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.

Neoadjuvant radiotherapy for resectable hepatocellular carcinoma with portal vein tumor thrombus:a systematic review

Background:The prognosis of hepatocellular carcinoma(HCC)with portal vein tumor thrombus(PVTT)is extremely poor.The clinical outcome of preoperative radiotherapy(RT)is still controversial.This study aimed to compare the clinical outcomes of combined neoadjuvant RT and hepatectomy with hepatectomy alone for HCC with PVTT.Methods:Comprehensive database searches were performed in PubMed,the Cochrane Library,EMBASE,and the Web of Science to retrieve studies published from the database creation to July 1,2020.Only comparative studies that measured survival between neoadjuvant RT followed by hepatectomy and hepatectomy alone were included.The characteristics of the included studies and patients were extracted,and the included data are presented as relative ratio(RR)estimates with 95%confidence intervals(CIs)for all outcomes.The RRs of each study were pooled using a fixed or random effects model with Review Manager(the Cochrane Collaboration,Oxford,UK)version 5.3.The response rate to RT and the overall survival(OS)rate in neoadjuvant RT followed by hepatectomy and hepatectomy alone were measured.Results:One randomized and two non-randomized controlled trials with 302 patients were included.Most patients were classified as Child-Pugh A,and Type II and III PVTT were the most common types.After RT,29(22.8%)patients were evaluated as partial response(PR)and had a positive RT response,but nine(7.1%)had progressive disease(PD).Neoadjuvant RT followed by hepatectomy was received by 127(42.1%)patients after excluding 15(5.0%)patients with severe complications or PD after RT,and 160(53.0%)patients received hepatectomy alone.In the randomized controlled trial(RCT),the 1-year OS rate in the neoadjuvant RT group and the surgery alone group was 75.2%and 43.1%,respectively(P<0.001).In the two non-randomized studies,a meta-analysis with a fixed effects model showed a longer OS in patients undergoing neoadjuvant RT followed by hepatectomy compared with hepatectomy alone at 1-year follow-up(RR=2.02;95%CI:1.45-2.80;P<0.0001).Conclusions:This systematic review showed that neoadjuvant RT followed by hepatectomy in patients with resectable HCC and PVTT was associated with a longer OS than patients who received hepatectomy alone.

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.

Potential predictive factors for pathologic complete response after the neoadjuvant treatment of rectal adenocarcinoma:a single center experience

Objective:To assess the response rate of patients with rectal adenocarcinoma to neoadjuvant therapy and to identify the predictors of histological regression after neoadjuvant radiotherapy(RT)or concurrent chemoradiotherapy(CCRT).Methods:This study recruited 64 patients.The patients had resectable cancer of the lower and the middle rectum(T3/T4 and/or N+)without distant metastasis and received neoadjuvant RT or CCRT followed by radical surgery with total mesorectal excision(TME)between January 2006 and December 2011.The patients were classified into non-response(NR),partial response(PR),and pathologic complete response(p CR)based on the Dworak tumor regression grading system.Results:The median age of patients was 57 years(ranging from 22 to 85).A total of 24 patients were treated with neoadjuvant CCRT,whereas 40 patients were treated with RT alone.Abdominoperineal resection(APR)was performed on 29 patients(45%).Anterior resection with TME was performed on 34 patients(53%).One patient had local resection.Histologically,12(19%),24(73%),and 28(44%)patients exhibited p CR,PR,and NR,respectively.Univariate analysis revealed that the predictors of tumor regression were as follows:the absence of lymph node involvement from initial imaging(c N0)(P=0.021);normal initial carcinoembryonic antigen(CEA)level(P=0.01);hemoglobin level≥12 g/dl(P=0.009);CCRT(P=0.021);and tumor downstaging in imaging(P=0.001).Multivariate analysis showed that the main predictors of p CR were CT combined with neoadjuvant RT,c N0stage,and tumor regression on imaging.Conclusions:Identifying the predictors of p CR following neoadjuvant therapy aids the selection of responsive patients for nonaggressive surgical treatment and possible surveillance.

The role of radiation for pancreatic adenocarcinoma

Pancreatic cancer is an aggressive malignancy with a high recurrence rate even after curative-intent resection.Improvements in survival have not been achieved in the last 25 years thus highlighting the need for effective multimodal treatment strategies.The role of radiation therapy for pancreatic cancer remains ill-defined due to historical lack of a standard definition of resectability,and the use of antiquated radiation delivery techniques and chemotherapy regimens.Current level I data regarding neoadjuvant chemoradiotherapy for resectable and borderline resectable pancreatic adenocarcinoma(PDAC)are limited to 2 randomized controlled trials and several retrospective studies and suggest that it may lead to an increased likelihood of a margin-negative resection and certainly allows for improved patient selection for pancreaticoduodenectomy when compared to upfront surgery.In the adjuvant setting,data are similarly lacking but suggest that chemoradiotherapy may be beneficial for patients at high risk of locoregional recurrence.Here we review existing data regarding the role of radiation in PDAC.