Effect Of Neoadjuvant Chemoradiotherapy Research Articles

Long-term bowel functional outcomes following anal sphincter-preserving surgery for upper and middle rectal cancer: a single-center longitudinal study.

Despite advances in neoadjuvant chemoradiotherapy and anal sphincter-preserving surgery for rectal cancer, bowel dysfunction is still unavoidable and negatively affects patients' quality of life. In this longitudinal study, we aimed to investigate the changes in bowel function with follow-up time and the effect of neoadjuvant chemoradiotherapy on bowel function following low anterior resection for rectal cancer. In this study, 171 patients with upper or middle rectal cancer who underwent low anterior resection between 2012 and 2018 were included. Bowel function was assessed longitudinally with Memorial Sloan Kettering Cancer Center Bowel Function Instrument and Wexner scores every 6 months after restoration of bowel continuity. Patients with at least 2 follow-up visits were included. Overall, 100 patients received neoadjuvant chemoradiotherapy. Urgency, soilage, and fecal incontinence were noted within 24 months in the patients treated with neoadjuvant chemoradiotherapy. After 2 years of follow-up, significant bowel dysfunction and fecal incontinence were observed in the neoadjuvant chemoradiotherapy group. Low tumor level and neoadjuvant chemoradiotherapy were associated with delayed bowel dysfunction. Neoadjuvant chemoradiotherapy in combination with low tumor level was significantly associated with delayed bowel dysfunction even after 2 years of follow-up. Therefore, careful selection and discussion with patients are paramount.

The Effect of Neoadjuvant Therapy on Esophagectomy for cT2N0M0 Esophageal Adenocarcinoma.

For cT2N0M0 esophageal adenocarcinomas, the effects of neoadjuvant chemoradiotherapy (NT) on surgical outcomes and the oncological benefits to the patients are debatable. In this study, we investigated the optimal management for cT2N0M0 adenocarcinoma (1) assessing the perioperative impact of NT on esophagectomy and (2) evaluating the oncologic effect of NT in a homogeneous group of patients with clinical stage IIA. We hypothesized that NT does not negatively affect perioperative outcomes and provides an oncologic benefit to selected patients with cT2N0M0 disease. The National Cancer Database was queried (2010-2019) for patients with cT2N0M0 esophageal adenocarcinoma undergoing esophagectomy. After propensity-matching to adjust for differences in patient and tumor characteristics, we compared postoperative outcomes (logistic regression) and survival (Kaplan-Meier and Cox regression) among those who underwent NT vs upfront surgery (S). This study included 3413 patients, of whom 2359 (69%) received NT, and 1054 (31%) S. In contrast to those who underwent S, in the matched cohort, patients treated with NT had comparable conversion rates (8% vs11.1%, p = 0.06), length of stay (9 vs 10 days, p = 0.078), unplanned readmission (5.4% vs 8.8%, p = 0.109), and 30- (3.9% vs 3.7%, p = 0.90) and 90-day mortality (5.7% vs 4.7%, p = 0.599). In addition, NT associated with improved survival in patients with cT2N0M0 tumors > 5 cm (HR 0.30, 95% CI 0.17-0.36). NT does not appear to increase technical complexity or to adversely affect postoperative outcomes after esophagectomy. Furthermore, minimally invasive esophagectomy is feasible following NT, with comparable conversion rates to those who had upfront surgery. Lastly, NT was selectively associated with improved survival in patients with cT2N0M0 esophageal cancer.

The effect of neoadjuvant chemoradiotherapy on the immune profile of pancreatic ductal adenocarcinoma: in-depth analysis of the PREOPANC-1 randomised controlled trial

The effect of neoadjuvant chemoradiotherapy on the immune profile of pancreatic ductal adenocarcinoma: in-depth analysis of the PREOPANC-1 randomised controlled trial

The effect of neoadjuvant chemoradiotherapy on the immune profile of pancreatic ductal adenocarcinoma: In-depth analysis of the PREOPANC-1 randomized controlled trial

The effect of neoadjuvant chemoradiotherapy on the immune profile of pancreatic ductal adenocarcinoma: In-depth analysis of the PREOPANC-1 randomized controlled trial

The effectiveness of neoadjuvant chemoradiotherapy in oesophageal adenocarcinoma with presence of extracellular mucin, signet-ring cells, and/or poorly cohesive cells.

Oesophageal adenocarcinomas may show different histopathological patterns, including excessive acellular mucin pools, signet-ring cells (SRCs), and poorly cohesive cells (PCCs). These components have been suggested to correlate with poor outcomes after neoadjuvant chemoradiotherapy (nCRT), which might influence patient management. However, these factors have not been studied independently of each other with adjustment for tumour differentiation grade (i.e. the presence of well-formed glands), which is a possible confounder. We studied the pre- and post-treatment presence of extracellular mucin, SRCs, and/or PCCs in relation to pathological response and prognosis after nCRT in patients with oesophageal or oesophagogastric junction adenocarcinoma. A total of 325 patients were retrospectively identified from institutional databases of two university hospitals. All patients were scheduled for ChemoRadiotherapy for Oesophageal cancer followed by Surgery Study (CROSS) nCRT and oesophagectomy between 2001 and 2019. Percentages of well-formed glands, extracellular mucin, SRCs, and PCCs were scored in pre-treatment biopsies and post-treatment resection specimens. The association between histopathological factors (≥1 and >10%) and tumour regression grade 3-4 (i.e. >10% residual tumour), overall survival, and disease-free survival (DFS) was evaluated, adjusted for tumour differentiation grade amongst other clinicopathological variables. In pre-treatment biopsies, ≥1% extracellular mucin was present in 66 of 325 patients (20%); ≥1% SRCs in 43 of 325 (13%), and ≥1% PCCs in 126 of 325 (39%). We show that pre-treatment histopathological factors were unrelated to tumour regression grade. Pre-treatment presence of >10% PCCs was associated with lower DFS (hazard ratio [HR] 1.73, 95% CI 1.19-2.53). Patients with post-treatment presence of ≥1% SRCs had higher risk of death (HR 1.81, 95% CI 1.10-2.99). In conclusion, pre-treatment presence of extracellular mucin, SRCs, and/or PCCs is unrelated to pathological response. The presence of these factors should not be an argument to refrain from CROSS. At least 10% PCCs pre-treatment and any SRCs post-treatment, irrespective of the tumour differentiation grade, seem indicative of inferior prognosis, but require further validation in larger cohorts.

A RADIOTERAPIA E QUIMIOTERAPIA NEOADJUVANTES PARA PACIENTES COM CÂNCER DE ESÔFAGO E JUNÇÃO GASTRO-ESOFÁGICA AFETAM OS RESULTADOS PÓS-OPERATÓRIOS? UM ESTUDO USANDO O SISTEMA DE REGRESSÃO TUMORAL DE BECKER E REGRESSÃO DE LINFONODOS

The effect of neoadjuvant chemoradiotherapy (nCRT) in patients with locally advanced esophageal cancer can be determined by assessing the Becker tumor regression grade in the primary tumor, as well as in lymph nodes. The aim of this study was to investigate the anatomopathological changes caused by neoadjuvant chemoradiotherapy and their impact on clinical parameters. Specifically, we analyzed the Becker tumor regression grade, lymph node status, and regression changes and evaluated their association with the Clavien-Dindo classification of surgical complications and overall patient survival. This is a retrospective and observational study including 139 patients diagnosed with adenocarcinoma or squamous cell carcinoma of the esophagus and treated with either neoadjuvant chemoradiotherapy followed by surgery or surgery alone. For the 94 patients who underwent neoadjuvant chemoradiotherapy, we evaluated tumor regression by Becker tumor regression grade in primary tumors. We also analyzed lymph node status and regression changes on lymph nodes with or without metastases. Overall survival analysis was performed using Kaplan-Meier curves. Becker tumor regression grade is associated with lower lymphatic permeation (p<0.01) and vascular invasion (p<0.001), but not with lymph node regression rate (p=0.10). Clavien-Dindo classification was associated neither with lymph node regression rate (odds ratio=0.784, p=0.795) nor with tumor regression grade (p=0.68). Patients who presented with lymphatic permeation and vascular invasion had statistically significantly lower median survival (17 vs. 30 months, p=0.006 for lymphatic permeation, and 14 vs. 29 months, p=0.024 for vascular invasion). In our series, we were unable to demonstrate an association between Becker tumor regression grade and lymph node regression rate with any postoperative complications. Patients with lower lymphatic permeation and vascular invasion have higher overall survival, correlating with a better response in the Becker tumor regression grade system.

Spleen-preserving D2 subtotal distal resection of the stomach and corpocaudal resection of the pancreas after neoadjuvant induction chemotherapy and chemoradiotherapy: case report and literature review

Background. Stomach cancer is one of the most common cancers worldwide. Long-term treatment outcomes in patients with locally advanced gastric cancer with invasion to adjacent structures are poor. In clinical recommendations of the Ministry of Health of the Russian Federation, it is recommended to treat these patients with perioperative chemotherapy according to the FLOT scheme. The effectiveness of neoadjuvant chemoradiotherapy is studied in many multicenter studies involving randomized clinical trials. Case description. We present a case of a successful treatment of a patient with locally advanced gastric cancer (сT4bN2M0 – IVA stage). The patient received neoadjuvant therapy (2 cycles according to the FLOT scheme) followed by chemoradiotherapy (total dose of 46 Gy with the concurrent chemotherapy with capecitabine and oxaliplatin). Neoadjuvant therapy was well tolerated (grade 1 gastrointestinal and hematological toxicity). The patient underwent distal subtotal resection of the stomach with D2 lymph node dissection and distal subtotal resection of the pancreas with preservation of the spleen. No postoperative complications were observed. Histological examination revealed complete pathological response of the primary tumor, including the area of earlier invasion into the pancreas; metastasis in one lymph node of the small omentum. The patient is alive with no evidence of disease 20 months after surgery. Conclusion. The feasibility of conducting safe multimodal neoadjuvant therapy followed by organ-preserving surgery in a patient with locally advanced gastric cancer (сT4bN2M0) was shown. The effective neoadjuvant therapy resulted in the achievement of complete pathologic response, which is a favorable prognostic factor.

Impact of gut microbiota and immune contexture on effectiveness of neo-adjuvant chemo-radiotherapy in locally advanced rectal cancer (LARC)

Abstract Objective Among patients affected by Locally Advanced Rectal Cancer (LARC), 15–20% ultimately reveal a complete pathological response to the neo-adjuvant chemo-radiotherapy nCRT), which might render the surgical resection no longer necessary. However, the possibility to adopt alternative management options, such as a “wait and see” strategy, is hampered by the lack of reliable indicators of complete responsiveness to nCRT. Our hypothesis is that the composition of LARC-associated microbiome and immune contexture may predict the responsiveness to nCRT. We therefore proceed to a quantitative and qualitative evaluation of gut microbiome composition and immune contexture in LARC bioptic tissues and we then comparatively evaluated those markers in complete responders (Tumor regression grade, TRG,1) versus others (TRG2-3-4). Methods FFPE (Formalin Fixed Paraffin Embedded) LARC tissues from diagnostic biopsies and corresponding resections from patients treated at our hospital from 2012 to December 2019 were collected. Following sample deparaffinization, n. 71 genomic DNA (gDNA) and total cellular RNA were extracted. DNA used for microbiome analysis, upon amplification and sequencing of the hypervariable V3-V4 region of 16S gene. Expression of immune cell genes was evaluated by the Nanostring PanCancer Immune profiling panel on extracted RNA. Results Regarding the Microbiome profile we found no difference in terms of biodiversity between complete responders and others. However, we found some species significantly disregulated, in particular an over-expression of Alloprevotella Rava and down-expression of Porphyromonas Asaccharolytica, Turicibacter Sanguinis, Leptotrichia Trevisanii, Fusobacterium Nucleatum. The immune contexture analysis revealead a significant disregulation of 41 genes. Conclusion FFPE tissues from diagnostic biopsies proved suitable for the analysis of LARC-associated microbiome and immune contexture. A specific microbiome signature appears to be associated with responsiveness to neo-adjuvant chemoradiotherapy. Defined immune related genes, in particular those associated with IFN-gamma response, are up-regulated in tumors exhibiting complete response. A possible associations between the bacterial species significantly disregulated and this favorable immune contexture is currently under investigation.

Neoadjuvant Chemoradiotherapy Versus Upfront Surgery for Resectable and Borderline Resectable Pancreatic Cancer: Long-Term Results of the Dutch Randomized PREOPANC Trial.

The benefit of neoadjuvant chemoradiotherapy in resectable and borderline resectable pancreatic cancer remains controversial. Initial results of the PREOPANC trial failed to demonstrate a statistically significant overall survival (OS) benefit. The long-term results are reported. In this multicenter, phase III trial, patients with resectable and borderline resectable pancreatic cancer were randomly assigned (1:1) to neoadjuvant chemoradiotherapy or upfront surgery in 16 Dutch centers. Neoadjuvant chemoradiotherapy consisted of three cycles of gemcitabine combined with 36 Gy radiotherapy in 15 fractions during the second cycle. After restaging, patients underwent surgery followed by four cycles of adjuvant gemcitabine. Patients in the upfront surgery group underwent surgery followed by six cycles of adjuvant gemcitabine. The primary outcome was OS by intention-to-treat. No safety data were collected beyond the initial report of the trial. Between April 24, 2013, and July 25, 2017, 246 eligible patients were randomly assigned to neoadjuvant chemoradiotherapy (n = 119) and upfront surgery (n = 127). At a median follow-up of 59 months, the OS was better in the neoadjuvant chemoradiotherapy group than in the upfront surgery group (hazard ratio, 0.73; 95% CI, 0.56 to 0.96; P = .025). Although the difference in median survival was only 1.4 months (15.7 months v 14.3 months), the 5-year OS rate was 20.5% (95% CI, 14.2 to 29.8) with neoadjuvant chemoradiotherapy and 6.5% (95% CI, 3.1 to 13.7) with upfront surgery. The effect of neoadjuvant chemoradiotherapy was consistent across the prespecified subgroups, including resectable and borderline resectable pancreatic cancer. Neoadjuvant gemcitabine-based chemoradiotherapy followed by surgery and adjuvant gemcitabine improves OS compared with upfront surgery and adjuvant gemcitabine in resectable and borderline resectable pancreatic cancer.

Low-Rank Matrix Denoising Algorithm-Based MRI Image Feature for Therapeutic Effect Evaluation of NCRT on Rectal Cancer.

This study aimed to explore the therapeutic effects of neoadjuvant chemoradiotherapy (NCRT) on rectal cancer patients using the MRI based on low-rank matrix denoising algorithm, which was then compared with the postoperative pathological examination to evaluate its application value in tumor staging after NCRT treatment. 15 patients with rectal cancer who met the requirements of radiotherapy and chemotherapy after conventional MRI were selected as the research subjects. The conventional MRI images before and after NCRT treatment were divided in two groups. One group was not processed and set as the conventional group; the other group was processed with low-rank matrix denoising algorithm and set as the optimized group. The two groups of images were observed for the changes in the ADC value and length and thickness of the tumor before and after NCRT treatment. The two groups were compared with the pathological examination for the complete remission of pathology (pCR) after the NCRT treatment and the tumor stage results. The results showed that Root Mean Square Error (RMSE) and Peak Signal to Noise Ratio (PSNR) (18.9121 and 74.9911 dB) after introducing the low-rank matrix denoising algorithm were significantly better than those before (20.1234 and 70.1234 dB) (P < 0.05); there were notable differences in the tumor index data within the two groups before and after NCRT treatment (P < 0.05), indicating that the NCRT treatment was effective. The pathological examination results of pCR data of the two groups were not much different (P > 0.05); the examination results between the two groups were different, but no notable difference was noted (P < 0.05); in the optimized group, there was no notable difference between the MRI results and the pathological examination results (P < 0.05), while in the conventional group, there were notable differences in the MRI results and pathological examination results (P < 0.05). In conclusion, MRI images based on low-rank matrix denoising algorithm are clearer, which can improve the diagnosis rate of patients and better display the changes of the microenvironment after NCRT treatment. It also indicates that NCRT treatment has significant clinical effects in the treatment of rectal cancer patients, which is worth promoting.

732 TUMOR INFILTRATING NEUTROPHILS ARE A POOR PROGNOSTIC MARKER FOR ESOPHAGEAL CANCER PATIENTS RECEIVING NEOADJUVANT CHEMORADIOTHERAPY

Abstract Significant advances have been made in our understanding of the tumor immune microenvironment (TIM) and tumor infiltrating lymphocytes (TILs). Nevertheless, there is little understanding of the changes in the TIM in response to neoadjuvant chemoradiotherapy (CRT). Thus, our aim was to investigate the changes in the TIM with neoadjuvant CRT in EC by assessing the immune cell infiltrate, the expression of immune related genes, and their association with treatment response and prognosis. Methods To decipher the effects of neoadjuvant CRT on the TIM, we obtained 58 paired pre-treatment and post neoadjuvant CRT treated EC specimens. TILs and tumor infiltrating neutrophils (TIN) were quantified in pre-treatment biopsies and surgical resection specimens following neoadjuvant CRT. To evaluate the immune transcriptomics, RNA was extracted from these specimens and gene expression was assessed using the Nanostring Platform based on the PanCancer Immune Profiling Panel. Immunohistochemistry (IHC) was performed to validate findings from the immune transcriptomics. Results TIL counts were not prognostic for disease specific survival (DSS). We observed higher expression of immune-suppressive inflammatory chemokines (TGFß-1 and IL-16) in post-neoadjuvant treated samples compared to pre-treatment biopsies. In samples collected after neoadjuvant CRT, low expression of genes related to anti-tumor T cell cytotoxic activity1 was significantly associated with disease recurrence. In patients with residual disease, multivariate analysis revealed a high neutrophil count, but not TIL count, was significantly associated with inferior DSS (HR 3.8 [1.3– 10.8]; p = 0.01). Conclusion In EC, the tumor microenvironment after neoadjuvant CRT remains largely immune-suppressive. We discovered that the presence of TINs in patients with residual disease post neoadjuvant CRT is an independent adverse prognostic factor. Collectively, our results suggest that an inflammatory pro-tumoral microenvironment associated with TINs may contribute to treatment resistance and progressive disease in EC.

Effects of neoadjuvant chemoradiotherapy on infiltrating immune cells in the tumor microenvironment of rectal cancer

To detect the changes in the number and phenotype of tumor infiltrating immune cells in rectal cancer tissues before and after neoadjuvant concurrent chemoradiotherapy (CRT) and analyze their correlation with the clinicopathological parameters of the patients. The protein expressions of CD3, CD4, CD8, CD56 and Foxp3 in biopsy specimens and postoperative pathological specimens collected from 20 rectal cancer patients before and after neoadjuvant CRT were detected using ElivisionTM Plus immunohistochemistry, and the results were statistically analyzed. Compared with the measurements before the therapy, neoadjuvant CRT resulted in significant increments in CD3 (21.8% vs 48.8%, P < 0.001), CD4(16.5% vs 42.2%, P < 0.001), CD8(8.3% vs 33.4%, P < 0.001)and CD56(0 vs 7.6%, P=0.012), obvious reduction in Foxp3 expression(26.0% vs 15.3%, P=0.005), but no significant changes in CD4/CD8 ratio of(2.7 vs 5.1).Multivariate analysis showed that the increase of CD3-positive cells(HR=0.16, P=0.028)and CD8-positive cells(HR=0.03, P=0.001)was positively correlated with the disease-free survival of the patients after the operation. Neoadjuvant CRT can significantly increase the proportions of infiltrating immune cells positive for CD3, CD4, CD8 and CD56 and decrease the proportion of Treg lymphocytes in the tumor tissues in patients with rectal cancer.The patients with increased CD3-and CD8-positive T lymphocytes may have longer disease-free survival after the surgery.

The effects of neoadjuvant chemoradiotherapy and an in-hospital exercise training programme on physical fitness and quality of life in locally advanced rectal cancer patients: a randomised controlled trial (The EMPOWER Trial)

BackgroundThe EMPOWER trial aimed to assess the effects of a 9-week exercise prehabilitation programme on physical fitness compared with a usual care control group. Secondary aims were to investigate the effect of (1) the exercise prehabilitation programme on psychological health; and (2) neoadjuvant chemoradiotherapy (NCRT) on physical fitness and psychological health.MethodsBetween October 2013 and December 2016, adults with locally advanced rectal cancer undergoing standardised NCRT and surgery were recruited to a multi-centre trial. Patients underwent cardiopulmonary exercise testing (CPET) and completed HRQoL questionnaires (EORTC-QLQ-C30 and EQ-5D-5L) pre-NCRT and post-NCRT (week 0/baseline). At week 0, patients were randomised to exercise prehabilitation or usual care (no intervention). CPET and HRQoL questionnaires were assessed at week 0, 3, 6 and 9, whilst semi-structured interviews were assessed at week 0 and week 9. Changes in oxygen uptake at anaerobic threshold (VO2 at AT (ml kg−1 min−1)) between groups were compared using linear mixed modelling.ResultsThirty-eight patients were recruited, mean age 64 (10.4) years. Of the 38 patients, 33 were randomised: 16 to usual care and 17 to exercise prehabilitation (26 males and 7 females). Exercise prehabilitation significantly improved VO2 at AT at week 9 compared to the usual care. The change from baseline to week 9, when adjusted for baseline, between the randomised groups was + 2.9 ml kg −1 min −1; (95% CI 0.8 to 5.1), p = 0.011.ConclusionA 9-week exercise prehabilitation programme significantly improved fitness following NCRT. These findings have informed the WesFit trial (NCT03509428) which is investigating the effects of community-based multimodal prehabilitation before cancer surgery.Trial registrationClinicalTrials.gov NCT01914068. Registered 1 August 2013.

Ten-Year Outcome of Neoadjuvant Chemoradiotherapy Plus Surgery for Esophageal Cancer: The Randomized Controlled CROSS Trial.

Preoperative chemoradiotherapy according to the chemoradiotherapy for esophageal cancer followed by surgery study (CROSS) has become a standard of care for patients with locally advanced resectable esophageal or junctional cancer. We aimed to assess long-term outcome of this regimen. From 2004 through 2008, we randomly assigned 366 patients to either five weekly cycles of carboplatin and paclitaxel with concurrent radiotherapy (41.4 Gy in 23 fractions, 5 days per week) followed by surgery, or surgery alone. Follow-up data were collected through 2018. Cox regression analyses were performed to compare overall survival, cause-specific survival, and risks of locoregional and distant relapse. The effect of neoadjuvant chemoradiotherapy beyond 5 years of follow-up was tested with time-dependent Cox regression and landmark analyses. The median follow-up was 147 months (interquartile range, 134-157). Patients receiving neoadjuvant chemoradiotherapy had better overall survival (hazard ratio [HR], 0.70; 95% CI, 0.55 to 0.89). The effect of neoadjuvant chemoradiotherapy on overall survival was not time-dependent (P value for interaction, P = .73), and landmark analyses suggested a stable effect on overall survival up to 10 years of follow-up. The absolute 10-year overall survival benefit was 13% (38% v 25%). Neoadjuvant chemoradiotherapy reduced risk of death from esophageal cancer (HR, 0.60; 95% CI, 0.46 to 0.80). Death from other causes was similar between study arms (HR, 1.17; 95% CI, 0.68 to 1.99). Although a clear effect on isolated locoregional (HR, 0.40; 95% CI, 0.21 to 0.72) and synchronous locoregional plus distant relapse (HR, 0.43; 95% CI, 0.26 to 0.72) persisted, isolated distant relapse was comparable (HR, 0.76; 95% CI, 0.52 to 1.13). The overall survival benefit of patients with locally advanced resectable esophageal or junctional cancer who receive preoperative chemoradiotherapy according to CROSS persists for at least 10 years.

Clinical outcomes in elderly rectal cancer patients treated with neoadjuvant chemoradiotherapy: impact of tumor regression grade : Tumor regression grade after neoadjuvant chemoradiotherapy in elderly rectal cancer patients.

The effect of neoadjuvant chemoradiotherapy (CRT) and the relationship between pathological complete response (pCR) with clinical outcomes has been evaluated in elderly locally advanced rectal cancer (LARC) patients. We retrospectively analyzed 117 LARC patients treated with conformal RT and concomitant fluoropirimidine-based chemotherapy. A dose of 4500cGy, on the pelvis, up to 5500cGy on the tumor was delivered. Multidisciplinary evaluation, including geriatric assessment, was previously performed to identify frail patients unsuitable for combined treatment. The median age was 75 (range 70-88years), and 103 (88%) patients had ECOG Performance Status (PS) = 0. All patients except one completed CRT. Ten (8.5%) patients temporarily suspended CRT for acute severe hematologic complication, diarrhea and/or proctitis and hypokalemia. Of the 103 operated patients (88%), a pCR, according to Mandard tumor regression grade (TRG) score, was obtained in 28 patients (27.2%), with TRG1-2 rate of 43.7%. The 3- and 5-year overall survival (OS) rates were 80.2% ± 4.2% and 68.0% ± 5.2%, 72.4% ± 4.5% and 57.8% ± 5.2% for disease-free survival (DFS), and 92.2% ± 2.8% and 89.5% ± 3.9% for loco-regional control. Patients with TRG1-2 had 3- and 5-year OS rates of 84.1% ± 6.6% and 84.1% ± 6.6% compared with 82.8% ± 5.5% and 67.7% ± 7.2% for patients with TRG3-5 (p = 0.012). The 3- and 5-year DFS rates for patients with TRG1-2 were 77.6% ± 7.0% and 74.2% ± 7.5% compared with 70.9% ± 6.3% and 54.7% ± 7.3% for patients with TRG3-5 (p = 0.009). Our results reported good tolerability and clinical outcomes of neoadjuvant CRT, with a benefit in patients ≥ 70years, confirming the prognostic role of pCR on clinical outcomes.

Direct effectiveness of adding local hyperthermia to the scheme of neoadjuvant chemoradiotherapy for locally advanced rectal cancer

Purpose of the study. Direct evaluation of the antitumor effectiveness of neoadjuvant chemoradiotherapy for rectal cancer using local electromagnetic hyperthermia. Materials and methods. The analysis of the direct results of treatment of patients with locally advanced rectal cancer in the clinic of the MRRC them. A.F.Tsyba is a branch of the Federal State Budgetary Institution Scientific Research Center for Radiology of the Ministry of Health of Russia from 2015 to 2018. The study included 2 groups of patients: the study group of 54 patients and the control group of 56 people. All patients underwent a comprehensive examination with the aim of staging and morphological verification of the tumor. Patients of the study group in the neoadjuvant mode received conventional radiation therapy with classical dose fractionation in ROD 2 Gy, up to SOD 50 Gy, for 5 weeks with CAPOX chemotherapy, and local electromagnetic hyperthermia on the Yacht 4 unit, in the amount of 6 sessions. Patients in the control group received neoadjuvant treatment in an absolutely identical manner, with the exception of local hyperthermia. After the end of neoadjuvant therapy after 8–10 weeks, a comprehensive examination was again performed to assess the response of the tumor and a decision was made to conduct surgical treatment. During the follow-up examination, the following parameters were evaluated: tumor regression according to clinical and radiological examination. After surgical treatment, a comprehensive evaluation of the removed drug was carried out, including an assessment of the degree of therapeutic tumor pathomorphism according to Lavnikova G. P. Results. When conducting a comparative analysis of the frequency of complete clinical regressions of the tumor in the thermo-chemoradiotherapy group, we more often recorded the full clinical response, 12 patients (22%), compared with the chemoradiotherapy group, 8 patients (14%). In terms of partial response and stabilization in the chemoradiotherapy group, partial regression was observed in 75% of patients, while in the thermochemioradiation group only in 52% of cases. Stabilization in the study and control groups was 14% and 6%, respectively. All patients of the study and control groups with partial tumor regression and stabilization underwent surgical treatment. As a result, the frequency of surgical operations in the control group was slightly higher than 48 (85.7%) versus 42 (77.7%) from the main group (p&gt;0.05). When analyzing the frequency of a complete pathomorphological response, we noted that in the thermochemo-radiation therapy group it was 34% versus 4% in the chemo-radiation therapy group. On the contrary, pathomorphism of the 1st degree was much more common in patients of the control group — 21% versus 2% in the study group. The differences in both cases are statistically highly significant (p&lt;0.001, χ2 15, χ27). Conclusion. The use of thermochemoradiotherapy with high statistical significance (p&lt;0.001) increases the frequency of complete pathomorphological response: 34% in the study group versus 4% in the chemoradiotherapy group.

Effect of neoadjuvant chemoradiotherapy on p53 and SOX2 protein expression in esophageal adenocarcinoma.

Aim: To determine if neoadjuvant chemoradiotherapy (nCRT) affects p53 and SOX2 expression in esophageal adenocarcinoma (EAC). Materials& methods: Comparison of p53 and SOX2 expression in 100paired pre- and post-nCRT EAC samples. Results: Aberrant p53 was largely concordant (75/83, 90%), while 13/18 (72%) pre-nCRT samples with wild-type (WT) p53 staining, showed aberrant staining in paired post-nCRT samples. Similarly, 31/45 (69%) with previous WT SOX2 showed SOX2 loss in paired post-nCRT samples, whereas aberrant SOX2 loss was concordant in 50/55 (91%) cases. The prognostic values of both markers regarding survival differ before and after nCRT. Conclusion: Aberrant expression of p53 and SOX2 staining in EAC tissue is unaffected by nCRT. Conversely, the WT-staining pattern frequently changed to aberrant expression.

Effect of neoadjuvant chemoradiotherapy on prognosis in resectable and borderline resectable pancreatic cancer with venous involvement.

343 Background: The efficacy of neoadjuvant treatment for pancreatic cancer (PC) remains to be established. In this study, we have retrospectively evaluated the impact of neoadjuvant chemoradiothrapy (NACRT) on perioperative and long-term clinical outcome in PC. Methods: One hundred eighty one patients who preoperatively received full-dose gemcitabine (1000mg/m2) with concurrent radiation of 54 Gy between 2006 and 2017 were analyzed. One hundred forty nine patients who proposed upfront surgery were served as control. Results: Among the 181 patients treated with NACRT, 23 (13%) couldn’t undergo pancreatic resection after NACRT because of distant metastasis in 10, tumor progression in 7 and poor PS in 6. While among the 149 patients who proposed upfront surgery, 10 (7%) couldn’t undergo pancreatic resection at laparotomy, because of distant metastasis in 8 and tumor progression in 2. In overall survival analysis of all patients with resected and unresected tumor, patients treated with NACRT had a better prognosis than those without (median survival time: 37.0 vs. 27.1M, P = 0.049). According to tumor resectability status including R (resectable), BR-P (borderline resectable with venous involvement) and BR-A (borderline resectable with arterial involvement) PC, in the R and BR-P group, overall survival was significantly better in the patients with NACRT (45.7 vs. 33.8M, P = 0.049, 61.7 vs. 14.6M, P = 0.002). Also only for resected tumors, patients treated with NACRT had a better prognosis than those without in the R and BR-P group (53 vs. 36.5M, P = 0.033, 61.7 vs. 14.6M, P = 0.002), while NACRT had no significant impact on prognosis in the BR-A group. The rate of pancreatic fistula, delayed gastric emptying and abdominal abscess were lower in the NACRT group than the control group. Furthermore, the lymph node metastasis rate, R0 resection rate and pathological stage were favorable in the NACRT group (P &lt; 0.001, P = 0.005, P &lt; 0.001). The completion rate of adjuvant chemotherapy was also higher in the NACRT group (P = 0.001). Conclusions: NACRT had a variety of favorable impact in PC treatment. In particular, it significantly improved the prognosis in the R and BR-P, but not BR-A.

The influence of neoadjuvant chemoradiotherapy on muscle mass in patients with rectal cancer

Background: The psoas major muscle accurately represents overall skeletal muscle mass. The skeletal muscle mass volume is related to outcomes in multiple surgical procedures including colorectal cancer. However, neoadjuvant chemoradiotherapy for rectal cancer may adversely affect muscle mass. Objective: Assess the effect of neoadjuvant chemoradiotherapy on muscle mass in rectal cancer patients as well as on outcomes. Design: Retrospective study. Setting: A large UK District General Hospital. Patients and Methods: Analysis of all rectal cancer patients between 2014 and 2017. Psoas major was measured at the L3 level using pre- and post-neoadjuvant chemoradiotherapy images. Psoas major to L3 cross-sectional area (PML3) was calculated for each patient. Main Outcome Measures: 30-day and 90-day mortality, inpatient stay, and postoperative complications. Sample Size: One hundred and twenty-one rectal cancer patients. Results: Median age was 72 years (IQR: 64–78 years). Male:Female ratio was 82:39. 30-day mortality was 0%, and 90-day mortality was 0.83%. Sixty-one patients underwent neoadjuvant chemoradiotherapy (50.4%). Thirty-one patients underwent abdominoperineal excision of the rectum (APER) (25.6%), 1 underwent proctocolectomy (0.83%), 1 underwent completion proctectomy (0.83%), and 88 patients underwent anterior resection (72.7%). Significant muscle loss occurred during neoadjuvant therapy (median loss: 25.9%, IQR: 12.6–36.8%) (P

PS02.113: NEOADJUVANT CHEMORADIOTHERAPY FOLLOWED BY ESOPHAGECTOMY FOR LOCALLY BORDERLINE RESECTABLE THORACIC ESOPHAGEAL CANCER

Abstract Background Nowadays, it has emerged that conventional neoadjuvant chemotherapy for locally borderline resectable esophageal cancer is not effective. However, it still remains controversial which treatment is best. We aimed to evaluate neoadjuvant chemoradiotherapy for locally borderline resectable esophageal cancer. Methods Twenty six patients (23 men, 3 women) who underwent esophagectomy after neoadjuvant chemoradiotherapy between January 2011 and December 2016 were subjected. Radiotherapy was administered at 40 Gy with concurrent chemotherapy which consisted of 5-fluorouracil and cisplatin for all 26 patients. The therapeutic effect of neoadjuvant chemoradiotherapy and surgical outcomes including rates of curative resection and pathological complete response, and postoperative complications were retrospectively reviewed. Postoperative complications were defined as any event requiring specific medical or surgical treatment, which were assessed by the Clavien-Dindo classification. The evaluation criteria of neoadjuvant chemoradiotherapy were assessed by the RECIST guideline (ver.1.1). Results For primary tumor, 24 patients showed partial response and 2 showed stable disease. Therefore, the response rate to the primary tumor was 92.3%. For metastatic lymph nodes, on the other hand, 11 patients showed partial response and 8 showed stable disease and 1 showed progressive disease, and the response rate was 55%. Two patients were unresectable, three patients had R2 resection, and the remaining 21 patients (81%) had curative resection (R0). In the R0 resected group, the 5-year survival rate was 57%. The median operative time, bleed loss, and postoperative hospital stays were 546 minutes (178–963), 720ml (262–5170) and 34days (17–99), respectively. Postoperative complications were observed in 22 patients. The incidences of more than grade2 postoperative pneumonia, vocal cord palsy, and anastomosis leakage were 8/26 (31%), 8/26 (31%) and 3/26 (12%). There were treatment-related mortality in 2 patients. Seven patients (27%) achieved histologically complete response. Conclusion Neoadjuvant chemoradiotherapy for locally borderline resectable esophageal cancer is effective in increasing curative resection rate. In addition, patients who underwent curative resection can expect long-term survival. Disclosure All authors have declared no conflicts of interest.