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Abstract Background The aim of this study was to analyze the distant metastases-free survival (DMFS), and disease-specific survival (DSS) after breast-conserving therapy (BCT) in older patients with breast cancer in a large, population-based, single-center cohort study with long-term follow-up. Material and Methods Analyses were based on 1,425 women aged 65 years and older with breast cancer treated with BCT. Patients were divided in three age categories: 65 – 70 years, 71 – 75 years, and >75 years. The study period extended over 30 years, divided in three decades. Multivariate survival analysis was carried out using Cox regression analysis. Results The two youngest age categories showed significant improvements over time in 12-year DMFS and DSS. For women aged 65 – 70 years, this improvement was noted in stage I and stage II disease, while for women aged 71 – 75 years this was mainly in stage II tumors. Women >75 years of age did not show any improvement over time, regardless of stage. Conclusion Among older Dutch women with breast cancer, outcomes with regard to DMFS and DSS after BCT differ between various age categories, showing the least gain in the very old. [ABSTRACT FROM AUTHOR]

Abstract Objective The aim of this study was to analyse the efficacy of breast-conserving therapy (BCT) for women with primary DCIS in a population-based setting. Methods Data were used from five Radiotherapy centres in The Netherlands from 2000 to 2010, all treated with BCT. Of all the cases, 59.2% received a boost of radiotherapy after their whole breast irradiation (WBI), irrespective of margin status. Results A total of 1248 cases with primary DCIS were analysed. The 10-years LRFS was 92.9%. Age ≤50 years and a positive margin were significantly related to local relapse free survival (LRFS). Having a boost had no impact on LRFS, showing a nearly equal recurrence pattern in patients with and without a boost. Separate analyses were done on patients who had received and not received a boost of radiotherapy after WBI. We noted 9.1% contra-lateral breast tumours. The 10-years disease specific survival (DSS) rate was 99.0%. Conclusions DCIS of the breast and treated with BCT results in excellent LRFS and DSS. Primary surgical lumpectomy with negative margins followed by WBI seems to be the treatment of choice in DCIS treated with BCS with respect to IBTR. [ABSTRACT FROM AUTHOR]

Purpose: To determine the effects of boost volume (BV) in relation to margin status and tumor size on the development of local recurrence with breast-conserving therapy. Methods and Materials: Between 1983 and 1995, 1,073 patients with invasive breast cancer underwent 1,101 breast-conserving therapies. Of these 1,101 BCTs, 967 were eligible for analysis. The BV was categorized into tertiles: <66 cm3 (n = 330), 66–98 cm3 (n = 326), and >98 cm3 (n = 311). The median follow-up was 141 months. Separate analyses were done for women ≤40 years and >40 years. Results: No significant difference in local recurrence was shown between the tertiles and the recurrence site. The 15-year local recurrence-free survival rate was 87.9% for the first tertile, 88.7% for the second, and 89% for the third. For women ≤40 years old, the corresponding 15-year local recurrence-free survival rate was 80%, 74.5%, and 69.2%. For women >40 years old, the corresponding rate was 88.7%, 89.5%, and 90.9%. At 5 years, women >40 years old had significantly more local failures in the first tertile; this difference disappeared with time. A test for trend showed significance at 5 years (p = 0.0105) for positive margins for ductal carcinoma in situ in women >40 years of age. Conclusion: The results of this study have shown that the size of the external BV has no major impact on local control. For women >40 years old, positive margins for ductal carcinoma in situ showed a trend with respect to BV at 5 years. The BV had no influence on local control in the case of positive margins for invasive carcinoma. [Copyright &y& Elsevier]

: PurposeTo identify the importance of positive margins for invasive carcinoma on local control in patients treated with breast-conservative treatment (BCT).: Methods and materialsA total of 1752 BCT with known margins were analyzed. Fifty-five patients had a second BCT, leaving 1697 patients for analysis. The margins were positive in 193/1752 BCT (11%). The median follow-up was 78 months.: ResultsThe 5- and 10-year local recurrence rates (LRR) were 3.1% and 6.9%, respectively, for negative margins vs. 5.6% and 12.2% for positive margins. A statistical interaction between age category and margin status was noted in relation to disease-free survival (DFS) and local relapse-free survival. The 5-year LRR for women ≤40 years was 8.4% for negative margins and 36.9% for positive margins (p = 0.005). In a multivariate analysis, a positive margin was significant. The 5-year LRR for women >40 years was 2.6% for negative and 2.2% for positive margins. The 5-year DFS for women ≤40 years was 27.4% for positive and 74.5% for negative margins (p = 0.001). The 5-year DFS for women >40 years was 84.3% for positive and 87.2% for negative margins.: ConclusionWomen ≤40 years are a special category of patients in breast cancer. Women ≤40 years must have negative margins for invasive carcinoma when treated with BCT. Minimum surgery for an optimal cosmetic result followed by irradiation, even with microscopic positive margins for invasive carcinoma, yields excellent results with regard to local control in patients older than 40 years. [Copyright &y& Elsevier]

Numerous studies have shown that older women with endometrial cancer have a higher risk of recurrence and cancer-related death. However, it remains unclear whether older age is a causal prognostic factor, or whether other risk factors become increasingly common with age. We aimed to address this question with a unique multimethod study design using state-of-the-art statistical and causal inference techniques on datasets of three large, randomised trials. In this multimethod analysis, data from 1801 women participating in the randomised PORTEC-1, PORTEC-2, and PORTEC-3 trials were used for statistical analyses and causal inference. The cohort included 714 patients with intermediate-risk endometrial cancer, 427 patients with high-intermediate risk endometrial cancer, and 660 patients with high-risk endometrial cancer. Associations of age with clinicopathological and molecular features were analysed using non-parametric tests. Multivariable competing risk analyses were performed to determine the independent prognostic value of age. To analyse age as a causal prognostic variable, a deep learning causal inference model called AutoCI was used. Median follow-up as estimated using the reversed Kaplan-Meier method was 12·3 years (95% CI 11·9–12·6) for PORTEC-1, 10·5 years (10·2–10·7) for PORTEC-2, and 6·1 years (5·9–6·3) for PORTEC-3. Both overall recurrence and endometrial cancer-specific death significantly increased with age. Moreover, older women had a higher frequency of deep myometrial invasion, serous tumour histology, and p53-abnormal tumours. Age was an independent risk factor for both overall recurrence (hazard ratio [HR] 1·02 per year, 95% CI 1·01–1·04; p=0·0012) and endometrial cancer-specific death (HR 1·03 per year, 1·01–1·05; p=0·0012) and was identified as a significant causal variable. This study showed that advanced age was associated with more aggressive tumour features in women with endometrial cancer, and was independently and causally related to worse oncological outcomes. Therefore, our findings suggest that older women with endometrial cancer should not be excluded from diagnostic assessments, molecular testing, and adjuvant therapy based on their age alone. None. [ABSTRACT FROM AUTHOR]

Purpose: The optimal sequence of radiotherapy and chemotherapy in breast-conserving therapy is unknown. Methods and Materials: From 1983 through 2007, a total of 641 patients with 653 instances of breast-conserving therapy (BCT), received both chemotherapy and radiotherapy and are the basis of this analysis. Patients were divided into three groups. Groups A and B comprised patients treated before 2005, Group A radiotherapy first and Group B chemotherapy first. Group C consisted of patients treated from 2005 onward, when we had a fixed sequence of radiotherapy first, followed by chemotherapy. Results: Local control did not show any differences among the three groups. For distant metastasis, no difference was shown between Groups A and B. Group C, when compared with Group A, showed, on univariate and multivariate analyses, a significantly better distant metastasis–free survival. The same was noted for disease-free survival. With respect to disease-specific survival, no differences were shown on multivariate analysis among the three groups. Conclusion: Radiotherapy, as an integral part of the primary treatment of BCT, should be administered first, followed by adjuvant chemotherapy. [ABSTRACT FROM AUTHOR]

Background Chemoradiation (RT-CT) is standard treatment for locally advanced cervical cancer (LACC). This study tried to establish if radiotherapy combined with hyperthermia (RT-HT) should be preferred in bulky and/or FIGO-stage ⩾III. Methods In this open-label, multicenter randomized trial, patients with LACC were randomly assigned by a computer-generated, biased coin minimization technique to RT-CT or RT-HT. Central randomization was done with stratification by FIGO-stage, tumour diameter and nodal status. Primary endpoint was event free survival (EFS). Secondary endpoints were pelvic recurrence free survival (PRFS), overall survival (OS) and treatment related toxicity. Analysis was done by intention to treat. Results The trial was closed prematurely (87 of 376 planned patients enrolled: 43 RT-CT; 44 RT-HT). Median follow-up time was 7.1 years. The cumulative incidence of an event was 33% in the RT-CT group and 35% in the RT-HT group. The corresponding hazard rate (HR) for EFS was 1.15 (CI: 0.56–2.36, p = 0.7). Also the hazards for PRFS (0.94; CI 0.36–2.44) and OS (1.04; CI 0.48–2.23) at 5 years were comparable between both treatment arms as was grade ⩾3 radiation related late toxicity (6 RT-CT and 5 RT-HT patients). Conclusion After 25% of intended accrual, data suggest comparable outcome for RT-CT and RT-HT. [ABSTRACT FROM AUTHOR]

Abstract: Only scarce data are available on the utilisation rate of primary radiotherapy (RT) for patients with breast cancer. In this study, we compared the use of primary RT for patients with stages I–III breast cancer in 4 of the 9 Dutch Comprehensive Cancer Centres, focussing specifically on time trends as well as age effects. From the population-based cancer registries, we selected all females diagnosed with breast cancer between 1997 and 2008 (N =65,966, about 50% of all Dutch breast cancer patients in this period). We observed an overall increase in the use of primary RT for breast cancer patients ranging from 55–61% in 1997 to 58–68% in 2008. This can be explained by a higher rate of breast-conserving surgery (BCS), which was followed by RT in 87–99% of cases, and a reduced rate of total mastectomy (TM) which was followed by RT in 26–47% of cases. Increasing age was associated with a reduced use of RT, especially for those above 75. Finally, we observed a decrease in time of observed regional variances in the use of RT after BCS as well as after TM (for stage III disease). These findings can be attributed to the development and implementation of the Dutch nationwide guidelines for treatment of breast cancer. [Copyright &y& Elsevier]

Purpose: To investigate whether the Geriatric 8 (G8) and the Timed Get Up and Go Test (TGUGT) and clinical and demographic patient characteristics were associated with acute toxicity of radiation therapy and noncompliance in elderly cancer patients being irradiated with curative intent.Methods and Materials: Patients were eligible if aged ≥65 years and diagnosed with breast, non-small cell lung, prostate, head and neck, rectal, or esophageal cancer, and were referred for curative radiation therapy. We recorded acute toxicity and noncompliance and identified potential predictors, including the G8 and TGUGT.Results: We investigated 402 patients with a median age of 72 years (range, 65-96 years). According to the G8, 44.4% of the patients were frail. Toxicity grade ≥3 was observed in 22% of patients who were frail according to the G8 and 9.1% of patients who were not frail. The difference was 13% (confidence interval 5.2%-20%; P=.0006). According to the TGUGT 18.8% of the patients were frail; 21% of the frail according to the TGUGT developed toxicity grade ≥3, compared with 13% who were not frail. The difference was 7.3% (confidence interval -2.7% to 17%; P=.11). Overall compliance was 95%. Toxicity was most strongly associated with type of primary tumor, chemotherapy, age, and World Health Organization performance status. Compliance was associated with type of primary tumor and age.Conclusions: The usefulness of the TGUGT and G8 score in daily practice seems to be limited. Type of primary tumor, chemoradiotherapy, age, and World Health Organization performance status were more strongly associated with acute toxicity. Only chemoradiotherapy and age were associated with noncompliance. Overall the compliance was very high. To allow better-informed treatment decisions, a more accurate prediction of toxicity is desirable. [ABSTRACT FROM AUTHOR]

Purpose: To study the course of quality of life (QoL) after radiation therapy for painful bone metastases.Patients and Methods: The Dutch Bone Metastasis Study randomized 1157 patients with painful bone metastases between a single fraction of 8 Gy and 6 fractions of 4 Gy between 1996 and 1998. The study showed a comparable pain response of 74%. Patients filled out weekly questionnaires for 13 weeks, then monthly for 2 years. In these analyses, physical, psychosocial, and functional QoL domain scores and a score of general health were studied. Mixed modeling was used to model the course of QoL and to study the influence of several characteristics.Results: In general, QoL stabilized after 1 month. Psychosocial QoL improved after treatment. The level of QoL remained stable, steeply deteriorating at the end of life. For most QoL domains, a high pain score and intake of opioids were associated with worse QoL, with small effect sizes (-0.11 to -0.27). A poor performance score was associated with worse functional QoL, with a medium effect size (0.41). There is no difference in QoL between patients receiving a single fraction of 8 Gy and 6 fractions of 4 Gy, except for a temporary worsening of physical QoL after 6 fractions.Conclusion: Although radiation therapy for painful bone metastases leads to a meaningful pain response, most domains of QoL do not improve after treatment. Only psychosocial QoL improves slightly after treatment. The level of QoL is related to the actual survival, with a rather stable course of QoL for most of the remaining survival time and afterward a sharp decrease, starting only a few weeks before the end of life. Six fractions of 4 Gy lead to a temporary worse physical QoL compared with a single fraction of 8 Gy. [ABSTRACT FROM AUTHOR]

Background: Investigators of registry-based studies report improved survival for breast-conserving surgery plus radiotherapy compared with mastectomy in early breast cancer. As these studies did not present long-term overall and breast cancer-specific survival, the effect of breast-conserving surgery plus radiotherapy might be overestimated. In this study, we aimed to evaluate 10 year overall and breast cancer-specific survival after breast-conserving surgery plus radiotherapy compared with mastectomy in Dutch women with early breast cancer.Methods: In this population-based study, we selected all women from the Netherlands Cancer Registry diagnosed with primary, invasive, stage T1-2, N0-1, M0 breast cancer between Jan 1, 2000, and Dec 31, 2004, given either breast-conserving surgery plus radiotherapy or mastectomy, irrespective of axillary staging or dissection or use of adjuvant systemic therapy. Primary outcomes were 10 year overall survival in the entire cohort and breast cancer-specific survival in a representative subcohort of patients diagnosed in 2003 with characteristics similar to the entire cohort. We estimated breast cancer-specific survival by calculating distant metastasis-free and relative survival for every tumour and nodal category. We did multivariable Cox proportional hazard analysis to estimate hazard ratios (HRs) for overall and distant metastasis-free survival. We estimated relative survival by calculating excess mortality ratios using life tables of the general population. We did multiple imputation to account for missing data.Findings: Of the 37 207 patients included in this study, 21 734 (58%) received breast-conserving surgery plus radiotherapy and 15 473 (42%) received mastectomy. The 2003 representative subcohort consisted of 7552 (20%) patients, of whom 4647 (62%) received breast-conserving surgery plus radiotherapy and 2905 (38%) received mastectomy. For both unadjusted and adjusted analysis accounting for various confounding factors, breast-conserving surgery plus radiotherapy was significantly associated with improved 10 year overall survival in the whole cohort overall compared with mastectomy (HR 0·51 [95% CI 0·49-0·53]; p<0·0001; adjusted HR 0·81 [0·78-0·85]; p<0·0001), and this improvement remained significant for all subgroups of different T and N stages of breast cancer. After adjustment for confounding variables, breast-conserving surgery plus radiotherapy did not significantly improve 10 year distant metastasis-free survival in the 2003 cohort overall compared with mastectomy (adjusted HR 0·88 [0·77-1·01]; p=0·07), but did in the T1N0 subgroup (adjusted 0·74 [0·58-0·94]; p=0·014). Breast-conserving surgery plus radiotherapy did significantly improve 10 year relative survival in the 2003 cohort overall (adjusted 0·76 [0·64-0·91]; p=0·003) and in the T1N0 subgroup (adjusted 0·60 [0·42-0·85]; p=0·004) compared with mastectomy.Interpretation: Adjusting for confounding variables, breast-conserving surgery plus radiotherapy showed improved 10 year overall and relative survival compared with mastectomy in early breast cancer, but 10 year distant metastasis-free survival was improved with breast-conserving surgery plus radiotherapy compared with mastectomy in the T1N0 subgroup only, indicating a possible role of confounding by severity. These results suggest that breast-conserving surgery plus radiotherapy is at least equivalent to mastectomy with respect to overall survival and may influence treatment decision making for patients with early breast cancer.Funding: None. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the long-term health-related quality of life (HRQL) after external beam radiation therapy (EBRT) or vaginal brachytherapy (VBT) among PORTEC-2 trial patients, evaluate long-term bowel and bladder symptoms, and assess the impact of cancer on these endometrial cancer (EC) survivors. Patients and Methods: In the PORTEC-2 trial, 427 patients with stage I high-intermediate-risk EC were randomly allocated to EBRT or VBT. The 7- and 10-year HRQL questionnaires consisted of EORTC QLQ-C30; subscales for bowel and bladder symptoms; the Impact of Cancer Questionnaire; and 14 questions on comorbidities, walking aids, and incontinence pads. Analysis was done using linear mixed models for subscales and (ordinal) logistic regression with random effects for single items. A two-sided P value <.01 was considered statistically significant. Results: Longitudinal HRQL analysis showed persisting higher rates of bowel symptoms with EBRT, without significant differences in global health or any of the functioning scales. At 7 years, clinically relevant fecal leakage was reported by 10.6% in the EBRT group, versus 1.8% for VBT (P=.03), diarrhea by 8.4% versus 0.9% (P=.04), limitations due to bowel symptoms by 10.5% versus 1.8% (P=.001), and bowel urgency by 23.3% versus 6.6% (P<.001). Urinary urgency was reported by 39.3% of EBRT patients, 25.5% for VBT, P=.05. No difference in sexual activity was seen between treatment arms. Long-term impact of cancer scores was higher among the patients who had an EC recurrence or second cancer. Conclusions: More than 7 years after treatment, EBRT patients reported more bowel symptoms with impact on daily activities, and a trend for more urinary symptoms, without impact on overall quality of life or difference in cancer survivorship issues. [ABSTRACT FROM AUTHOR]

Background Lymph-vascular space invasion (LVSI) is an important adverse prognostic factor in endometrial cancer (EC). However, its role in relation to type of recurrence and adjuvant treatment is not well defined, and there is significant interobserver variation. This study aimed to quantify LVSI and correlate this to risk and type of recurrence. Methods In the post operative radiation therapy in endometrial carcinoma (PORTEC)-trials stage I EC patients were randomised to receive external beam radiotherapy (EBRT) versus no additional treatment after surgery (PORTEC-1, n = 714), or to EBRT versus vaginal brachytherapy (PORTEC-2, n = 427). In tumour samples of 926 (81.2%) patients with endometrioid tumours LVSI was quantified using 2-, 3- and 4-tiered scoring systems. Cox proportional hazard models were used for time-to-event analysis. Results Any degree of LVSI was identified in 129 cases (13.9%). Substantial LVSI ( n = 44, 4.8%) using the 3-tiered approach had the strongest impact on the risk of distant metastasis (hazard ratio (HR) 4.5 confidence interval (CI) 2.4–8.5). In multivariate analysis (including: age, depth of myometrial invasion, grade, treatment) substantial LVSI remained the strongest independent prognostic factor for pelvic regional recurrence (HR 6.2 CI 2.4–16), distant metastasis (HR 3.6 CI 1.9–6.8) and overall survival (HR 2.0 CI 1.3–3.1). Only EBRT (HR 0.3 CI 0.1–0.8) reduced the risk of pelvic regional recurrence. Conclusions Substantial LVSI, in contrast to focal or no LVSI, was the strongest independent prognostic factor for pelvic regional recurrence, distant metastasis and overall survival. Therapeutic decisions should be based on the presence of substantial, not ‘any’ LVSI. Adjuvant EBRT and/or chemotherapy should be considered for stage I EC with substantial LVSI. [ABSTRACT FROM AUTHOR]

Background Postoperative radiation therapy for stage I endometrial cancer improves locoregional control but is without survival benefit. To facilitate treatment decision support for individual patients, accurate statistical models to predict locoregional relapse (LRR), distant relapse (DR), overall survival (OS), and disease-free survival (DFS) are required. Methods and Materials Clinical trial data from the randomized Post Operative Radiation Therapy for Endometrial Cancer (PORTEC-1; N=714 patients) and PORTEC-2 (N=427 patients) trials and registered group (grade 3 and deep invasion, n=99) were pooled for analysis (N=1240). For most patients (86%) pathology review data were available; otherwise original pathology data were used. Trial variables which were clinically relevant and eligible according to data constraints were age, stage, given treatment (pelvic external beam radiation therapy (EBRT), vaginal brachytherapy (VBT), or no adjuvant treatment, FIGO histological grade, depth of invasion, and lymph-vascular invasion (LVSI). Multivariate analyses were based on Cox proportional hazards regression model. Predictors were selected based on a backward elimination scheme. Model results were expressed by the c-index (0.5-1.0; random to perfect prediction). Two validation sets (n=244 and 291 patients) were used. Results Accuracy of the developed models was good, with training accuracies between 0.71 and 0.78. The nomograms validated well for DR (0.73), DFS (0.69), and OS (0.70), but validation was only fair for LRR (0.59). Ranking of variables as to their predictive power showed that age, tumor grade, and LVSI were highly predictive for all outcomes, and given treatment for LRR and DFS. The nomograms were able to significantly distinguish low- from high-probability patients for these outcomes. Conclusions The nomograms are internally validated and able to accurately predict long-term outcome for endometrial cancer patients with observation, pelvic EBRT, or VBT after surgery. These models facilitate decision support in daily clinical practice and can be used for patient counseling and shared decision making, selecting patients who benefit most from adjuvant treatment, and generating new hypotheses. [ABSTRACT FROM AUTHOR]

Abstract: Background: The PORTEC-2 trial showed efficacy and reduced side-effects of vaginal brachytherapy (VBT) compared with external beam pelvic radiotherapy (EBRT) for patients with high-intermediate risk endometrial cancer. The current analysis was done to evaluate long-term health related quality of life (HRQL), and compare HRQL of patients to an age-matched norm population. Methods: Patients were randomly allocated to EBRT (n =214) or VBT (n =213). HRQL was assessed using EORTC QLQ-C30 and subscales from PR25 and OV28 (bladder, bowel, sexual symptoms); and compared to norm data. Findings: Median follow-up was 65 months; 348 (81%) patients were evaluable for HRQL (EBRT n =166, VBT n =182). At baseline, patient functioning was at lowest level, increasing during and after radiotherapy to reach a plateau after 12 months, within range of scores of the norm population. VBT patients reported better social functioning (p =0.005) and lower symptom scores for diarrhoea, faecal leakage, need to stay close to a toilet and limitation in daily activities due to bowel symptoms (p ⩽0.001), compared to EBRT. There were no differences in sexual functioning or symptoms between the treatment groups; however, sexual functioning was lower and sexual symptoms more frequent in both treatment groups compared to the norm population. Interpretation: Patients who received EBRT reported clinically relevant higher levels of bowel symptoms and related limitations in daily activities with lower social functioning, 5 years after treatment. VBT provides a better HRQL, which remained similar to that of an age-matched norm population, except for sexual symptoms which were more frequent in both treatment groups. [Copyright &y& Elsevier]

Purpose: To report response rate, pelvic tumor control, survival, and late toxicity after treatment with combined radiotherapy and hyperthermia (RHT) for patients with locally advanced cervical carcinoma (LACC) and compare the results with other published series. Methods and Materials: From 1996 to 2005, a total of 378 patients with LACC (International Federation of Gynecology and Obstetrics Stage IB2–IVA) were treated with RHT. External beam radiotherapy (RT) was applied to 46–50.4 Gy and combined with brachytherapy. The hyperthermia (HT) was prescribed once weekly. Primary end points were complete response (CR) and local control. Secondary end points were overall survival, disease-specific survival, and late toxicity. Patient, tumor, and treatment characteristics predictive for the end points were identified in univariate and multivariate analyses. Results: Overall, a CR was achieved in 77% of patients. At 5 years, local control, disease-specific survival, and incidence of late toxicity Common Terminology Criteria for Adverse Events Grade 3 or higher were 53%, 47%, and 12%, respectively. In multivariate analysis, number of HT treatments emerged as a predictor of outcome in addition to commonly identified prognostic factors. Conclusions: The CR, local control, and survival rates are similar to previously observed results of RHT in the randomized Dutch Deep Hyperthermia Trial. Reported treatment results for currently applied combined treatment modalities (i.e., RT with chemotherapy and/or HT) do not permit definite conclusions about which combination is superior. The present results confirm previously shown beneficial effects from adding HT to RT and justify the application of RHT as first-line treatment in patients with LACC as an alternative to chemoradiation. [Copyright &y& Elsevier]

Purpose: The local failure rate in patients with locoregionally advanced cervical cancer is 41–72% after radiotherapy (RT) alone, whereas local control is a prerequisite for cure. The Dutch Deep Hyperthermia Trial showed that combining RT with hyperthermia (HT) improved 3-year local control rates of 41–61%, as we reported earlier. In this study, we evaluate long-term results of the Dutch Deep Hyperthermia Trial after 12 years of follow-up. Methods and Materials: From 1990 to 1996, a total of 114 women with locoregionally advanced cervical carcinoma were randomly assigned to RT or RT + HT. The RT was applied to a median total dose of 68 Gy. The HT was given once weekly. The primary end point was local control. Secondary end points were overall survival and late toxicity. Results: At the 12-year follow-up, local control remained better in the RT + HT group (37% vs. 56%; p = 0.01). Survival was persistently better after 12 years: 20% (RT) and 37% (RT + HT; p = 0.03). World Health Organization (WHO) performance status was a significant prognostic factor for local control. The WHO performance status, International Federation of Gynaecology and Obstetrics (FIGO) stage, and tumor diameter were significant for survival. The benefit of HT remained significant after correction for these factors. European Organization for Research and Treatment of Cancer Grade 3 or higher radiation-induced late toxicities were similar in both groups. Conclusions: For locoregionally advanced cervical cancer, the addition of HT to RT resulted in long-term major improvement in local control and survival without increasing late toxicity. This combined treatment should be considered for patients who are unfit to receive chemotherapy. For other patients, the optimal treatment strategy is the subject of ongoing research. [Copyright &y& Elsevier]

Purpose: In 2000, the results of the multicenter Post Operative Radiation Therapy in Endometrial Carcinoma (PORTEC) trial were published. This trial included 714 Stage I endometrial carcinoma patients randomly assigned to postoperative pelvic radiotherapy (RT) or no further treatment, excluding those with Stage IC, Grade 3, or Stage IB, Grade 1 lesions. Radiotherapy significantly decreased the risk of locoregional recurrence (4% vs. 14%), without affecting overall survival. In this report the long-term outcome and results with central pathology review are presented. Methods and Materials: The slides of 569 patients (80%) could be obtained for pathology review. Median follow-up for patients alive was 97 months. Analysis was done according to the intention-to-treat principle. The primary study endpoints were locoregional recurrence and death. Results: Ten-year locoregional relapse rates were 5% (RT) and 14% (controls; p < 0.0001), and 10-year overall survival was 66% and 73%, respectively (p = 0.09). Endometrial cancer related death rates were 11% (RT) and 9% (controls; p = 0.47). Pathology review showed a substantial shift from Grade 2 to Grade 1, but no significant difference for Grade 3. When cases diagnosed at review as Grade 1 with superficial myometrial invasion were excluded from the analysis, the results remained essentially the same, with 10-year locoregional recurrence rates of 5% (RT) and 17% (controls; p < 0.0001). Conclusions: In view of the significant locoregional control benefit, radiotherapy remains indicated in Stage I endometrial carcinoma patients with high-risk features for locoregional relapse. [Copyright &y& Elsevier]

Purpose: To evaluate the very long-term results of the randomized Post Operative Radiation Therapy in Endometrial Carcinoma (PORTEC)-1 trial for patients with Stage I endometrial carcinoma (EC), focusing on the role of prognostic factors for treatment selection and the long-term risk of second cancers. Patients and Methods: The PORTEC trial (1990–1997) included 714 patients with Stage IC Grade 1–2 or Stage IB Grade 2–3 EC. After surgery, patients were randomly allocated to external-beam pelvic radiotherapy (EBRT) or no additional treatment (NAT). Analysis was by intention to treat. Results: 426 patients were alive at the date of analysis. The median follow-up time was 13.3 years. The 15-year actuarial locoregional recurrence (LRR) rates were 6% for EBRT vs. 15.5% for NAT (p < 0.0001). The 15-year overall survival was 52% vs. 60% (p = 0.14), and the failure-free survival was 50% vs. 54% (p = 0.94). For patients with high-intermediate risk criteria, the 15-year overall survival was 41% vs. 48% (p = 0.51), and the 15-year EC-related death was 14% vs. 13%. Most LRR in the NAT group were vaginal recurrences (11.0% of 15.5%). The 15-year rates of distant metastases were 9% vs. 7% (p = 0.25). Second primary cancers had been diagnosed over 15 years in 19% of all patients, 22% vs. 16% for EBRT vs. NAT (p = 0.10), with observed vs. expected ratios of 1.6 (EBRT) and 1.2 (NAT) compared with a matched population (p = NS). Multivariate analysis confirmed the prognostic significance of Grade 3 for LRR (hazard ratio [HR] 3.4, p = 0.0003) and for EC death (HR 7.3, p < 0.0001), of age >60 (HR 3.9, p = 0.002 for LRR and 2.7, p = 0.01 for EC death) and myometrial invasion >50% (HR 1.9, p = 0.03 and HR 1.9, p = 0.02). Conclusions: The 15-year outcomes of PORTEC-1 confirm the relevance of HIR criteria for treatment selection, and a trend for long-term risk of second cancers. EBRT should be avoided in patients with low- and intermediate-risk EC. [ABSTRACT FROM AUTHOR]