Endoscopic ultrasonography-related diagnostic accuracy and clinical significance on small rectal neuroendocrine neoplasms

This research aimed to examine the diagnostic accuracy and clinical significance of endoscopic ultrasonography(EUS)in the context of small rectal neuroendocrine neoplasms(NENs).A total of 108 patients with rectal subepithelial lesions(SELs)with a diameter of<20 mm were included in the analysis.The diagnosis and depth assessment of EUS was compared to the histology findings.The prevalence of NENs in rectal SELs was 78.7%(85/108).The sensitivity of EUS in detecting rectal NENs was 98.9%(84/85),while the specificity was 52.2%(12/23).Overall,the diagnostic accuracy of EUS in identifying rectal NENs was 88.9%(96/108).The overall accuracy rate for EUS in assessing the depth of invasion in rectal NENs was 92.9%(78/84).Therefore,EUS demonstrates reasonable diagnostic accuracy in detecting small rectal NENs,with good sensitivity but inferior specificity.EUS may also assist physicians in assessing the depth of invasion in small rectal NENs before endoscopic excision.

Implications of recent neoadjuvant clinical trials on the future practice of radiotherapy in locally advanced rectal cancer

Over the last two decades, the standard treatment for locally advanced rectal cancer(LARC) has been neoadjuvant chemoradiotherapy plus total mesorectal excision followed by adjuvant chemotherapy. Total neoadjuvant treatment(TNT) and immunotherapy are two major issues in the treatment of LARC. In the two latest phase Ⅲ randomized controlled trials(RAPIDO and PRODIGE23), the TNT approach achieved higher rates of pathologic complete response and distant metastasis-free survival than conventional chemoradiotherapy. Phase I/II clinical trials have reported promising response rates to neoadjuvant(chemo)-radiotherapy combined with immunotherapy. Accordingly, the treatment paradigm for LARC is shifting toward methods that increase the oncologic outcomes and organ preservation rate. However, despite the progress of these combined modality treatment strategies for LARC, the radiotherapy details in clinical trials have not changed significantly. To guide future radiotherapy for LARC with clinical and radiobiological evidence, this study reviewed recent neoadjuvant clinical trials evaluating TNT and immunotherapy from a radiation oncologist’s perspective.

Genetic polymorphisms in genes regulating cell death and prognosis of patients with rectal cancer receiving postoperative chemoradiotherapy

Objective:The identification of biomarkers for predicting chemoradiotherapy efficacy is essential to optimize personalized treatment.This study determined the effects of genetic variations in genes involved in apoptosis,pyroptosis,and ferroptosis on the prognosis of patients with locally advanced rectal cancer receiving postoperative chemoradiotherapy(CRT).Methods:The Sequenom MassARRAY was used to detect 217 genetic variations in 40 genes from 300 patients with rectal cancer who received postoperative CRT.The associations between genetic variations and overall survival(OS)were evaluated using hazard ratios(HRs)and 95%confidence intervals(CIs)computed using a Cox proportional regression model.Functional experiments were performed to determine the functions of the arachidonate 5-lipoxygenase(ALOX5)gene and the ALOX5 rs702365 variant.Results:We detected 16 genetic polymorphisms in CASP3,CASP7,TRAILR2,GSDME,CASP4,HO-1,ALOX5,GPX4,and NRF2 that were significantly associated with OS in the additive model(P<0.05).There was a substantial cumulative effect of three genetic polymorphisms(CASP4 rs571407,ALOX5 rs2242332,and HO-1 rs17883419)on OS.Genetic variations in the CASP4 and ALOX5 gene haplotypes were associated with a higher OS.We demonstrated,for the first time,that rs702365[G]>[C]represses ALOX5 transcription and corollary experiments suggested that ALOX5 may promote colon cancer cell growth by mediating an inflammatory response.Conclusions:Polymorphisms in genes regulating cell death may play essential roles in the prognosis of patients with rectal cancer who are treated with postoperative CRT and may serve as potential genetic biomarkers for individualized treatment.

Transanal Endoscopic Microsurgery (TEM) for Rectal Neoplasms

Introduction: The abdominal approach for the treatment of rectal tumors is associated with a considerable rate of morbidity. Transanal Endoscopic Microsurgery (TEM) is an alternative technique that is less invasive than radical surgery, and therefore has a lower associated morbidity. Moreover, with proper patient selection, TEM presents oncological outcomes comparable to radical surgery. The aim of this study is to review our results obtained with TEM and discuss its role in the treatment of malignant rectal lesions. Patients and Methods: A prospective descriptive study from June 2008 until February 2011. The indications for TEM were: early rectal neoplastic lesions (T1N0M0) with good prognostic factors;neoplastic lesions in more advanced stages in selected patients (high surgical risk, refusal of radical surgery or stoma, and palliative intention). Results: Resection by TEM was performed on 19 patients. The average hospital stay was 5.7 days with an associated morbidity of 16.7%. R0 resection was 88.8%. During the follow-up of 15 (3 - 31) months, no recurrence has been shown. Conclusions: TEM is a safe and effective procedure for the treatment of selected early malignant rectal lesions and is associated with low morbidity. It is a therapeutic strategy based on a multidisciplinary team, careful patient selection, an audited surgical technique and a strict follow-up protocol.

Feasibility and safety of minimally invasive multivisceral resection for T4b rectal cancer:A 9-year review

BACKGROUND Colorectal cancer is the third most common cancer and the second highest cause of cancer-related mortality worldwide.About 5%-10%of patients are diagnosed with locally advanced rectal cancer(LARC)on presentation.For LARC invading into other structures(i.e.T4b),multivisceral resection(MVR)and/or pelvic ex-enteration(PE)remains the only potential curative surgical treatment.MVR and/or PE is a major and complex surgery with high post-operative morbidity.Minimally invasive surgery(MIS)has been shown to improve short-term post-operative outcomes in other gastrointestinal malignancies,but there is little evi-dence on its use in MVR,especially so for robotic MVR.This is a single-center retrospective cohort study from 1st January 2015 to 31st March 2023.Inclusion criteria were patients diagnosed with cT4b rectal cancer and underwent MVR,or stage 4 disease with resectable systemic metastases.Pa-tients who underwent curative MVR for locally recurrent rectal cancer,or me-tachronous rectal cancer were also included.Exclusion criteria were patients with systemic metastases with non-resectable disease.All patients planned for elective surgery were enrolled into the standard enhanced recovery after surgery pathway with standard peri-operative management for colorectal surgery.Complex sur-gery was defined based on technical difficulty of surgery(i.e.total PE,bladder-sparing prostatectomy,pelvic lymph node dissection or need for flap creation).Our primary outcomes were the margin status,and complication rates.Cate-gorical values were described as percentages and analysed by the chi-square test.Continuous variables were expressed as median(range)and analysed by Mann-Whitney U test.Cumulative overall survival(OS)and recurrence-free survival(RFS)were analysed using Kaplan-Meier estimates with life table analysis.Log-rank test was performed to determine statistical significance between cumulative estimates.Statistical significance was defined as P<0.05.Meier estimates with life table analysis.Log-rank test was performed to determine statistical significance between cumulative estimates.Statistical significance was defined as P<0.05.RESULTS A total of 46 patients were included in this study[open MVR(oMVR):12(26.1%),miMVR:36(73.9%)].Patients’American Society of Anesthesiologists score,body mass index and co-morbidities were comparable between oMVR and miMVR.There is an increasing trend towards robotic MVR from 2015 to 2023.MiMVR was associated with lower estimated blood loss(EBL)(median 450 vs 1200 mL,P=0.008),major morbidity(14.7%vs 50.0%,P=0.014),post-operative intra-abdominal collections(11.8%vs 50.0%,P=0.006),post-operative ileus(32.4%vs 66.7%,P=0.04)and surgical site infection(11.8%vs 50.0%,P=0.006)compared with oMVR.Length of stay was also shorter for miMVR compared with oMVR(median 10 vs 30 d,P=0.001).Oncological outcomes-R0 resection,recurrence,OS and RFS were comparable between miMVR and oMVR.There was no 30-d mortality.More patients underwent robotic compared with laparoscopic MVR for complex cases(robotic 57.1%vs laparoscopic 7.7%,P=0.004).The operating time was longer for robotic compared with laparoscopic MVR[robotic:602(400-900)min,laparoscopic:Median 455(275-675)min,P<0.001].Incidence of R0 resection was similar(laparoscopic:84.6%vs robotic:76.2%,P=0.555).Overall complication rates,major morbidity rates and 30-d readmission rates were similar between la-paroscopic and robotic MVR.Interestingly,3-year OS(robotic 83.1%vs 58.6%,P=0.008)and RFS(robotic 72.9%vs 34.3%,P=0.002)was superior for robotic compared with laparoscopic MVR.CONCLUSION MiMVR had lower post-operative complications compared to oMVR.Robotic MVR was also safe,with acceptable post-operative complication rates.Prospective studies should be conducted to compare short-term and long-term outcomes between robotic vs laparoscopic MVR.

Impact of technology on indications and limitations for transanal surgical removal of rectal neoplasms

Transanal surgery has and continues to be well accepted for local excision of benign rectal disease not amenable to endoscopic resection. More recently, there has been increasing interest in applying transanal surgery to local resection of early malignant disease. In addition, some groups have started utilizing a transanal route in order to accomplish total mesorectal excision(TME) for more advanced rectal malignancies. We aim to review the role of various transanal and endoscopic techniquesin the local resection of benign and malignant rectal disease based on published trial data. Preliminary data on the use of transanal platforms to accomplish TME will also be highlighted. For endoscopically unresectable rectal adenomas, transanal surgery remains a widely accepted method with minimal morbidity that avoids the downsides of a major abdomino-pelvic operation. Transanal endoscopic microsurgery and transanal minimally invasive surgery offer improved visualization and magnification, allowing for finer and more precise dissection of more proximal and larger rectal lesions without compromising patient outcome. Some studies have demonstrated efficacy in utilizing transanal platforms in the surgical management of early rectal malignancies in selected patients. There is an overall higher recurrence rate with transanal surgery with the concern that neither chemoradiation nor salvage surgery may compensate for previous approach and correct the inferior outcome. Application of transanal platforms to accomplish transanal TME in a natural orifice fashion are still in their infancy and currently should be considered experimental. The current data demonstrate that transanal surgery remains an excellent option in the surgical management of benign rectal disease. However, care should be used when selecting patients with malignant disease. The application of transanal platforms continues to evolve. While the new uses of transanal platforms in TME for more advanced rectal malignancy are exciting, it is important to remain cognizant and not sacrifice long term survival for short term decrease in morbidity and improved cosmesis.

Advances in radiotherapy and targeted therapies for rectal cancer

The last decade witnessed a significant progress in understanding the biology and immunology of colorectal cancer alongside with the technical innovations in radiotherapy.The stepwise implementation of intensitymodulated and image-guided radiation therapy by means of megavolt computed tomography and helical tomotherapy enabled us to anatomically sculpt dose delivery,reducing treatment related toxicity.In addition,the administration of a simultaneous integrated boost offers excellent local control rates.The novel challenge is the development of treatment strategies for medically inoperable patient and organ preserving approaches.However,distant control remains unsatisfactory and indicates an urgent need for biomarkers that predict the risk of tumor spread.The expected benefit of target?ed therapies that exploit the tumor genome alone is so far hindered by high cost techniques and pharmaceuticals,hence hardly justifying rather modest improvements in patient outcomes.On the other hand,the immune landscape of colorectal cancer is now better clarified with regard to the immunosuppressive network that promotes immune escape.Both N2 neutrophils and myeloid-derived suppressor cells(MDSC)emerge as useful clinical biomarkers of poor prognosis,while the growing list of anti-MDSC agents shows promising ability to boost antitumor T-cell immunity in preclinical settings.Therefore,integration of genetic and immune biomarkers is the next logical step towards effective targeted therapies in the context of personalized cancer treatment.

Three-dimensional conformal radiotherapy combined with FOLFOX4 chemotherapy for unresectable recurrent rectal cancer

瞄准：为 unresectable 与 FOLFOX4 化疗在联合调查三维的保角的放射疗法(3-DCRT ) 的效果周期性的直肠的癌症。方法：有 unresectable 的 48 个病人周期性的直肠的癌症被与在 2001 年 9 月和 2003 年 10 月之间的 FOLFOX4 化疗相结合的 3-DCRT 或 3-DCRT 使随机化并且对待。为没有优先的放射历史的病人，起始的放射被传统的方法与 40 Gy 的肿瘤剂量给整个骨盆，为周期性的损害由 3-DCRT 列在后面到 60 Gy (范围 56-66 Gy ) 的中部的全部的累积肿瘤剂量；为放射以后的周期性的病人， 3-DCRT 直接为周期性的损害被给 40 Gy (36-46 Gy ) 的中部的肿瘤剂量。为在学习组的病人，有 FOLFOX4 政体的二周期化疗与放射疗法并发地被给，为收到常规骨盆放射的病人交上第五个星期，第一个周期和第二个周期与放射的开始同时给或为直接收到 3-DCRT 的病人交上 3-DCRT 的最后星期。顺序的 FOLFOX4 政体化疗在学习被给病人的另外一个 2-4 周期(一般水准 3.6 周期) 组织，在在 chemoradiation 以后的 2-3 wk 开始。症状 relieve，肿瘤反应，幸存和毒性的结果在学习组和控制组之间被记录并且比较。结果：为学习组和控制组，疼痛缓和率是 95.2% 和 91.3%(P 】 0.05 ) ；全面反应率是 56.5% 和 40.0%(P 】 0.05 ) ；1 年、 2 年的幸存率是 86.9% ， 50.2% 和 80.0% ， 23.9% ，与 25 瞬间和 16 瞬间的中部的生存时间(P 【 0.05 ) ；2 年的远转移率是 39.1% 和 56.0%(P = 0.054 ) 分别地。副作用，除了是的外部神经病，相对，在学习的 severer 组织，是类似的在二个组和井容忍了。结论：三维的保角的放射疗法为周期性的直肠的癌症是的 unresectable 与 FOLFOX4 化疗结合了一条可行、有效的治疗学的途径，和罐头减少远转移率并且改进幸存率。

Down-staging depth score to predict outcomes in locally advanced rectal cancer achieving ypl stage after neoadjuvant chemo-radiotherapy versus de novo stage pl cohort:A propensity score-matched analysis

Objective：Prognosis of patients with locally advanced rectal cancer（LARC）but achieving yp T1–2N0 stage after neoadjuvant concurrent chemo-radiotherapy（CRT）has been shown to be favorable.This study aims to determine whether the long-term outcome of yp T1–2N0 cases can be comparable to that of p T1–2N0 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 at4–8 weeks after completion of CRT,and those achieving stage yp I were identified as a group.As a comparison,stage p I 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 yp I and p I 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 p I vs.yp I 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 yp I group,LC,DMFS,DFS and OS resulted in no significant differences in comparison with the p I group（P=0.384,0.368,0.277 and0.458,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 yp I group whose longterm oncologic outcomes are as good as those of stage p I cohort.

Selective lateral lymph node dissection after neoadjuvant chemoradiotherapy in rectal cancer

BACKGROUND Lateral lymph node metastasis is one of the leading causes of local recurrence in patients with advanced mid or low rectal cancer.Neoadjuvant chemoradiotherapy(NCRT)can effectively reduce the postoperative recurrence rate;thus,NCRT with total mesorectal excision(TME)is the most widely accepted standard of care for rectal cancer.The addition of lateral lymph node dissection(LLND)after NCRT remains a controversial topic.AIM To investigate the surgical outcomes of TME plus LLND,and the possible risk factors for lateral lymph node metastasis after NCRT.METHODS This retrospective study reviewed 89 consecutive patients with clinical stage II-III mid or low rectal cancer who underwent TME and LLND from June 2016 to October 2018.In the NCRT group,TME plus LLND was performed in patients with short axis(SA)of the lateral lymph node greater than 5 mm.In the non-NCRT group,TME plus LLND was performed in patients with SA of the lateral lymph node greater than 10 mm.Data regarding patient demographics,clinical workup,surgical procedure,complications,and outcomes were collected.Multivariate logistic regression analysis was performed to evaluate the possible risk factors for lateral lymph node metastasis in NCRT patients.RESULTS LLN metastasis was pathologically confirmed in 35 patients(39.3%):26(41.3%)in the NCRT group and 9(34.6%)in the non-NCRT group.The most common site of metastasis was around the obturator nerve(21/35)followed by the internal iliac artery region(12/35).In the NCRT patients,46%of patients with SA of LLN greater than 7 mm were positive.The postoperative 30-d mortality rate was 0%.Two(2.2%)patients suffered from lateral local recurrence in the 2-year follow up.Multivariate analysis showed that cT4 stage(odds ratio[OR]=5.124,95%confidence interval[CI]:1.419-18.508;P=0.013),poor differentiation type(OR=4.014,95%CI:1.038-15.520;P=0.044),and SA≥7 mm(OR=7.539,95%CI:1.487-38.214;P=0.015)were statistically significant risk factors associated with LLN metastasis.CONCLUSION NCRT is not sufficient as a stand-alone therapy to eradicate LLN metastasis in lower rectal cancer patients and surgeons should consider performing selective LLND in patients with greater LLN SA diameter,poorer histological differentiation,or advanced T stage.Selective LLND for NCRT patients can have a favorable oncological outcome.

Second primary malignancy risk after radiotherapy in rectal cancer survivors

AIM To investigate second primary malignancy(SPM) risk after radiotherapy in rectal cancer survivors METHODS We used Taiwan's National Health Insurance Research Database to identify rectal cancer patients between 1996 and 2011. Surgery-alone, preoperative short course, preoperative long course, and post-operative radiotherapy groups were defined. The overall and sitespecific SPM incidence rates were compared among the radiotherapy groups by multivariate Cox regression, taking chemotherapy and comorbidities into account. Sensitivity tests were performed for attained-year adjustment and long-term survivors analysis. RESULTS A total of 28220 patients were analyzed. The 10-year cumulative SPM incidence was 7.8% [95% confidence interval(CI): 7.2%-8.2%] using a competing risk model. The most common sites of SPM were the lung, liver, and prostate. Radiotherapy was not associated with increased SPM risk in multi-variate Cox model(hazard ratio = 1.05, 95%CI: 0.91-1.21, P = 0.494). The SPM hazard remained unchanged in 10-yearsurvivors. In addition, no SPM risk difference was found between the preoperative radiotherapy and postoperative radiotherapy groups.CONCLUSION In this large population-based cohort study, we demonstrated that radiotherapy had no increase in SPM.

Neoadjuvant Therapy for Advanced Rectal Carcinoma in China:Whether Radiochemotherapy Is Superior to Radiotherapy?

Objective： To verify whether the 30 Gy preoperative radiotherapy regimen is effective to advanced rectal cancer, and whether the preoperative chemoradiation offers an advantage in sphincter preservation and tumor control compared with irradiation alone. Methods： A total of 141 patients administered neoadjuvant treatment with resectable lower rectal carcinoma from 2002 to 2006 were collected retrospectively. The patients were divided into two groups： preoperative radiotherapy alone （30Gy by 10 fractions） （PRT group） and preoperative chemoradiotherapy （PCRT group）. All patients underwent radical surgery after neoadjuvant treatment. Results： The overall sphincter-preservation rate was 68.8% （97/141）, with no significant difference between the two groups. The overall downstaging rate was 48.2% （68/141）, including 4 patients completely response （2.8%）. The T and N downstaging rate were 30.5% （43/141） and 53.8% （57/106） respectively, showing no statistically difference between the two groups. The 2-year overall survival rate was 93.6%; no survival benefit were observed in PCRT group. The 2-year cumulative local recurrence rates were similar as well （4.2% vs 6.7%, P=0.63）. Two patients with severe marrow suppression higher than grade 3 and 1 patient with severe perineum ulcer was observed in PCRT group, which did not occur in PRT group. Conclusion： The preoperative adjuvant treatment of 30Gy radiotherapy alone may be an optional treatment for Chinese lower rectal carcinoma. Preoperative chemoradiotherapy does not show actual superiority compared with radiotherapy alone.

Neoadjuvant radiotherapy dose escalation for locally advanced rectal cancers in the new era of radiotherapy:A review of literature

BACKGROUND The standard treatment of locally advanced rectal cancers(LARC)consists on neoadjuvant chemoradiotherapy followed by total mesorectal excision.Different data in literature showed a benefit on tumor downstaging and pathological complete response(pCR)rate using radiotherapy dose escalation,however there is shortage of studies regarding dose escalation using the innovative techniques for LARC(T3-4 or N1-2).AIM To analyze the role of neoadjuvant radiotherapy dose escalation for LARC using innovative radiotherapy techniques.METHODS In December 2020,we conducted a comprehensive literature search of the following electronic databases:PubMed,Web of Science,Scopus and Cochrane library.The limit period of research included articles published from January 2009 to December 2020.Screening by title and abstract was carried out to identify only studies using radiation doses equivalent dose 2 Gy fraction(EQD2)≥54 Gy and Volumetric Modulated Arc Therapy(VMAT),intensity-modulated radiotherapy or image-guided radiotherapy(IGRT)techniques.The authors’searches generated a total of 2287 results and,according to PRISMA Group(2009)screening process,21 publications fulfil selection criteria and were included for the review.RESULTS The main radiotherapy technique used consisted in VMAT and IGRT modality.The mainly dose prescription was 55 Gy to high risk volume and 45 Gy as prophylactic volume in 25 fractions given with simultaneous integrated boosts technique(42.85%).The mean pCR was 28.2%with no correlation between dose prescribed and response rates(P value≥0.5).The R0 margins and sphincter preservation rates were 98.88%and 76.03%,respectively.After a mean follow-up of 35 months local control was 92.29%.G3 or higher toxicity was 11.06%with no correlation between dose prescription and toxicities.Patients receiving EQD2 dose>58.9 Gy and BED>70.7 Gy had higher surgical complications rates compared to other group(P value=0.047).CONCLUSION Dose escalation neoadjuvant radiotherapy using innovative techniques is safe for LARC achieving higher rates of pCR.EQD2 doses>58.9 Gy is associated with higher rate of surgical complications.

Factors influencing comfort level in head and neck neoplasm patients receiving radiotherapy

Objective:To determine factors that influence comfort in head and neck neoplasm patients receiving radiotherapy.Methods:In total,200 head and neck neoplasm patients receiving radiotherapy were recruited from three tertiary first class hospitals.They were assessed by Radiotherapy Comfort Questionnaire for patients with head and neck neoplasm,Social Support Scale,and Medical Coping Modes Questionnaire.Results:The total score of comfort was 60.54±8.32.Multiple linear regression analysis indicated that number of radiation treatments,family accompaniment,educational level,resignation coping mode,complications due to diabetes,accompanying chemotherapy,and the utilization of social support significantly influenced comfort level(p<0.05).Among these,number of radiation treatments,complications due to diabetes,accompanying chemotherapy,and resignation coping were negative factors.Conclusion:Encouraging utilization of social support systems and a positive coping mode is important for increasing comfort level in head and neck neoplasm patients during radiotherapy.Nurses should pay particular attention to those patients during later stages of radiotherapy or chemotherapy,with diabetes,without family accompaniment,and with lower education level.

Neoadjuvant vs adjuvant pelvic radiotherapy for locally advanced rectal cancer: Which is superior?

The treatment of locally advanced rectal cancer including timing and dosage of radiotherapy, degree of sphincter preservation with neoadjuvant radiotherapy, and short and long term effects of radiotherapy are controversial topics. The MEDLINE, Cochrane Library databases, and meeting proceedings from the American Society of Clinical Oncology, were searched for reports of randomized controlled trials and meta-analyses comparing neoadjuvant and adjuvant radiotherapy with surgery to surgery alone for rectal cancer. Neoadjuvant radiotherapy shows superior results in terms of local control compared to adjuvant radiotherapy. Neither adjuvant or neoadjuvant radiotherapy impacts overall survival. Short course versus long course neoadjuvant radiotherapy remains controversial. There is insufficient data to conclude that neoadjuvant therapy improves rates of sphincter preserving surgery. Radiation significantly impacts anorectal and sexual function and includes both acute and long term toxicity. Data demonstrate that neoadjuvant radiation causes less toxicity compared to adjuvant radiotherapy, and specifically short course neoadjuvant radiation results in less toxicity than long course neoadjuvant radiation. Neoadjuvant radiotherapy is the preferred modality for administering radiation in locally advanced rectal cancer. There are significant side effects from radiation, including anorectal and sexual dysfunction, which may be less with short course neoadjuvant radiation.

Neoadjuvant hyperfractionated accelerated radiotherapy plus concomitant 5-fluorouracil infusion in locally advanced rectal cancer: A phase Ⅱ study

AIM To evaluate the efficacy and tolerability of neoadjuvant hyperfractionated accelerated radiotherapy(HART)and concurrent chemotherapy in patients with locally advanced infraperitoneal rectal cancer. METHODS A total of 30 patients with histopathologically confirmed T2-3/N0+ infraperitoneal adenocarcinoma of rectum cancer patients received preoperative 42 Gy/1.5 Gy/18 days/bid radiotherapy and continuous infusion of 5-fluorouracil(325 mg/m^2). All patients were operated 4-8 wk after neoadjuvant concomitant therapy. RESULTS In the early phase of treatment, 6 patients had grade Ⅲ-Ⅳ gastrointestinal toxicity, 2 patients had grade Ⅲ-Ⅳ hematologic toxicity, and 1 patient had grade Ⅴ toxicity due to postoperative sepsis during chemotherapy. Only 1 patient had radiotherapy-related late side effects, i.e., grade Ⅳ tenesmus. Complete pathological response was achieved in 6 patients(21%), while near-complete pathological response was obtained in 9(31%). After a median follow-up period of 60 mo, the local tumor control rate was 96.6%. In 13 patients, distant metastasis occurred. Disease-free survival rates at 2 and 5 years were 63.3% and 53%, and corresponding overall survival rates were 70% and 53.1%, respectively.CONCLUSION Although it has excellent local control and complete pathological response rates, neoadjuvant HART concurrent chemotherapy appears to not be a feasible treatment regimen in locally advanced rectal cancer, having high perioperative complication and intolerable side effects. Effects of reduced 5-fluorouracil dose or omission of chemotherapy with the aim of reducing toxicity may be examined in further studies.

Efficacy and safety of intraoperative radiotherapy in rectal cancer:A systematic review and meta-analysis

BACKGROUND In recent years,intraoperative radiotherapy(IORT)has been increasingly used for the treatment of rectal cancer.However,the efficacy and safety of IORT for the treatment of rectal cancer are still controversial.AIM To evaluate the value of IORT for patients with rectal cancer.METHODS We searched PubMed,Embase,Cochrane Library,Web of Science databases,and conference abstracts and included randomized controlled trials and observational studies on IORT vs non-IORT for rectal cancer.Dichotomous variables were evaluated by odds ratio(OR)and 95%confidence interval(CI),hazard ratio(HR)and 95%CI was used as a summary statistic of survival outcomes.Statistical analyses were performed using Stata V.15.0 and Review Manager 5.3 software.RESULTS In this study,3 randomized controlled studies and 12 observational studies were included with a total of 1460 patients,who are mainly residents of Europe,the United States,and Asia.Our results did not show significant differences in 5-year overall survival(HR=0.80,95%CI=0.60-1.06;P=0.126);5-year disease-free survival(HR=0.94,95%CI=0.73-1.22;P=0.650);abscess(OR=1.10,95%CI=0.67-1.80;P=0.713),fistulae(OR=0.79,95%CI=0.33-1.89;P=0.600);wound complication(OR=1.21,95%CI=0.62-2.36;P=0.575);anastomotic leakage(OR=1.09,95%CI=0.59-2.02;P=0.775);and neurogenic bladder dysfunction(OR=0.69,95%CI=0.31-1.55;P=0.369).However,the meta-analysis of 5-year local control was significantly different(OR=3.07,95%CI=1.66-5.66;P=0.000).CONCLUSION The advantage of IORT is mainly reflected in 5-year local control,but it is not statistically significant for 5-year overall survival,5-year disease-free survival,and complications.

Dosimetric Comparison of Volumetric Modulated Arc Therapy (VMAT), 5F Intensity Modulated Radiotherapy (IMRT) and 3D Conformal Radiotherapy (3DCRT) in Rectal Carcinoma Receiving Neoadjuvant Chemoradiotherapy

Objective: To investigate better dosimetric distribution of volumetric modulated arc therapy (VMAT) vs. 5F intensity modulated radiotherapy (IMRT) and 3D conformal radiotherapy (3DCRT) in patients with locally advanced rectal cancer (LARC) when treated with neoadjuvant chemoradiotherapy. Methods: 3D-CRT, 5F-IMRT and VMAT plans for preoperative radiotherapy were 66011designed in 12 patients with locally advanced rectal cancer. The conformity index (CI) and homogeneity index (HI) in target volume, and the dose and volume of the organs at risk (OAR) irradiated including small bowel, bladder and bilatera1 femoral heads were compared among the three plans. Results: The CI for planning target volume (PTV) 2 and HI for PTV1 of VMRT and 5F-IMRT were superior to 3D-CRT. The CI of VMAT, 5F-IMRT and 3D-CRT plans were 0.71, 0.69 and 0.62 (p = 0.011 and p = 0.019, respectively). The HI of the VMAT and 5F-IMRT plans were both 1.04 and 3D-CRT planning was 1.06 (p = 0.022 and p = 0.006, respectively). The V35 - V45 of small bowel in VMAT were significantly less than in 5F-IMRT and 3D-CRT. V35 was 47.0, 56.4, and 72.8 cm3 for VMAT, 5F-IMRT, and 3D-CRT (p = 0.021 and p = 0.034, respectively), while V40 was 30.5, 35.5, 45.1 cm3 (p = 0.024 and p = 0.032, respectively) and V45 was 15.1, 18.1, 30.0 cm3 (p = 0.033 and p = 0.032, respectively). The D5, V30 and V50 of bladder in 3D-CRT were less than in VMAT and 5F-IMRT planning (p = 0.034, 0.004, 0.002 and p = 0.027, 0.003, 0.002, respectively). The Dmean of left femoral head in VMAT and 5F-IMRT were less than in 3D-CRT planning (p = 0.028 and p = 0.022, respectively) and the Dmean, V30 of right femoral head in VMAT and 5F-IMRT were better than in 3D-CRT planning (p = 0.044, 0.036 and p = 0.023, 0.028, respectively). Conclusions: Dosimetric analyses demonstrated that IMRT is superior to 3D-CRT in the conformity and homogeneity of dose distribution to the target volume, and provide a better protection to OARs sparing in patients with locally advanced rectal cancer for preoperative radiotherapy. With similar target coverage, VMRT is superior to 5F-IMRT in normal tissue sparing.

Usefulness of two independent hist classifications of tumor regression iUsefulness of two independent histopathological classifications of tumor regression in patients with rectal cancer submitted to hyperfractionated pre-operative radiotherapy

AIM: To assess the usefulness of two independent histopathological classifications of rectal cancer regression following neo-adjuvant therapy. METHODS: Forty patients at the initial stage cT3NxM0 submitted to preoperative radiotherapy (42 Gy during 18 d) and then to radical surgical treatment. The relationship between “T-downstaging” versus regressive changes expressed by tumor regression grade (TRG 1-5) and Nasierowska-Guttmejer classification (NG 1-3) was studied as well as the relationship between TRG and NG versus local tumor stage ypT and lymph nodes status, ypN. RESULTS: Complete regression (ypT0, TRG 1) was found in one patient. “T-downstaging” was observed in 11 (27.5%) patients. There was a weak statistical significance of the relationship between “T-downstaging” and TRG staging and NG stage. Patients with ypT1 were diagnosed as TRG 2-3 while those with ypT3 as TRG5. No lymph node metastases were found in patients with TRG 1-2. None of the patients without lymph node metastases were diagnosed as TRG 5. Patients in the ypT1 stage were NG 1-2. No lymph node metastases were found in NG 1. There was a significant correlation between TRG and NG. CONCLUSION: Histopathological classifications may be useful in the monitoring of the effects of hyperfractionated preoperative radiotherapy in patientswith rectal cancer at the stage of cT3NxM0. There is no unequivocal relationship between “T-downstaging” and TRG and NG. There is some concordance in the assessment of lymph node status with ypT, TRG and NG. TRG and NG are of limited value for the risk assessment of the lymph node involvement.

Neo-adjuvant radiotherapy in rectal cancer

In rectal cancer treatment,attention has focused on the local primary tumour and the regional tumour cell deposits to diminish the risk of a loco-regional recurrence.Several large randomized trials have also shown that combinations of surgery,radiotherapy and chemotherapy have markedly reduced the risk of a locoregional recurrence,but this has not yet had any major influence on overall survival.The best results have been achieved when the radiotherapy has been given preoperatively.Preoperative radiotherapy improves loco-regional control even when surgery has been optimized to improve lateral clearance,i.e.,when a total mesorectal excision has been performed.The relative reduction is then 50%-70%.The value of radiotherapy has not been tested in combination with more extensive surgery including lateral lymph node clearance,as practised in some Asian countries.Many details about how the radiotherapy is performed are still open for discussion,and practice varies between countries.A highly fractionated radiation schedule(5 Gy×5),proven efficacious in many trials,has gained much popularity in some countries,whereas a conventionally fractionated regimen(1.8-2.0 Gy×25-28),often combined with chemotherapy,is used in other countries.The additional therapy adds morbidity to the morbidity that surgery causes,and should therefore be administered only when the risk of loco-regional recurrence is sufficiently high.The best integration of the weakest modality,to date the drugs(conventional cytotoxics and biologicals)is not known.A new generation of trials exploring the best sequence of treatments is required.Furthermore,there is a great need to develop predictors of response,so that treatment can be further individualized and not solely based upon clinical factors and anatomic imaging.