Coping with modesty during radiotherapy for breast cancer: a multicentric study.

PURPOSE: Breast cancer is the most frequently diagnosed tumour, representing nearly 30% of all new cases in women. Radiotherapy (RT) plays a crucial role in the management of breast cancer. The objective of this study is to assess modesty in patients undergoing RT for breast cancer and take their suggestions and ideas into consideration to enhance the quality of treatment in this regard. METHODS: The study enrolled 555 breast cancer patients undergoing adjuvant RT in three Italian centres. Patients completed a self-test questionnaire assessing their comfort level concerning modesty during therapy and their relationship with strangers and healthcare professionals. The impact of religious views and potential changes in sexuality were also examined. RESULTS: Results showed that modesty was a common concern across the overall cohort of patients, with discomfort in being undressed during RT correlating with discomfort experienced in other daily life situations. Most patients felt more at ease with same sex healthcare workers. Age was also a major factor with younger patients generally feeling more comfortable with healthcare workers of the same age group. Interestingly, the surgical technique used (mastectomy vs. quadrantectomy) did not significantly influence modesty perceptions. Patients provided valuable suggestions to improve privacy and modesty during RT. CONCLUSION: This study demonstrates that modesty is an important issue for women undergoing RT, which can be influenced by personal characteristics and hospital-related factors. A reflection about the need to address modesty concerns and to incorporate dedicated interventions for protecting patients' physical and emotional well-being is warranted. Initiatives to improve communication, involvement, and body image support should also be integrated into the care path of patients to better their overall therapeutic experience. This study paves the way for broader research and interventions in daily cancer care.

Efficacy of stereotactic body radiotherapy and response prediction using artificial intelligence in oligometastatic gynaecologic cancer.

PURPOSE: We present a large real-world multicentric dataset of ovarian, uterine and cervical oligometastatic lesions treated with SBRT exploring efficacy and clinical outcomes. In addition, an exploratory machine learning analysis was performed. METHODS: A pooled analysis of gynecological oligometastases in terms of efficacy and clinical outcomes as well an exploratory machine learning model to predict the CR to SBRT were carried out. The CR rate following radiotherapy (RT) was the study main endpoint. The secondary endpoints included the 2-year actuarial LC, DMFS, PFS, and OS. RESULTS: 501 patients from 21 radiation oncology institutions with 846 gynecological metastases were analyzed, mainly ovarian (53.1%) and uterine metastases(32.1%).Multiple fraction radiotherapy was used in 762 metastases(90.1%).The most frequent schedule was 24 Gy in 3 fractions(13.4%). CR was observed in 538(63.7%) lesions. The Machine learning analysis showed a poor ability to find covariates strong enough to predict CR in the whole series. Analyzing them separately, in uterine cancer, if RT dose≥78.3Gy, the CR probability was 75.4%; if volume was <13.7 cc, the CR probability became 85.1%. In ovarian cancer, if the lesion was a lymph node, the CR probability was 71.4%; if volume was <17 cc, the CR probability rose to 78.4%. No covariate predicted the CR for cervical lesions. The overall 2-year actuarial LC was 79.2%, however it was 91.5% for CR and 52.5% for not CR lesions(p < 0.001). The overall 2-year DMFS, PFS and OS rate were 27.3%, 24.8% and 71.0%, with significant differences between CR and not CR. CONCLUSIONS: CR was substantially associated to patient outcomes in our series of gynecological cancer oligometastatic lesions. The ability to predict a CR through artificial intelligence could also drive treatment choices in the context of personalized oncology.

TRImodal DEfinitive invasive vagiNal carcinoma Treatment (TRIDENT protocol): how a standardized approach may change prognostic outcomes.

OBJECTIVE: Vaginal carcinoma is a rare malignancy accounting for 1-2% of all gynecological cancers. Surgery has a limited role, while definitive radiotherapy-chemotherapy followed by interventional radiotherapy is considered a valid alternative. The aim of the TRIDENT (TRImodal DEfinitive invasive vagiNal carcinoma Treatment) pilot study was to report the results of a modern standardized trimodal protocol treatment consisting of image guided definitive radiotherapy-chemotherapy followed by image guided interventional radiotherapy in terms of safety and efficacy. METHODS: Between January 2019 and December 2021, we analyzed 21 consecutive patients with primary vaginal cancer who had received radiotherapy-chemotherapy followed by interventional radiotherapy. The primary study endpoint was local control, and secondary endpoints were metastasis free survival, overall survival, and rate and severity of acute and late toxicities. RESULTS: 14 patients had FIGO (International Federation of Gynecology and Obstetrics) stage II, five patients had stage III, and two had stage IVB disease. Median total external beam radiotherapy dose for the tumor was 45 Gy. Median total dose on positive nodes was 60 Gy. Median total dose for interventional radiotherapy was 28 Gy over four high dose rate fractions to achieve between 85 and 95 Gy equivalent dose, in 2 Gy fractions (EQD2)α/ß10, to the high risk clinical target volume, and 60 Gy EQD2α/ß10 to the intermediate risk clinical target volume. All patients received weekly platinum based chemotherapy. Median follow-up was 20 months (range 10-56 months). Two year actuarial local control, metastasis free survival, and overall survival rate were 79.4%, 90.5%, and 79.4%, respectively. In terms of acute toxicity, there were no grade 4 events and only one acute grade (G) 3 toxicity (skin). Only vaginal stenosis (G3) was documented 12 months after therapy due to late toxicity. CONCLUSIONS: In this study, definitive radiotherapy-chemotherapy followed by interventional radiotherapy was a safe and effective treatment modality for primary vaginal cancer.

Definitive chemoradiation in vulvar squamous cell carcinoma: outcome and toxicity from an observational multicenter Italian study on vulvar cancer (OLDLADY 1.1).

BACKGROUND: Vulvar carcinoma is a rather uncommon gynecological malignancy affecting elderly women and the treatment of loco-regional advanced carcinoma of the vulva (LAVC) is a challenge for both gynecologic and radiation oncologists. Definitive chemoradiation (CRT) is the treatment of choice, but with disappointing results. In this multicenter study (OLDLADY-1.1), several institutions have combined their retrospective data on LAVC patients to produce a real-world dataset aimed at collecting data on efficacy and safety of CRT. METHODS: The primary study end-point was 2-year-local control (LC), secondary end-points were 2-year-metastasis free-survival (MFS), 2-year-overall survival (OS) and the rate and severity of acute and late toxicities. Participating centers were required to fill data sets including age, stage, histology, grading as well as technical/dosimetric details of CRT. Data about response, local and regional recurrence, acute and late toxicities, follow-up and outcome measures were also collected. The toxicity was a posteriori documented through the Common Terminology Criteria for Adverse Events version 5 scale. RESULTS: Retrospective analysis was performed on 65 patients with primary or recurrent LAVC treated at five different radiation oncology institutions covering 11-year time interval (February 2010-November 2021). Median age at diagnosis was 72 years (range 32-89). With a median follow-up of 19 months (range 1-114 months), 2-year actuarial LC, MFS and OS rate were 43.2%, 84.9% and 59.7%, respectively. In 29 patients (44%), CRT was temporarily stopped (median 5 days, range 1-53 days) due to toxicity. The treatment interruption was statistically significant at univariate analysis of factors predicting LC (p: 0.05) and OS rate (p: 0.011), and it was confirmed at the multivariate analysis for LC rate (p: 0.032). In terms of toxicity profile, no G4 event was recorded. Most adverse events were reported as grade 1 or 2. Only 14 acute G3 toxicities, all cutaneous, and 7 late G3 events (3 genitourinary, 3 cutaneous, and 1 vaginal stenosis) were recorded. CONCLUSION: In the context of CRT for LAVC, the present study reports encouraging results even if there is clearly room for further improvements, in terms of both treatment outcomes, toxicity and treatment interruption management.

Radiomics-enhanced early regression index for predicting treatment response in rectal cancer: a multi-institutional 0.35 T MRI-guided radiotherapy study.

PURPOSE: The accurate prediction of treatment response in locally advanced rectal cancer (LARC) patients undergoing MRI-guided radiotherapy (MRIgRT) is essential for optimising treatment strategies. This multi-institutional study aimed to investigate the potential of radiomics in enhancing the predictive power of a known radiobiological parameter (Early Regression Index, ERITCP) to evaluate treatment response in LARC patients treated with MRIgRT. METHODS: Patients from three international sites were included and divided into training and validation sets. 0.35 T T2*/T1-weighted MR images were acquired during simulation and at each treatment fraction. The biologically effective dose (BED) conversion was used to account for different radiotherapy schemes: gross tumour volume was delineated on the MR images corresponding to specific BED levels and radiomic features were then extracted. Multiple logistic regression models were calculated, combining ERITCP with other radiomic features. The predictive performance of the different models was evaluated on both training and validation sets by calculating the receiver operating characteristic (ROC) curves. RESULTS: A total of 91 patients was enrolled: 58 were used as training, 33 as validation. Overall, pCR was observed in 25 cases. The model showing the highest performance was obtained combining ERITCP at BED = 26 Gy with a radiomic feature (10th percentile of grey level histogram, 10GLH) calculated at BED = 40 Gy. The area under ROC curve (AUC) of this combined model was 0.98 for training set and 0.92 for validation set, significantly higher (p = 0.04) than the AUC value obtained using ERITCP alone (0.94 in training and 0.89 in validation set). CONCLUSION: The integration of the radiomic analysis with ERITCP improves the pCR prediction in LARC patients, offering more precise predictive models to further personalise 0.35 T MRIgRT treatments of LARC patients.

The Italian version of the Pediatric Quality of Life Inventory™ (PEDSQL™) 3.0 healthcare satisfaction hematology/oncology module: reliability and validity in radiation oncology.

BACKGROUND: Health-related quality of life (HRQOL) measurement has become an important health care outcome even in oncological pediatric scenario. During radiation therapy care path, pediatric patients and their relatives may suffer from emotional and psychosocial distress not only related to cancer diagnosis, but also due to the procedure and the required daily routine. Despite the high prevalence of psychosocial consequences in this setting, instruments that inquire pediatric HRQOL and healthcare satisfaction have rarely been studied in Italy. Purpose of this study was to investigate reliability and linguistic validation of the PedsQL™ healthcare satisfaction Hematology/Oncology module from its original English version to Italian language. METHODS: Three phases standard procedure of cross-culture adaptation were used to create Italian version of PedsQL™ healthcare satisfaction Hematology/Oncology module. Forward translations and backward translations were performed. Finally, a pilot-testing for understandability of the 'pre-final' version was conducted with parents of children attending our Radiotherapy Center using two methodologies of Cognitive Interviewing ("Think-aloud Interviews" and "Respondent Debriefing"), in order to obtain the final Italian version of the PedsQL™ healthcare satisfaction Hematology/Oncology module. RESULTS: Twenty-five parents (2 father, 23 mothers) were recruited during their children's radiotherapy treatment and the grammatically and conceptually acceptable pre-final version of the PedsQL™ Healthcare Satisfaction Hematology/Oncology Module was administered. The questionnaire was well understood reflecting its linguistic adaptation. Compliance with questionnaire administration was optimal. All subjects stated that the questions were interesting to express their opinion, most of them reported that all the questions of each section were clearly comprehensible and easy to understand, suggesting minimal changes that were double-checked with back translation. Furthermore, six of them spontaneously asked to complete the questionnaire in order to review the assistance received during radiotherapy. CONCLUSION: Our Italian version of the PedsQL™ 3.0 Healthcare Satisfaction Hematology/Oncology Module seems to be a valid and functional instrument to indagate Healthcare Satisfaction.

Magnetic resonance-guided stereotactic body radiation therapy (MRgSBRT) for oligometastatic patients: a single-center experience.

PURPOSE: Stereotactic body radiotherapy is increasingly used for the treatment of oligometastatic disease. Magnetic resonance-guided stereotactic radiotherapy (MRgSBRT) offers the opportunity to perform dose escalation protocols while reducing the unnecessary irradiation of the surrounding organs at risk. The aim of this retrospective, monoinstitutional study is to evaluate the feasibility and clinical benefit (CB) of MRgSBRT in the setting of oligometastatic patients. MATERIALS AND METHODS: Data from oligometastatic patients treated with MRgSBRT were collected. The primary objectives were to define the 12-month progression-free survival (PFS) and local progression-free survival (LPFS) and 24-month overall survival (OS) rate. The objective response rate (ORR) included complete response (CR) and partial response (PR). CB was defined as the achievement of ORR and stable disease (SD). Toxicities were also assessed according to the CTCAE version 5.0 scale. RESULTS: From February 2017 to March 2021, 59 consecutive patients with a total of 80 lesions were treated by MRgSBRT on a 0.35 T hybrid unit. CR and PR as well as SD were observed in 30 (37.5%), 7 (8.75%), and 17 (21.25%) lesions, respectively. Furthermore, CB was evaluated at a rate of 67.5% with an ORR of 46.25%. Median follow-up time was 14 months (range: 3-46 months). The 12-month LPFS and PFS rates were 70% and 23%, while 24-month OS rate was 93%. No acute toxicity was reported, whereas late pulmonary fibrosis G1 was observed in 9 patients (15.25%). CONCLUSION: MRgSBRT was well tolerated by patients with reported low toxicity levels and a satisfying CB.

Pattern of care for re-irradiation in locally recurrent rectal cancer: a national survey on behalf of the AIRO gastrointestinal tumors study group.

PURPOSE: Radical resection (R0) represents the best curative treatment for local recurrence (LR) rectal cancer. Re-irradiation (re-RT) can increase the rate of R0 resection. Currently, there is a lack of guidelines on Re-RT for LR rectal cancer. The Italian Association of Radiation and clinical oncology for gastrointestinal tumors (AIRO-GI) study group released a national survey to investigate the current clinical practice of external beam radiation therapy in these patients. MATERIAL AND METHODS: In February 2021, the survey was designed and distributed to members of the GI working group. The questionnaire consisted of 40 questions regarding center characteristics, clinical indications, doses, and treatment techniques of re-RT for LR rectal cancer. RESULTS: A total of 37 questionnaires were collected. Re-RT was reported as an option for neoadjuvant treatment in resectable and unresectable disease by 55% and 75% of respondents, respectively. Long-course treatment with 30-40 Gy (1.8-2 Gy/die, 1.2 Gy bid) and hypofractionated regimen of 30-35 Gy in 5 fractions were used in most centers. A total dose of 90-100 Gy as EqD2 dose (α/ß = 5 Gy) was delivered by 46% of the respondents considering the previous treatment. Modern conformal techniques and daily image-guided radiation therapy protocols were used in 94% of centers. CONCLUSION: Our survey showed that re-RT treatment is performed with advanced technology that allow a good management of LR rectal cancer. Significant variations were observed in terms of dose and fractionation, highlighting the need for a consensus on a common treatment strategy that could be validated in prospective studies.

Rectal Sparing Approach After Neoadjuvant Therapy in Patients with Rectal Cancer: The Preliminary Results of the ReSARCh Trial.

BACKGROUND: Rectum-preservation for locally advanced rectal cancer has been proposed as an alternative to total mesorectal excision (TME) in patients with major (mCR) or complete clinical response (cCR) after neoadjuvant therapy. The purpose of this study was to report on the short-term outcomes of ReSARCh (Rectal Sparing Approach after preoperative Radio- and/or Chemotherapy) trial, which is a prospective, multicenter, observational trial that investigated the role of transanal local excision (LE) and watch-and-wait (WW) as integrated approaches after neoadjuvant therapy for rectal cancer. METHODS: Patients with mid-low rectal cancer who achieved mCR or cCR after neoadjuvant therapy and were fit for major surgery were enrolled. Clinical response was evaluated at 8 and 12 weeks after completion of chemoradiotherapy. Treatment approach, incidence, and reasons for subsequent TME were recorded. RESULTS: From 2016 to 2019, 160 patients were enrolled; mCR or cCR at 12 weeks was achieved in 64 and 96 of patients, respectively. Overall, 98 patients were managed with LE and 62 with WW. In the LE group, Clavien-Dindo 3+ complications occurred in three patients. The rate of cCR increased from 8- to 12-week restaging. Thirty-three (94.3%) of 35 patients with cCR had ypT0-1 tumor. At a median 24 months follow-up, a tumor regrowth was found in 15 (24.2%) patients undergoing WW. CONCLUSIONS: LE for patients achieving cCR or mCR is safe. A 12-week interval from chemoradiotherapy completion to LE is correlated with an increased cCR rate. The risk of ypT > is reduced when LE is performed after cCR.

THUNDER 2: THeragnostic Utilities for Neoplastic DisEases of the Rectum by MRI guided radiotherapy.

BACKGROUND: Neoadjuvant chemoradiation therapy (nCRT) is the standard treatment modality in locally advanced rectal cancer (LARC). Since response to radiotherapy (RT) is dose dependent in rectal cancer, dose escalation may lead to higher complete response rates. The possibility to predict patients who will achieve complete response (CR) is fundamental. Recently, an early tumour regression index (ERI) was introduced to predict pathological CR (pCR) after nCRT in LARC patients. The primary endpoints will be the increase of CR rate and the evaluation of feasibility of delta radiomics-based predictive MRI guided Radiotherapy (MRgRT) model. METHODS: Patients affected by LARC cT2-3, N0-2 or cT4 for anal sphincter involvement N0-2a, M0 without high risk features will be enrolled in the trial. Neoadjuvant CRT will be administered using MRgRT. The initial RT treatment will consist in delivering 55 Gy in 25 fractions on Gross Tumor Volume (GTV) plus the corresponding mesorectum and 45 Gy in 25 fractions on the drainage nodes. Chemotherapy with 5-fluoracil (5-FU) or oral capecitabine will be administered continuously. A 0.35 Tesla MRI will be acquired at simulation and every day during MRgRT. At fraction 10, ERI will be calculated: if ERI will be inferior than 13.1, the patient will continue the original treatment; if ERI will be higher than 13.1 the treatment plan will be reoptimized, intensifying the dose to the residual tumor at the 11th fraction to reach 60.1 Gy. At the end of nCRT instrumental examinations are to be performed in order to restage patients. In case of stable disease or progression, the patient will undergo surgery. In case of major or complete clinical response, conservative approaches may be chosen. Patients will be followed up to evaluate toxicity and quality of life. The number of cases to be enrolled will be 63: all the patients will be treated at Fondazione Policlinico Universitario A. Gemelli IRCCS in Rome. DISCUSSION: This clinical trial investigates the impact of RT dose escalation in poor responder LARC patients identified using ERI, with the aim of increasing the probability of CR and consequently an organ preservation benefit in this group of patients. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04815694 (25/03/2021).

Contact skin radiotherapy (brachytherapy) for the treatment of non-melanoma skin cancers during COVID-19 pandemic.

In the context of the SARS-CoV-2 pandemic, it is important to ensure the quality of cancer treatment as well as patients and health professionals' safety. Individual-based treatment options should be considered in patients with advanced epithelial skin cancer, who are typically elderly and frail. Aim of this study was to assess feasibility and safety of Contact Skin Radiation Therapy (CSRT) to treat basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) during SARS-CoV-2 pandemic. Patients with advanced and difficult-to-treat BCC or SCC were discussed at skin multidisciplinary tumor board (S-MDTB) from February the 21st to May the 4th (phase 1 Italian Pandemic) and retrospectively analyzed. Patient's triage following internal recommendations was daily performed. CSRT was delivered in 8 fractions of 5 Gy each, twice a day. Beyond the clinical outcomes, treatment success indicators, such as the completion of CSRT without SARS-CoV-2 occurrence, were identified to evaluate the feasibility of CSRT during pandemic. A post-treatment psychological assessment regarding patient's safety perception was performed. Six male patients (median age 80 years; range 62-92) with histologically confirmed BCC or SCC were treated with CSRT. Complete clinical remission was achieved in 5/6 patients (83.4%). No high-grade acute toxicities occurred during treatment. No patients or healthcare personnel developed SARS-CoV-2 infection. All the treatment success indicators were achieved. CSRT represents a safe, and feasible treatment option even during the pandemic emergency period. Hypofractionation could be an option to reduce total number of fractions and, consequently, infective risk exposition.

Management of oligometastatic ovarian cancer recurrence during PARP inhibitor maintenance.

OBJECTIVE: The benefit of surgery and maintenance treatment with PARP inhibitors (PARPi) has been clearly demonstrated in ovarian cancer. Also, the efficacy and safety of stereotactic body radiotherapy has been shown in patients with metastatic, persistent, and recurrent disease. The aim of this study is to evaluate the management of oligometastatic progression during PARPi maintenance treatment. METHODS: This is an observational, retrospective, single-arm study conducted from June 2017 to December 2020 in patients with recurrent ovarian cancer with oligometastatic progression under PARPi maintenance treatment and receiving surgery or stereotactic body radiotherapy for such recurrence. PARPi treatment was continued until further progression of the disease. The primary objective of the study was the median prolongation of the treatment-free interval-p (without platinum) after local treatment. RESULTS: A total of 186 patients with ovarian cancer were treated with PARPi at recurrence. Of these, 30 (16%) developed oligometastatic progression. The median age was 49.5 years (range 35-73). Olaparib, niraparib and rucaparib were administered to 33%, 60%, and 7% of patients, respectively. The median prolongation of the treatment-free interval-p of patients treated with surgery or stereotactic body radiotherapy was 6 and 10 months, respectively (p=0.53). The median treatment-free interval-p of patients treated with surgery or stereotactic body radiotherapy at the time of oligometastatic progression was 32 and 29 months, respectively (p=0.44). At the time of this publication, 50% of patients are still on treatment with PARPi following progression. CONCLUSIONS: Patients with recurrent ovarian cancer who have oligometastic progression during PARPi maintenance may continue to benefit from PARPi if combined with local treatment.

Efficacy and safety of stereotactic body radiotherapy (SBRT) in oligometastatic/persistent/recurrent ovarian cancer: a prospective, multicenter phase II study (MITO-RT3/RAD).

BACKGROUND: Stereotactic body radiotherapy (SBRT) has shown promising results in the clinical setting of oligometastatic, persistent, or recurrent disease in several malignancies including ovarian cancer. PRIMARY OBJECTIVE: The MITO-RT3/RAD trial is a prospective, multicenter phase II study aimed at identifying potential predictors of response and clinical outcome after SBRT treatment. STUDY HYPOTHESIS: Radiotherapy delivered by pre-defined SBRT treatment schedules and shared constraints could improve the rate of complete response. TRIAL DESIGN: All patients accrued will be treated with a radiotherapy dose in the range of 30-50 Gy by 1, 3, or 5 SBRT daily fractions to all sites of active metastatic disease according to diagnostic imaging. Schedules of treatment and dose prescription have been established before considering target sites and healthy organ dose constraints. Follow-up and monitoring of side effects will be carried out every 3 months for the first year with imaging and clinical evalutation, and every 4 months within the second year; thereafter, surveillance will be carried out every 6 months. The best response on a per lesion basis will be evaluated by computed tomographic (CT) scan, positron emission tomography/CT, or magnetic resonance imaging in case of brain lesions, every 3 months. MAJOR INCLUSION/EXCLUSION CRITERIA: The study includes patients with oligometastatic, persistent, or recurrent ovarian cancer for which salvage surgery or other local therapies are not feasible due to any relative contra-indication to further systemic therapy because of serious co-morbidities, previous severe toxicity, unavailability of potentially active systemic therapy, or patient refusal. PRIMARY ENDPOINT: The primary endpoint of the study is the clinical complete response rate to SBRT by imaging on a per lesion basis. SAMPLE SIZE: Approximately 205 lesions will be treated (90 lymph nodes and 115 parenchyma lesions). ESTIMATED DATES FOR COMPLETING ACCRUAL AND PRESENTING RESULTS: Fifty-two centers have expressed their intention to participate. Enrollment should be completed by March 2023 and analysis will be completed in September 2023. TRIAL REGISTRATION: NCT04593381.

Stereotactic body radiotherapy in oligometastatic cervical cancer (MITO-RT2/RAD study): a collaboration of MITO, AIRO GYN, and MaNGO groups.

OBJECTIVE: This retrospective, multicenter study analyzes the efficacy and safety of stereotactic body radiotherapy in a large cohort of patients with oligometastatic/persistent/recurrent cervical cancer. METHODS: A standardized data collection from several radiotherapy centers that treated patients by stereotactic body radiotherapy between March 2006 and February 2021 was set up. Clinical and stereotactic body radiotherapy parameters were collected. Objective response rate was defined as a composite of complete and partial response, while clinical benefit included objective response rate plus stable disease. Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer and Common Terminology Criteria for Adverse Events scales were used to grade toxicities. The primary endpoints were the rate of complete response to stereotactic body radiotherapy, and the 2 year actuarial local control rate on a 'per lesion' basis. The secondary end points were progression-free survival and overall survival, as well as toxicity. RESULTS: A total of 83 patients with oligometastatic/persistent/recurrent cervical cancer bearing 125 lesions treated by stereotactic body radiotherapy at 15 different centers were selected for analysis. Of the sites of metastatic disease, lymph node metastases were most common (55.2%), followed by parenchyma lesions (44.8%). Median total dose was 35 Gy (range 10-60), in five fractions (range 1-10), with a median dose/fraction of 7 Gy (range 4-26). Complete, partial, and stable response were found in 73 (58.4%), 29 (23.2%), and 16 (12.8%) lesions, respectively, reaching 94.4% of the clinical benefit rate. Forty-six (55.4%) patients had a complete response. Patients achieving complete response on a 'per lesion' basis experienced a 2 year actuarial local control rate of 89.0% versus 22.1% in lesions not achieving complete response (p<0.001). The 2 year actuarial progression-free survival rate was 42.5% in patients with complete response versus 7.8% in patients with partial response or stable or progressive disease (p=0.001). The 2 year actuarial overall survival rate was 68.9% in patients with complete response versus 44.3% in patients with partial response or stable or progressive disease (p=0.015). Fifteen patients (18.1%) had mild acute toxicity, totaling 29 side events. Late toxicity was documented in four patients (4.8%) totaling seven adverse events. CONCLUSION: Our analysis confirmed the efficacy of stereotactic body radiotherapy in oligometastatic/persistent/recurrent cervical cancer patients. The low toxicity profile encourages the wider use of stereotactic body radiotherapy in this setting.

Radiomics-based prediction of two-year clinical outcome in locally advanced cervical cancer patients undergoing neoadjuvant chemoradiotherapy.

PURPOSE: The aim of this study is to determine if radiomics features extracted from staging magnetic resonance (MR) images could predict 2-year long-term clinical outcome in patients with locally advanced cervical cancer (LACC) after neoadjuvant chemoradiotherapy (NACRT). MATERIALS AND METHODS: We retrospectively enrolled patients with LACC diagnosis who underwent NACRT followed by radical surgery in two different institutions. Radiomics features were extracted from pre-treatment 1.5 T T2w MR images. The predictive performance of each feature was quantified in terms of Wilcoxon-Mann-Whitney test. Among the significant features, Pearson correlation coefficient (PCC) was calculated to quantify the correlation among the different predictors. A logistic regression model was calculated considering the two most significant features at the univariate analysis showing the lowest PCC value. The predictive performance of the model created was quantified out using the area under the receiver operating characteristic curve (AUC). RESULTS: A total of 175 patients were retrospectively enrolled (142 for the training cohort and 33 for the validation one). 1896 radiomic feature were extracted, 91 of which showed significance (p < 0.05) at the univariate analysis. The radiomic model showing the highest predictive value combined the features calculated starting from the gray level co-occurrence-based features. This model achieved an AUC of 0.73 in the training set and 0.91 in the validation set. CONCLUSIONS: The proposed radiomic model showed promising performances in predicting 2-year overall survival before NACRT. Nevertheless, the observed results should be tested in larger studies with consistent external validation cohorts, to confirm their potential clinical use.

Does restaging MRI radiomics analysis improve pathological complete response prediction in rectal cancer patients? A prognostic model development.

PURPOSE: Our study investigated the contribution that the application of radiomics analysis on post-treatment magnetic resonance imaging can add to the assessments performed by an experienced disease-specific multidisciplinary tumor board (MTB) for the prediction of pathological complete response (pCR) after neoadjuvant chemoradiotherapy (nCRT) in locally advanced rectal cancer (LARC). MATERIALS AND METHODS: This analysis included consecutively retrospective LARC patients who obtained a complete or near-complete response after nCRT and/or a pCR after surgery between January 2010 and September 2019. A three-step radiomics features selection was performed and three models were generated: a radiomics model (rRM), a multidisciplinary tumor board model (yMTB) and a combined model (CM). The predictive performance of models was quantified using the receiver operating characteristic (ROC) curve, evaluating the area under curve (AUC). RESULTS: The analysis involved 144 LARC patients; a total of 232 radiomics features were extracted from the MR images acquired post-nCRT. The yMTB, rRM and CM predicted pCR with an AUC of 0.82, 0.73 and 0.84, respectively. ROC comparison was not significant (p = 0.6) between yMTB and CM. CONCLUSION: Radiomics analysis showed good performance in identifying complete responders, which increased when combined with standard clinical evaluation; this increase was not statistically significant but did improve the prediction of clinical response.

EROS 2.0 study: evaluation of two interventional radiotherapy (brachytherapy) schedules for endometrial cancer: a comparison of late vaginal toxicity rates.

BACKGROUND: To compare the late toxicity rates after two different high dose rate (HDR) adjuvant intravaginal interventional radiotherapy (IRT-brachytherapy) dose schedules in stage I-II endometrial cancer. METHODS: Stage I-II patients with endometrial cancer treated with surgery (with or without lymphadenectomy) and adjuvant HDR-IRT between 2014 and 2020 were included in this analysis. Patients were treated with two schedules. In the first cohort (C1), 21 Gy were delivered in three weekly fractions (7 Gy) prescribed 0.5 cm from the applicator surface. In the second cohort (C2), 24 Gy were delivered in four weekly fractions (6 Gy). The clinical target volume was the upper third of the vagina for C1 and the upper 3 cm for C2. HDR-IRT technique and point prescription (5 mm depth from the applicator surface) were the same for all patients. Vaginal toxicity was scored according to the CTCAE 5.0 scale in terms of the presence versus absence of any toxicity grade. The correlation among toxicity and clinical covariates (age, lymphadenectomy, fractionation, stage) was tested by Pearson correlation test (univariate) and by logistic regression (multivariable). RESULTS: 114 stage I and three stage II patients, median age 62 (range: 32-85) years, were included in this analysis. The mean follow-up was 56.3 months in C1 (40-76) and 20 months in C2 (8-42). Vaginal late toxicity was recorded in 40 and 15 patients in C1 and 2, respectively. Age, lymphadenectomy, and fractionation were significantly correlated with toxicity at univariate analysis (p value = 0.029, 0.006, and 0.002, respectively), while stepwise logistic regression confirmed only age and fractionation as significantly correlated parameters (p value = 0.02 and 0.001, respectively). Three-year local relapse-free, distant metastasis-free and cause-specific survival rates were 96.6%, 94.8%, and 99.1%, respectively. CONCLUSIONS: This analysis showed lower vaginal late toxicity rate in C2 compared to C1.

Assessment of Sexual Dysfunction in Cervical Cancer Patients after Different Treatment Modality: A Systematic Review.

Background and Objectives: Cervical cancer is a leading cause of mortality among women. Chemo-radiation followed by interventional radiotherapy (IRT) is the standard of care for stage IB-IVA FIGO. Several studies have shown that image-guided adaptive IRT resulted in excellent local and pelvic control, but it is associated with vaginal toxicity and intercourse problems. The purpose of this review is to evaluate the dysfunctions of the sexual sphere in patients with cervical cancer undergoing different cervix cancer treatments. Materials and Methods: We performed a comprehensive literature search using Pub med, Scopus and Cochrane to identify all the full articles evaluating the dysfunctions of the sexual sphere. ClinicalTrials.gov was searched for ongoing or recently completed trials, and PROSPERO was searched for ongoing or recently completed systematic reviews. Results: One thousand three hundred fifty-six women included in five studies published from 2016 to 2022 were analyzed. The median age was 50 years (range 46-56 years). The median follow-up was 12 months (range 0-60). Cervical cancer diagnosis and treatment (radiotherapy, chemotherapy and surgery) negatively affected sexual intercourse. Sexual symptoms such as fibrosis, strictures, decreased elasticity and depth and mucosal atrophy promote sexual dysfunction by causing frigidity, lack of lubrication, arousal, orgasm and libido and dyspareunia. Conclusions: Physical, physiological and social factors all contribute to the modification of the sexual sphere. Cervical cancer survivors who were irradiated have lower sexual and vaginal function than the normal population. Although there are cures for reducing discomfort, effective communication about sexual dysfunctions following treatment is essential.

Long-Term Outcomes of Local Excision Following Neoadjuvant Chemoradiotherapy for Locally Advanced Rectal Cancer.

BACKGROUND: Local excision might represent an alternative to total mesorectal excision for patients with locally advanced rectal cancer who achieve a major or complete clinical response after neoadjuvant chemoradiotherapy. METHODS: Between August 2005 and July 2011, 63 patients with mid-low rectal adenocarcinoma who had a major/complete clinical response after neoadjuvant chemoradiotherapy were enrolled in a multicenter prospective phase 2 trial and underwent transanal full thickness local excision. The main endpoint of this study was to evaluate the 5- and 10-year overall, relapse-free, local, and distant relapse-free survival, which were calculated by applying the Kaplan-Meier method. The rate of patients with rectum preserved and without stoma were also calculated. RESULTS: Of 63 patients, 38 (60%) were male and 25 (40%) were female, with a median (range) age of 64 (25-82) years. At baseline, the following clinical stages were found: cT2, n = 21 (33.3%); cT3, n = 42 (66.6%), 39 (61.9%) patients were cN+. At a median (range) follow-up of 108 (32-166) months, the estimated cumulative 5- and 10-year overall survival, relapse-free survival, local recurrence-free survival, and distant recurrence-free survival were 87% (95% CI 76-93) and 79% (95% CI 66-87), 89% (95% CI 78-94) and 82% (95% CI 66-91), both 91% (95% CI 81-96), and 90% (95% CI 80-95) and 86% (95% CI 73-93), respectively. Overall, 49 (77.8%) patients had their rectum preserved, and 54 (84.1%) were stoma-free. CONCLUSION: In highly selected patients, the local excision approach after neoadjuvant chemoradiotherapy is associated with excellent long-term outcomes, high rates of rectum preservation and absence of permanent stoma.

Perspectives and limits of cancer treatment in an oldest old population.

BACKGROUND: Population of oldest old will grow dramatically in the next future and cancer, physiologically related to aging, will be very prevalent among them. Lack of evidence is a huge problem to manage cancer in oldest old and will be more and more in the next years. AIMS: Our purpose was to investigate the characteristics of a population of oldest old patients with cancer treated in the Radiation Oncology Unit of Fondazione Policlinico A. Gemelli IRCCS. METHODS: We conducted a retrospective study. The primary outcome was to evaluate which characteristics of the population could influence the choice of oncological treatment (with radical or non-radical intent). RESULTS: We identified a total of 348 patients: 140 were on follow-up; 177 were under treatment; 31 were considered not eligible for treatments. Patients under treatment had a high comorbidity index (mean Charlson Comorbidity Index 5.4), and a high prevalence of polypharmacy (mean number of drugs 5.6). More than half (53.1%) was treated with radical intent. Patients treated with radical intent were 1 year younger (87.1 years old vs 88.1 years old), more performant (ECOG 0.7 vs 1.3), and had less prevalence of metastatic neoplasia (6.4% vs 34.9%); comorbidities and drugs did not show differences in the two groups. CONCLUSION: Oldest old, usually not considered in international guidelines, are treated for oncological disease, often with radical intent. The treatment seems not to be tailored considering comorbidities but on performance status.