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.

Adjuvant therapy for orbital non-rhabdomyosarcoma soft tissue sarcoma:comparison of long-term outcome between radiotherapy and chemotherapy

AIM:To illustrate clinicopathological features of orbital non-rhabdomyosarcoma soft tissue sarcoma(NRSTS),and to compare the treatment outcome between postoperative radiotherapy(RT) and chemotherapy in a retrospective analysis nearly 20y.METHODS:A retrospective cohort study of 56 patients with orbital NRSTS were reviewed,34 of whom received postoperative RT,and 22 received postoperative chemotherapy.The clinicopathological features,local recurrence,metastases,and survival data were recorded.Survival analysis was performed using the Kaplan-Meier method.RESULTS:During follow-up(111.8mo,ranged 8-233mo) for 56 patients,19 patients of them developed local recurrence,and 7 patients developed distant metastases.Fifteen patients died during follow-up period.Overall survival rates considering the whole study group was 78.57% at 5y,and 72.16% at 10y after the initial diagnosis.Compared with chemotherapy,RT was associated with lower risk of local recurrence [hazard ratio for RT vs chemotherapy,0.263,95% confidence interval(CI),0.095-0.728,P=0.0015];with lower risk of distant metastasis(hazard ratio for RT vs chemotherapy,0.073,95%CI,0.015-0.364,P=0.0014);and with lower risk of death from disease(hazard ratio for RT vs chemotherapy,0.066,95%CI,0.022-0.200,P<0.0001).The 5-year survival rate in RT group was 97.06% compared to 50% in chemotherapy group.CONCLUSION:In patients with orbital NRSTS,postoperative RT provides better control of local recurrence,distant metastasis,and death from disease than chemotherapy.RT is the more preferrable adjuvant therapy compared to chemotherapy possibly.

Effect of postoperative adjuvant chemotherapyon the prognosis of patients with ypT0-3N0 rectalcancer undergoing neoadjuvant chemoradiotherapy

Objective The aim of this study was to investigate the effect of adjuvant chemotherapy (AC) on theprognosis of patients with ypT0-3N0 rectal cancer undergoing neoadjuvant chemoradiotherapy.Methods The study participants were 110 patients with locally advanced rectal cancer. Thirty-fourpatients did not receive postoperative AC treatment, and the other 76 patients received postoperative ACtreatment. The differences in the 5-year overall survival (OS) and disease-free survival (DFS) between thetwo groups were compared.Results Age was an important determinant of the patients’ decision to undergo postoperative treatment.Patients who did not receive AC treatment were significantly older than those who received AC treatment(P < 0.05). The tumor location (distance above anal margin) in the AC group was significantly larger thanthat in the non-AC group (P < 0.05). Moreover, there was no significant difference in the 5-year DFS andOS between the two groups. Postoperative AC did not significantly improve the prognosis of patients withrectal cancer. Age, tumor differentiation, and the number of resected lymph nodes were independent factorsaffecting the OS of patients (P < 0.05). Older patients, patients with lower degree of tumor differentiation,and patients with <12 resected lymph nodes showed worse prognosis (P < 0.05).Conclusion Patients with rectal cancer whose ypT0-3N0 stage is reduced after neoadjuvantchemoradiotherapy, especially those without adverse prognostic factors, do not need AC after surgery.

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 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.

Adjuvant Pelvic Radiotherapy vs.Sequential Chemoradiotherapy for High-Risk StageⅠ-ⅡEndometrial Carcinoma

Objective To explore if the addition of adjuvant chemotherapy with paclitaxel and carboplatin to radiotherapy confers an advantage for overall survival （OAS）, and progression free survival （PFS）; to assess the incidence of relapses over standard pelvic radiotherapy; and to evaluate the related toxicity in high-risk stage I-II endometrial carcinoma Methods Medical records were reviewed to identify high-risk stage I-1I endometrial carcinoma cases treated in the Clinical Oncology and Nuclear Medicine department between 2002 and 2008 with adjuvant radiotherapy alone （arm Ⅰ）（57 patients） or with sequential carboplatin （AUCS-6） and paclitaxel （135-175 mg/m^2） with radiotherapy （arm Ⅱ） （51 patients）. Radiotherapy was performed through the four-field box technique at doses of 45-50 Gy （1.8 Gy/day × 5 days/week）. Results The toxicity was manageable and predominantly hematologic with a grade 3 neutropenia and thrombocytopenia in 9.8% and 6% of the patients in arm Ⅰ and arm Ⅱ, respectively, without febrile neutropenia. All patients experienced hair loss. Chernoradiotherapy arm was associated with a lower incidence rate of relapse （9.8% vs. 22.7%）. After a median follow-up period of 48 months, the 5-year OAS and PFS rates for chemoradiotherapy-treated patients were significantly more favorable than those who did not receive chemotherapy （P=0.02 and 0.03, respectively）. In arm I, the OAS and PFS rates were 73.7% and 66.7% compared with those in arm II, whose rates were 90.2% and 84.3%. Conclusions Adjuvant chemoradiation with paclitaxel and carboplatin improved the survival rates and decreased the recurrence rates in patients with high-risk stage Ⅰ-Ⅱ endometrial carcinoma. Chemotherapy was associated with an acceptable rate of toxicity. However, a prospective study with a larger number of patients is needed to define a standard adjuvant treatment for high-risk stage Ⅰ-Ⅱ endometrial carcinoma.

Benefit of adjuvant chemoradiotherapy in patients with pathologically lymph node-positive and locally advanced gastric cancer

Objective This study aimed to compare the effectiveness of adjuvant chemoradiotherapy(CRT)and adjuvant chemotherapy(ChT)for T3–4/N+gastric cancer(GC)following D2/R0 dissection,and identify the specific subgroups that could benefit from adjuvant CRT.Methods All eligible patients were divided into the CRT group and ChT group.We assessed the survival outcomes and patterns of recurrence for each group,and determined the prognostic factors for survival by performing Cox proportional risk regression analyses.Results A total of 192 gastric cancer patients were included in the study.The estimated 3-year and 5-year disease-free survival(DFS)probabilities in the CRT and ChT groups were 52.9%vs.36.7%(P=0.024)and 41.2%vs.31.1%(P=0.148),respectively,and the estimated 3-year and 5-year overall survival(OS)probabilities were 82.4%vs.70.0%(P=0.044)and 52.0%vs.35.6%(P=0.022).Patients in the CRT group had a lower risk of locoregional recurrence than those in the ChT group(20.6%vs.34.4%;P=0.031).The subset analyses revealed that patients with stage N1–2 disease were more likely to benefit from adjuvant CRT than from adjuvant ChT(DFS:53.1%vs.36.4%;P=0.039;OS:53.1%vs.38.6%;P=0.036).Conclusion For locally advanced gastric cancer patients with LN+,adjuvant CRT showed superior survival benefits compared with adjuvant ChT alone.Patients with N1–2 achieved better survival from adjuvant CRT.

Radiotherapy with neoadjuvant chemotherapy versus concurrent chemoradiotherapy for ascending-type nasopharyngeal carcinoma:a retrospective comparison of toxicity and prognosis

Background:In the era of intensity?modulated radiotherapy(IMRT),the role of neoadjuvant chemotherapy(NACT)in treating ascending?type nasopharyngeal carcinoma(NPC)is under?evaluated.This study was to compare the efficacy of NACT followed by IMRT(NACT+RT)with the efficacy of concurrent chemoradiotherapy(CCRT)on ascending?type NPC.Methods:Clinical data of 214 patients with ascending?type NPC treated with NACT+RT or CCRT between Decem?ber 2009 and July 2011 were analyzed.Of the 214 patients,98 were treated with NACT followed by IMRT,and 116 were treated with CCRT.The survival rates were assessed using Kaplan–Meier analysis,and the survival curves were compared using a log?rank test.Results:The 4?year overall survival,locoregional failure?free survival,distant failure?free survival,and failure?free sur?vival rates were not significantly different between the two groups(all P>0.05).However,patients in the CCRT group exhibited more severe acute adverse events than did patients in the NACT+RT group during radiotherapy,includ?ing leukopenia(30.2%vs.15.3%,P=0.016),neutropenia(25.9%vs.11.2%,P=0.011),and mucositis(57.8%vs.40.8%,P=0.028).After radiotherapy,patients in the CCRT group exhibited significantly higher rates of xerostomia(21.6%vs.Conclusions:The treatment outcomes of the NACT+RT and CCRT groups were similar;however,CCRT led to higher rates of acute and late toxicities.NACT+RT may therefore be a better treatment strategy for ascending?type NPC.

Adjuvant chemoradiotherapy vs adjuvant chemotherapy in locally advanced Siewert type Ⅱ/Ⅲ adenocarcinoma of gastroesophageal junction after D2/R0 resection

BACKGROUND For Siewert type Ⅱ/Ⅲ adenocarcinoma of gastroesophageal junction(AGE), the efficacy of adjuvant chemoradiotherapy(CRT) after D2/R0 resection remains uncertain.AIM To determine whether CRT was superior to chemotherapy(CT) alone after D2/R0 resection for locally advanced Siewert type Ⅱ/Ⅲ AGE.METHODS We identified 316 locally advanced Siewert type Ⅱ/Ⅲ AGE patients who were treated with D2/R0 resection at National Cancer Center from 2011 to 2018.57 patients received adjuvant CRT and 259 patients received adjuvant CT.We followed patients for overall survival(OS), relapse-free survival, and recurrence pattern.RESULTS Five-year OS rates of the CRT group and the CT group for all patients were 66.7% and 41.9%(P = 0.010).Five-year OS rates of the CRT group and the CT group for Siewert type Ⅲ AGE patients were 65.7% and 43.9%(P = 0.006).Among the 195 patients whose recurrence information could be obtained, 18 cases(34.6%) and 61 cases(42.7%) were diagnosed as recurrence in the CRT group and CT group, respectively.The local and regional recurrence rates in the CRT group were lower than that in the CT group(22.2% vs 24.6%, 27.8% vs 39.3%).Multivariable cox regression analysis showed that vascular invasion, nerve invasion, and adjuvant CRT were important prognostic factors for Siewert type Ⅲ AGE.CONCLUSION For locally advanced Siewert type Ⅲ AGE, adjuvant CRT may prolong OS and reduce the regional recurrence rate.

Neoadjuvant chemoradiotherapy plus surgery in the treatment of potentially resectable thoracic esophageal squamous cell carcinoma

BACKGROUNDIn recent years, neoadjuvant chemoradiotherapy (NCRT) combined with surgeryhas been gradually applied in patients with locally advanced thoracic esophagealcancer, but its effectiveness and safety remains unclear. In this clinical trial, weprospectively investigated the efficacy and safety of NCRT plus surgery in thetreatment of thoracic esophageal squamous cell carcinoma (TESCC).AIMTo investigate the efficacy and safety of NCRT combined with surgery in thetreatment of potentially resectable TESCC.METHODSThirty patients with advanced TESCC hospitalized in our hospital from July2016 to June 2019 were prospectively studied. All patients received NCRT, whichincluded intensity modulated conformal radiotherapy (40-44 Gy/20-22f, 2 Gy/f)and chemotherapy (paclitaxel 150-175 mg/m2d1, 22 + lobaplatin 25-30 mg/m2d2,23 for two cycles). Surgery was performed after radiotherapy and chemotherapy.The effectiveness and safety of these treatments were observed.RESULTSAmong these 30 patients, complete response was achieved in two cases (6.7%) andpartial response in 26 cases (86.7%), yielding an objective response rate of 100%.All patients underwent radical surgery successfully. The R0 resection rate was100%, and the pathologic complete response rate was 33.3%. The incidence ofgrade III- IV granulocytopenia was 10% during the NCRT, and anastomoticleakage occurred in one patient after surgery.CONCLUSIONFor patients with potentially resectable TESCC, NCRT can effectively reduce thetumor size, increase R0 resection rate, and achieve obvious pathologicaldegradation, with mild adverse reactions. Thus, it is worthy of wider clinicalapplication.

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.

Adjuvant chemoradiotherapy versus surgery alone for gastric adenocarcinoma

Objective:Despite resection with curative intent,a majority of patients with gastric cancer will develop disease recurrence.Postoperative adjuvant chemo-radiotherapy increase the curability of surgery,prevent local recurrence and improve survival.Methods:Between December 2005 and February 2010,33 patients were eligible for the study,17 patients were randomly assigned for chemo-radiotherapy (GI) and 16 patients with surgery alone (GII).Patients in GI received chemotherapy (fluorouracil,425 mg/m 2/day,and leucovorin,20 mg/m 2/day,for 5 days) was initiated on day 1 and was followed by chemo-radiotherapy beginning 28 days after the start of the initial cycle of chemotherapy.Chemo-radiotherapy consisted of 4500 cGy of radiation at 180 cGy/day,five days/week for five weeks,with fluorouracil (400 mg/m 2/day) and leucovorin (20 mg/m 2/day) on the first four and the last four days of radiotherapy.One month after the completion of radiotherapy,two five-day cycles of fluorouracil (425 mg/m 2/day) plus leucovorin (20 mg/m 2/day) were given one month apart.Results:Grade 3 gastrointestinal toxicity was more common (23.2%) while grade 3 hematological toxicity were (5.8%).Both 3-year survival (53%) and disease free survival (41%) rates were higher in GI than in GII in which they were 43.7% and 31% respectively.Relapse rate was higher in GII (56.3%) than in GI (35.3%).Conclusion:The present study revealed that chemo-radiotherapy after gastric resection in patients with gastric adenocarcinoma improves survival and relapse rates with manageable toxicities.However,studies with larger number of patients are recommended to confirm our results.

High-risk endometrial cancer may be benefit from adjuvant radiotherapy plus chemotherapy

Objective： To present patterns of practice and outcomes in the adjuvant treatment of intermediate- and high-risk endometrial cancer. Methods： Retrospective data on 224 women with intermediate-risk and high-risk endometrial cancer from 1999 to 2006 were reviewed. All patients underwent surgical staging. Patterns of adjuvant treatment, consisting of pelvic radiotherapy, chemotherapy, and radiotherapy plus chemotherapy, were assessed. The 3- and 5-year disease-specific survival （DSS） rates were calculated using the Kaplan-Meier method. Results： The difference in 5-year DSS rate was statistically significant between adjuvant group and non-adjuvant group （80.65% vs. 63.80%, P=0.040）. In 110 high-risk patients who underwent adjuvant treatment, both 5-year DSS rate and recurrent rate were significantly different in combined radiotherapy and chemotherapy group compared with radiotherapy alone and chemotherapy alone groups （DSS rate, P=0.049; recurrent rate, P=0.047）. In 83 intermediate-risk women who underwent adjuvant treatment, there was no significant difference in 5-year DSS rate and recurrence rate among the combined radiotherapy and chemotherapy, radiotherapy alone and chemotherapy alone groups （DSS rate, P=0.776; recurrent rate, P=0.937）.

Neoadjuvant chemoradiotherapy before resection of perihilar cholangiocarcinoma: A systematic review

Background: Treatment with neoadjuvant chemoradiotherapy followed by liver transplantation yields promising results in perihilar cholangiocarcinoma (PH-CCA). This study reviews the literature to assess whether there is evidence to justify modern phase Ⅱ studies of neoadjuvant chemoradiotherapy prior to resection of PH-CCA.Data sources: A systematic review of the literature for reports of patients undergoing resection of PH- CCA after neoadjuvant chemoradiotherapy was performed using MEDLINE and EMBASE databases for the period between 1990 and 2019. The keywords and MeSH headings "hilar cholangiocarcinoma", "Klatskin", "chemoradiotherapy" and "chemotherapy" were used. Data were extracted on demographic profile, dis- ease staging, chemoradiotherapy protocols, complications and outcome. Risks of bias were assessed using Cochrane methodology. Results: There were seven reports on this topic, with median recruitment period of 14 (range 4–31) years. The total number of patients in these studies was 87. Interval from completion of neoadjuvant treatment to surgery varied from 3 days to 6 months. Resection was by hepatectomy with three studies reporting an R0 rate of 100%, 24% and 63%, respectively. Three studies reported histopathological evidence of prior treatment response. There were two treatment related deaths at 90 days. Median survival was 19 (95% CI: 9.9–28) months and 5-year survival 20%. Conclusions: There are potential benefits of treatment on both R0 rate and complete response in resected specimens. Scientific equipoise exists in relation to neoadjuvant chemoradiotherapy for PH-CCA.

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.

Fifty-Year-Follow-up Results Compared with Shorter Follow-up of Breast Cancer Patients Undergoing Radical Mastectomy with or without Adjuvant Radiotherapy

Background: To evaluate the effect of follow-up length on the outcome of breast cancer patients, we compared the 50- and 25-year follow-up results in terms of cure rate, overall mortality and mortalities from breast cancer, second cancer, and benign diseases. Methods: 763 patients treated for breast cancer between February 1953 and September 1976, were followed up until December 2014. They were divided into two cohorts;earlier cohort exclusively underwent radical mastectomy plus adjuvant radiotherapy, while later cohort had radical mastectomy alone. Assuming that in all patients follow-up was terminated at 50 or 25 years after diagnosis, likelihood ratio test and stratified Log-rank tests were performed to evaluate the differences in cure rate and overall survival between the two cohorts. Results: During the 50 years, radical mastectomy alone compared with radical mastectomy plus adjuvant radiotherapy is associated with a significantly higher cure rate, and higher survivals regardless of whether the death was from breast cancer, second cancer, benign causes or any causes. However, if follow-up information is limited to 25 years, the advantage of radical mastectomy alone is partly offset and the survival difference between the two cohorts becomes less significant. Conclusion: Radiotherapy to breast cancer may adversely affect not only mortality from breast cancer, but mortalities unrelated to breast cancer. Since such deaths occur later, they may fail to be detected unless follow-up is long enough. Thus, deleterious effects of radiotherapy may be underestimated. Exceedingly long follow-up is required to accurately estimate the cure rate and the long-term effect of radiotherapy.

Neoadjuvant chemoradiotherapy for esophageal cancer:Impact on extracapsular lymph node involvement

AIM:To assess the effects of neoadjuvant chemoradiotherapy(CRT) on the presence of extracapsular lymph node involvement(LNI) and its prognostic value in patients with resected esophageal cancer.METHODS:Two hundred and ninety-eight patients with advanced esophageal cancer underwent esophagectomy between 1997 and 2006.One hundred and ninety patients(63.8%) were treated with neoadjuvant CRT prior to resection.A total of 986 metastatic LNs were examined.Survival of the patients was analyzed according to intra-and extra-capsular LNI.RESULTS:Five-year survival rate was 22.5% for the entire patient population.Patients with extracapsular LNI had a 5-year survival rate of 16.7%,which was comparable to the 15.8% in patients with infiltrated nodes of the celiac trunk(pM1lymph).In contrast to patients treated with surgery alone,neoadjuvant therapy resulted in signif icantly(P = 0.001) more patients with pN0/M0(51.6% vs 25.0%).In 17.6% of the patients with surgery alone vs 16.8% with neoadjuvant CRT,extracapsular LNI was detected.Neoadjuvant therapy does not reduce the occurrence of extracapsular LNI.CONCLUSION:Extracapsular LNI is an independent negative prognostic factor not influenced by neoadjuvant CRT.In a revised staging system for esophageal cancer,extracapsular LNI should be considered.

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.

Role of adjuvant chemoradiotherapy and chemotherapy in patients with resected gallbladder carcinoma: a multiinstitutional analysis (KROG 19-04)

Objective:The effectiveness of adjuvant treatments for resected gallbladder carcinoma(GBC)has remained unclear due to lack of randomized controlled trials;thus,the aim of present study was to evaluate the role of adjuvant treatments,including chemoradiotherapy(CRT)and/or chemotherapy(CTx),in patients with resected GBC.Methods:A total of 733 GBC patients who received curative-intent surgical resection were identified in a multi-institutional database.Of 733 patients,372(50.8%)did not receive adjuvant treatment,whereas 215(29.3%)and 146(19.9%)received adjuvant CTx and CRT,respectively.The locoregional recurrence-free survival(LRFS),recurrence-free survival(RFS),and overall survival(OS)of the adjuvant treatment groups were compared according to tumor stage(stage II vs.stage III–IV).Results:In stage II disease(n=381),the 5-year LRFS,RFS,and OS were not significantly different among the no-adjuvant therapy,CTx,and CRT groups,and positive resection margin,presence of perineural invasion,and Nx classification were consistently associated with worse LRFS,RFS,and OS in the multivariate analysis(P<0.05).For stage III–IV(n=352),the CRT group had significantly higher 5-year LRFS,RFS,and OS than the no-adjuvant therapy and CTx groups(67.8%,45.2%,and 56.9%;37.9%,28.8%,and 35.4%;and 45.0%,30.0%,and 45.7%,respectively)(P<0.05).Conclusions:CRT has value as adjuvant treatment for resected GBC with stage III–IV disease.Further study is needed for stage II disease with high-risk features.

Stereotactic body radiotherapy in pancreatic adenocarcinoma

Background:Stereotactic body radiotherapy(SBRT)in pancreatic cancer allows high delivery of radiation doses on tumors without affecting surrounding tissue.This review aimed at the SBRT application in the treatment of pancreatic cancer.Data sources:We retrieved articles published in MEDLINE/PubMed from January 2017 to December 2022.Keywords used in the search included:“pancreatic adenocarcinoma”OR“pancreatic cancer”AND“stereotactic ablative radiotherapy(SABR)”OR“stereotactic body radiotherapy(SBRT)”OR“chemoradiotherapy(CRT)”.English language articles with information on technical characteristics,doses and fractionation,indications,recurrence patterns,local control and toxicities of SBRT in pancreatic tumors were included.All articles were assessed for validity and relevant content.Results:Optimal doses and fractionation have not yet been defined.However,SBRT could be the standard treatment in patients with pancreatic adenocarcinoma in addition to CRT.Furthermore,the combination of SBRT with chemotherapy may have additive or synergic effect on pancreatic adenocarcinoma.Conclusions:SBRT is an effective modality for patients with pancreatic cancer,supported by clinical practice guidelines as it has demonstrated good tolerance and good disease control.SBRT opens a possibility of improving outcomes for these patients,both in neoadjuvant treatment and with radical intent.