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Background: The impact of body composition and sarcopenia in locally advanced rectal cancer (LARC) is still unclear, even several studies have been published on this issue. Our study aims to analyze the impact of sarcopenia on neoadjuvant chemoradiotherapy (nCRT) tolerance and survival outcomes. Methods: This is a retrospective, monocentric study where LARC patients treated between 2010 and 2020 were enrolled. A single slice, from the pre-therapy simulation computed tomography (CT) scan, was used to perform the body composition analysis with dedicated software. The primary endpoint was the impact of body composition on radiotherapy (RT) interruption secondarily on overall survival (OS), disease-free survival (DFS), and local control (LC). Results: The study included 628 LARC patients (40.9 % female, mean age 63.4 years): 24 % had low skeletal muscle index (SMI), 30 % had low muscle density (MD) and 17 (10.3 % of obese) were sarcopenic obese. Higher BMI (OR 2.38, 95 % CI 1.36–4.01) and lower SMI (0.73, 95 % CI 0.55–0.94) resulted as independent predictors of RT interruption. Sarcopenic obesity (HR 2.83, 95 % CI 1.24–6.45) was related to worse OS, while MD (0.96, 95 % CI 0.93–0.98), and higher SMI (0.97, 95 % CI 0.95–0.99) were related to better OS; a lower MD remained also associated even in adjusted multivariable analysis (0.96, 95 % CI0.93–0.98). Moreover, higher visceral adipose tissue (VAT) resulted associated with worse DFS (1.02, 95 % CI 1.01–1.03), while higher SMI was related to better Local Control (0.96, 95 % CI 0.93–0.99). Conclusions: Body composition analysis, particularly of muscle and fat masses, may be a useful tool for better management of LARC patients undergoing RT. Increased collaboration between radiation oncologists and clinical nutritionists is advisable, to enable early nutritional support of LARC.

Purpose: To compare the differences between involved-field irradiation (IFI) and elective nodal irradiation (ENI) in selecting the optimal target area for neoadjuvant chemoradiotherapy (nCRT) in patients with locally advanced esophageal squamous cell carcinoma (LA-ESCC). Materials and methods: We retrospectively analyzed 267 patients with LA-ESCC, of whom 165 underwent ENI and 102 underwent IFI. Dosimetry, treatmentrelated complications, pathological responses, recurrence/metastasis patterns, and survival were compared between the two groups. Results: The median follow-up duration was 27.9 months. The R0 resection rates in the IFI and ENI groups were 95.1% and 92.7%, respectively (p=0.441), while the pathological complete response (pCR) rates were 42.2% and 34.5%, respectively (p=0.12). The ENI group received higher radiation doses to the heart (HV30:23.9% vs. 18%, p=0.033) and lungs (LV30:7.7% vs. 4.9%, p<0.001) than the IFI group. Consequently, the ENI group showed a higher incidence of grade 2 or higher radiation pneumonitis (30.3% vs. 17.6%, p=0.004) and pericardial effusion (26.7% vs. 11.8%, p=0.021) than the IFI group. Post-operation fistulas were observed in 3 (2.9%) and 17 cases (10.3%) in the IFI and ENI groups, respectively (p=0.026). In the multivariate analysis, smoking, positive lymph node involvement (pN+), and anastomotic fistula were independent predictors of overall survival (OS). The pN+ patients exhibited a greater propensity for recurrence compared to pN-patients, especially in the first year of follow-up (6.67% vs. 0.56%, p=0.003). Conclusion: The ENI group had a higher incidence of radiation-induced adverse events compared to the IFI group, likely due to the higher radiation doses to normal tissues. Considering the similar disease-free survival (DFS) and OS rates in the two groups, IFI may be suitable for nCRT in patients with LA-ESCC, although further prospective studies are warranted. [ABSTRACT FROM AUTHOR]

PurposeTo compare the differences between involved-field irradiation (IFI) and elective nodal irradiation (ENI) in selecting the optimal target area for neoadjuvant chemoradiotherapy (nCRT) in patients with locally advanced esophageal squamous cell carcinoma (LA-ESCC).Materials and methodsWe retrospectively analyzed 267 patients with LA-ESCC, of whom 165 underwent ENI and 102 underwent IFI. Dosimetry, treatment-related complications, pathological responses, recurrence/metastasis patterns, and survival were compared between the two groups.ResultsThe median follow-up duration was 27.9 months. The R0 resection rates in the IFI and ENI groups were 95.1% and 92.7%, respectively (p=0.441), while the pathological complete response (pCR) rates were 42.2% and 34.5%, respectively (p=0.12). The ENI group received higher radiation doses to the heart (HV30:23.9% vs. 18%, p=0.033) and lungs (LV30:7.7% vs. 4.9%, p

Aim: To evaluate the prognostic significance of the NAR score and develop nomograms for locally advanced rectal cancer (LARC) treated after neoadjuvant chemo-radiotherapy (nCRT) combined with total meso-rectal excision (TME) surgery to predict prognostic. Methods: Retrospective collection among LARC patients treated at Fujian Medical University Union Hospital (training cohort) and Fujian Medical University Affiliated Zhangzhou Hospital (external validation cohort) between Jan 10, 2011 and Dec 28, 2021. The NAR score was calculated by formula: [5pN-3(cT-pT) + 12]^2/9.61. NAR score low (< 8), intermediate (8–16), and high (> 16). Results: 1665 patients in the training cohort and 256 patients in the external validation cohorts were enrolled. Lower NAR score was significantly associated with better cumulative incidence of OS, DFS, local recurrence (LR), and distant metastasis (DM) (all P < 0.001). Multivariate Cox regression analysis indicates that NAR score, distance to the anal verge, no.253 LN metastasis, post-CRT carbohydrate antigen 19–9, tumor regression grade, and surgery method are independent predictors of OS and DFS (all P < 0.001). Among these independent factors, the NAR score had the highest area under the curve (AUC) and the nomograms to predict OS and DFS were generated. The AUCs for the accuracy of the prediction OS were 1 year = 0.742, 3 years = 0.749, 5 years = 0.713; prediction DFS were 1 year = 0.727, 3 years = 0.739, 5 years = 0.718, the models have good accuracy. Conclusions: The NAR score can effectively classify patients with LARC into groups with varying outcomes of OS, DFS, LR, and DM. Moreover, the novel nomograms comprising the NAR score were developed and validated to help predict OS and DFS. [ABSTRACT FROM AUTHOR]

Neoadjuvant chemo-radiotherapy (nCRT) of locally advanced rectal cancer is associated with challenging surgical treatment and increased postoperative morbidity. Robotic technology overcomes laparoscopy limitations by enlarged 3D view, improved anatomical transection accuracy, and physiologic tremor reduction. Patients with UICC stage II–III rectal cancer, consecutively referred to our institution between March 2015 and June 2020 (n = 102) were treated with robotic (Rob-G, n = 38) or laparoscopic (Lap-G, n = 64) low anterior resection (LAR) for total meso-rectal excision (TME) following highly standardized and successful nCRT treatment. Feasibility, conversion rates, stoma creation, morbidity and clinical/pathological outcome were comparatively analysed. Sex, age, BMI, ASA scores, cTN stages and tumour distance from dentate line were comparable in the two groups. Robotic resection was always feasible without conversion to open surgery, which was necessary in 11/64 (17%) Lap-G operations (p = 0.006). Primary or secondary stomata were created in 17/38 (45%) Rob-G and 52/64 (81%) Lap-G patients (p < 0.001). Major morbidity occurred in 7/38 (18.4%) Rob-G and 6/64 (9.3%) Lap-G patients (p = 0.225). Although median operation time was longer in Rob-G compared with Lap-G (376; IQR: 330–417 min vs. 300; IQR: 270–358 min; p < 0.001), the difference was not significant in patients (Rob-G, n = 6; Lap-G, n = 10) with ≥30 BMI (p = 0.106). Number of resected lymph nodes, ypTN staging and circumferential resection margins (CRM) were comparable. Resection was complete in 87% of Rob-G and 89% of Lap-G patients (p = 0.750). Robotic LAR is not inferior to laparoscopic LAR following nCRT. Larger, randomized studies are needed to confirm lower conversion in robotic, compared to laparoscopic resection. [ABSTRACT FROM AUTHOR]

A watch-and-wait approach was suggested to avoid the possible complications related to surgery in patients with rectal carcinoma showing clinical complete response after neoadjuvant chemo-radiotherapy (CRT). Since clinical response may not correlate with pathological response, markers with higher accuracy are needed to identify patients who are likely responders and could be spared surgery. This study aims to assess whether H3K27me3 immunohistochemical expression in pre-treatment rectal carcinoma predicts response to neoadjuvant CRT or shows prognostic relevance. We assessed H3K27me3 immunostaining in 46 endoscopic biopsies of rectal carcinomas treated with neoadjuvant CRT and surgery. H3K27me3 immunostaining was lost in 20, retained in 19, and inconclusive (absent in neoplastic and non-neoplastic cells) in 7 cases. Retained H3K27me3 immuno-expression was significantly associated with ypTNM stage 0 (p = 0.0111) and high tumor regression, measured using either five-tiered (p = 0.0042) or two-tiered Dworak tumor regression grade (p = 0.0009). Poor differentiation, determined counting the number of poorly differentiated clusters (PDC grade) or tumor budding (TB) foci (TB grade), in the pre-treatment biopsy, was significantly associated with a shorter time to progression after surgery (p = 0.008; p = 0.0093). However, only PDC grade (p = 0.0023), together with radial margin involvement (p = 0.0001), retained prognostic significance in the multivariate analysis. The assessment of H3K27me3 immunostaining in pre-treatment endoscopic biopsy of rectal carcinoma could be useful to predict response to neo-adjuvant CRT and to identify patients who could safely undergo watch-and-wait approach. PDC and TB grade in the pre-treatment biopsy could provide additional prognostic information in patients with rectal carcinoma treated with neoadjuvant CRT and surgery. [ABSTRACT FROM AUTHOR]

Abstract Background Patients with locally advanced rectal cancer generally have different response rates to preoperative neoadjuvant chemo-radiotherapy. This study investigated the value of the apparent diffusion coefficient (ADC) as a predictor to forecast the response to neoadjuvant chemo-radiotherapy in patients with locally advanced rectal cancer. Methods Ninety-one locally advanced rectal cancer patients who underwent neoadjuvant chemo-radiotherapy between 2015 and 2018 were enrolled. Diffusion-weighted magnetic resonance imaging was performed before treatment and within 4 weeks after the completion of neoadjuvant chemo-radiotherapy. Mean ADC values of regions of interest were evaluated by two radiologists. The tumor response was evaluated according to RESCIST 1.1. The cut-off value for the mean ADC and increasing percentage (ΔADC%) after neoadjuvant chemo-radiotherapy was calculated using the receiver operating characteristic curve. The response rate of pre-ADC and ΔADC% above/below the cut-off values was determined using the chi-square test, respectively. Primary tumor progression-free survival (PFS) was analyzed using the Kaplan–Meier method, based on the pre-ADC and ΔADC% cut-off values. Results The cut-off value of mean pre-ADC and ΔADC% was 0.94 × 10–3 mm2/s (80.36% sensitivity, 74.29% specificity) and 26.0% (73.21% sensitivity, 77.14% specificity), respectively. Lower mean pre-ADC values were related to a better response rate (83.3% vs 29.7%, P

Introduction. Stomach cancer remains one of the most common malignancies with an unfavorable prognosis. It is the 5-th most frequent cancer and the 3rd leading cause of cancer death worldwide and in Russia as well. Combined modality treatment including radical surgery and perioperative / adjuvant therapy is the current therapeutic strategy for locally advanced gastric cancer. New approaches to combined modality treatment including neoadjuvant chemoradiotherapy for locally advanced gastric cancer were developed at A. Tsyb Medical Radiological Research Center (Obninsk, Russia) and tested in a phase 2 randomized clinical trial. The results obtained showed the safety and high efficiency of the method. To objectify the results, a multicenter randomized trial was initiated in 2016. the main objective of the study was to assess the immediate efficacy and safety of neoadjuvant chemoradiotherapy using pathological response criteria and to evaluate the frequency/severity of toxic reactions and postoperative complications. Additional objectives of the study were to assess the accuracy of preoperative staging of gastric cancer; tumor regression grade of the primary tumor and regional lymph node metastases according to CT findings; treatment outcomes according to the criteria of frequency and time to recurrence/metastasis; 1-, 2 -, and 3-year survival rates. Material and methods. The study included 70 patients with equal distribution between the treatment groups. There were more males than women; the median age was 62 years. The main criterion for inclusion of patients into the study was morphologically confirmed gastric cancer of сT2–4N1–3, сT3–4N0–3; сМ0, IIA-IIIC stages. Patients of the first (investigated) group were treated with neoadjuvant chemoradiotherapy (total dose of 46 Gy in 23 fractions and chemotherapy with capecitabine and oxaliplatin) followed by surgery (gastrectomy/subtotal resection of the stomach with D2 lymph node dissection) and 4 cycles of adjuvant chemotherapy. Patients of the second (control) group underwent surgery (gastrectomy/subtotal resection of the stomach with D2 lymph node dissection) followed by 6 cycles of adjuvant chemotherapy. Results. The tumor was localized in the middle and lower thirds of the stomach in most cases. There were mostly low-grade adenocarcinomas (47 patients). None of the patients showed the presence of distant metastases; 2B and 3 clinical tumor stages were mostly observed. The comparison of clinical and pathomorphological stages in the control (surgical) group showed that a comprehensive examination, including CT and laparoscopy, allowed the correct assessment of the tumor stage and formation of the control group according to the main inclusion criteria in more than 90 % of patients. Comparison of patients between the study and control groups showed that they were well balanced on the main prognostically important factors. The differences between all parameters were not statistically significant (p>0.05).

The prevalence of pancreatic cancer is sharply increasing recently, which significantly increases the economic burden of the population. At present, the primary treatment of resectable pancreatic cancer is surgical resection, followed by chemotherapy with or without radiation. However, the recurrence rates remain high even after R0 resection. This treatment strategy does not distinguish undetected metastatic disease, and it is prone to postoperative complications. Neoadjuvant therapies, including neoadjuvant chemotherapy and radiotherapy, is being increasingly utilized in borderline resectable as well as resectable pancreatic cancer. This review summarized and discussed clinical trials of neoadjuvant therapy for pancreatic cancer, comparing resection rates, outcome measures, and adverse reactions between neoadjuvant chemotherapy and neoadjuvant chemoradiotherapy.

The prevalence of pancreatic cancer is sharply increasing recently, which significantly increases the economic burden of the population. At present, the primary treatment of resectable pancreatic cancer is surgical resection, followed by chemotherapy with or without radiation. However, the recurrence rates remain high even after R0 resection. This treatment strategy does not distinguish undetected metastatic disease, and it is prone to postoperative complications. Neoadjuvant therapies, including neoadjuvant chemotherapy and radiotherapy, is being increasingly utilized in borderline resectable as well as resectable pancreatic cancer. This review summarized and discussed clinical trials of neoadjuvant therapy for pancreatic cancer, comparing resection rates, outcome measures, and adverse reactions between neoadjuvant chemotherapy and neoadjuvant chemoradiotherapy. [ABSTRACT FROM AUTHOR]

A watch-and-wait approach was suggested to avoid the possible complications related to surgery in patients with rectal carcinoma showing clinical complete response after neoadjuvant chemo-radiotherapy (CRT). Since clinical response may not correlate with pathological response, markers with higher accuracy are needed to identify patients who are likely responders and could be spared surgery. This study aims to assess whether H3K27me3 immunohistochemical expression in pre-treatment rectal carcinoma predicts response to neoadjuvant CRT or shows prognostic relevance. We assessed H3K27me3 immunostaining in 46 endoscopic biopsies of rectal carcinomas treated with neoadjuvant CRT and surgery. H3K27me3 immunostaining was lost in 20, retained in 19, and inconclusive (absent in neoplastic and non-neoplastic cells) in 7 cases. Retained H3K27me3 immuno-expression was significantly associated with ypTNM stage 0 (p = 0.0111) and high tumor regression, measured using either five-tiered (p = 0.0042) or two-tiered Dworak tumor regression grade (p = 0.0009). Poor differentiation, determined counting the number of poorly differentiated clusters (PDC grade) or tumor budding (TB) foci (TB grade), in the pre-treatment biopsy, was significantly associated with a shorter time to progression after surgery (p = 0.008; p = 0.0093). However, only PDC grade (p = 0.0023), together with radial margin involvement (p = 0.0001), retained prognostic significance in the multivariate analysis. The assessment of H3K27me3 immunostaining in pre-treatment endoscopic biopsy of rectal carcinoma could be useful to predict response to neo-adjuvant CRT and to identify patients who could safely undergo watch-and-wait approach. PDC and TB grade in the pre-treatment biopsy could provide additional prognostic information in patients with rectal carcinoma treated with neoadjuvant CRT and surgery.

Background: Patients with locally advanced rectal cancer generally have different response rates to preoperative neoadjuvant chemo-radiotherapy. This study investigated the value of the apparent diffusion coefficient (ADC) as a predictor to forecast the response to neoadjuvant chemo-radiotherapy in patients with locally advanced rectal cancer.Methods: Ninety-one locally advanced rectal cancer patients who underwent neoadjuvant chemo-radiotherapy between 2015 and 2018 were enrolled. Diffusion-weighted magnetic resonance imaging was performed before treatment and within 4 weeks after the completion of neoadjuvant chemo-radiotherapy. Mean ADC values of regions of interest were evaluated by two radiologists. The tumor response was evaluated according to RESCIST 1.1. The cut-off value for the mean ADC and increasing percentage (ΔADC%) after neoadjuvant chemo-radiotherapy was calculated using the receiver operating characteristic curve. The response rate of pre-ADC and ΔADC% above/below the cut-off values was determined using the chi-square test, respectively. Primary tumor progression-free survival (PFS) was analyzed using the Kaplan-Meier method, based on the pre-ADC and ΔADC% cut-off values.Results: The cut-off value of mean pre-ADC and ΔADC% was 0.94 × 10-3 mm2/s (80.36% sensitivity, 74.29% specificity) and 26.0% (73.21% sensitivity, 77.14% specificity), respectively. Lower mean pre-ADC values were related to a better response rate (83.3% vs 29.7%, P < 0.001) and PFS (26.12 vs 17.70 months, P = 0.004). ΔADC% above the cut-off value was also related to a better response rate (83.7% vs 35.7%, P < 0.001) and PFS (26.93 vs 15.65 months, P = 0.034).Conclusions: The mean ADC pre-treatment value and ΔADC% were potential predictors for the tumor response in locally advanced rectal cancer patients treated with neoadjuvant chemo-radiotherapy. [ABSTRACT FROM AUTHOR]

Background: The impact of body composition and sarcopenia in locally advanced rectal cancer (LARC) is still unclear, even several studies have been published on this issue. Our study aims to analyze the impact of sarcopenia on neoadjuvant chemoradiotherapy (nCRT) tolerance and survival outcomes., Methods: This is a retrospective, monocentric study where LARC patients treated between 2010 and 2020 were enrolled. A single slice, from the pre-therapy simulation computed tomography (CT) scan, was used to perform the body composition analysis with dedicated software. The primary endpoint was the impact of body composition on radiotherapy (RT) interruption secondarily on overall survival (OS), disease-free survival (DFS), and local control (LC)., Results: The study included 628 LARC patients (40.9 % female, mean age 63.4 years): 24 % had low skeletal muscle index (SMI), 30 % had low muscle density (MD) and 17 (10.3 % of obese) were sarcopenic obese. Higher BMI (OR 2.38, 95 % CI 1.36-4.01) and lower SMI (0.73, 95 % CI 0.55-0.94) resulted as independent predictors of RT interruption. Sarcopenic obesity (HR 2.83, 95 % CI 1.24-6.45) was related to worse OS, while MD (0.96, 95 % CI 0.93-0.98), and higher SMI (0.97, 95 % CI 0.95-0.99) were related to better OS; a lower MD remained also associated even in adjusted multivariable analysis (0.96, 95 % CI0.93-0.98). Moreover, higher visceral adipose tissue (VAT) resulted associated with worse DFS (1.02, 95 % CI 1.01-1.03), while higher SMI was related to better Local Control (0.96, 95 % CI 0.93-0.99)., Conclusions: Body composition analysis, particularly of muscle and fat masses, may be a useful tool for better management of LARC patients undergoing RT. Increased collaboration between radiation oncologists and clinical nutritionists is advisable, to enable early nutritional support of LARC., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Purpose: To determine whether MRI T2-weighted sequences-based texture analysis (TA) can predict histopathological tumor regression grade (TRG) in patients with locally advanced rectal cancer (LARC) undergoing neoadjuvant chemo-radiotherapy (nCRT). Methods: Data on patients undergoing curative-intent surgery for LARC were collected. Patients with a complete pathological response, or TRG1 according to Mandard's system were classified as responders, while patients with TRG ≥ 2 were classified as non-responders. Tumor TA was performed on each patient's paraxial T2w MRI in both pre- and post-nCRT scans, in order to extract histograms, gray-level co-occurrence matrix (GLCM) and run-length matrix (RLM) texture parameters. For features that showed a significant difference between the two groups, a receiver operating characteristic (ROC) curve was drawn. Results: Overall, 62 patients with LARC, treated with nCRT and resective surgery at our institution between 2013 and 2019 were identified. Only post-nCRT GLCM maximum probability showed a significant difference between the two groups (2909 ± 4479 in responders vs. 6515 ± 8990 in non- responders; p = 0.039); at the ROC curve, Youden index showed a sensitivity of 14% and a specificity of 100% for this parameter. Conclusions: MRI T2-weighted sequences-based TA was not effective in predicting pathological complete response to nCRT in patients with LARC. Further studies are needed to thoroughly investigate the potential of MRI TA in this setting. [ABSTRACT FROM AUTHOR]

Introduction. The prognosis for surgical treatment of locally advanced gastric cancer remains disappointing. Neoadjuvant chemo-radiation therapy is relatively new and the least researched method of treatment, it is attracting more and more attention, mainly abroad in recent years. The aims of neoadjuvant therapy is the earliest start of systemic therapy, damage of the primary tumor and regional metastases, an increase in the percentage of radical operations, improving treatment outcome. Material and methods. The planning study is a multicenter, randomized clinical phase II trial. Patients of the first (experimental) group will be treated as the followes: neoadjuvant chemo-radiotherapy (total tumor dose of 46 Gy in 23 fractions with the concurrent modified CapOX scheme) followed by D2 gastrectomy and adjuvant chemotherapy. Patients of the second (control) group will be treated with D2 gastrectomy and adjuvant chemotherapy. Adjuvant chemotherapy will be carried out under the following schemes (optional for the researchers): CapOX or FOLFOX. Toxicity evaluation of neoadjuvant chemo-radiotherapy and adjuvant chemotherapy will be conducted with NCI CTC Toxicity Scale Version 3.0. The main objectives of the trial are to assess the safety and immediate effectiveness of neoadjuvant chemo-radiotherapy according to the criteria of the frequency and severity of postoperative complications and mortality, and tumor response. We are planning to include 80 patients with morphologically confirmed gastric cancer сT2–4N1–3, сT3–4N0–3; М0. The proposed trial will be carried out in accordance with the principles of the Helsinki Declaration, it has been approved by local ethic committees of the participated institutions. Results. As a result of this multicenter randomized trial it is planned to show the reproducibility of obtained in MRRC and a number of foreign centers results – that is, the safety and high immediate effectiveness of neoadjuvant chemo-radiotherapy in patients with locally advanced gastric cancer. Conclusion. If we reach the goals of the planning trial, the results would allow to reasonably recommend the start of large international phase III trials for the final evaluation of the proposed neoadjuvant treatment as a standard one in patients with locally advanced gastric cancer.

Purpose: To compare the differences between involved-field irradiation (IFI) and elective nodal irradiation (ENI) in selecting the optimal target area for neoadjuvant chemoradiotherapy (nCRT) in patients with locally advanced esophageal squamous cell carcinoma (LA-ESCC)., Materials and Methods: We retrospectively analyzed 267 patients with LA-ESCC, of whom 165 underwent ENI and 102 underwent IFI. Dosimetry, treatment-related complications, pathological responses, recurrence/metastasis patterns, and survival were compared between the two groups., Results: The median follow-up duration was 27.9 months. The R0 resection rates in the IFI and ENI groups were 95.1% and 92.7%, respectively ( p =0.441), while the pathological complete response (pCR) rates were 42.2% and 34.5%, respectively ( p =0.12). The ENI group received higher radiation doses to the heart (HV 30 :23.9% vs . 18%, p =0.033) and lungs (LV 30 :7.7% vs. 4.9%, p <0.001) than the IFI group. Consequently, the ENI group showed a higher incidence of grade 2 or higher radiation pneumonitis (30.3% vs. 17.6%, p =0.004) and pericardial effusion (26.7% vs. 11.8%, p =0.021) than the IFI group. Post-operation fistulas were observed in 3 (2.9%) and 17 cases (10.3%) in the IFI and ENI groups, respectively ( p =0.026). In the multivariate analysis, smoking, positive lymph node involvement (pN+), and anastomotic fistula were independent predictors of overall survival (OS). The pN+ patients exhibited a greater propensity for recurrence compared to pN- patients, especially in the first year of follow-up (6.67% vs. 0.56%, p =0.003)., Conclusion: The ENI group had a higher incidence of radiation-induced adverse events compared to the IFI group, likely due to the higher radiation doses to normal tissues. Considering the similar disease-free survival (DFS) and OS rates in the two groups, IFI may be suitable for nCRT in patients with LA-ESCC, although further prospective studies are warranted., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Chen, Zhang, Zhou, Wang, Na, Zhou, Xu, Zou, Xue, Liu and Gong.)

Aim In patients with rectal cancer, surgery and chemoradiotherapy may affect anal sphincter function. Few studies have evaluated anorectal function after neoadjuvant chemoradiotherapy (n-CRT) and/or transanal endoscopic microsurgery (TEM). The aim of this study was to evaluate the effects of n-CRT and TEM on anorectal function. Method Thirty-seven patients with rectal cancer underwent anorectal manometry and Wexner scoring for faecal incontinence at baseline, after n-CRT (cT2-T3N0 cancer) and at 4 and 12 months after surgery. Water-perfused manometry measured anal tone at rest and during squeezing, rectal sensitivity and compliance. Twenty-seven and 10 patients, respectively, underwent TEM without (Group A) or with n-CRT (Group B). Results In Group A, anal resting pressure decreased from 68 ± 23 to 54 ± 26 mmHg at 4 months ( P = 0.04) and improved 12 months after surgery (60 ± 30 mmHg). The Wexner score showed a significant increase in gas incontinence (59%), soiling (44%) and urgency (37%) rates at 4 months, followed by clinical improvement at 1 year (41%, 26% and 18%, respectively). In group B, anal resting pressure decreased from 65 ± 23 to 50 ± 18 mmHg at 4 months but remained stable at 12 months (44 ± 11 mmHg, P = 0.02 vs preoperative values - no significant difference compared with evaluation at 4 months). Gas incontinence, soiling and urgency were observed in 50%, 50%, 25% and in 38%, 12% and 12% of cases, respectively, 4 and 12 months after treatment. Conclusion TEM does not significantly affect anal function. Instead, n-CRT does affect anal function but without causing major anal incontinence. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the potential of DCE-MRI to discriminate responders from non-responders after neoadjuvant chemo-radiotherapy (CRT) for locally advanced rectal cancer (LARC). We investigated several shape parameters for the time-intensity curve (TIC) in order to identify the best combination of parameters between two linear parameter classifiers. Methods: Seventy-four consecutive patients with LARC were enrolled in a prospective study approved by our ethics committee. Each patient gave written informed consent. After surgery, pathological TNM and tumour regression grade (TRG) were estimated. DCE-MRI semi-quantitative analysis (sqMRI) was performed to identify the best parameter or parameter combination to discriminate responders from non-responders in response monitoring to CRT. Percentage changes of TIC shape descriptors from the baseline to the presurgical scan were assessed and correlated with TRG. Receiver operating characteristic analysis and linear classifier were applied. Results: Forty-six patients (62.2 %) were classified as responders, while 28 subjects (37.8 %) were considered as non-responders. sqMRI reached a sensitivity of 93.5 % and a specificity of 82.1 % combining the percentage change in Maximum Signal Difference (ΔMSD) and Wash-out Slope (ΔWOS), the Standardized Index of Shape (SIS). Conclusions: SIS obtains the best result in discriminating responders from non-responders after CRT in LARC, with a cut-off value of −3.0 %. Key Points: • DCE-MRI shape descriptors are investigated to assess preoperative CRT response in LARC. • Identification of the best TIC shape descriptors combination through a linear classifier. • Identification of a single MRI index to predict neoadjuvant treatment response. [ABSTRACT FROM AUTHOR]

Purpose: Vascular endothelial growth factor receptor-2 (VEGFR-2), epidermal growth factor receptor-1 (EGFR), and cyclooxygenase-2 (COX-2) stimulate key processes involved in tumor progression and are important targets for cancer drugs. F-FDG maximum standardized uptake value (SUVmax) is a marker of tumor metabolic activity. The purpose of this study was to measure SUVmax combined with VEGFR-2, EGFR and COX-2 proteins in pretreatment tumor biopsies from patients with locally advanced rectal cancer receiving intensive neoadjuvant treatment and to correlate the findings with clinical outcome. Methods: VEGFR-2, EGFR and COX-2 were measured using the immunoreactive score (IRS). SUVmax (median 8.4) was quantified in tumors with molecular overexpression (IRS ≥3 + SUVmax ≥ 8.4 indicating active tumors; SUVmax <8.4 indicating inactive tumors). The Cox proportional hazards model was used to explore associations between tumor markers, disease-free survival (DFS) and overall survival (OS). Results: The study group comprised 38 patients with a median follow-up of 69.3 months (range 4.5 - 92 months). Multivariate analysis showed that active tumors (overexpressing VEGFR-2, high SUVmax) were associated with worse DFS (HR 4.73, 95 % CI 1.18 - 22.17; p = 0.04) and OS (HR 4.28, 95 % CI 1.04 - 20.12; p = 0.05). Conclusion: Active tumors overexpressing VEGFR-2 are associated with a worse overall outcome in patients with rectal cancer treated with induction chemotherapy followed by pelvic chemoradiation and surgery. The optimal diagnostic cut-off level for this novel biomarker association should be investigated. Evaluation in a clinical trial is required to determine whether selected patients could benefit from a VEGFR-targeting drug. [ABSTRACT FROM AUTHOR]

Objecive It has recently been reported that up to one-third of patients with nonmetastatic distal rectal cancer managed with neoadjuvant chemoradiation therapy (CRT) had a complete clinical response (cCR) to treatment. In the selected cases, this has been used as the sole treatment. The aim of this study was to determine the frequency of complete pathological response for patients receiving CRT in one centre in the UK. Method Patients receiving 6 weeks of neoadjuvant CRT were identified using the two cancer audit databases in two different tertiary hospitals from January 2002 to November 2007. Pathology was reviewed and the histopathological response of the resected specimen to CRT was evaluated using the Mandard classification (1 = complete response, 5 = no response) Results One hundred and thirty-two consecutive patients [median age 61 (range 44–86) years, 90 men] with nonmetastatic locally advanced rectal cancer received neoadjuvant chemo radiotherapy between 2002 and 2007 followed by resection of the tumour. Data were available from 129 patients. Conclusion Only 13 out of 132 (10%) of patients had a complete pathological response. This is one-third of the cCR previously reported. Nonsurgical therapy for rectal cancer using the Habr-Gama treatment algorithm may only be effective in a very small proportion of patients with rectal cancer in the UK and nonoperative treatment would not be recommended. [ABSTRACT FROM AUTHOR]

We evaluated the correlation of radiological findings obtained by MRI study with pathological diagnosis in invasive bladder cancer treated with neoadjuvant chemotherapy, with or without radiation. Twenty-seven patients, who underwent total or partial cystectomy for invasive bladder tumors, were enrolled into the present study. Eight cases had received neoadjuvant chemotherapy following the staging biopsy (group A), ten cases had received chemo-radiation therapy following the staging biopsy (group B), and nine cases had received preoperative staging biopsy alone (group C). As a final treatment, 12 of the 27 patients underwent total cystectomy and the other 15 patients underwent partial cystectomy. MRI was conducted prior to total or partial cystectomy in each case. The pathological stage was assessed by histological examination of the entire layer of the bladder wall. Tumor stage assessed by MRI was consistent with pathological findings in 16 of the 27 cases (59.3%), while MRI produced over-staging in 7 cases and under-staging in 4 cases. The accuracy of staging was 75.0, 30.0, and 77.8% in groups A, B, and C, respectively. The accuracy of MRI staging in group B was lower than that in group C ( P < 0.05). There was no difference in the accuracy of MRI staging between groups A and C. MRI is useful for the staging of bladder cancer. However, care needs to be taken when staging invasive bladder tumors treated with neoadjuvant chemo-radiation therapy, because inflammatory infiltrations and/or fibrous changes caused by the chemotherapy or chemo-radiation therapy make precise staging with MRI difficult. [ABSTRACT FROM AUTHOR]

Objective: Prognosis of patients with locally advanced rectal cancer (LARC) but achieving ypT1-2N0 stage after neoadjuvant concurrent chemo-radiotherapy (CRT) has been shown to be favorable. This study aims to determine whether the long-term outcome of ypT1-2N0 cases can be comparable to that of pT1-2N0 cohort that received definitive surgery for early disease., Method: From January 2008 to December 2013, 449 consecutive patients with rectal cancer were treated and their outcome maintained in a database. Patients with LARC underwent total mesorectal excision (TME) surgery at 4-8 weeks after completion of CRT, and those achieving stage ypI were identified as a group. As a comparison, stage pI group pertains to patients whose initially limited disease was not upstaged after TME surgery alone. After propensity score matching (PSM), comparisons of local regional control (LC), distant metastasis-free survival (DMFS), disease-free survival (DFS) and overall survival (OS) were performed using Kaplan-Meier analysis and log-rank test between ypI and pI groups. Down-staging depth score (DDS), a novel method of evaluating CRT response, was used for subset analysis., Results: Of the 449 patients, 168 matched cases were generated for analysis. Five-year LC, DMFS, DFS and OS for stage pI vs . ypI groups were 96.7% vs . 96.4% (P=0.796), 92.7% vs . 73.6% (P=0.025), 91.2% vs . 73.6% (P=0.080) and 93.1% vs . 72.3% (P=0.040), respectively. In the DDS-favorable subset of the ypI group, LC, DMFS, DFS and OS resulted in no significant differences in comparison with the pI group (P=0.384, 0.368, 0.277 and 0.458, respectively)., Conclusions: LC was comparable in both groups; however, distant metastasis developed more frequently in down-staged LARC than de novo early stage cases, reflecting the need to improve the efficacy of systemic treatment despite excellent pathologic response. DDS can be an indicator to identify a subset of the ypI group whose long-term oncologic outcomes are as good as those of stage pI cohort.

Purpose: To investigate dynamic contrast enhanced-MRI (DCE-MRI) in the preoperative chemo-radiotherapy (CRT) assessment for locally advanced rectal cancer (LARC) compared to18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT)., Methods: 75 consecutive patients with LARC were enrolled in a prospective study. DCE-MRI analysis was performed measuring SIS: linear combination of percentage change (Δ) of maximum signal difference (MSD) and wash-out slope (WOS). 18F-FDG PET/CT analysis was performed using SUV maximum (SUVmax). Tumor regression grade (TRG) were estimated after surgery. Non-parametric tests, receiver operating characteristic were evaluated., Results: 55 patients (TRG1-2) were classified as responders while 20 subjects as non responders. ΔSIS reached sensitivity of 93%, specificity of 80% and accuracy of 89% (cut-off 6%) to differentiate responders by non responders, sensitivity of 93%, specificity of 69% and accuracy of 79% (cut-off 30%) to identify pathological complete response (pCR). Therapy assessment via ΔSUVmax reached sensitivity of 67%, specificity of 75% and accuracy of 70% (cut-off 60%) to differentiate responders by non responders and sensitivity of 80%, specificity of 31% and accuracy of 51% (cut-off 44%) to identify pCR., Conclusions: CRT response assessment by DCE-MRI analysis shows a higher predictive ability than 18F-FDG PET/CT in LARC patients allowing to better discriminate significant and pCR.

Management of rectal cancer has markedly evolved over the last two decades. New technologies of staging have allowed a more precise definition of tumor extension. Refinements in surgical concepts and techniques have resulted in higher rates of sphincter preservation and better functional outcome for patients with this malignancy. Although, preoperative chemoradiotherapy followed by total mesorectal excision has become the standard of care for locally advanced tumors, many controversial matters in management of rectal cancer still need to be defined. These include the feasibility of a non-surgical approach after a favorable response to neoadjuvant therapy, the ideal margins of surgical resection for sphincter preservation and the adequacy of minimally invasive techniques of tumor resection. In this article, after an extensive search in PubMed and Embase databases, we critically review the current strategies and the most debatable matters in treatment of rectal cancer.

Fifteen percent to twenty-five percent of patients affected by colorectal cancer presents with liver metastases at diagnosis. In resectable cases, surgery is the only potentially curative treatment and achieves survival rates up to 50% at 5 years. Management is complex, as colorectal resection, liver resection, chemotherapy, and, in locally advanced mid/low rectal tumors, radiotherapy have to be integrated. Modern medical practice usually relies on evidence-based protocols. Levels of evidence for synchronous metastases are poor: published studies include few recent prospective series and several retrospective analyses collecting a limited number of patients across long periods of time. Data are difficult to be generalized and are mainly representative of single centre's experience, biased by local recruitment, indications and surgical technique. In this context, surgeons have to renounce to "evidence-based medicine" and to adopt a sort of "experience-based medicine". Anyway, some suggestions are possible. Simultaneous colorectal and liver resection can be safely performed whenever minor hepatectomies are planned, while a case-by-case evaluation is mandatory in case of more complex procedures. Neoadjuvant chemotherapy is preferentially scheduled for patients with advanced metastatic tumors to assess disease biology and to control lesions. It can be safely performed with primary tumor in situ, even planning simultaneous resection at its end. Locally advanced mid/low rectal tumor represents a further indication to neoadjuvant therapies, even if treatment's schedule is not yet standardized. In summary, several issues have to be solved, but every single HPB centre should define its proper strategy to optimize patient's selection, disease control and safety and completeness of surgery.