Vaginal dilator use more than 9 months is a main prognostic factor for reducing G2­late vaginal complications in 3D­vaginal­cuff brachytherapy (interventional radiotherapy)?

PURPOSE: Analyse the impact of different prognostic factors on G2-late vaginal complications after vaginal brachytherapy (VBT) ± external beam radiotherapy (EBRT) in postoperative endometrial cancer (PEC). METHODS: One hundred and twenty-six PEC patients treated with VBT ± EBRT were retrospectively analysed considering age, body mass index, applicator diameter, clinical target volume (CTV), use of dilators, chemotherapy and EQD2(α/ß=3) at the most exposed 2 cm3 of the CTV as prognostic factors for vaginal complications. Late vaginal complications were evaluated using objective LENT-SOMA criteria. STATISTICS: descriptive analysis, Chi-square, Fisher and Student tests were applied. Univariate and multivariate analyses were performed with the Baptista-Pike exact method and multiple logistic regression. RESULTS: Mean age was 65 years (SD ± 10), and median follow-up was 66 months (8-104). 19/126 patients (15%) showed G2-late vaginal complications, and 107/126 (85%) G0-G1. Univariate analysis showed: CTV ≤ 9 cm3 (p = 0.036), use of dilators < 9 months (p = 0.015), and total ≥ 68 Gy EQD2 received by 2 cm3 of CTV (p = 0.039) were associated with G2-late vaginal toxicity. Multivariate analysis showed the use of dilators < 9 months as an independent prognostic factor for G2-late vaginal toxicity (p = 0.043, OR 8.59, CI 1.59-159.9). CONCLUSION: The use of dilators < 9 months in VBT ± EBRT for PEC was an independent prognostic factor for G2-late vaginal toxicity. The use of vaginal dilators ≥ 9 months requires further analysis in studies evaluating late vaginal toxicity.

Exclusive 3D-brachytherapy as a good option for stage-I inoperable endometrial cancer: a retrospective analysis in the gynaecological cancer GEC-ESTRO Working Group.

PURPOSE: Analyse outcomes of stage-I inoperable endometrial cancer (EC) patients from seven European centres treated with 3D-image-guided brachytherapy (IGBT) alone. MATERIALS AND METHODS: From 2004 to 2018, 62 patients (41 stage-IA and 21 IB) were retrospectively studied, analysing anaesthetic procedure, applicator type, BT-planning imaging, clinical target volume (CTV), BT schedule, overall daily-dose equivalent to 2 Gy (EQD2(α/ß=4.5 or 3)) to the CTV(α/ß=4.5) and D2 cm3(α/ß=3) for organs at risk. Complications were evaluated using CTCAEv4 scores. The 2 and 5 year survival was calculated [cancer-specific survival (CSS), disease-free survival (DFS), local relapse-free survival (LRFS), loco-regional relapse-free survival (LRRFS) and distant metastasis-free survival (DMFS)]. Descriptive analysis and the Kaplan-Meier method were used for survival analysis. RESULTS: Mean follow-up: 32.8 months (SD 33.7). Spinal anaesthesia (38/62) followed by none (16/62) were the most common. Y-shaped Rotte applicators were used in 74% of patients. High-dose rate brachytherapy was administered in 89%. Median D90 to the CTV was 58.9 Gy (8.66-144 Gy). Eight patients presented relapse: four uterine, four nodal and four distant. The 2 and 5 year CSS was 93.3 and 80.5%, DFS 84.8 and 80.5%, LRFS was 93.1 and 88.7%, LRRFS was 91 and 91% and DMFS was 90.2 and 90.2%, respectively, CSS was better in stage-IA vs. IB (p = 0.043). Late vaginal and bladder G3-complication rates were 2.1%, respectively. CONCLUSION: Inoperable EC patients can be safely treated by BT with 2 and 5 year CSS of 93 and 80.5%, respectively, with even better results for IA cases. Prospective studies on 3D-IGBT are necessary to better analyse EC patient outcomes based on dose and treated volumes.

Analgesic effects of low-dose radiotherapy in greater trochanteric pain syndrome: results in a clinical series of 155 patients with recurrent or refractory symptoms.

PURPOSE: This prospective study assessed the effects of low-dose radiotherapy in patients diagnosed with greater trochanteric pain syndrome (GTPS) with recurrent symptoms or refractory to previous conservative measures. METHODS: We evaluated a total of 155 patients (90.3% women, mean age 69 years). Most patients (n = 136) received 10 Gy (1 Gy/day/3 fractions per week on alternate days), but after recommendations of DEGRO guidelines published in 2015, the remaining 19 patients (12.2%) received 6 Gy (1 Gy/day/3 fractions per week on alternate days). RESULTS: At the pre-treatment visit, the mean (standard deviation, SD) visual analog scale (VAS) score was 8), which decreased to 5 (SD 2.2) after 1 month of the end of treatment and to 4 (SD 2.3) after 4 months. An objective symptom response with increased mobility, better sleep quality, and reduction of analgesic medication was found in 56% of patients at 1 month. In 129 patients (83.2%), there was a decrease of at least 1 point in the VAS score, and in 49 patients (29.0%), the VAS score was lower than 3. The mean length of follow-up was 45 months. The probability of maintaining the analgesic response estimated by the Kaplan-Meier method was 53% at 5 years. CONCLUSION: Low dose radiotherapy effectively improved pain in the trochanteric area in most patients with recurrent or refractory GTPS, allowing a reduction in the need for analgesic medications and, more, importantly, better functioning and mobility. Further randomized studies in selected populations of GTPS are needed to define the treatment position of low-dose radiotherapy in this clinical setting.

Daily schedule for high-dose-rate brachytherapy in postoperative treatment of endometrial carcinoma.

PURPOSE: To analyze the results of daily high-dose-rate brachytherapy (HDRBT) on local control and toxicity in the postoperative treatment of endometrial carcinoma (EC). MATERIALS AND METHODS: From January 2007 to September 2010, 112 patients were treated with HDRBT after surgery for EC. FIGO staging: 24-IA, 48-IB, 14-II, 12-IIIA, 2-IIIB, 8-IIIC1 and 4-IIIC2. Pathology 99/112 endometrioid and 23/112 other types. Radiotherapy patients were divided into two groups-Group 1 (70/112) consists of external beam irradiation (EBI) plus HDRBT (2 fractions of 5-6 Gy) and Group 2 (42/112) consists of HDRBT alone (4 fractions of 5-6 Gy). Toxicity evaluation RTOG scores for bladder and rectum, and the objective criteria of LENT-SOMA for vagina. Statistics bivariate analysis of Chi-square and Fisher exact tests. RESULTS: With a mean follow-up of 29.52 months (range 9.60-53.57) no patient developed vaginal-cuff relapse. In Group 1 early toxicity appeared in 9 % in rectum, 8.5 % in bladder (G1-G2) and 1.4 % in vagina (G1); late toxicity was present in 8.5 % in rectum (all G1-G2 but 1 G3) and in 25 % in vagina (all G1-G2 but one G4). In Group 2, 9.4 % developed G1-G2 bladder and 6.9 % acute vagina (G1-G2) toxicity. Only 2.3 % had a G1 rectal score and 6.9 % had G1-G2 as vaginal scores for late problems. CONCLUSIONS: (1) Daily HDRBT using two fractions of 5-6 Gy after EBI and four fractions of 5-6 Gy as exclusive treatment was a safe regime. (2) Group 1 showed a higher incidence of late vaginal toxicity.

Endometrial stromal sarcoma. Is there a place for radiotherapy?

OBJECTIVES: The optimal approach in the management of endometrial stromal sarcoma (ESS) remains unclear. The aim of the present study was to retrospectively report the outcome of patients treated for ESS in our hospital over a 27-year period in order to evaluate the treatment results and the role of radiotherapy. PATIENTS AND METHODS: From 1979 to 2006, 13 patients with ESS were treated at the Hospital Clínic of Barcelona. Patients underwent abdominal hysterectomy and bilateral salpingo-oophorectomy. The 1989 FIGO classification for endometrial carcinoma was used in this retrospective study. Seven patients presented stage I (6 IB and 1 IC), 1 stage II, 3 stage III and 2 stage IV. Nine patients had high-grade tumours with an infiltration of the outer 50% of the myometrium. Postoperative radiotherapy was administered in 10 patients. RESULTS: The mean follow-up of the patients was 54.6 months (range between 3 and 190). Patients with stage IB had a better outcome in comparison to more advanced stages. Five of the six patients with stage IB received adjuvant radiotherapy and none developed local recurrence, while one patient who received no treatment with radiotherapy had a relapse. Seven of the 13 patients had stages over IB: 5 who had received radiotherapy after surgery had locoregional control and 2 who did not receive radiotherapy had local relapse. Nine patients had high-grade tumours, 6 received radiotherapy after surgery and only one had local relapse. Of the three who did not receive radiotherapy, 2 relapsed locally. Local control rate of the patients who received adjuvant radiotherapy was higher than in the patients who did not (88.9% vs. 50%). CONCLUSIONS: Our data reveal that deep myometrial invasion and stage over IB are significantly associated with poor overall survival and this finding is similar to those of studies in patients with endometrial cancer. The present study showed that the local control was higher in patients receiving radiotherapy.

How to deal with prognostic factors and radiotherapy results in uterine neoplasms with a sarcomatous component?

PURPOSE: Uterine tumours with a sarcomatous component are rare neoplasms with a wide pathologic heterogeneity in which the stage is the main prognostic factor. These aspects and their aggressiveness make the analysis of prognostic factors and radiotherapy difficult. The aim of this study was to evaluate the prognostic factors by stages and to assess the impact of prognostic factors and the effect of radiotherapy on the outcome of the disease. METHODS AND MATERIALS: Eighty-one patients diagnosed and treated for uterine tumours with a sarcomatous component at the Hospital Clinic in Barcelona between 1975 and 2003 were retrospectively studied; 76/81 patients underwent surgery (total hysterectomy plus bilateral salpingo-oophorectomy, and in 13/76 of these patients an additional pelvic lymphadenectomy was performed). All 76 patients were staged after pathological evaluation of the surgical specimen by FIGO classification with 54 patients being stages I-II and 27 patients stages III-IVA. Only 5 patients were clinically staged as III-IVA. Radiotherapy was administered in 21 women with early-stage tumours and in 16 with advanced neoplasms. 5/81 patients received complementary chemotherapy to the surgery and 5 patients received chemotherapy as treatment of local and distant relapse (All the patients were treated with a different chemotherapy schedule). The impact of pathologic prognostic factors and radiotherapy on specific overall survival (OS), disease-free survival (DFS), local relapse-free survival (LRFS) and distant metastasis-free survival (DMFS) were analysed by Log Rank test and Cox proportional risk models. The effect of each risk factor was studied by the hazard ratio and 95% confidence interval. RESULTS: An increased frequency of several adverse prognostic factors was observed in tumours with advanced stages compared to early neoplasms in deep myometrial invasion (83% vs. 27%), VLSI (75% vs. 29%), tumour size >8 cm (50% vs. 30%) and multicentricity (36% vs. 10%), and similar values were found for necrosis (79% vs. 78%) and high mitotic index (78% vs. 80%). For pathological type the frequency by advanced vs. early stages was 54% vs. 52% for carcinosarcomas, 33.5% vs. 17.5% for leiomyosarcoma, and 30.5% and 12.5% for adenosarcoma and endometrial stromal sarcoma, respectively. Univariate analysis showed that the stage was the only independent prognostic factor. Stratification by early (I-II) and advanced stages (III, IV) revealed tumour size >8 cm was the only prognostic factor significantly associated with OS, DFS, LRFS and DMFS on univariate analysis for early stages (HR: OS 2.52, DFS 3.10, LRFS 3.10 and DMFS 2.63). For advanced stages, radiotherapy was the only prognostic factor associated with OS, DFS, LRFS and DMFS on multivariate analysis (HR: OS 4.26, DFS 3.14, LRFS 3.25 and DMFS 3.66). CONCLUSIONS: Uterine tumours with a sarcomatous component have a poor outcome in spite of treatment in comparison to endometrial carcinoma, probably due to the higher frequency of adverse prognostic factors. In early stages tumour size was the most determining factor for OS, DFS, LRFS and DMFS. Radiotherapy significantly improved these survivals in advanced cases.

Acoustic voice analysis in different phonetic contexts after larynx radiotherapy for T1 vocal cord carcinoma.

INTRODUCTION: Radiotherapy for early vocal cord carcinoma affects quality of voice. Nevertheless, most patients refer to having a high satisfaction level with their voice. The few acoustic studies on quality of voice have been performed only in prolonged vowel production, which is not a usual speech situation. The present study has been done with the aim of establishing which phonetic situations reflect a greater alteration in voice production related to irradiation. MATERIAL AND METHODS: Eighteen male patients irradiated for Tis-T1 vocal cord carcinoma and a control group of 31 non-irradiated subjects were included in a study of acoustic voice analysis. This analysis was performed one year after radiotherapy. Patients and control group voices were tape recorded in extended vowel production, oral reading of a standard paragraph, spontaneous speech and in a song. Acoustic analysis was performed by a Kay Elemetric's Computerized Speech Lab (model CSL #4300). Fundamental frequency, jitter, shimmer and harmonics-to-noise ratio were obtained in both groups. Statistical test: Lin concordance coefficient and Pearson's correlation coefficient, Student's t-test and ROC curves. RESULTS: Concordance and correlation studies did not allow selection of any subgroup in acoustic parameters and different acoustic situations. Acoustic parameters had higher median values in irradiated patients. Student's t-test showed significant differences for fundamental frequency in sustained vowel production and spontaneous speech; for jitter there was statistical significance in all the acoustic situations and for shimmer in oral reading and song. Jitter showed a cut-off of 2.02% with a sensitivity of 89% and specificity of 97% in classifying irradiated and non-irradiated groups. The ROC curve for jitter correctly classified 94% of subjects into irradiated or non-irradiated groups. CONCLUSIONS: The present study showed that jitter obtained from spontaneous speech was the most relevant parameter in discriminating voice in irradiated patients by acoustic analysis. Jitter in spontaneous speech is in need of more analysis in bigger series and in more advanced stages of larynx cancer as its relevance has been demonstrated.