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.

Machine-learning prediction of treatment response to stereotactic body radiation therapy in oligometastatic gynecological cancer: A multi-institutional study.

BACKGROUND AND PURPOSE: We aimed to develop and validate different machine-learning (ML) prediction models for the complete response of oligometastatic gynecological cancer after SBRT. MATERIAL AND METHODS: One hundred fifty-seven patients with 272 lesions from 14 different institutions and treated with SBRT with radical intent were included. Thirteen datasets including 222 lesions were combined for model training and internal validation purposes, with an 80:20 ratio. The external testing dataset was selected as the fourteenth Institution with 50 lesions. Lesions that achieved complete response (CR) were defined as responders. Prognostic clinical and dosimetric variables were selected using the LASSO algorithm. Six supervised ML models, including logistic regression (LR), classification and regression tree analysis (CART) and support vector machine (SVM) using four different kernels, were trained and tested to predict the complete response of uterine lesions after SBRT. The performance of models was assessed by receiver operating characteristic curves (ROC), area under the curve (AUC) and calibration curves. An explainable approach based on SHapley Additive exPlanations (SHAP) method was deployed to generate individual explanations of the model's decisions. RESULTS: 63.6% of lesions had a complete response and were used as ground truth for the supervised models. LASSO strongly associated complete response with three variables, namely the lesion volume (PTV), the type of lesions (lymph-nodal versus parenchymal), and the biological effective dose (BED10), that were used as input for ML modeling. In the training set, the AUCs for complete response were 0.751 (95% CI: 0.716-0.786), 0.766 (95% CI: 0.729-0.802) and 0.800 (95% CI: 0.742-0.857) for the LR, CART and SVM with a radial basis function kernel, respectively. These models achieve AUC values of 0.727 (95% CI: 0.669-0.795), 0.734 (95% CI: 0.649-0.815) and 0.771 (95% CI: 0.717-0.824) in the external testing set, demonstrating excellent generalizability. CONCLUSION: ML models enable a reliable prediction of the treatment response of oligometastatic lesions receiving SBRT. This approach may assist radiation oncologists to tailor more individualized treatment plans for oligometastatic patients.

Efficacy and Safety of Stereotactic Body Radiation Therapy in Oligometastatic Uterine Cancer (MITO-RT2/RAD): A Large, Real-World Study in Collaboration With Italian Association of Radiation Oncology, Multicenter Italian Trials in Ovarian Cancer, and Mario Negri Gynecologic Oncology Group Groups.

PURPOSE: This retrospective, multicenter study analyzes the efficacy and safety of stereotactic body radiation therapy in a large cohort of patients with oligometastatic/persistent/recurrent uterine cancer. METHODS AND MATERIALS: Clinical and radiation therapy data from several radiation therapy centers treating patients by stereotactic body radiation therapy between March 2006 and October 2021 were collected. Objective response rate was defined as complete and partial response, and 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. Primary endpoints were the rate of complete response to stereotactic body radiation therapy, and the 2-year actuarial local control rate "per-lesion" basis. Secondary endpoints were progression-free survival and overall survival, as well as toxicity. RESULTS: In the study, 157 patients with oligometastatic/persistent/recurrent uterine cancer bearing 272 lesions treated by stereotactic body radiation therapy at 14 centers were analyzed. Lymph node metastases (137, 50.4%) were prevalent, followed by parenchyma lesions (135, 49.6%). Median total dose was 35 Gy (10-75.2), in 5 fractions (range, 1-10). Complete and partial responses were 174 (64.0%), and 54 (19.9%), respectively. Stable disease was registered in 29 (10.6%), and 15 (5.5%) lesions progressed. Type of lesion (lymph node), volume (≤13.7 cc) and total dose (BED10 >59.5 Gy) were significantly associated with a higher probability of achieving complete response. Patients achieving complete response (CR) "per-lesion" basis experienced a 2-year actuarial local control rate of 92.4% versus 33.5% in lesions not achieving complete response (NCR; P < .001). Moreover, the 2-year actuarial progression-free survival rate in patients with CR was 45.4%, and patients with NCR had a 2-year rate of 17.6% (P < .001). Finally, patients who had a CR had a 2-year overall survival rate of 82.7%, compared with 56.5% for NCR patients (P <.001). Severe acute toxicity was around 2%, including one toxic death due to gastric perforation, and severe late toxicity around 4%. CONCLUSIONS: The efficacy of stereotactic body radiation therapy in this setting was confirmed. The low toxicity profile and the high local control rate in complete responder patients encourage the wider use of this approach.

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.

Exclusive Radiotherapy for Early-stage Glottic Cancer: A Single-institution Retrospective Analysis with a Focus on Voice Quality.

AIM: To report on clinical outcomes of patients with early-stage glottic cancer treated with exclusive radiotherapy with specific analysis of voice quality. PATIENTS AND METHODS: A consecutive cohort of 55 patients with early glottic cancer was retrospectively analyzed. Patients were treated with exclusive radiation up to a conventionally fractionated total dose of 66-70 Gy with a 3-dimensional conformal technique. Oncological outcomes and toxicity profiles were investigated. A sub-sample of this cohort was also analyzed in terms of voice quality employing subjective and objective tools such as the Voice Handicap Index-10 (VHI-10) and the Multidimensional Voice Program (MDVP™) software and was compared to a group of similar patients treated with CO2 laser cordectomy. RESULTS: after a median observation time of 74.5 months, 5- and 10-year local control was 89% [95% confidence interval (CI)=70.7-93.1%] and 86% (95% CI=68.7-89.6%), respectively. Larynx-preservation rate was 91.8% (95% CI=82.4%-94.9%) at 10 years. Five- and 10-year actuarial overall survival was 72% (95% CI=50.4-79.2%) and 56% (95% CI=48.7-64.3%). Maximum detected acute toxicity included G3 dermatitis (5.4%) and G4 dyspnea (1.8%). Late toxicity profile was mild. VHI-10 scores showed a mild voice disability in both groups, with no statistically significant difference (p=0.12), even when investigating different domains. Patients treated with radiation had a lower deterioration rate in all parameters excluding low voice, interruptions of sound and diplophony. CONCLUSION: Exclusive radiation proved an effective treatment for patients with early glottic cancer in terms of both oncological outcome and voice quality.

Conventional 2D (2DRT) and 3D conformal radiotherapy (3DCRT) versus intensity-modulated radiotherapy (IMRT) for nasopharyngeal cancer treatment.

PURPOSE: Nasopharyngeal carcinoma represents a distinct entity as compared to other head and neck tumours. Radio-chemotherapy is the treatment of first choice in non-metastatic disease. Intensity-modulated radiation therapy (IMRT) allows the sparing of parotid glands, improving the toxicity profile. The aim of this study was to compare the results obtained with IMRT with those obtained with conventional 2D (2DRT) and 3D conformal radiation therapy (3DCRT) in terms of tumour control, survival, acute and late toxicity. MATERIALS AND METHODS: We reviewed the clinical records of 52 patients with histologically proven carcinoma of the nasopharynx (stage I-IVB according to the 2002 American Joint Committee on Cancer staging system) treated with curative intent between January 2003 and August 2011: 26 patients were treated with 2D or 3D technique (arm A) and 26 with IMRT technique (arm B) with simultaneous integrated boost. Fifty patients (96 %) received chemotherapy. Local control (LC), locoregional control (LRC), disease-free survival (DFS), overall survival (OS), acute and late toxicity were retrospectively evaluated. RESULTS: After a median follow-up of 37.6 months (69 months in arm A and 23 months in arm B), 69 % of patients were alive and disease-free, 10 % were alive with disease and 21 % died of disease, with an OS of 81 % at 2 years and 79 % at 5 years, a LC rate of 88 % at 2 years and 78 % at 5 years, a LRC rate of 80 % at 2 years and 73 % at 5 years and a DFS of 74 % at 2 years and 65 % at 5 years, with no statistically significant differences between IMRT and 2DRT/3DCRT. In multivariate analysis, the TNM stage and the volume treated at high dose correlated with DFS. No factor was found to be related to OS. Chronic toxicity was not statistically different in the two study groups and in particular ≥ G2 xerostomia rates were 67 and 41 % in arm A and B, respectively (p = 0.10). CONCLUSIONS: The findings of this study confirm that IMRT associated with chemotherapy, even with moderately hypofractionated regimens, allows good disease control with better results in terms of late xerostomia, although without statistically significant differences compared to 2DRT and 3DCRT. The hypothesis of an impact of IMRT on survival has yet to be confirmed.

Concurrent intra-arterial carboplatin administration and radiation therapy for the treatment of advanced head and neck squamous cell carcinoma: short term results.

BACKGROUND: The aim of the present study was to evaluate the survival, efficacy and safety of a modified RADPLAT-like protocol using carboplatin instead of cisplatin. METHODS: Fifty-six patients with primary head and neck squamous cell carcinoma received 4 cycles of intra-arterial carboplatin (350 mg/m2 per cycle every 2 weeks), with concurrent three-dimensional conformal radiation therapy. RESULTS: Two major and 4 minor complications were observed. Forty-five of the 56 patients (80%) completed the protocol, while 11 (20%) patients had to discontinue the intra-arterial infusions due to the occurrence of severe haematological toxicity, but were able to complete radiotherapy. Forty-four (98%) of the 45 patients who completed the protocol and 10 (91%) of the 11 who did not, were free of disease at the end of the treatment, for a comprehensive 96% of CR overall. After a median 23.55 months (range: 2 to 58 months) of follow-up, 40 patients (71%) are alive and disease-free, 1 (2%) is alive but affected by disease and 15 (27%) have died of the disease or other causes. CONCLUSION: Intra-arterial carboplatin administration with concurrent three-dimensional conformal radiation therapy seems to be a promising alternative to RADPLAT in the treatment of advanced head and neck tumours. Haematological and non-haematological toxicities are virtually similar, but carboplatin has the advantage in that it is not nephrotoxic and can be used at very high doses without any significant increase in the extent of side effects.

Usability of institutional cancer web sites: an Italian case study.

In order to evaluate if and to what extent Italian speaking cancer patients can benefit from information available on cancer web sites, an "in vitro" usability (ISO definition) study has been carried out. It investigated the usability of the web sites of the most representative Italian Institutions in the oncological field for the adult patients needing to find information about head and neck cancer. Specific evaluation criteria from the literature were used. The results point out some problems about accessibility, in line with other studies, and about the usefulness of the contents, in particular in the web sites of care delivery institutions: a grey present situation, but there are already grounds for significant improvement. Institutions and organizations must not waste the opportunity of being valuable sources in order to build the so called "informed patient," and the usability of their web sites could make the difference.