Use Of Neoadjuvant Chemoradiotherapy Research Articles

An integrated multiomics analysis of rectal cancer patients identified POU2F3 as a putative druggable target and entinostat as a cytotoxic enhancer of 5-fluorouracil.

Rectal cancer (RC) accounts for one-third of colorectal cancers (CRC), and 40% of these are locally advanced rectal cancers (LARC). The use of neoadjuvant chemoradiotherapy (nCRT) significantly reduces the rate of local recurrence compared to adjuvant therapy or surgery alone. However, after nCRT, up to 40%-60% of patients show a poor pathological response, while only about 20% achieve a pathological complete response. In this scenario, the identification of novel predictors of tumor response to nCRT is urgently needed to reduce LARC mortality and to spare poorly responding patients from unnecessary treatments. Therefore, by combining gene and microRNA expression datasets with proteomic data from LARC patients, we developed an integrated network centered on seven hub-genes putatively involved in the response to nCRT. In an independent validation cohort of LARC patients, we confirmed that differential expression of NFKB1, TRAF6 and STAT3 is correlated with the response to nCRT. In addition, the functional enrichment analysis also revealed that these genes are strongly related to hallmarks of cancer and inflammation, whose dysfunction may causatively affect LARC patient's response to nCRT. Furthermore, by constructing the transcription factor-module network, we hypothesized a protective role of POU2F3 gene, which could be used as a new drug target in LARC patients. Finally, we identified and tested in vitro entinostat, a histone deacetylase inhibitor, as a chemical compound that could be combined with a classical therapeutic regimen in order to design more efficient therapeutic strategies in LARC management.

Surgical management of cancer of the stomach and gastroesophageal junction after neoadjuvant therapy: the experience of the MRRC and literature review

Itroduction. Gastric cancer incidence and mortality rates remain very high worldwide, including the Russian Federation. More than 50 % of gastric cancers are locally advanced at presentation [1]. Perioperative or adjuvant chemotherapy is a standard treatment for gastric cancer patients. The use of neoadjuvant chemoradiotherapy is considered very promising.Material and Methods. We present the analysis of the results of surgical treatment of cancer of the stomach and gastrooesophageal junction after various options of neoadjuvant therapy: chemotherapy, chemoradiotherapy, and their combinations. The experience of the Medical Radiological Research Centre (MRRC), including 5 clinical prospective studies and one randomized multicenter clinical trial, was analyzed. A total of 237 patients with histologically proven locally advanced cancer of the stomach and gastro-oesophageal junction were included into the study. Of these patients, 202 received neoadjuvant therapy. Our treatment outcomes were compared with those of randomized trials published over the last 15 years.Results. Of 202 patients who received neoadjuvant therapy, 190 (94 %) underwent surgery (R0 resection: 184 patients). In the early postoperative period, complications were observed in 62 patients (32.6 %). Re-surgery was performed in 11 (5.8 %) patients. Postoperative mortality was 1.6 % (3 patients). Multicenter randomized studies and meta-analyses, as well as the long-term experience of MRRC, have shown that neoadjuvant therapy does not increase the number of postoperative complications and mortality, increases the rate of R0 resections and improves long-term treatment outcomes in patients with resectable locally advanced cancer of the stomach and gastro-oesophageal junction.Conclusion. Analysis of long-term clinical studies conducted at the MRRC as well as the treatment results published by other authors show that in some cases neoadjuvant therapy can lead to soft tissue changes in a surgical area and may complicate surgical management; however, it does not have a negative impact on the rates of postoperative complications and mortality.

Impact of neoadjuvant chemoradiation in early stage esophageal and gastro-esophageal junction adenocarcinoma

Background: Esophageal adenocarcinoma (EAC) poses a therapeutic challenge due to late-stage presentation, requiring multimodal management, with ensuing high-mortality, despite our best efforts. Current guidelines recommend use of neoadjuvant chemoradiation on patients with T1a EAC patients due to reported increased rates of R0 resection attained. However, recent literature has challenged the morbidity and survival benefits of the use of neoadjuvant radiation.

Neoadjuvant chemoradiation does not improve outcomes for patients undergoing resection for upper rectal cancer: A US Rectal Cancer Consortium analysis.

143 Background: The use of neoadjuvant chemoradiation (NCRT) for upper rectal cancer remains controversial. Our aim was to determine whether NCRT was associated with improved outcomes. Methods: The US Rectal Cancer Consortium was queried for patients who underwent resection of non-metastatic upper rectal cancer (≥12cm from anal verge) from 2007-2017. Primary outcomes were recurrence-free (RFS) and overall survival (OS). Secondary outcomes were postoperative complications. Results: 193 pts met inclusion criteria; 100 (52%) did not receive NCRT and 93 (48%) did. Median age was similar between groups (non-NCRT: 62 yrs; NCRT: 57 yrs; p=0.71). Patients in each group had similar gender and pathological stage (non-NCRT: 22% stage I, 32% stage II, 36% stage III; NCRT: 21% stage I, 23% stage II, 33% stage III; p=0.143). Median follow-up was 31 months (non-NCRT) and 34 months (NCRT). On Kaplan-Meier analysis, NCRT was not associated with improved RFS compared to non-NCRT (3-year RFS 85% vs. 80%; p=0.34) or OS (3-year OS 88% vs. 90%; p=0.49). This finding persisted on multivariable cox regression. R0 resection rate was similar between groups at 99% (non-NCRT) and 97% (NCRT; p=0.27). Anastomotic leak occurred in 11% of both cohorts. Creation of a diverting loop ileostomy (DLI) was nearly 3 times higher in NCRT (82%) versus non-NCRT patients (29%; p<0.001). Conclusions: Among patients with non-metastatic upper rectal cancer, NCRT did not improve survival or recurrence rates, but was associated with a nearly threefold higher DLI rate. Although NCRT is a mainstay of treatment for lower rectal cancer, our results do not support its use in upper rectal cancer. [Table: see text]

Evaluation of lateral lymph node metastasis in mid-low rectal cancer and planning of multi-disciplinary treatment

After the implementation of neoadjuvant chemoradiotherapy and total mesorectal excision, lateral local recurrence becomes the major type of local recurrence after surgery in rectal cancer. Most lateral recurrence develops from enlarged lateral lymph nodes on an initial imaging study. Evidence is accumulating to support the combined use of neoadjuvant chemoradiotherapy and lateral lymph node dissection. The accuracy of diagnosing lateral lymph node metastasis remains poor. The size of lateral lymph nodes is still the most commonly used variable with the most consistent accuracy and the cut-off value ranging from 5 to 8 mm on short axis. The morphological features, differentiation of the primary tumor, circumferential margin, extramural venous invasion, and response to chemoradiotherapy are among other risk factors to predict lateral lymph node metastasis. Planning multiple disciplinary treatment strategies for patients with suspected nodes must consider both the risk of local recurrence and distant metastasis. Total neoadjuvant chemoradiotherapy is the most promising regimen for patients with a high risk of recurrence. Simultaneous Integrated Boost Intensity-Modulated Radiation Therapy seemingly improves the local control of positive lateral nodes. However, its impact on the safety of surgery in patients with no response to the treatment or regrowth of lateral nodes remains unclear. For patients with smaller nodes below the cut-off value or shrunken nodes after treatment, a close follow-up strategy must be performed to detect the recurrence early and perform a salvage surgery. For patients with stratified lateral lymph node metastasis risks, plans containing different multiple disciplinary treatments must be carefully designed for long-term survival and better quality of life.

Neoadjuvant Chemoradiotherapy Significantly Improved R0 Resection Rate in Unresectable Locally Advanced Colon Cancer: The Initial Analysis from the Randomized Controlled Phase 3 Trial

<h3>Purpose/Objective(s)</h3> Neoadjuvant chemotherapy (NACT) is often used for tumor downstaging in locally advanced colon cancer (LACC) and improves the R0 resection rate. Based on previous findings, we hypothesized that neoadjuvant chemoradiotherapy (NACRT) might bring a higher R0 resection rate and survival benefit to patients with unresectable LACC. Our perspective study aimed at comparing NACRT versus NACT for unresectable LACC to confirm our hypothesis. <h3>Materials/Methods</h3> We performed the world's first randomized controlled phase 3 trial on NACRT for LACC at our institution. Eligible patients had newly diagnosed unresectable LACC. We randomly allocated patients open-label to the NACT group (control group) or the NACRT group (research group). Chemotherapy regimen was XELOX (oxaliplatin 100-130mg/m2, iv drip, d1, every 3 weeks; capecitabine 1,000mg/m2, bid, d1-d14, every 3 weeks). Patients allocated radiotherapy received a daily irradiation schedule (GTV:50Gy/25F/5W, CTV:45Gy/25F/5W). Surgery scheduled 6–8 weeks after radiotherapy and adjuvant chemotherapy were given if patients transformed into resectable LACC. <h3>Results</h3> Between July 2019 and July 2021, 49 patients with unresectable LACC underwent randomization and 45 patients (4 excluded) were analyzed for efficacy finally. There were 23, 6, 8, 7 and 1 patients with primary tumor location at sigmoid colon, descending colon, transverse colon, ascending colon and ileocecus. The median follow-up time was 20.7 months. Allocated groups were balanced, with 25 patients receiving NACRT and 20 patients receiving NACT. Twenty-one (84%) patients in the NACRT group transformed to resectable LACC after planned neoadjuvant treatment and received surgery while there were only 5 (20%) patients in the NACT group. Compared to NACT, the use of NACRT improved the R0 resection rate (80% vs 20%) significantly. The 2-year progression-free survival is 72.2% in the NACRT group and 37.4% in the NACT group (p=0·029). The 2-year overall survival is 95.5% in the NACRT group and 73.1% in the NACT group (p=0·035). No increasing toxicities and postsurgical complications were observed from the NACRT group compared with the NACT group. The trial is terminated since the R0 resection rate and survival between the two groups had shown a significant difference. Also, the patients' MMR/MSI status was not considered at the beginning of the study design. <h3>Conclusion</h3> Based on neoadjuvant chemotherapy, the addition of radiotherapy provided a higher R0 resection rate, longer progression-free survival and even might improve overall survival for patients with unresectable LACC. We concluded that this approach is safe, feasible and might associate with a better survival benefit. We are designing new clinical studies to further demonstrate the value of NACRT in LACC. This trial is registered with ClinicalTrials.gov, number NCT03970694.

Tumour-stroma ratio to predict pathological response to neo-adjuvant treatment in rectal cancer

IntroductionManagement of rectal cancer has advanced, with an increasing use of neoadjuvant chemoradiotherapy (nCRT). This opens options for organ preserving treatment for those with a major response to nCRT. However, the degree of clinical response, based on MRI and post-treatment biopsies, only poorly matches the degree of actual pathological response. In order to select patients with major pathological response without surgical resection, it is of importance to define tumour markers predicting the degree of pathological response to nCRT. The intra-tumoural tumour-stroma ratio (TSR) might be this marker. MethodsTSR in pre-treatment biopsies was estimated according to the method described by van Pelt et al. The degree of pathological response was assessed on the tumour resection according to tumour regression grading (TRG) by Mandard. The primary endpoint of this study was the difference in pathological response to nCRT between TSR-high and TSR-low groups. ResultsWe found that 26.2% of patients with major response was classified as TSR-high, while 73.8% of patients were classified as TSR-low. A high TSR in pre-treatment biopsies was associated with a lower chance of major-response to nCRT (OR = 0.37, 95%CI; 0.19–0.73), p = 0.004), independent of tumour stage and time between nCRT and surgery. ConclusionIn rectal cancer, TSR in pre-treatment biopsies predicts pathologic response to nCRT, with a high TSR bringing twice the risk of poor to no response compared to low TSR. In future, assessment of TSR may fulfil a role in a therapeutic algorithm identifying patients who will or will not respond to nCRT prior to treatment initiation.

Neoadjuvant therapy use and association with postoperative outcomes and overall survival in patients with extrahepatic cholangiocarcinoma.

Evidence for neoadjuvant therapy (NAT) in extrahepatic cholangiocarcinoma (eCCA) is limited. Our objectives were to: (1) characterize treatment trends, (2) identify factors associated with receipt of NAT, and (3) evaluate associations between NAT and postoperative outcomes. Retrospective cohort study of the National Cancer Database (2004-2017). Multivariable logistic regression assessed associations between NAT and postoperative outcomes. Stratified analysis evaluated differences between surgery first, neoadjuvant chemotherapy, and neoadjuvant chemoradiation (CRT). Among 8040 patients, 417 (5.2%) received NAT. NAT increased during the study period 2.9%-8.4% (p < 0.001). Factors associated with receipt of NAT included age <50 (vs. >75, odds ratio [OR] 4.32, p < 0.001) and stage 3 disease (vs. 1, OR 1.68, p = 0.01). Compared with surgery first, patients who received NAT had higher odds of R0 resection (OR 1.49, p = 0.01) and lower 30-day mortality (OR 0.51, p = 0.04). On stratified analysis, neoadjuvant chemotherapy was not associated with differences in any outcomes. However, neoadjuvant CRT was associated with improvement in R0 resection (OR 3.52, <0.001) and median survival (47.8 vs. 25.3 months, log-rank < 0.001) compared to surgery first. NAT, particularly neoadjuvant CRT, was associated with improved postoperative outcomes. These data suggest expanding the use of neoadjuvant CRT for eCCA.

Oncological outcome after lateral pelvic lymphadenectomy for low rectal carcinoma: not only an N-status matter.

Tumour deposits (TDs), novel pathological entities, should be considered when estimating the regional and systemic spread of rectal carcinoma and formulating treatment strategies. In fact, TDs may have more severe prognostic impact than lymph node positivity or the lymph node ratio. The assessment of the presence of TDs can be performed only through accurate postoperative pathological examination; however, the detection of TDs is not part of any of the procedures currently used to assess preoperative or intraoperative staging. This review aims to analyse and discuss the impact of TDs on the oncological outcome of patients who undergo surgery for advanced low rectal carcinoma. No prospective study has evaluated the impact of lateral pelvic TDs on oncological outcomes following total mesorectal excision with lateral pelvic lymphadenectomy. Although adequate total mesorectal excision allows for the excision of intramesorectal TDs, lateral pelvic lymph node dissection cannot guarantee the removal of lateral pelvic TDs; moreover, it remains to be determined whether surgical excision of lateral pelvic TDs can impact long-term outcomes. However, the identification of lateral pelvic TDs strengthens the 'staging effect' and limits the 'therapeutic effect' of lateral pelvic lymphadenectomy, supporting the rationale for the use of neoadjuvant chemoradiotherapy for rectal cancer. When evaluating the oncological outcomes after total mesorectal excision with lateral pelvic lymphadenectomy, the impact of lateral pelvic TDs should be considered.

Rectal MRI Interpretation After Neoadjuvant Therapy.

In recent years, several key advances in the management of locally advanced rectal cancer have been made, including the implementation of total mesorectal excision as the standard surgical approach; use of neoadjuvant chemoradiotherapy in selected patients with a high risk of local recurrence, and finally, adoption of organ preservation strategies, through either local excision or nonoperative management in selected patients with clinical complete response following neoadjuvant chemoradiotherapy. This review aims to shed light on the role of rectal MRI in the assessment of treatment response after neoadjuvant therapy, which is especially important given the growing feasibility of nonoperative management. First, an overview of current neoadjuvant therapies and response assessment based on digital rectal examination, endoscopy, and MRI will be provided. Second, the use of a high-quality restaging rectal MRI protocol will be presented. Third, a step-by-step approach to assessing treatment response on restaging rectal MRI following neoadjuvant treatment will be outlined, acknowledging challenges faced by radiologists during MRI interpretation. Finally, research related to response assessment will be discussed. LEVEL OF EVIDENCE: 4 TECHNICAL EFFICACY: Stage 3.

STUDY OF ANORECTAL PHYSIOLOGY PRE AND POS NEOADJUVANT THERAPY FOR RECTAL CANCER BY ANORECTAL MANOMETRY AND JORGE-WEXNER SCORE.

The treatment of distal rectal cancer may be accompanied by evacuation disorders of multifactorial etiology. Neoadjuvant chemoradiotherapy (NCRT) is part of the standard treatment for patients with locally advanced extraperitoneal rectal cancer. The assessment of anorectal function after long-term NCRT in patients with cancer of the extraperitoneal rectum has been poorly evaluated. The aim of the present study was to evaluate the effects of NCRT on anorectal function and continence in patients with extraperitoneal rectal cancer. Rectal adenocarcinoma patients undergoing neoadjuvant therapy were submitted to functional evaluation by anorectal manometry and the degree of fecal incontinence using the Jorge-Wexner score, before and eight weeks after NCRT. The manometric parameters evaluated were mean resting anal pressure (ARp), maximum voluntary contraction anal pressure (MaxSp) and average voluntary contraction anal pressure (ASp). All patients underwent the same NCRT protocol based on the application of fluoropyrimidine (5-FU) at a dosage of 350 mg/m2 associated with folic acid at a dosage of 20 mg/m2, intravenously, in the first and last week of treatment, concomitantly with conformational radiotherapy with a total dose of 50.4Gy, divided into 28 daily fractions of 1.8Gy. For statistical analysis of the quantitative variables with normal distribution, the mean, standard deviation, median and interquartile range were calculated. For comparison of two related samples (before and eight weeks after NCRT), Wilcoxon's non-parametric test was used. Forty-eight patients with rectal cancer were included in the study, with a mean age of 62.8 (39-81) years, 36 (75%) of whom were male. The use of NCRT was associated with a decrease in the values of ARp (55.0 mmHg vs 39.1 mmHg, P<0.05) and ASp (161.9 mmHg vs 141.9 mmHg, P<0.05) without changing MaxSp values (185,5 mmHg vs 173 mmHg, P=0.05). There was no worsening of the incontinence score eight weeks after the use of NCRT (3.0 vs 3.3; P>0.05). NCRT was associated with a reduction in the values of ARp and the ASp. There was no change in MaxSp, as well as in the degree of fecal continence by the Jorge-Wexner score.

Survival and complications after neoadjuvant chemoradiotherapy versus neoadjuvant chemotherapy for esophageal squamous cell cancer: A meta-analysis.

To compare the survival and complications of neoadjuvant chemoradiation (NCRT) versus neoadjuvant chemotherapy (NCT) for esophageal squamous cell carcinoma (ESCC). We conducted a systematic literature search of the PubMed, Web of Science, Cochrane Library, EMBASE, CNKI, Wanfang Data, CBM, and VIP databases from inception to November 2021. Meta-analyses were performed using RevMan (version 5.3) and Stata version 15.0. A total of 18 studies were included, which involved 3137 patients, The results of the metaanalysis showed that the pathological complete remission rate (odds ratio [OR] = 5.21, 95% confidence interval [CI]: 2.85-9.50, p<0.00001) and complete tumor resection rate (OR = 2.31, 95% CI: 1.57-3.41, p<0.0001) in the NCRT group were significantly better than those in the NCT group. Our meta-analysis results showed that 1-, 3-, and 5-year survival rates (1-year overall survival [OS]: OR = 1.51, 95% CI: 1.11-2.05, p = 0.009; 3-year OS: OR = 1.73, 95% CI: 1.36-2.21, p<0.0001; 5-year OS: OR = 1.61, 95% CI: 1.30-1.99, p<0.00001) in the NCRT group were significantly higher than those in the NCT group. NCRT can lead a significant survival benefit compared with NCT and there was no significant difference between the two neoadjuvant treatments in terms of postoperative complications. The use of NCRT in the treatment of patients with ESCC patients showed significant advantages in terms of survival and safety relative to the use of NCT.

High Dose Rate Brachytherapy Boost After Chemoradiation in Rectal Cancer Patients: A Retrospective Study

Background: The use of neoadjuvant chemoradiation has enhanced local control in rectal cancer patients. Objectives: The aim of this study was to evaluate the feasibility and efficacy of adding a high dose rate (HDR) brachytherapy (BRT) boost in locally advanced rectal cancer. Methods: This retrospective trial was conducted based on the medical records of patients with rectal cancer, who were referred to a tertiary hospital for neoadjuvant treatment. Fifteen patients who were treated with HDR brachytherapy boost after completion of external beam radiotherapy (EBRT) and concurrent chemotherapy were enrolled in the intervention group and 15 patients who were clinically matched (age, sex, stage, and distance of tumor from anal verge) were selected as the control group. EBRT schedule and concurrent chemotherapy regimen were similar in the two groups. The rate of pathological complete response (PCR), downstaging (T staging), and frequency of side effects were compared between the two groups of the study. Results: The mean age of patients was 57.97 ± 9.11 years and 18 patients (60%) were male. The results showed that T 3 and N 1 rectal cancer had the highest frequency among patients. Downstaging was observed in 66.7% and 80% of the control and intervention groups, respectively (P: 0.40). The rate of PCR was not different in the two groups (13.3% in both groups, P &gt; 0.99). There were no significant differences in terms of treatment complications between the two groups, as well. Conclusions: HDR-BRT boost for rectal cancer is feasible and might improve downstaging in rectal cancer, but not PCR.

Neoadjuvant therapy in pancreatic cancer: a review and update on recent trials.

Neoadjuvant therapy (NAT) has been enthusiastically embraced for patients with operable pancreatic cancer (PDAC) in hopes of improving survival. However, the rapid integration of clinical trial data has made it difficult to discern optimal treatment strategies. The goal of this review is to summarize notable recent trials and their contributions to the field. The results of ESPAC-5F, NEOLAP-AIO-PAK-0113, SWOG1505, PREOPANC, HyperAcutePancreas, and ALLIANCE A021501 are reviewed in detail. These studies sequentially evaluate the different neoadjuvant treatment strategies, use of neoadjuvant chemoradiation, and immunotherapy in resectable, borderline-resectable, and locally advanced PDAC. Resection rate ranged from 24.4 to 95.7% (median 64.9%). These trials demonstrate median survival ranging from 14.9 to 41.0 months with progression-free survival ranging from 7.7 to 24.2 months. Survival results may be confounded by ability to reach resection, use of modern chemotherapy vs. gemcitabine monotherapy, and inclusion of locally advanced PDAC. Several upcoming trials will directly examine efficacy of NAT vs. adjuvant therapy, chemoradiation in the NAT setting, and molecular testing-driven chemotherapy selection. NAT is associated with improved survival for patients with borderline resectable PDAC but broader efficacy for resectable PDAC and optimal treatment strategy have yet to be defined.

The clinical impact of modified transpancreatic mattress sutures with polyglactin 910 woven mesh on postoperative pancreatic fistula in distal pancreatectomy

BackgroundWe previously reported the stump closure method for the remnant pancreas in distal pancreatectomy, in which soft coagulation and polyglycolic acid felt attached with fibrin glue were utilized. Transpancreatic mattress suture with polyglactin 910 woven mesh was recently reported as a novel stump closure technique. We developed the modified transpancreatic mattress suture with polyglactin 910 woven mesh method, which combined our polyglycolic acid felt method with the transpancreatic mattress suture with polyglactin 910 woven mesh method. MethodsThe polyglycolic acid felt group included patients undergoing distal pancreatectomy in whom the pancreatic stump was closed with the polyglycolic acid felt method from 2017 to 2018 (n = 54); whereas the modified transpancreatic mattress suture with polyglactin 910 woven mesh group included those whose stump was closed with the modified transpancreatic mattress suture with polyglactin 910 woven mesh method from 2019 to 2020 (n = 51). Perioperative parameters, including grade B/C postoperative pancreatic fistula (clinically relevant postoperative pancreatic fistula), were assessed according to the stump closure method. ResultsThe incidence of clinically relevant postoperative pancreatic fistula was significantly lower in the modified transpancreatic mattress suture with polyglactin 910 woven mesh group than in the polyglycolic acid felt group (7.8% vs 22.2%, P = .036). In multivariate analysis, the use of neoadjuvant chemoradiotherapy and the transpancreatic mattress suture with polyglactin 910 woven mesh method were independent factors for preventing clinically relevant postoperative pancreatic fistula (P = .011 and 0.0038, respectively). Moreover, in the modified transpancreatic mattress suture with polyglactin 910 woven mesh group, the incidence of clinically relevant postoperative pancreatic fistula in patients with a thick pancreas (≥13 mm, 6.7%) was comparably as low as that in patients with a thin pancreas (<13 mm, 9.5%). ConclusionThe modified transpancreatic mattress suture with polyglactin 910 woven mesh method is an effective stump closure technique to prevent clinically relevant postoperative pancreatic fistula after distal pancreatectomy. Our results warrant further prospective investigation to evaluate the efficacy of the modified transpancreatic mattress suture with polyglactin 910 woven mesh method compared with other standard closure methods (eg, stapler closure or hand-sewn closure).

SP5.1.12 Discrete Event Micro Simulation Modeling for the Treatment of Resectable Malignancy of the Oesophagus and Gastrooesophageal Junction

Abstract Aims To assist decision-making by creation of a statistical model that simulates treatment pathways and subsequent outcomes for the management of resectable malignancy of the oesophagus and gastrooesophageal junction. Methods: Discrete Event Simulation (DES) modelling is a statistical modelling technique that models the operation of a system as a sequence of events in time to support decision-making. This approach lends itself well to disease modelling by incorporating different treatment strategies targeted at different groups. It offers an advantage over previous decision analysis studies that have relied on Markov modelling which can have reduced accuracy due to lack of memory within the Markov model, the effect of depletion of susceptibles, and the timing of transitioning within the model. This simulation model was populated with data from best available evidence from contemporary randomised controlled trials and ran over 100,000 iterations. Results Neoadjuvant chemoradiotherapy was the superior treatment pathway with superior pathway selection frequency of 87.16%. For squamous cell carcinoma neoadjuvant chemoradiotherapy was the superior treatment option with 73.30 months survival time (65.60 QALMs) and had a superior pathway selection frequency of 100%. Conclusions DES simulation modeling for decision analysis in treatment of resectable malignancy of the oesophagus and gastrooesophageal junction supports the use of neoadjuvant chemoradiotherapy.

Minimal access rectal cancer surgery: an observational study of patient outcomes from a district general hospital with over a decade of experience with robotic rectal cancer surgery.

Robotic surgery for colorectal cancer has become established more slowly than in other specialities. The aim of this study was to assess the risks and benefits of the use of robotic rectal cancer surgery in comparison with laparoscopic surgery within the confines of a subspecialist rectal cancer service in a district general hospital. Outcomes from consecutive patients undergoing minimal access rectal cancer surgery between July 2008 and January 2020 were analysed. Comparisons were made between short-term outcomes including conversion rates, anastomotic leakage and pathological outcomes as well as long-term survival and cancer recurrence. A total of 337 patients were included in the analysis, 204 (60.5%) of whom underwent robotic surgery. Demographic characteristics and use of neoadjuvant chemoradiotherapy were similar between groups. However, patients having robotic surgery had significantly lower tumours than in the laparoscopic group (7.6cm vs. 9.8cm, p=0.003). Conversion to open surgery in the robotic group was significantly less likely (9.8% vs. 22.6%, p=0.001). Operative mortality, clinical leakage and major complications were similar between groups. While asymptomatic 'radiological' leaks were significantly more common following robotic surgery (13.7% vs. 5.3%, p=0.017) this did not affect the long-term stoma closure rate. Pathological outcomes were similar with the exception of shorter mean distal resection margins (25.9mm vs. 32.8mm, p=0.001) for the robotic group of patients. There was no statistical difference in 5-year survival between groups (78.7% robotic vs. 85.4% laparoscopic, p=0.263) nor local recurrence (2.0% robotic vs. 3.8% laparoscopic, p=0.253). These results illustrate how the selective use of robotic surgery by a dedicated rectal cancer team can achieve low rates of cancer recurrence and low permanent stoma rates.

Is Biotechnological Next-Generation Therapeutics Promising Enough in Clinical Development to Treat Advanced Colon Cancer?

Colon cancer is the second leading cause of cancer related deaths worldwide with about 1.2 million new cases identified annually. While considering swift progress in the field of molecular biology, new horizons in the treatment approaches have been materialized in colon cancer with conventional methods being replaced with targeted therapies. In this review, we focused on the existing conventional therapies utilized for colon cancer by comparing the effectiveness of various standard/conventional therapies with respect to overall survival parameter. Regardless of all the conventional treatments and scientific research, the disease remains to be the one of the major cause of cancer related death and rising as societal burden due to its co morbidities. Thus, we have also discussed briefly in this review, all the possible biotechnological next-generation therapeutics including nucleic acid medicines, CRISPR-Cas9 technology, adoptive cell therapy, cancer stem cells and therapy, gut microbiome, and personalized medicines, which might be promising after effective clinical trials. From our study, we suggest that the use of neoadjuvant chemoradiotherapy in resected patients was found to be safe and effective therapy in treating colon cancer and thereby improving overall survival in patients. From considering the total estimate of our meta-analysis plot, we state that the existing therapies are not much satisfying to improve the overall survival and more research has to be carried out in this field to find an effective therapy to treat colon cancer. As existing therapies are not much satisfying and are unable to improve the overall survival, we brought together a diversity of possible approaches focusing on biotechnological nextgeneration therapeutics to treat colon cancer. Hence, various multi-disciplinary choices are mandatory in order to provide patients with distended access to tailored treatments.

CRANIOFACIAL OSTEOSARCOMA: A CASE REPORT

<h3>Background</h3> Osteosarcoma is the most common primary bone tumor, with 10% of cases affecting the head and neck. Demographics of head and neck osteosarcoma are different from those elsewhere in the musculoskeletal system. Prognosis is strongly dependent on negative resection margins with the use of neoadjuvant chemoradiotherapy in select cases. <h3>Description</h3> We present a case of a 58-year-old male nonsmoker patient who presented with a lump in his left upper jaw. Clinical examination revealed an exophytic mass in the upper left tuberosity of the maxilla suspicious for squamous cell carcinoma with no associated lymphadenopathy. <h3>Findings</h3> Radiological investigations revealed a metabolically active left maxillary lesion with destruction of the maxillary sinus. Histologic examination of a superficial biopsy initially suggested a proliferative fibro-osseous lesion; however, a second deeper biopsy was diagnostic of osteosarcoma, and the patient was referred to a sarcoma center. Immunohistochemistry showed AE1/AE3 and CK(MNF.116) positivity in occasional cells with a Ki67 proliferation index of 60%. This was diagnostic of grade 2-3 osteosarcoma. Multidisciplinary management of the patient included neoadjuvant chemotherapy and total maxillectomy and dental prosthetic rehabilitation. The patient is still under follow-up. <h3>Conclusions</h3> This case of primary osteosarcoma of the maxilla is rare and scarcely reported in the literature. Clinical differential diagnoses include squamous cell carcinoma, and histologic differential diagnosis includes fibro-osseous proliferative lesions in undersampled cases. It is important to consider osteosarcoma in destructive lesions, as it requires prompt and early specialist intervention to maximize the chances of negative surgical margins, which is the mainstay of treatment for this disease for prognosis.

Clinical staging accuracy and the use of neoadjuvant chemoradiotherapy for cT3N0 rectal cancer: Propensity score matched National Cancer Database analysis

BackgroundWhile neoadjuvant chemoradiation therapy (nCRT) is accepted as standard of care for locally advanced rectal cancer, the approach to treatment of patients with clinically staged T3N0 disease has been increasingly debated. This study examines the accuracy of clinical staging for cT3N0 rectal cancer as recorded in the National Cancer Data Base and evaluates the role of nCRT in treating these patients. MethodsTotal of 15,843 patients with clinically staged T3N0M0 rectal cancer who either received nCRT or proceeded to surgery-first met inclusion criteria. Propensity score matching was employed to balance the groups. Results23% of cT3N0 patients undergoing surgery-first were found to have pathologically positive nodes. Another 16% turned out to have < stage II disease on surgical pathology. Survival curves for matched nCRT and surgery-first groups demonstrated a survival advantage for cT3N0 patients treated with nCRT. ConclusionsPoor clinical staging accuracy can result in both undertreatment and overtreatment of cT3N0 rectal cancer.