Adjuvant chemoradiotherapy versus radiotherapy alone in women with high-risk endometrial cancer (PORTEC-3): patterns of recurrence and post-hoc survival analysis of a randomised phase 3 trial.
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SUBMITTER: de Boer SM
PROVIDER: S-EPMC6722042 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundAlthough women with endometrial cancer generally have a favourable prognosis, those with high-risk disease features are at increased risk of recurrence. The PORTEC-3 trial was initiated to investigate the benefit of adjuvant chemotherapy during and after radiotherapy (chemoradiotherapy) versus pelvic radiotherapy alone for women with high-risk endometrial cancer.MethodsPORTEC-3 was an open-label, international, randomised, phase 3 trial involving 103 centres in six clinical trials collaborating in the Gynaecological Cancer Intergroup. Eligible women had high-risk endometrial cancer with FIGO 2009 stage I, endometrioid-type grade 3 with deep myometrial invasion or lymph-vascular space invasion (or both), endometrioid-type stage II or III, or stage I to III with serous or clear cell histology. Women were randomly assigned (1:1) to receive radiotherapy alone (48·6 Gy in 1·8 Gy fractions given on 5 days per week) or radiotherapy and chemotherapy (consisting of two cycles of cisplatin 50 mg/m2 given during radiotherapy, followed by four cycles of carboplatin AUC5 and paclitaxel 175 mg/m2) using a biased-coin minimisation procedure with stratification for participating centre, lymphadenectomy, stage of cancer, and histological type. The co-primary endpoints were overall survival and failure-free survival. We used the Kaplan-Meier method, log-rank test, and Cox regression analysis for final analysis by intention to treat and adjusted for stratification factors. The study was closed on Dec 20, 2013, after achieving complete accrual; follow-up is ongoing. PORTEC-3 is registered with ISRCTN, number ISRCTN14387080, and ClinicalTrials.gov, number NCT00411138.Results686 women were enrolled between Nov 23, 2006, and Dec 20, 2013. 660 eligible patients were included in the final analysis, of whom 330 were assigned to chemoradiotherapy and 330 were assigned to radiotherapy. Median follow-up was 60·2 months (IQR 48·1-73·1). 5-year overall survival was 81·8% (95% CI 77·5-86·2) with chemoradiotherapy versus 76·7% (72·1-81·6) with radiotherapy (adjusted hazard ratio [HR] 0·76, 95% CI 0·54-1·06; p=0·11); 5-year failure-free survival was 75·5% (95% CI 70·3-79·9) versus 68·6% (63·1-73·4; HR 0·71, 95% CI 0·53-0·95; p=0·022). Grade 3 or worse adverse events during treatment occurred in 198 (60%) of 330 who received chemoradiotherapy versus 41 (12%) of 330 patients who received radiotherapy (p<0·0001). Neuropathy (grade 2 or worse) persisted significantly more often after chemoradiotherapy than after radiotherapy (20 [8%] women vs one [1%] at 3 years; p<0·0001). Most deaths were due to endometrial cancer; in four patients (two in each group), the cause of death was uncertain. One death in the radiotherapy group was due to either disease progression or late treatment complications; three deaths (two in the chemoradiotherapy group and one in the radiotherapy group) were due to either intercurrent disease or late treatment-related toxicity.InterpretationAdjuvant chemotherapy given during and after radiotherapy for high-risk endometrial cancer did not improve 5-year overall survival, although it did increase failure-free survival. Women with high-risk endometrial cancer should be individually counselled about this combined treatment. Continued follow-up is needed to evaluate long-term survival.FundingDutch Cancer Society, Cancer Research UK, National Health and Medical Research Council Project Grant and Cancer Australia, L'Agenzia Italiana del Farmaco, and Canadian Cancer Society Research Institute.
| S-EPMC5840256 | biostudies-literature
Project description:Purpose: To evaluate the recurrent patterns and effect of clinicopathological factors on survival after recurrence (R-OS) in early stage endometrial cancer (EC). Methods: Patients with FIGO stage I-II EC, who underwent post-surgery radiotherapy (RT) at our institution between 2000 and 2017, were enrolled. First recurrent patterns, overall survival (OS), and R-OS were evaluated. Univariate and multivariate analyses (MVA) were used to evaluate factors associated with R-OS. Results: 756 patients were analyzed including 510 patients who received vaginal brachytherapy (VBT) and 246 patients who received external beam radiotherapy (EBRT) ± VBT, of whom 66 patients experienced recurrence, including 21 locoregional relapses and 45 distant metastases. Outside RT field recurrence predominated intra-RT field recurrence (106 versus 10 lesions). The 5-year OS rates for patients with and without recurrence were 62.2% and 98.2%, respectively (p<0.001). Among patients who underwent previous VBT, the 5-year OS rates were 61.1%, 92.3%, and 99.1% for distant metastasis, locoregional relapse, and non-recurrence, respectively (p<0.001); among patients who received EBRT ± VBT, the 5-year OS rates were 51.4%, 50.0%, and 98.3%, respectively (p<0.001).On Cox MVA of R-OS for locoregional recurrence patients, para-aortic lymph node metastasis was associated with poorer R-OS (hazard ratio [HR] 10.047, p=0.039), and salvage RT was superior to other therapies (HR 0.06, p=0.026). On Cox MVA of R-OS for distant metastasis, patients with brain metastasis (p=0.041) had the worst R-OS and patients benefited most from combined therapy (HR 0.02, p=0.001). Conclusion: Recurrent patterns were dominated by outside RT field and distant metastasis for early-stage ECs after adjuvant RT. The modality of prior RT had an impact on the choice of salvage therapy. RT could still be an effective salvage treatment for patients who develop locoregional recurrence. Patients with distant metastasis may benefit from combined therapies.
| S-EPMC8692693 | biostudies-literature
Project description:IntroductionWe aimed to evaluate the efficacy and toxicity of the combination of 6 cycles of chemotherapy and radiation therapy compared with chemotherapy alone as postoperative adjuvant therapy for patients with stage III endometrial cancer.MethodsThis retrospective cohort study included patients with stage III endometrial cancer who received postoperative chemoradiotherapy or chemotherapy alone at 6 hospitals between January 2009 and December 2019. The progression-free survival (PFS) and overall survival (OS) for each treatment group were analyzed using the Kaplan-Meier method. We also assessed differences in toxicity profiles between the treatment groups.ResultsA total of 133 patients met the inclusion criteria. Of these, 80 patients (60.2%) received adjuvant chemoradiotherapy and 53 (39.8%) received chemotherapy alone. The PFS and OS did not differ significantly between the groups. For patients with stage IIIC endometrioid subtype, the chemoradiotherapy group had significantly longer PFS rate than did the chemotherapy alone group (log-rank test, P = .019), although there was no significant difference in the OS (log-rank test, P = .100). CRT was identified as a favorable prognostic factor for PFS in multivariate analysis (adjusted HR, .37; 95% CI, .16-.87; P = .022). Patients treated with chemoradiotherapy more frequently suffered from grade 4 neutropenia (73.8% vs 52.8%; P = .018) and grade 3 or worse thrombocytopenia (36.3% vs 9.4%; P = .001) compared with the chemotherapy alone group. There were no differences between the 2 treatment groups in the frequency of toxicity-related treatment discontinuation or dose reduction.ConclusionWe confirmed that chemoradiotherapy yields longer progression-free survival than does chemotherapy alone for patients with stage IIIC endometrioid endometrial cancer, with an acceptable toxicity profile.
| S-EPMC9297464 | biostudies-literature
Project description:PurposeThe molecular classification of endometrial cancer (EC) has proven to have prognostic value and is predictive of response to adjuvant chemotherapy. Here, we investigate its predictive value for response to external beam radiotherapy (EBRT) and vaginal brachytherapy (VBT) in early-stage endometrioid EC (EEC).MethodsData of the randomized PORTEC-1 trial (n = 714) comparing pelvic EBRT with no adjuvant therapy in early-stage intermediate-risk EC and the PORTEC-2 trial (n = 427) comparing VBT with EBRT in early-stage high-intermediate-risk EC were used. Locoregional (including vaginal and pelvic) recurrence-free survival was compared between treatment groups across the four molecular classes using Kaplan-Meier's methodology and log-rank tests.ResultsA total of 880 molecularly classified ECs, 484 from PORTEC-1 and 396 from PORTEC-2, were included. The majority were FIGO-2009 stage I EEC (97.2%). The median follow-up was 11.3 years. No locoregional recurrences were observed in EC with a pathogenic mutation of DNA polymerase-ε (POLEmut EC). In mismatch repair-deficient (MMRd) EC, locoregional recurrence-free survival was similar after EBRT (94.2%), VBT (94.2%), and no adjuvant therapy (90.3%; P = .74). In EC with a p53 abnormality (p53abn EC), EBRT (96.9%) had a substantial benefit over VBT (64.3%) and no adjuvant therapy (72.2%; P = .048). In EC with no specific molecular profile (NSMP EC), both EBRT (98.3%) and VBT (96.2%) yielded better locoregional control than no adjuvant therapy (87.7%; P < .0001).ConclusionThe molecular classification of EC predicts response to radiotherapy in stage I EEC and may guide adjuvant treatment decisions. Omitting radiotherapy seems to be safe in POLEmut EC. The benefit of radiotherapy seems to be limited in MMRd EC. EBRT yields a significantly better locoregional recurrence-free survival than VBT or no adjuvant therapy in p53abn EC. VBT is the treatment of choice for NSMP EC as it is as effective as EBRT and significantly better than no adjuvant therapy for locoregional tumor control.
| S-EPMC10522107 | biostudies-literature
Project description:BackgroundEndometrial cancer is one of the most common gynecological cancer in the world. However, the available adjuvant therapies, chemotherapy (CT) and radiotherapy (RT), demonstrated several limitations when used alone. Therefore, we conducted a meta-analysis to investigate the clinical effectiveness of chemoradiotherapy (CRT) based on overall survival (OS) and disease-free survival (DFS).MethodsA literature search was performed on five databases and one clinical trial registry to obtain all relevant articles. Search for studies was completed on September 9, 2021. A meta-analysis was conducted to determine the overall hazard ratio with the 95% Confidence Interval.ResultsA total of 17 articles with 23,975 patients in the CRT vs RT group and 50,502 patients in the CRT vs CT group were included. The OS Hazard Ratios (HR) of CRT compared to RT was 0.66 (95% CI [0.59-0.75]; P < 0.00001). Compared to CT, the OS HR was 0.70 (95% CI [0.64-0.78]; P < 0.00001). CRT also significantly improved the DFS compared to CT only (HR 0.79, 95% CI [0.64-0.97]; P = 0.02) However, CRT did not improve the DFS compared to RT only, with HR of 0.71 (95% CI [0.46-1.09]; P = 0.12).ConclusionAdjuvant CRT can significantly improve OS compared to CT or RT alone and improve the DFS compared to CT alone in patients with advanced endometrial cancer. Further research is needed to identify the optimal CRT regimen, and to whom CRT will be most beneficial.
| S-EPMC9695495 | biostudies-literature
Project description:The purpose of this study was to compare the results of postoperative adjuvant radiotherapy (RT) and concurrent chemoradiotherapy (CRT) in stage I-II endometrial carcinoma.We analyzed a total of 64 patients with surgically staged I-II endometrial carcinoma who were treated with postoperative adjuvant RT or concurrent CRT between March 1999 and July 2013. Thirty-two patients who received postoperative RT alone were matched with those who received postoperative CRT (n=32) in accordance to age, stage, and tumor histology. Overall survival and relapse-free survival, as well as toxicity of the RT and CRT arms were evaluated and compared.The 5-year overall survival rate was 90.0% for the RT arm and 91.6% for the CRT arm. There was no significant difference in overall survival between the two treatment arms (p=0.798). The 5-year relapse-free survival rate was 87.2% in the RT arm and 88.0% in the CRT arm. Again, no significant difference in relapse-free survival was seen between the two arms (p=0.913). In a multivariate analysis, tumor histology was an independent prognostic factor for relapse-free survival (hazard ratio, 3.67; 95% of CI, 2.34 to 7.65; p=0.045). Acute grade 3 or 4 hematologic toxicities in the CRT arm were significantly higher than in the RT alone arm (6.2% vs. 31.2%, p=0.010).Adjuvant pelvic concurrent chemoradioherapy did not show superior results in overall survival and relapse-free survival compared to RT alone in stage I-II endometrial carcinoma.
| S-EPMC4398106 | biostudies-other
Project description: Not available
| S-EPMC6517188 | biostudies-literature
Project description:PurposeIn a post hoc analysis of the CATNON trial (NCT00626990), we explored whether adding temozolomide to radiotherapy improves outcome in patients with IDH1/2 wildtype (wt) anaplastic astrocytomas with molecular features of glioblastoma [redesignated as glioblastoma, isocitrate dehydrogenase-wildtype (IDH-wt) in the 2021 World Health Organization (WHO) classification of central nervous system tumors].Patients and methodsFrom the randomized phase III CATNON study examining the addition of adjuvant and concurrent temozolomide to radiotherapy in anaplastic astrocytomas, we selected a subgroup of IDH1/2wt and H3F3Awt tumors with presence of TERT promoter mutations and/or EGFR amplifications and/or combined gain of chromosome 7 and loss of chromosome 10. Molecular abnormalities including MGMT promoter methylation status were determined by next-generation sequencing, DNA methylation profiling, and SNaPshot analysis.ResultsOf the 751 patients entered in the CATNON study, 670 had fully molecularly characterized tumors. A total of 159 of these tumors met the WHO 2021 molecular criteria for glioblastoma, IDH-wt. Of these patients, 47 received radiotherapy only and 112 received a combination of radiotherapy and temozolomide. There was no added effect of temozolomide on either overall survival [HR, 1.19; 95% confidence interval (CI), 0.82-1.71] or progression-free survival (HR, 0.87; 95% CI, 0.61-1.24). MGMT promoter methylation was prognostic for overall survival, but was not predictive for outcome to temozolomide treatment either with respect to overall survival or progression-free survival.ConclusionsIn this cohort of patients with glioblastoma, IDH-wt temozolomide treatment did not add benefit beyond that observed from radiotherapy, regardless of MGMT promoter status. These findings require a new well-powered prospective clinical study to explore the efficacy of temozolomide treatment in this patient population.
| S-EPMC9297529 | biostudies-literature
Project description:BackgroundIt has become increasingly common to incorporate adjuvant chemotherapy with radiotherapy in the treatment of resected anaplastic astrocytoma based on results from recent phase II/III randomized trials. However, whether or not combined chemoradiotherapy is associated with improved survival outcome in patients who undergo "biopsy only" is less clear.MethodsThe US National Cancer Database was used to identify patients with histologically confirmed, biopsy-only anaplastic astrocytoma who received either radiotherapy alone or combined chemoradiotherapy from 2006 through 2014.ResultsIn total, 1896 patients with biopsy-only anaplastic astrocytoma were included, among whom 363 (19.1%) received radiotherapy alone and 1533 (80.9%) received combined chemoradiotherapy. The median age at diagnosis was 60 years. Combined chemoradiotherapy was associated with a significant survival benefit when compared with radiotherapy alone on univariable analysis (median, 13.2 versus 5.6 months; hazard ratio [HR], 0.57; 95% confidence interval [CI], 0.50-0.65; p < 0.001) and on multivariable analysis (HR, 0.62; 95% CI, 0.55-0.71; p < 0.001). A significant survival benefit for combined chemoradiotherapy persisted in a propensity score-matched analysis (HR, 0.67; 95% CI, 0.56-0.78; p<0.001).ConclusionsOur results suggest that combined chemoradiotherapy may be associated with significantly improved survival over radiotherapy alone in patients with anaplastic astrocytoma who undergo biopsy only.
| S-EPMC5620319 | biostudies-literature
Project description:BackgroundVaginal brachytherapy is currently recommended as adjuvant treatment in patients with high-intermediate risk endometrial cancer to maximize local control and has only mild side effects and no or limited impact on quality of life. However, there is still considerable overtreatment and also some undertreatment, which may be reduced by tailoring adjuvant treatment to the patients' risk of recurrence based on molecular tumor characteristics.Primary objectivesTo compare the rates of vaginal recurrence in women with high-intermediate risk endometrial cancer, treated after surgery with molecular-integrated risk profile-based recommendations for either observation, vaginal brachytherapy or external pelvic beam radiotherapy or with standard adjuvant vaginal brachytherapy STUDY HYPOTHESIS: Adjuvant treatment based on a molecular-integrated risk profile provides similar local control and recurrence-free survival as current standard adjuvant brachytherapy in patients with high-intermediate risk endometrial cancer, while sparing many patients the morbidity of adjuvant treatment and reducing healthcare costs.Trial designA multicenter, international phase III randomized trial (2:1) of molecular-integrated risk profile-based adjuvant treatment (experimental arm) or adjuvant vaginal brachytherapy (standard arm).Major inclusion/exclusion criteriaWomen aged 18 years and over with a histological diagnosis of high-intermediate risk endometrioid endometrial cancer after total abdominal or laparoscopic hysterectomy and bilateral salpingo-oophorectomy. High-intermediate risk factors are defined as: (i) International Federation of Gynecology and Obstetrics stage IA (with invasion) and grade 3; (ii) stage IB grade 1 or 2 with age ?60 and/or lymph-vascular space invasion; (iii) stage IB, grade 3 without lymph-vascular space invasion; or (iv) stage II (microscopic and grade 1).EndpointsThe primary endpoint is vaginal recurrence. Secondary endpoints are recurrence-free and overall survival; pelvic and distant recurrence; 5-year vaginal control (including treatment for relapse); adverse events and patient-reported symptoms and quality of life; and endometrial cancer-related healthcare costs.Sample size500 eligible and evaluable patients.Estimated dates for completing accrual and presenting resultsEstimated date for completing accrual will be late 2021. Estimated date for presentation of (first) results is expected in 2023.Trial registrationThe trial is registered at clinicaltrials.gov (NCT03469674) and ISRCTN (11659025).
| S-EPMC7788476 | biostudies-literature