The "Sandwich" Schedule: A Well-Tolerated Adjuvant Treatment Both in Intermediate-High- and High-Risk Endometrial Cancer.

(1) Background: In intermediate-high- and high-risk endometrial cancer (EC), radiotherapy (RT) and chemotherapy (CT) play a basic role. However, there is controversy regarding the optimal timing of their combination. The "sandwich" schedule involves adjuvant CT followed by RT and subsequent CT. The aim of this study is to assess the tolerability and efficacy of the "sandwich" schedule. (2) Methods: A retrospective study was conducted in two gynecological oncology units in Torino, Italy, from 1 January 2003 until 31 December 2021. Intermediate-high- and high-risk patients with available clinical data were included. Compliance with treatment, CT and RT toxicities, disease-free survival (DFS), cancer-specific survival (CSS) and overall survival (OS) were analyzed. (3) Results: A total of 118 patients were selected: 27.1% FIGO I-II stages and 72.9% III-IV. Most of the patients (75.4%) received a carboplatin-paclitaxel combination, and as much as 94.9% of CT cycles were completed. Chemotherapy-related G3-4 toxicities were detected in 5.3% of the patients, almost half of which were hematological. Grade 2 gastrointestinal and genitourinary toxicities were reported in 8.4% and 4.2% of cases, respectively. With a median follow-up of 46 months, DFS was 77.6%, CSS was 70% and 5-year OS was 54%. (4) Conclusions: The "sandwich" schedule for CT and RT combination is an effective adjuvant treatment with low toxicity both in intermediate-high- and high-risk EC.

Adjuvant vaginal interventional radiotherapy in early-stage non-endometrioid carcinoma of corpus uteri: a systematic review.

PURPOSE: This systematic review focused on rare histological types of corpus uteri malignancy, including uterine carcinosarcoma (UCS), uterine clear cell carcinoma (UCCC), and uterine papillary serous carcinoma (UPSC), and it is proposed to assist with clinical decision-making. Adjuvant treatment decisions must be made based on available evidences. We mainly investigated the role of vaginal interventional radiotherapy (VIRt) in UCS, UCCC, and UPSC managements. MATERIAL AND METHODS: A systematic research using PubMed and Cochrane library was conducted to identify full articles evaluating the efficacy of VIRt in early-stage UPSC, UCCC, and UCS. A search in ClinicalTrials.gov was performed in order to detect ongoing or recently completed trials as well as in PROSPERO for ongoing or recently completed systematic reviews. Survival outcomes and toxicity rates were obtained. RESULTS: All studies were retrospective. For UCS, the number of evaluated patients was 432. The 2- to 5-year average local control (LC) was 91% (range, 74.2-96%), disease-free survival (DFS) 88% (range, 82-94%), overall survival (OS) 79% (range, 53.8-84.3%), the average 5-year cancer-specific survival (CSS) was 70% (range, 70-94%), and G3-G4 toxicity was 0%. For UCCC, the number of investigated patients was 335 (UCCC - 124, mixed - 211), with an average 5-year LC of 100%, DFS of 83% (range, 82-90%), OS of 93% (range, 83-100%), and G3-G4 toxicity of 0%. For UPSC, the number of examined patients was 1,092 (UPSC - 866, mixed - 226). The average 5-year LC was 97% (range, 87.1-100%), DFS 84% (range, 74.7-95.6%), OS 93% (range, 71.9-100%), CSS 89% (range, 78.9-94%), and G3-G4 toxicity was 0%. CONCLUSIONS: These data suggest that in adequately selected early-stage UPSC and UCCC patients, VIRt alone may be suitable in women who underwent surgical staging and received adjuvant chemotherapy. In early-stage UCS, a multidisciplinary therapeutic approach has to be planned, considering high-rate of pelvic and distant relapses.

The role of radiation therapy technologist in interventional radiotherapy (brachytherapy) in Italy: Italian Association of Radiotherapy and Clinical Oncology (AIRO) and Italian Association of Radiation Therapy and Medical Physics Technologists (AITRO) joint project.

PURPOSE: Interventional radiotherapy (IRT, brachytherapy and intra-operative radiotherapy) is a complex treatment approach that requires a multi-professional approach. The aim of this work was to assess the role of radiation therapy technologist (RTT) in IRT team, with a special focus on brachytherapy as well as to define more appropriate ways to improve skills and training to promote cooperation of multi-professional team. MATERIAL AND METHODS: A nationwide survey consisting of 16 questions was proposed between April and May 2020, with collaboration between the Italian Association of Radiation Therapy and Medical Physics Technologists (AITRO) and the Interventional Radiotherapy Study Group of Italian Association of Radiotherapy and Clinical Oncology (AIRO). The survey was sent through the AITRO contact list to RTTs' contacts from all Italian radiotherapy (RT) departments. RESULTS: A total of 37 answered questionnaires returned (36% of all contacts reached), each from different center. 23 centers (62%) presented with dedicated team for IRT treatments, while 15 centers (41%) had dedicated RTT staff. The majority of RTT (86%) did not consider undergraduate training adequate to acquire the skills required to work in IRT departments or units. CONCLUSIONS: This survey underlines the need of additional education and training for RTTs that should focus on treatment management optimization in development of an IRT multi-professional team. Specific updates could be the key to develop further collaboration and to improve cancer patient care.

The role of vaginal brachytherapy in stage I endometrial serous cancer: a systematic review.

PURPOSE: Serous adenocarcinoma (uterine serous carcinoma - USC) is a rare and aggressive histologic subtype of endometrial cancer, with a high-rate of recurrence and poor prognosis. The adjuvant treatment for stage I patients is unclear. The purpose of this study was to evaluate the outcomes of stage I USC treated exclusively with chemotherapy plus vaginal brachytherapy (VBT). MATERIAL AND METHODS: A systematic research using PubMed, Scopus, and Cochrane library was conducted to identify full articles evaluating the efficacy of VBT in patients with stage I USC. A search in ClinicalTrials.gov was performed in order to detect ongoing or recently completed trials, and in PROSPERO for searching ongoing or recently completed systematic reviews. RESULTS: All studies were retrospective and 364 of evaluated patients were found. The average local control was 97.5% (range, 91-100%), the disease free-survival was 88% (range, 82-94%), the overall survival was 93% (range, 72-100%), the specific cancer survival was 89.4% (range, 84.8-94%), and the G3-G4 toxicity was 0-8%. CONCLUSIONS: These data support the concept that in adequately selected patients, VBT alone may be a suitable radiotherapy technique in women with stage I USC who underwent surgical staging and received adjuvant chemotherapy.

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.

BACKGROUND: The PORTEC-3 trial investigated the benefit of combined adjuvant chemotherapy and radiotherapy versus pelvic radiotherapy alone for women with high-risk endometrial cancer. We updated the analysis to investigate patterns of recurrence and did a post-hoc survival analysis. METHODS: In the multicentre randomised phase 3 PORTEC-3 trial, women with high-risk endometrial cancer were eligible if they had International Federation of Gynaecology and Obstetrics (FIGO) 2009 stage I, endometrioid grade 3 cancer with deep myometrial invasion or lymphovascular space invasion, or both; stage II or III disease; or stage I-III disease with serous or clear cell histology; were aged 18 years and older; and had a WHO performance status of 0-2. Participants were randomly assigned (1:1) to receive radiotherapy alone (48·6 Gy in 1·8 Gy fractions given on 5 days per week) or chemoradiotherapy (two cycles of cisplatin 50 mg/m2 given intravenously during radiotherapy, followed by four cycles of carboplatin AUC5 and paclitaxel 175 mg/m2 given intravenously), by use of a biased coin minimisation procedure with stratification for participating centre, lymphadenectomy, stage, and histological type. The co-primary endpoints were overall survival and failure-free survival. Secondary endpoints of vaginal, pelvic, and distant recurrence were analysed according to the first site of recurrence. Survival endpoints were analysed by intention-to-treat, and adjusted for stratification factors. Competing risk methods were used for failure-free survival and recurrence. We did a post-hoc analysis to analyse patterns of recurrence with 1 additional year of follow-up. The study was closed on Dec 20, 2013; follow-up is ongoing. This study is registered with ISRCTN, number ISRCTN14387080, and ClinicalTrials.gov, number NCT00411138. FINDINGS: Between Nov 23, 2006, and Dec 20, 2013, 686 women were enrolled, of whom 660 were eligible and evaluable (330 in the chemoradiotherapy group, and 330 in the radiotherapy-alone group). At a median follow-up of 72·6 months (IQR 59·9-85·6), 5-year overall survival was 81·4% (95% CI 77·2-85·8) with chemoradiotherapy versus 76·1% (71·6-80·9) with radiotherapy alone (adjusted hazard ratio [HR] 0·70 [95% CI 0·51-0·97], p=0·034), and 5-year failure-free survival was 76·5% (95% CI 71·5-80·7) versus 69·1% (63·8-73·8; HR 0·70 [0·52-0·94], p=0·016). Distant metastases were the first site of recurrence in most patients with a relapse, occurring in 78 of 330 women (5-year probability 21·4%; 95% CI 17·3-26·3) in the chemoradiotherapy group versus 98 of 330 (5-year probability 29·1%; 24·4-34·3) in the radiotherapy-alone group (HR 0·74 [95% CI 0·55-0·99]; p=0·047). Isolated vaginal recurrence was the first site of recurrence in one patient (0·3%; 95% CI 0·0-2·1) in both groups (HR 0·99 [95% CI 0·06-15·90]; p=0·99), and isolated pelvic recurrence was the first site of recurrence in three women (0·9% [95% CI 0·3-2·8]) in the chemoradiotherapy group versus four (0·9% [95% CI 0·3-2·8]) in the radiotherapy-alone group (HR 0·75 [95% CI 0·17-3·33]; p=0·71). At 5 years, only one grade 4 adverse event (ileus or obstruction) was reported (in the chemoradiotherapy group). At 5 years, reported grade 3 adverse events did not differ significantly between the two groups, occurring in 16 (8%) of 201 women in the chemoradiotherapy group versus ten (5%) of 187 in the radiotherapy-alone group (p=0·24). The most common grade 3 adverse event was hypertension (in four [2%] women in both groups). At 5 years, grade 2 or worse adverse events were reported in 76 (38%) of 201 women in the chemoradiotherapy group versus 43 (23%) of 187 in the radiotherapy-alone group (p=0·002). Sensory neuropathy persisted more often after chemoradiotherapy than after radiotherapy alone, with 5-year rates of grade 2 or worse neuropathy of 6% (13 of 201 women) versus 0% (0 of 187). No treatment-related deaths were reported. INTERPRETATION: This updated analysis shows significantly improved overall survival and failure-free survival with chemoradiotherapy versus radiotherapy alone. This treatment schedule should be discussed and recommended, especially for women with stage III or serous cancers, or both, as part of shared decision making between doctors and patients. Follow-up is ongoing to evaluate long-term survival. FUNDING: Dutch Cancer Society, Cancer Research UK, National Health and Medical Research Council, Project Grant, Cancer Australia Grant, Italian Medicines Agency, and the Canadian Cancer Society Research Institute.

Survey on gynecological cancer treatment by Piedmont, Liguria, and Valle d'Aosta group of AIRO (Italian Association of Radiation Oncology).

PURPOSE: We focused the attention on radiation therapy practices about the gynecological malignancies in Piedmont, Liguria, and Valle d'Aosta to know the current treatment practice and to improve the quality of care. MATERIAL AND METHODS: We proposed a cognitive survey to evaluate the standard practice patterns for gynecological cancer management, adopted from 2012 to 2014 by radiotherapy (RT) centers with a large amount of gynecological cancer cases. There were three topics: 1. Taking care and multidisciplinary approach, 2. Radiotherapy treatment and brachytherapy, 3. Follow-up. RESULTS: Nineteen centers treated gynecological malignancies and 12 of these had a multidisciplinary dedicated team. Radiotherapy option has been used in all clinical setting: definitive, adjuvant, and palliative. In general, 1978 patients were treated. There were 834 brachytherapy (BRT) treatments. The fusion between diagnostic imaging (magnetic resonance imaging - MRI, positron emission tomography - PET) and computed tomography (CT) simulation was used for contouring in all centers. Conformal RT and intensity modulated radiation therapy (IMRT) were the most frequent techniques. The image guided radiation therapy (IGRT) was used in 10/19 centers. There were 8 active BRT centers. Brachytherapy was performed both with radical intent and as boost, mostly by HDR (6/8 centers). The doses for exclusive BRT were between 20 to 30 Gy. The doses for BRT boost were between 10 and 20 Gy. Four centers used CT-MRI compatible applicators but only one used MRI for planning. The BRT plans on vaginal cuff were still performed on traditional radiographies in 2 centers. The plan sum was evaluated in only 1 center. Only 1 center performed in vivo dosimetry. CONCLUSIONS: In the last three years, multidisciplinary approach, contouring, treatment techniques, doses, and control systems were similar in Liguria-Piedmont and Valle d'Aosta. However, the technology implementation didn't translate in a real treatment innovation so far.

Target volume delineation for preoperative radiotherapy of rectal cancer: inter-observer variability and potential impact of FDG-PET/CT imaging.

To analyze the inter-observer variability and the potential impact of (18)F-fluorodeoxyglucose (FDG)-positron emission tomography/computed tomography (PET/CT) imaging for target volume delineation in preoperative radiotherapy of rectal cancer. Gross tumor volume (GTV) and clinical target volume (CTV) in 2 cases of rectal cancer were contoured by 10 radiation oncologists, 5 on CT and 5 on PET/CT images. Resulting volumes were analyzed by coefficient of variation (CV) and concordance index (CI). Mean GTV was 120 cc +/- 20.4 cc in case A and 119 cc +/- 35.7 cc in case B. Mean CTV was 723 cc +/- 147.5 cc in case A and 739 cc +/- 195.6 cc in case B. CV was lower and CI was similar or higher across the observers contouring GTV on PET/CT. CTV variability was less influenced by the use of PET/CT. PET/CT may allow reducing inter-observer variability in GTV delineation.