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.

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.

Targeting the organelle for radiosensitization in cancer radiotherapy

Radiotherapy is a well-established cytotoxic therapy for local solid cancers, utilizing high-energy ionizing radiation to destroy cancer cells. However, this method has several limitations, including low radiation energy deposition, severe damage to surrounding normal cells, and high tumor resistance to radiation. Among various radiotherapy methods, boron neutron capture therapy (BNCT) has emerged as a principal approach to improve the therapeutic ratio of malignancies and reduce lethality to surrounding normal tissue, but it remains deficient in terms of insufficient boron accumulation as well as short retention time, which limits the curative effect. Recently, a series of radiosensitizers that can selectively accumulate in specific organelles of cancer cells have been developed to precisely target radiotherapy, thereby reducing side effects of normal tissue damage, overcoming radioresistance, and improving radiosensitivity. In this review, we mainly focus on the field of nanomedicine-based cancer radiotherapy and discuss the organelle-targeted radiosensitizers, specifically including nucleus, mitochondria, endoplasmic reticulum and lysosomes. Furthermore, the organelle-targeted boron carriers used in BNCT are particularly presented. Through demonstrating recent developments in organelle-targeted radiosensitization, we hope to provide insight into the design of organelle-targeted radiosensitizers for clinical cancer treatment.

Distal margin distance in radical resection of locally advanced rectal cancer after neoadjuvant therapy

Colorectal cancer has a high incidence and mortality rate in China, with the majority of cases being middle and low rectal cancer. Surgical intervention is currently the main treatment modality for locally advanced rectal cancer, with the common goal of improving oncological outcomes while preserving function. The controversy regarding the circumferential resection margin distance in rectal cancer surgery has been resolved. With the promotion of neoadjuvant therapy concepts and advancements in technology, treatment strategies have become more diverse.Following tumor downstaging, there is an increasing trend towards extending the safe distance of distal rectal margin. This provides more opportunities for patients with low rectal cancer to preserve their anal function.However, there is currently no consensus on the specific distance of distal resection margin.

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.

Precision radiotherapy for brain tumors A 10-year bibliometric analysis

OBJECTIVE： Precision radiotherapy plays an important role in the management of brain tumors. This study aimed to identify global research trends in precision radiotherapy for brain tumors using a bibliometric analysis of the Web of Science. DATA RETRIEVAL： We performed a bibliometric analysis of data retrievals for precision radiotherapy for brain tumors containing the key words cerebral tumor, brain tumor, intensity-modulated radiotherapy, stereotactic body radiation therapy, stereotactic ablative radiotherapy, imaging-guided radiotherapy, dose-guided radiotherapy, stereotactic brachytherapy, and stereotactic radiotherapy using the Web of Science. SELECTION CRITERIA： Inclusion criteria： （a） peer-reviewed articles on precision radiotherapy for brain tumors which were published and indexed in the Web of Science; （b） type of articles： original research articles and reviews; （c） year of publication： 2002-2011. Exclusion criteria： （a） articles that required manual searching or telephone access; （b） Corrected papers or book chapters. MAIN OUTCOME MEASURES： （1） Annual publication output; （2） distribution according to country; （3） distribution according to institution; （4） top cited publications; （5） distribution according to journals; and （6） comparison of study results on precision radiotherapy for brain tumors. RESULTS： The stereotactic radiotherapy, intensity-modulated radiotherapy, and imaging-guided radiotherapy are three major methods of precision radiotherapy for brain tumors. There were 260 research articles addressing precision radiotherapy for brain tumors found within the Web of Science. The USA published the most papers on precision radiotherapy for brain tumors, followed by Germany and France. European Synchrotron Radiation Facility, German Cancer Research Center and Heidelberg University were the most prolific research institutes for publications on precision radiotherapy for brain tumors. Among the top 13 research institutes publishing in this field, seven are in the USA, three are in Germany, two are in France, and there is one institute in India. Research interests including urology and nephrology, clinical neurology, as well as rehabilitation are involved in precision radiotherapy for brain tumors studies. CONCLUSION： Precision radiotherapy for brain tumors remains a highly active area of research and development.

Developments and challenges in neoadjuvant therapy for locally advanced pancreatic cancer

Pancreatic ductal adenocarcinoma(PDAC)remains a significant public health challenge and is currently the fourth leading cause of cancer-related mortality in developed countries.Despite advances in cancer treatment,the 5-year survival rate for patients with PDAC remains less than 5%.In recent years,neoadjuvant therapy(NAT)has emerged as a promising treatment option for many cancer types,including locally advanced PDAC,with the potential to improve patient outcomes.To analyze the role of NAT in the setting of locally advanced PDAC over the past decade,a systematic literature search was conducted using PubMed and Web of Science.The results suggest that NAT may reduce the local mass size,promote tumor downstaging,and increase the likelihood of resection.These findings are supported by the latest evidence-based medical literature and the clinical experience of our center.Despite the potential benefits of NAT,there are still challenges that need to be addressed.One such challenge is the lack of consensus on the optimal timing and duration of NAT.Improved criteria for patient selection are needed to further identify PDAC patients likely to respond to NAT.In conclusion,NAT has emerged as a promising treatment option for locally advanced PDAC.However,further research is needed to optimize its use and to better understand the role of NAT in the management of this challenging disease.With continued advances in cancer treatment,there is hope of improving the outcomes of patients with PDAC in the future.

A multicenter study on efficacy of dual-target neoadjuvant therapy for HER2-positive breast cancer and a consistent analysis of efficacy evaluation of neoadjuvant therapy by Miller-Payne and RCB pathological evaluation systems(CSBrS-026)

Objective: The aim of this study was to investigate the factors influencing pathological complete response(pCR)rate in early breast cancer patients receiving neoadjuvant dual-target [trastuzumab(H) + pertuzumab(P)] therapy combined with chemotherapy. Additionally, the consistency of the Miller-Payne and residual cancer burden(RCB)systems in evaluating the efficacy of neoadjuvant therapy for early human epidermal growth factor receptor-2(HER2)+ breast cancer was analyzed.Methods: The clinicopathological data of female patients with early-stage HER2+ breast cancer who received dual-target neoadjuvant therapy at 26 hospitals of the Chinese Society of Breast Surgery(CSBrS) from March 2019 to December 2021 were collected. Patients were allocated to four groups: the HER2 immunohistochemistry(IHC)3+/hormone receptor(HR)-, IHC3+/HR+, IHC2+ in situ hybridization(ISH)+/HR-and IHC2+ ISH+/HR+groups. The overall pCR rate for patients, the pCR rate in each group and the factors affecting the pCR rate were analyzed. The consistency between the Miller-Payne and RCB systems in assessing the efficacy of neoadjuvant therapy was analyzed.Results: From March 1, 2019, to December 31, 2021, 77,376 female patients with early-stage breast cancer were treated at 26 hospitals;18,853(24.4%) of these patients were HER2+. After exclusion of unqualified patients, 2,395 patients who received neoadjuvant dual-target(H+P) therapy combined with chemotherapy were included in this study. The overall pCR rate was 53.0%, and the patients' HR statuses and different HER2+ statuses were significantly correlated with the pCR rate(P<0.05). The consistency of the pathological efficacy assessed by the Miller-Payne and RCB systems was 88.0%(κ=0.717, P<0.001).Conclusions: Different HER2 expression statuses and HR expression statuses are correlated with the pCR rate after dual-target neoadjuvant therapy in HER2+ breast cancer patients. There is a relatively good consistency between Miller-Payne and RCB systems in evaluating the pathologic efficacy of neoadjuvant therapy for HER2+breast cancer.

A machine learning model to predict efficacy of neoadjuvant therapy in breast cancer based on dynamic changes in systemic immunity

Objective:Neoadjuvant therapy(NAT)has been widely implemented as an essential treatment to improve therapeutic efficacy in patients with locally-advanced cancer to reduce tumor burden and prolong survival,particularly for human epidermal growth receptor 2-positive and triple-negative breast cancer.The role of peripheral immune components in predicting therapeutic responses has received limited attention.Herein we determined the relationship between dynamic changes in peripheral immune indices and therapeutic responses during NAT administration.Methods:Peripheral immune index data were collected from 134 patients before and after NAT.Logistic regression and machine learning algorithms were applied to the feature selection and model construction processes,respectively.Results:Peripheral immune status with a greater number of CD3^(+)T cells before and after NAT,and a greater number of CD8^(+)T cells,fewer CD4^(+)T cells,and fewer NK cells after NAT was significantly related to a pathological complete response(P<0.05).The post-NAT NK cell-to-pre-NAT NK cell ratio was negatively correlated with the response to NAT(HR=0.13,P=0.008).Based on the results of logistic regression,14 reliable features(P<0.05)were selected to construct the machine learning model.The random forest model exhibited the best power to predict efficacy of NAT among 10 machine learning model approaches(AUC=0.733).Conclusions:Statistically significant relationships between several specific immune indices and the efficacy of NAT were revealed.A random forest model based on dynamic changes in peripheral immune indices showed robust performance in predicting NAT efficacy.

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 laparoscopic vs open gastrectomy after neoadjuvant therapy for locally advanced gastric cancer

BACKGROUND Laparoscopic gastrectomy(LG)is widely accepted as a minimally invasive approach for the treatment of early gastric cancer.However,its role in locally advanced gastric cancer(LAGC)after neoadjuvant therapy(NAT)remains controversial.This study aimed to compare the efficacy and safety of LG vs open gastrectomy(OG)after NAT for the treatment of LAGC.AIM To compare the efficacy and safety of LG vs OG after NAT for LAGC.METHODS We conducted a prospective study of 76 patients with LAGC who underwent NAT followed by LG(n=38)or OG(n=38)between 2021 and 2023.The primary endpoint was overall survival(OS),and the secondary endpoints were diseasefree survival(DFS),surgical complications,and quality of life(QOL).RESULTS The two groups had comparable baseline characteristics,with a median follow-up period of 24 mo.The 3-year OS rates in the LG and OG groups were 68.4%and 60.5%,respectively(P=0.42).The 3-year DFS rates in the LG and OG groups were 57.9%and 50.0%,respectively(P=0.51).The LG group had significantly less blood loss(P<0.001),a shorter hospital stay(P<0.001),and a lower incidence of surgical site infection(P=0.04)than the OG group.There were no significant differences in other surgical complications between the groups,including anastomotic leakage,intra-abdominal abscess,or wound dehiscence.The LG group had significantly better QOL scores than the OG group regarding physical functioning,role functioning,global health status,fatigue,pain,appetite loss,and body image at 6 months postoperatively(P<0.05).CONCLUSION LG after NAT is a viable and safe alternative to OG for the treatment of LAGC,with similar survival outcomes and superior short-term recovery and QOL.LG patients had less blood loss,shorter hospitalizations,and a lower incidence of surgical site infections than OG patients.Moreover,the LG group had better QOL scores in multiple domains 6 mo postoperatively.Therefore,LG should be considered a valid option for patients with LAGC who undergo NAT,particularly for those who prioritize postoperative recovery and QOL.

Neoadjuvant radiotherapy for rectal cancer management

Thirty per cent of all colorectal tumours develop in the rectum.The location of the rectum within the bony pelvis and its proximity to vital structures presents significant therapeutic challenges when considering neoadjuvant options and surgical interventions.Most patients with early rectal cancer can be adequately managed by surgery alone.However,a significant proportion of patients with rectal cancer present with locally advanced disease and will potentially benefit from down staging prior to surgery.Neoadjuvant therapy involves a variety of options including radiotherapy,chemotherapy used alone or in combination.Neoadjuvant radiotherapy in rectal cancer has been shown to be effective in reducing tumour burden in advance of curative surgery.The gold standard surgical rectal cancer management aims to achieve surgical removal of the tumour and all draining lymph nodes,within an intact mesorectal package,in order to minimise local recurrence.It is critically important that all rectal cancer cases are discussed at a multidisciplinary meeting represented by all relevant specialties.Pre-operative staging including CT thorax,abdomen,pelvis to assess for distal disease and magnetic resonance imaging to assess local involvement is essential.Staging radiology and MDT discussion are integral in identifying patients who require neoadjuvant radiotherapy.While Neoadjuvant radiotherapy is potentially beneficial it may also result in morbidity and thus should be reserved for those patients who are at a high risk of local failure,which includes patients with nodal involvement,extramural venous invasion and threatened circumferential margin.The aim of this review is to discuss the role of neoadjuvant radiotherapy in the management of rectal cancer.

Neoadjuvant chemotherapy plus intensity-modulated radiotherapy versus concurrent chemoradiotherapy plus adjuvant chemotherapy for the treatment of locoregionally advanced nasopharyngeal carcinoma:a retrospective controlled study

Background:In the era of intensity-modulated radiotherapy(IMRT),the role of neoadjuvant chemotherapy(NAC)for locoregionally advanced nasopharyngeal carcinoma(NPC)is under-evaluated.The aim of this study was to compare the efficacy of NAC plus IMRT and concurrent chemoradiotherapy(CCRT)plus adjuvant chemotherapy(AC)on locoregionally advanced NPC.Methods:Between January 2004 and December 2008,240 cases of locoregionally advanced NPC confirmed by pathologic assessment in Sun Yat-sen University Cancer Center were reviewed.Of the 240 patients,117 received NAC followed by IMRT,and 123 were treated with CCRT plus AC.The NAC+IMRT group received a regimen that included cisplatin and 5-fluorouracil(5-FU).The CCRT+AC group received cisplatin concurrently with radiotherapy,and subsequently received adjuvant cisplatin and 5-FU.The survival rates were assessed by Kaplan-Meier analysis,and the survival curves were compared using a log-rank test.Multivariate analysis was conducted using the Cox proportional hazard regression model.Results:The 5-year overall survival(OS),locoregional relapse-free survival(LRRFS),distant metastasis-free survival(DMFS),and disease-free survival(DFS)were 78.0,87.9,79.0,and 69.8%,respectively,for the NAC+IMRT group and78.7,84.8,76.2,and 65.6%,respectively,for the CCRT+AC group.There were no significant differences in survival between the two groups.In multivariate analysis,age(<50 years vs.>50 years)and overall stage(Ⅲvs.Ⅳ)were found to be independent predictors for OS and DFS;furthermore,the overall stage was a significant prognostic factor for DMFS.Compared with the CCRT+AC protocol,the NAC+IMRT protocol significantly reduced the occurrence rates of grade 3-4 nausea-vomiting(6.5 vs.1.5%,P=0.023)and leukopenia(9.7 vs.0.8%,P=0.006).Conclusions:The treatment outcomes of the NAC+IMRT and CCRT+AC groups were similar.Distant metastasis remained the predominant mode of treatment failure.

Lymphovascular invasion in rectal cancer following neoadjuvant radiotherapy: A retrospective cohort study

AIM: To investigate the meaning of lymphovascular invasion (LVI) in rectal cancer after neoadjuvant radiotherapy. METHODS: A total of 325 patients who underwent radical resection using total mesorectal excision (TME) from January 2000 to January 2005 in Beijing cancer hospital were included retrospectively, divided into a preoperative radiotherapy (PRT) group and a control group, according to whether or not they underwent preoperative radiation. Histological assessments of tumor specimens were made and the correlation of LVI and prognosis were evaluated by univariate and multivariate analysis. RESULTS: The occurrence of LVI in the PRT and control groups was 21.4% and 26.1% respectively. In the control group, LVI was signifi cantly associated with histological differentiation and pathologic TNM stage, whereas these associations were not observed in the PRT group. LVI was closely correlated to disease progression and 5-year overall survival (OS) in both groups. Among the patients with disease progression, LVI positive patients in the PRT group had a signifi cantly longer median disease-free period (22.5 mo vs 11.5 mo, P = 0.023) and overall survival time (42.5 mo vs 26.5 mo, P = 0.035) compared to those in the control group, despite the fact that no signifi cant difference in 5-year OS rate was observed (54.4% vs 48.3%, P = 0.137). Multivariate analysis showed the distance of tumor from the anal verge, pretreatment serum carcinoembryonic antigen level, pathologic TNM stage and LVI were the major factors affecting OS. CONCLUSION: Neoadjuvant radiotherapy does not reduce LVI significantly; however, the prognostic meaning of LVI has changed. Patients with LVI may benefi t from neoadjuvant radiotherapy.

Technological advances in radiotherapy for esophageal cancer

Radiotherapy with concurrent chemotherapy and surgery represent the main treatment modalities in esophageal cancer.The goal of modern radiotherapy approaches,based on recent technological advances,is to minimize post-treatment complications by improving the gross tumor volume definition (positron emission tomography-based planning),reducing interfraction motion (image-guided radiotherapy) and intrafraction motion (respiratory-gated radiotherapy),and by better dose delivery to the precisely defined planning target volume (intensity-modulated radiotherapy and proton therapy).Reduction of radiotherapy-related toxicity is fundamental to the improvement of clinical results in esophageal cancer,although the dose escalation concept is controversial.

Fat clearance and conventional fixation identified ypN0 rectal cancers following intermediate neoadjuvant radiotherapy have similar long-term outcomes

BACKGROUND As a prognostic factor for colorectal cancer,lymph node(LN)status,particularly the number of LN harvested,has been demonstrated to be essential in the evaluation of quality control in terms of surgical specimen.Neoadjuvant chemoradiation,however,decreases the LN harvest.Therefore,certain approaches(such as fat clearance or methylene blue)has drawn significant attention in order to raise LN yield.AIM To compare the long-term oncologic outcome of ypN0 rectal cancer identified using fat clearance(FC)or conventional fixation(CF)following 30 Gy in 10 fractions(30 Gy/10f)of neoadjuvant radiotherapy(nRT).METHODS Three hundred and eighty-two patients with resectable and locally advanced rectal cancer were treated by 30 Gy/10f intermediate nRT(biologically equivalent dose of 36 Gy)plus total mesorectal excision.Two specimen fixation methods(FC or CF)were non-randomly used.The ypN0 status was identified in 124 and 101 patients in the FL and CF groups,respectively.Primary endpoints were local recurrence-free survival(LRFS)and cancer-specific survival(CSS).RESULTS The median follow-up of patients was 5.1 years.The median numbers of retrieved LNs in the FC and CF groups were 19.5(range,4-47)and 12(range,0-44),respectively,with a significant difference(P=0.000).The percentages of patients with 12 or more retrieved nodes were 82.3%and 50.5%(101/159)in the FC and CF groups,respectively,with a significant difference(P=0.000).The LRFS at 5 years were 95.7%and 94.6%in the FC and CF groups,respectively,without statistical difference(P=0.819).The CSS at 5 years were 92.0%and 87.2%in the FC and CF groups,respectively,without statistical difference(P=0.482).CONCLUSION For patients with ypN0 rectal cancer who underwent 30 Gy/10f preoperative radiotherapy,the increased retrieval of LNs using fat clearance is not associated with survival benefit.This time-consuming fixation method has a low efficacy as a routine practice.

Helical tomotherapy and volumetric modulated arc therapy:New therapeutic arms in the breast cancer radiotherapy

AIM To analyse clinical and dosimetric results of helical tomotherapy(HT) and volumetric modulated arc therapy(VMAT) in complex adjuvant breast and nodes irradiation.METHODS Seventy-three patients were included(31 HT and 42 VMAT). Dose were 63.8 Gy(HT) and 63.2 Gy(VMAT) in the tumour bed, 52.2 Gy in the breast, 50.4 Gy in supraclavicular nodes(SCN) and internal mammary chain(IMC) with HT and 52.2 Gy and 49.3 Gy in IMC and SCN with VMAT in 29 fractions. Margins to particle tracking velocimetry were greater in the VMAT cohort(7 mm vs 5 mm).RESULTS For the HT cohort, the coverage of clinical target volumes was as follows: Tumour bed: 99.4% ± 2.4%; breast: 98.4% ± 4.3%; SCN: 99.5% ± 1.2%; IMC:96.5% ± 13.9%. For the VMAT cohort, the coverage was as follows: Tumour bed: 99.7% ± 0.5%, breast: 99.3% ± 0.7%; SCN: 99.6% ± 1.4%; IMC: 99.3% ± 3%. For ipsilateral lung, Dmean and V20 were 13.6 ± 1.2 Gy, 21.1% ± 5%(HT) and 13.6 ± 1.4 Gy, 20.1% ± 3.2%(VMAT). Dmean and V30 of the heart were 7.4 ± 1.4 Gy, 1% ± 1%(HT) and 10.3 ± 4.2 Gy, 2.5% ± 3.9%(VMAT). For controlateral breast Dmean was 3.6 ± 0.2 Gy(HT) and 4.6 ± 0.9 Gy(VMAT). Acute skin toxicity grade 3 was 5% in the two cohorts.CONCLUSION HT and VMAT in complex adjuvant breast irradiation allow a good coverage of target volumes with an acceptable acute tolerance. A longer follow-up is needed to assess the impact of low doses to healthy tissues.

Trends with neoadjuvant radiotherapy and clinical staging for those with rectal malignancies

AIM To see how patterns of care changed over time,and how institution type effected these decisions.METHODS A retrospective analysis was performed using the National Cancer Database,looking at all patients that were diagnosed with rectal cancer from 1998 to 2011. We tested differences in rates of treatment and stage migration using χ~2 tests and logistic regression models. RESULTS A review of ninety thousand five hundred and ninety four subjects underwent multimodality therapy for cancer of the rectum. Staging and response to treatment varied greatly between centers. Forty-six percent of the time staging was missing in academic practices,vs fiftyfour percent of the time in community centers(P < 0.001). As a result,twenty-percent were down-staged and eight percent up-staged in academia,whereas only fifteen percent were down-staged and 8% up-staged in community practices(P < 0.001). Forty-two percent of individuals underwent radiation before surgery in 1998.Within two years this increased to fifty-three percent. This increased to eighty-six percent by 2011(P < 0.001). Institution specific treatment varied greatly. Fifty-one percent received therapy before surgery in academic centers in 1998. Thirty-nine percent followed this pattern in the same year in the community(P < 0.001). By 2011,ninety-one percent received radiation before their procedure in academic centers,vs eighty-four percent in the community(P < 0.001). Rates of adoption were better in academia,although an increase was seen in both center types. CONCLUSION From the study dates of 1998 to 2011,preoperative treatment with radiation has been on the rise. There is certainly an increased rate of use of radiation in academia,however,this trend is also seen in the community. Practice patterns have evolved over time,although rates of assigning clinical stage are grossly underreported prior to initiation of preoperative therapy.

PhaseⅠ/Ⅱtrial evaluating concurrent carbon-ion radiotherapy plus chemotherapy for salvage treatment of locally recurrent nasopharyngeal carcinoma

Background: After deinitive chemoradiotherapy for non-metastatic nasopharyngeal carcinoma(NPC), more than 10% of patients will experience a local recurrence. Salvage treatments present signiicant challenges for locally recurrent NPC. Surgery, stereotactic ablative body radiotherapy, and brachytherapy have been used to treat locally recurrent NPC. However, only patients with small-volume tumors can beneit from these treatments. Re-irradiation with X-ray—based intensity-modulated radiotherapy(IMXT) has been more widely used for salvage treatment of locally recurrent NPC with a large tumor burden, but over-irradiation to the surrounding normal tissues has been shown to cause frequent and severe toxicities. Furthermore, locally recurrent NPC represents a clinical entity that is more radioresistant than its primary counterpart. Due to the inherent physical advantages of heavy-particle therapy, precise dose delivery to the target volume(s), without exposing the surrounding organs at risk to extra doses, is highly feasible with carbon-ion radiotherapy(CIRT). In addition, CIRT is a high linear energy transfer(LET) radiation and provides an increased relative biological efectiveness compared with photon and proton radiotherapy. Our prior work showed that CIRT alone to 57.5 Gy E(gray equivalent), at 2.5 Gy E per daily fraction, was well tolerated in patients who were previously treated for NPC with a deinitive dose of IMXT. The short-term response rates at 3–6 months were also acceptable. However, no patients were treated with concurrent chemotherapy. Whether the addition of concurrent chemotherapy to CIRT can beneit locally recurrent NPC patients over CIRT alone has never been addressed. It is possible that the beneits of high-LET CIRT may make radiosensitizing chemotherapy unnecessary. We therefore implemented a phase I/II clinical trial to address these questions and present our methodology and results.Methods and design: The maximal tolerated dose(MTD) of re-treatment using raster-scanning CIRT plus concurrent cisplatin will be determined in the phase I, dose-escalating stage of this study. CIRT dose escalation from 52.5 to 65 Gy E(2.5 Gy E × 21–26 fractions) will be delivered, with the primary endpoints being acute and subacute toxicities. Eicacy in terms of overall survival(OS) and local progression-free survival of patients after concurrent chemotherapy plus CIRT at the determined MTD will then be studied in the phase II stage of the trial. We hypothesize that CIRT plus chemotherapy can improve the 2-year OS rate from the historical 50% to at least 70%.Conclusions: Re-treatment of locally recurrent NPC using photon radiation techniques, including IMXT, provides moderate eicacy but causes potentially severe toxicities. Improved outcomes in terms of eicacy and toxicity proile are expected with CIRT plus chemotherapy. However, the MTD of CIRT used concurrently with cisplatin-based chemotherapy for locally recurrent NPC remains to be determined. In addition, whether the addition of chemotherapy to CIRT is needed remains unknown. These questions will be evaluated in the dose-escalating phase I and randomized phase II trials.

Interpretation of the development of neoadjuvant therapy for gastric cancer based on the vicissitudes of the NCCN guidelines

Gastric cancer is one of the most common digestive system tumors in China,and locally advanced gastric cancer(LAGC)accounts for a high proportion of newly diagnosed cases.Although surgery is the main treatment for gastric cancer,surgical excision alone cannot achieve satisfactory outcomes in LAGC patients.Neoadjuvant therapy(NAT)has gradually become the standard treatment for patients with LAGC,and this treatment can not only achieve tumor downstaging and improve surgical rate and the R0 resection rate,but it also significantly improves the long-term prognosis of patients.Peri/preoperative neoadjuvant chemotherapy and preoperative chemoradiotherapy are both recommended according to a large number of studies,and the regimens have also been evolved in the past decades.Since the NCCN guidelines for gastric cancer are one of the most authoritative evidence-based guidelines worldwide,here,we demonstrate the development course and major breakthroughs of NAT for gastric cancer based on the vicissitudes of the NCCN guidelines from 2007 to 2019,and also discuss the future of NAT.