewed in this article.

Objective: In general, the typical outcome of patients with locally advanced esophageal squamous cell carcinoma is poor. Recently, attempts have been made to improve survival of patients with esophageal cancer using preoperative chemoradiotherapy followed by surgery. The experience of a single center in Southern Taiwan with esophageal squamous cell carcinoma was reviewed to determine which clinicopathologic variables could predict survival. Methods: One hundred and one patients with diagnosed esophageal squamous cell carcinoma who were treated with preoperative chemoradiotherapy followed by surgery at Kaohsiung Chang Gung Memorial Hospital were retrospectively reviewed. Univariate and multivariate survival analyses were performed using log-rank and Cox proportional hazards models. Results: Of these 101 patients, 26% (26 of 101) achieved a pathologic complete response to treatment. Univariate analysis revealed that clinical T4 disease and absence of pathologic complete response were significantly associated with worse overall survival and disease-free survival. The 3-year overall survival rates were 50% and 24% in patients with clinical T1~3 and T4 disease, respectively (P = 0.01). The 3-year overall survival rates were 68% and 28% in patients with and without pathologic complete response, respectively (P = 0.001). Multivariate analysis also showed that clinical T4 disease and absence of pathologic complete response were independently associated with inferior overall and disease-free survival. Conclusions: Clinical T4 disease and absence of pathologic complete response were associated with significantly worse survival in patients with esophageal squamous cell carcinoma receiving preoperative chemoradiotherapy followed by surgery.

Background: The prognostic role of post-chemoradiotherapy (CRT) carcinoembryonic antigen (CEA) level is not clear. We evaluated the prognostic significance of post-CRT CEA level in patients with rectal cancer after preoperative CRT.Methods: We reviewed 659 consecutive patients who underwent preoperative CRT and total mesorectal excision for non-metastatic rectal cancer. Patients were categorized into two groups according to post-CRT serum CEA level: low CEA (< 5 ng/mL) and high CEA (≥ 5 ng/mL).Results: Median post-CRT CEA level was 1.7 ng/mL (range, 0.1-207.0). A high post-CRT level was significantly associated with ypStage, ypT category, tumor regression grade, and pre-CRT CEA level. The 5-year overall survival rate of the 659 patients was 87.8% with a median follow-up period of 57.0 months (range, 1.4-176.4). When the post-CRT CEA groups were divided into groups according to pre-CRT CEA level, the 5-year overall survival rates were significantly different (P < 0.001 and P = 0.001, respectively). Post-CRT CEA level was an independent prognostic factor for overall survival. Multivariate analysis revealed that operation method, differentiation, perineural invasion, postoperative chemotherapy, tumor regression grade, and post-CRT CEA level were independent prognostic factors for overall survival.Conclusion: The level of serum CEA after preoperative CRT was an independent prognostic factor for overall survival in patients with rectal cancer. [ABSTRACT FROM AUTHOR]

The specific role of human epidermal growth factor receptor-2 (HER2) status in rectal cancers remains unclear. This study therefore aimed to explore clinicopathologic and molecular characteristics, and prognostic value of HER2-positivity in residual mid- and/or low-rectal cancers after preoperative chemoradiotherapy (CRT). Surgical specimens from 145 patients with residual rectal cancer after preoperative CRT between January 2006 and January 2011 were used to evaluate HER2 status. HER2 protein expression and gene amplification were determined using immunohistochemistry (IHC) and silver in situ hybridization (SISH) on whole tissue sections, respectively. Polymerase chain reaction was used to analyze molecular characteristics, including microsatellite instability (MSI) and mutations in KRAS exon 2 (codon 12 and 13) and BRAF V600E mutation. Of 139 eligible patients, 8 (5.8%) had HER2 overexpression (IHC 2+ and 3+) that was not associated with clinicopathologic characteristics and patient survival, except positive circumferential resection margin (CRM) (P = 0.012). SISH was performed on 24 patient samples with IHC 1+ (n = 16), 2+ (n = 6), and 3+ (n = 2). HER2 amplification was identified in 3 patients (2.2%); however, this was also associated with positive CRM (P = 0.009) but not survival (all P > 0.05). Moreover, HER2 overexpression and amplification had no relationship with KRAS or BRAF mutations, and MSI status (all P > 0.05). HER2 positivity was found in a minority of rectal cancer patients and was not significantly associated with clinicopathologic and molecular characteristics. Our findings can be helpful in understanding the clinicopathologic bases of HER2 status in rectal cancers. [ABSTRACT FROM AUTHOR]

Identifying patients who may or may not achieve pathologic complete response (pathCR) allows for treatment with alternative approaches in the preoperative setting. The aim of the current study was to investigate whether aneuploidy of chromosome 8 and mutations of circulating tumor cells (CTCs) could predict the response of patients with rectal cancer to preoperative chemoradiotherapy. A total of 33 patients with locally advanced rectal cancer (cT3-T4 and/or cN+) treated with neoadjuvant chemoradiotherapy between September 2014 and March 2015 were recruited. Blood samples were collected from 33 patients with pre-chemoradiotherapy rectal cancer. It was demonstrated that ≥5 copies of chromosome 8 was associated with pathCR (univariate logistic regression, P=0.042). Of the 6 patients whose CTCs had <5 copies of chromosome 8, 3 achieved pathCR (3/6, 50%), and of the 27 patients whose CTCs had ≥5 copies of chromosome 8 obtained 3 pathCR (3/27, 11.1%; Chi-square test, P=0.0255). Of the 33 patients with mutations assessed, 8 significant nonsynonymous mutations in CTCs were identified as associated with pathCR (Chi-square test, P-values range, 0.0004-0.0298; mutations in ARID1A, HDAC1, APC, ERBB3, TP53, AMER1 and AR). These results suggest that ≥5 copies of chromosome 8 and 8 nonsynonymous mutations in ARID1A, HDAC1, APC, ERBB3, TP53, AMER1 AR in CTCs were associated with pathCR. This conclusion should be validated further in larger prospective studies and the long-term follow-up survival data of this study will also be reported in the future. [ABSTRACT FROM AUTHOR]

Objective To investigate the associations between genetic variations in DNA mismatch repair genes and sensitivity as well as prognosis to preoperative chemoradiotherapy in patients with locally advanced rectal cancer. Methods Fourteen haplotype-tagging single nucleotide polymorphisms (htSNPs) of MLH1, MLH3 and MSH2 genes were genotyped by Sequenom MassARRAY method in 146 patients with locally advanced rectal cancer who received preoperative chemoradiotherapy. The associations between genotypes and response to capecitabine-based neoadjuvant chemoradiotherapy ( nCRT) were measured by odds ratios ( ORs) and 95% confidence intervals ( CIs) , adjusted for sex, age, clinical stages and kamofsky performance score ( KPS) by unconditional logistic regression model. The survival analyses were performed by the hazard ratios (好Rs) and 95% CIs by Cox proportional regression model. Results Among 146 cases, 64 patients were nCRT responders with a response rate of 43.8%. MLH3 rs175057 C>T and MSH2 rs13019654 G>T loci were associated with the sensitivity to preoperative chemoradiotherapy. Compared with the rs175057 CC genotype, the adjusted OR for patients with CT and TT genotypes was 0.42 (95% CI: 0.19­0.91; P= 0.029). Moreover, for rs13019654, the adjusted OR for patients with the GT or TT genotypes was 0.49 (95% CI： 0.24-0.98； P = 0.047) than those with GG genotype. The remaining 12 SNPs, including rs1540354,rs4026175,rs1981929,rs2042649,rs2303428,rs3771273,rs4608577, rs4952887, rs6544991, rs6544997, rs10188090 and rs10191478, were not significantly associated with therapeutic response to preoperative chemoradiotherapy. Meanwhile, MLH3 rs175057 C>T locus was also associated with longer overall survival time in locally advanced rectal cancer ( HR = 0.44, 95% CI ： 0.20-0.96, P = 0.038), whereas MSH2 rs3771273 T>A, rs10188090 A>G and rs10191478 T>G loci were associated with shorter overall survival time (HR= 1.74, 95% CI: 1.06-2.84, P = 0.028; HR= 1.64, 95% CI: 1.01-2.66, P = 0.046; HR = 1.71, 95% CI: 1.01-2.91, P= 0.047, respectively). The remaining 10 SNPs, including rs1540354,rs4026175,rs1981929,rs2042649,rs2303428,rs4608577,rs4952887,rs6544991, rs6544997 and rs13019654, were not significantly associated with prognosis. Conclusions Genetic polymorphisms of MLH3 rs175057 and MSH2 rs13019654 loci can predict the nCRT response, while MLH3 rs175057 as well as MSH2 rs3771273, rs10188090 and rs10191478 may predict prognosis in patients with locally advanced rectal cancer who received preoperative chemoradiotherapy. Therefore, these SNPs could be used as potential genetic markers in the personalized therapy of rectal cancer. [ABSTRACT FROM AUTHOR]

At the moment there are some scientific data supporting the use of adjuvant chemotherapy in patients with rectal cancer after neoadjuvant chemoradiotherapy and surgical treatment. The paper below presents some arguments for the use of adjuvant chemotherapy in the above clinical situation. The majority of deaths in patients with rectal cancer are caused by the presence of distant metastases, therefore there are significant grounds for the use of adjuvant chemotherapy in this group of patients. Summarising, there is no clear or scientific evidence against the use of adjuvant chemotherapy in patients with rectal cancer after preoperative chemoradiotherapy. In order to make a conclusive statement about the lack of any benefits from adjuvant therapy, it is necessary to carry out randomised studies on a homogeneous and standardised group of patients. Therefore, it seems appropriate to apply this therapy especially for patients with the N (+) features (with a tumour location between 10 cm and 15 cm), similar to colon cancer cases. [ABSTRACT FROM AUTHOR]

Background/Aims: The neoadjuvant therapy for locally advanced rectal cancer has been changed from radiotherapy (RT) to chemoradiotherapy (CRT). This study is aimed at evaluating the benefit of CRT in patients with stage II or III lower rectal cancer, with regard to the impact on recurrence. Methods: A total of 474 patients with clinical stage II or III lower rectal cancer who received either preoperative RT (n = 221) or CRT (n = 253) followed by total mesorectal excision were identified from our institutional database. Propensity score analysis was performed to mitigate selection biases. Results: Among stage II patients, the CRT group showed a significantly lower 5-year local recurrence rate than the RT group (3.0 vs. 14.8%, p = 0.002). In contrast, among stage III patients, the CRT group showed a significantly lower 5-year distant recurrence rate than the RT group (27.8 vs. 42.6%, p = 0.04) and also a better 5-year recurrence-free survival (64.2 vs. 48.3%, p = 0.03). Conclusions: Addition of concurrent chemotherapy to preoperative RT significantly enhanced the local control in stage II patients and decreased distant recurrence in stage III patients. The oncological benefit of CRT may differ between patients with stage II or III rectal cancer. [ABSTRACT FROM AUTHOR]

The aim of this study was to elucidate differences in the histological features of rectal cancer between patients treated with preoperative chemoradiotherapy and those treated with preoperative chemotherapy. Area of residual tumor (ART) was also evaluated for its utility as a potential prognostic marker between them. Sixty‐eight patients with rectal cancer who underwent sphincter‐saving surgery were enrolled in this study. Of these, 39 patients received preoperative chemoradiotherapy (CRT group) and 29 patients received preoperative (neoadjuvant) chemotherapy (NAC group). Area of residual tumor was determined by using morphometric software. Tumors in the two groups were compared for differences in their histological features and clinical outcomes. Tumors in the CRT and NAC groups varied greatly with regard to their histological features after preoperative therapy. Tumors in the CRT group showed more marked fibrosis than those in the NAC group. The total ART were significantly smaller in tumors in the CRT group than those in the NAC group. However, in circumferential resection margin‐negative pathologic stage 0‐III cases, clinical outcomes were not statistically different between the CRT and NAC groups. Both ART and pathologic TNM classification were associated with clinical outcome in preoperative CRT and NAC groups, but Dworak regression grade and fibrotic change were not. Tumors in those undergoing preoperative CRT and NAC were shown to differ significantly in their histological features. Area of residual tumor‐based assessment may provide useful prognostic information, regardless of preoperative therapy. [ABSTRACT FROM AUTHOR]

The efficacy and toxicity of hypofractionated preoperative chemoradiotherapy (HPCRT) combined with oral capecitabine was evaluated in patients with rectal cancer. HPCRT was delivered by intensity-modulated radiotherapy of either 33 Gy to the whole pelvis or 35 Gy in 10 fractions to the primary tumor and 33 Gy to the surrounding pelvis. Surgery was performed 4–8 weeks after HPCRT completion. Oral capecitabine was administered concurrently. A total of 76 patients were eligible for this study, and patient numbers in clinical stages I, II, III and IVA were 5, 29, 36 and 6, respectively. Tumor response, toxicity and survival were analyzed. A total of 9/76 patients (11.8%) achieved a pathological complete response. Sphincter preservation was achieved in 23/32 (71.9%) and 44/44 (100%) of patients with a distal extent from the anal verge of ≤5 and >5 cm, respectively. A total of 28/76 patients (36.8%) achieved tumor-downstaging and 25/76 (32.9%) achieved nodal (N)-downstaging. The 5-year disease-free survival (DFS) and overall survival rates were 76.5% and 90.6%, respectively. In the multivariate analysis for DFS, pathological N stage and lymphovascular space invasion were notable prognostic factors. A total of 6 patients in stage IVA underwent salvage treatments for lung or liver metastasis after HPCRT completion, and all 6 were alive at the last follow-up. Only 4 patients experienced grade 3 postoperative complications. No grade 4 toxicities were observed. HPCRT of 33 or 35 Gy in 10 fractions showed similar results to those of long-course fractionation. This fractionation scheme could be beneficial for patients with early stage disease, locally advanced rectal cancer, simultaneous distant metastasis requiring early intervention or for patients who wish to avoid multiple hospital visits. [ABSTRACT FROM AUTHOR]