Stereotactic body radiotherapy for primary renal cell carcinoma: a systematic review and practice guideline from the International Society of Stereotactic Radiosurgery (ISRS).

Surgery is the standard of care for patients with primary renal cell carcinoma. Stereotactic body radiotherapy (SBRT) is a novel alternative for patients who are medically inoperable, technically high risk, or who decline surgery. Evidence for using SBRT in the primary renal cell carcinoma setting is growing, including several rigorously conducted prospective clinical trials. This systematic review was performed to assess the safety and efficacy of SBRT for primary renal cell carcinoma. Review results then formed the basis for the practice guidelines described, on behalf of the International Stereotactic Radiosurgery Society. 3972 publications were screened and 36 studies (822 patients) were included in the analysis. Median local control rate was 94·1% (range 70·0-100), 5-year progression-free survival was 80·5% (95% CI 72-92), and 5-year overall survival was 77·2% (95% CI 65-89). These practice guidelines addressed four key clinical questions. First, the optimal dose fractionation was 25-26 Gy in one fraction, or 42-48 Gy in three fractions for larger tumours. Second, routine post-treatment biopsy is not recommended as it is not predictive of patient outcome. Third, SBRT for primary renal cell carcinoma in a solitary kidney is safe and effective. Finally, guidelines for post-treatment follow-up are described, which include cross-axial imaging of the abdomen including both kidneys, adrenals, and surveillance of the chest initially every 6 months. This systematic review and practice guideline support the practice of SBRT for primary renal cell carcinoma as a safe and effective standard treatment option. Randomised trials with surgery and invasive ablative therapies are needed to further define best practice.

Long term update on toxicity and survival of a phase II trial of linac-based stereotactic body radiation therapy for low-intermediate risk prostate cancer.

BACKGROUND: In 2016 we published a phase II study exploring safety and efficacy of Stereotactic Body Radiation Therapy (SBRT) delivered with Volumetric Modulated Arc Therapy (VMAT) and Flattening Filter Free (FFF) beams techniques in prostate cancer (PC) patients. We present herein the updated results on late toxicity and long-term survival. METHODS: Patients enrolled in the study had a biopsy-confirmed localized PC and the features of a low- or intermediate-risk disease (National Comprehensive Network Criteria). The radiotherapy (RT) schedule consisted of 35 Gy delivered in five fractions every other day. Toxicities were registered according to the common toxicity adverse events v4.0. Biochemical recurrence was defined as an increase of prostate specific antigen after nadir, confirmed at least once. Local recurrence (LR) and distant metastases were detected either with Choline- or PSMA-PET/CT scans. Kaplan-Meier curves for Biochemical Recurrence-Free Survival (BFS), Local Control (LC), Distant Metastasis Free Survival (DMFS) and Cancer Specific Survival, were calculated by using MedCalc. RESULTS: Ninety patients were submitted to SBRT between February 2012 and March 2015. Fifty-eight patients (64.5%) had a Gleason Score of 6, while 32 (35.5%) had a Gleason Score of 7. A late grade 1 Genito-Urinary toxicity was observed in 54.5% of patients while a grade 2 in 3.3%. A late Gastro-intestinal grade 1 toxicity was reported in 18.9% of patients, while a grade 2 in 2.2%. Erectile dysfunction was reported by 13% of patients No heavier toxicities were observed. At a median follow-up of 102 months, 5- and 8-year BFS were 93.0% and 84.4% respectively, 5- and 8-year LC were 95.2% and 87.0% respectively, 5- and 8-year DMFS were 95.3% and 88.4%, respectively. CONCLUSIONS: This long-term update confirms that SBRT is a valid therapeutic strategy for low-intermediate risk PC. RT with VMAT and FFF warrants optimal results in terms of toxicity and disease control.

Repeat Gamma Knife radiosurgery for recurrent trigeminal neuralgia in patients with multiple sclerosis: a single-center retrospective study.

PURPOSE: Gamma Knife radiosurgery (GKRS) has emerged as an effective treatment option for trigeminal neuralgia (TN) in patients with multiple sclerosis (MS). To date, the outcomes of repeat GKRS for patients with TN and MS with recurrent pain have been investigated in a few patients. This study aims to report the outcomes and predictive factors of pain reduction for MS patients undergoing repeat GKRS for recurrent TN. METHODS: Eighteen patients with MS underwent repeat GKRS for recurrent TN. A retrospective chart review and telephone interviews were conducted to determine background medical history, dosimetric data, and outcomes of the procedure. Facial pain and sensory function were evaluated using the Barrow Neurological Institute (BNI) scales. RESULTS: Fifteen patients achieved a BNI pain score of IIIa or better, indicating pain reduction, within a median period of 21 days after repeat GKRS. The maximum dose for repeat GKRS ranged from 70 to 85 Gy. Pain recurred in 5 patients after a median period of 12 months after GKRS. Percentages of patients with pain reduction at 1, 2, 3, 5, and 7 years were 60%, 60%, 50%, 50%, and 50%, respectively. Older age at repeat GKRS predicted sustained pain reduction (P = 0.01). Seven patients developed facial sensory disturbances, which were bothersome in two patients. CONCLUSIONS: Repeat GKRS may be used as an effective treatment modality for prolonging the duration of pain reduction time in patients with MS and TN. After repeat GKRS, facial sensory disturbances are common; however, they are often not bothersome.

Supramaximal resection: retrospective study on IDH-wildtype Glioblastomas based on the new RANO-Resect classification.

BACKGROUND: The prognostic value of the extent of resection in the management of Glioblastoma is a long-debated topic, recently widened by the 2022 RANO-Resect Classification, which advocates for the resection of the non-enhancing disease surrounding the main core of tumors (supramaximal resection, SUPR) to achieve additional survival benefits. We conducted a retrospective analysis to corroborate the role of SUPR by the RANO-Resect Classification in a single center, homogenous cohort of patients. METHODS: Records of patients operated for WHO-2021 Glioblastomas at our institution between 2007 and 2018 were retrospectively reviewed; volumetric data of resected lesions were computed and classified by RANO-Resect criteria. Survival and correlation analyses were conducted excluding patients below near-total resection. RESULTS: 117 patients met the inclusion criteria, encompassing 45 near-total resections (NTR), 31 complete resections (CR), and 41 SUPR. Median progression-free and overall survival were 11 and 15 months for NTR, 13 and 17 months or CR, 20 and 24 months for SUPR, respectively (p < 0.001), with inverse correlation observed between survival and FLAIR residual volume (r -0.28). SUPR was not significantly associated with larger preoperative volumes or higher rates of postoperative deficits, although it was less associated with preoperative neurological deficits (OR 3.37, p = 0.003). The impact of SUPR on OS varied between MGMT unmethylated (HR 0.606, p = 0.044) and methylated (HR 0.273, p = 0.002) patient groups. CONCLUSIONS: Results of the present study support the validity of supramaximal resection by the new RANO-Resect classification, also highlighting a possible surgical difference between tumors with methylated and unmethylated MGMT promoter.

Deep learning and atlas-based models to streamline the segmentation workflow of total marrow and lymphoid irradiation.

PURPOSE: To improve the workflow of total marrow and lymphoid irradiation (TMLI) by enhancing the delineation of organs at risk (OARs) and clinical target volume (CTV) using deep learning (DL) and atlas-based (AB) segmentation models. MATERIALS AND METHODS: Ninety-five TMLI plans optimized in our institute were analyzed. Two commercial DL software were tested for segmenting 18 OARs. An AB model for lymph node CTV (CTV_LN) delineation was built using 20 TMLI patients. The AB model was evaluated on 20 independent patients, and a semiautomatic approach was tested by correcting the automatic contours. The generated OARs and CTV_LN contours were compared to manual contours in terms of topological agreement, dose statistics, and time workload. A clinical decision tree was developed to define a specific contouring strategy for each OAR. RESULTS: The two DL models achieved a median [interquartile range] dice similarity coefficient (DSC) of 0.84 [0.71;0.93] and 0.85 [0.70;0.93] across the OARs. The absolute median Dmean difference between manual and the two DL models was 2.0 [0.7;6.6]% and 2.4 [0.9;7.1]%. The AB model achieved a median DSC of 0.70 [0.66;0.74] for CTV_LN delineation, increasing to 0.94 [0.94;0.95] after manual revision, with minimal Dmean differences. Since September 2022, our institution has implemented DL and AB models for all TMLI patients, reducing from 5 to 2 h the time required to complete the entire segmentation process. CONCLUSION: DL models can streamline the TMLI contouring process of OARs. Manual revision is still necessary for lymph node delineation using AB models.

Metastases-directed stereotactic body radiotherapy in combination with targeted therapy or immunotherapy: systematic review and consensus recommendations by the EORTC-ESTRO OligoCare consortium.

Stereotactic body radiotherapy (SBRT) for patients with metastatic cancer, especially when characterised by a low tumour burden (ie, oligometastatic disease), receiving targeted therapy or immunotherapy has become a frequently practised and guideline-supported treatment strategy. Despite the increasing use in routine clinical practice, there is little information on the safety of combining SBRT with modern targeted therapy or immunotherapy and a paucity of high-level evidence to guide clinical management. A systematic literature review was performed to identify the toxicity profiles of combined metastases-directed SBRT and targeted therapy or immunotherapy. These results served as the basis for an international Delphi consensus process among 28 interdisciplinary experts who are members of the European Society for Radiotherapy and Oncology (ESTRO) and European Organisation for Research and Treatment of Cancer (EORTC) OligoCare consortium. Consensus was sought about risk mitigation strategies of metastases-directed SBRT combined with targeted therapy or immunotherapy; a potential need for and length of interruption to targeted therapy or immunotherapy around SBRT delivery; and potential adaptations of radiation dose and fractionation. Results of this systematic review and consensus process compile the best available evidence for safe combination of metastases-directed SBRT and targeted therapy or immunotherapy for patients with metastatic or oligometastatic cancer and aim to guide today's clinical practice and the design of future clinical trials.

PSMA guided approach for bIoCHEmical relapse after prostatectomy- (PSICHE) trial (NCT05022914). Detection rate and treatment decision after 68Ga-PSMA PET/CT within a prospective study.

BACKGROUND: Ultrasensitive imaging has been demonstrated to influence biochemical relapse treatment. PSICHE is a multicentric prospective study, aimed at exploring detection rate with 68Ga-PSMA-11 positron emission tomography/computed tomography (PET/CT) and outcomes with a predefined treatment algorithm tailored to the imaging. METHODS: Patients affected by biochemical recurrence after surgery (prostate specific antigen [PSA] > 0.2 < 1 ng/mL) underwent staging with 68Ga-PSMA PET/CT. Management followed this treatment algorithm accordingly with PSMA results: prostate bed salvage radiotherapy (SRT) if negative or positive within prostate bed, stereotactic body radiotherapy (SBRT) if pelvic nodal recurrences or oligometastatic disease, androgen deprivation therapy (ADT) if nonoligometastatic disease. Chi-square test was used to evaluate the relationship between baseline features and rate of positive PSMA PET/CT. RESULTS: One hundred patients were enrolled. PSMA results were negative/positive in the prostate bed in 72 patients, pelvic nodal or extrapelvic metastatic disease were detected in 23 and 5 patients. Twenty-one patients underwent observation because of prior postoperative radiotherapy (RT)/treatment refusal. Fifty patients were treated with prostate bed SRT, 23 patients underwent SBRT to pelvic nodal disease, five patients were treated with SBRT to oligometastatic disease. One patient underwent ADT. NCCN high-risk features, stage > pT3 and ISUP score >3 reported a significantly higher rate of positive PSMA PET/CT after restaging (p = 0.01, p = 0.02, and p = 0.002). By quartiles of PSA, rate of positive PSMA PET/CT was 26.9% (>0.2; <0.29 ng/mL), 24% (>0.3; <0.37 ng/mL), 26.9% (>0.38; <0.51 ng/mL), and 34.7% (>0. 52; <0.98 ng/mL). CONCLUSIONS: PSICHE trial constitute a useful platform to collect data within a clinical framework where modern imaging and metastasis-directed therapy are integrated.

Sentinel lymph node biopsy versus axillary lymph node dissection in breast cancer patients undergoing mastectomy with one to two metastatic sentinel lymph nodes: sub-analysis of the SINODAR-ONE multicentre randomized clinical trial and reopening of enrolment.

BACKGROUND: The initial results of the SINODAR-ONE randomized clinical trial reported that patients with T1-2 breast cancer and one to two macrometastatic sentinel lymph nodes treated with breast-conserving surgery, sentinel lymph node biopsy only, and adjuvant therapy did not present worse 3-year survival, regional recurrence, or distant recurrence rates compared with those treated with axillary lymph node dissection. To extend the recommendation of axillary lymph node dissection omission even in patients treated with mastectomy, a sub-analysis of the SINODAR-ONE trial is presented here. METHODS: Patients with T1-2 breast cancer and no more than two metastatic sentinel lymph nodes undergoing mastectomy were analysed. After sentinel lymph node biopsy, patients were randomly assigned to receive either axillary lymph node dissection followed by adjuvant treatment (standard arm) or adjuvant treatment alone (experimental arm). The primary endpoint was overall survival. The secondary endpoint was recurrence-free survival. RESULTS: A total of 218 patients were treated with mastectomy; 111 were randomly assigned to the axillary lymph node dissection group and 107 to the sentinel lymph node biopsy-only group. At a median follow-up of 33.0 months, there were three deaths (two deaths in the axillary lymph node dissection group and one death in the sentinel lymph node biopsy-only group). There were five recurrences in each treatment arm. No axillary lymph node recurrence was observed. The 5-year overall survival rates were 97.8 and 98.7 per cent in the axillary lymph node dissection treatment arm and the sentinel lymph node biopsy-only treatment arm, respectively (P = 0.597). The 5-year recurrence-free survival rates were 95.7 and 94.1 per cent in the axillary lymph node dissection treatment arm and the sentinel lymph node biopsy treatment arm, respectively (P = 0.821). CONCLUSION: In patients with T1-2 breast cancer and one to two macrometastatic sentinel lymph nodes treated with mastectomy, the overall survival and recurrence-free survival rates of patients treated with sentinel lymph node biopsy only were not inferior to those treated with axillary lymph node dissection. To strengthen the conclusion of the trial, the enrolment of patients treated with mastectomy was reopened as a single-arm experimental study. REGISTRATION NUMBER: NCT05160324 (http://www.clinicaltrials.gov).

Automatic planning of the lower extremities for total marrow irradiation using volumetric modulated arc therapy.

PURPOSE: Total marrow (and lymphoid) irradiation (TMI-TMLI) is limited by the couch travel range of modern linacs, which forces the treatment delivery to be split into two plans with opposite orientations: a head-first supine upper-body plan, and a feet-first supine lower extremities plan. A specific field junction is thus needed to obtain adequate target coverage in the overlap region of the two plans. In this study, an automatic procedure was developed for field junction creation and lower extremities plan optimization. METHODS: Ten patients treated with TMI-TMLI at our institution were selected retrospectively. The planning of the lower extremities was performed automatically. Target volume parameters (CTV_J­V98% > 98%) at the junction region and several dose statistics (D98%, Dmean, and D2%) were compared between automatic and manual plans. The modulation complexity score (MCS) was used to assess plan complexity. RESULTS: The automatic procedure required 60-90 min, depending on the case. All automatic plans achieved clinically acceptable dosimetric results (CTV_J­V98% > 98%), with significant differences found at the junction region, where Dmean and D2% increased on average by 2.4% (p < 0.03) and 3.0% (p < 0.02), respectively. Similar plan complexity was observed (median MCS = 0.12). Since March 2022, the automatic procedure has been introduced in our clinic, reducing the TMI-TMLI simulation-to-delivery schedule by 2 days. CONCLUSION: The developed procedure allowed treatment planning of TMI-TMLI to be streamlined, increasing efficiency and standardization, preventing human errors, while maintaining the dosimetric plan quality and complexity of manual plans. Automated strategies can simplify the future adoption and clinical implementation of TMI-TMLI treatments in new centers.

The Effect of Adjuvant Radiotherapy on One- and Two-Stage Prosthetic Breast Reconstruction and on Autologous Reconstruction: A Multicenter Italian Study among 18 Senonetwork Breast Centres.

Purpose: In modern breast cancer treatment, a growing role has been observed for breast reconstruction together with an increase in clinical indications for postmastectomy radiotherapy (PMRT). Choosing the optimum type of reconstructive technique is a clinical challenge. We therefore conducted a national multicenter study to analyze the impact of PMRT on breast reconstruction. Methods: We conducted a retrospective case-control multicenter study on women undergoing breast reconstruction. Data were collected from 18 Italian Breast Centres and stored in a cumulative database which included the following: autologous reconstruction, direct-to-implant (DTI), and tissue expander/immediate (TE/I). For all patients, we described complications and surgical endpoints to complications such as reconstruction failure, explant, change in type of reconstruction, and reintervention. Results: From 2001 to April 2020, 3116 patients were evaluated. The risk for any complication was significantly increased in patients receiving PMRT (aOR, 1.73; 95% CI, 1.33-2.24; p < 0.001). PMRT was associated with a significant increase in the risk of capsular contracture in the DTI and TE/I groups (aOR, 2.24; 95% CI, 1.57-3.20; p < 0.001). Comparing type of procedures, the risk of failure (aOR, 1.82; 95% CI, 1.06-3.12, p=0.030), explant (aOR, 3.34; 95% CI, 3.85-7.83, p < 0.001), and severe complications (aOR, 2.54; 95% CI, 1.88-3.43, p < 0.001) were significantly higher in the group undergoing DTI reconstruction as compared to TE/I reconstruction. Conclusion: Our study confirms that autologous reconstruction is the procedure least impacted by PMRT, while DTI appears to be the most impacted by PMRT, when compared with TE/I which shows a lower rate of explant and reconstruction failure. The trial is registered with NCT04783818, and the date of registration is 1 March, 2021, retrospectively registered.

Oncological outcomes of cervical esophageal cancer treated primarily with surgery: a systematic review and meta-analysis.

PURPOSE: To determine the oncological outcomes of cervical esophageal cancer (CEC) treated primarily with surgery. METHODS: A systematic review and meta-analysis was performed according to the PRISMA guidelines. RESULTS: A total of 868 patients were included from 18 studies. Estimated pooled Overall Survival (OS) rates (95% Confidence Interval, CI) at 1 and 5 years were 74.4% (66.5-83.3), and 26.6% (20.3-34.7), respectively. Larynx non-preserving surgery (n = 229) showed an estimated pooled OS rates (95% CI) at 1 and 5 years of 59.3% (51.5-68.2) and 14.6% (8.8-24.3), respectively. On the other hand, larynx preserving surgery (n = 213) showed an estimated pooled OS rates (95% CI) at 1 and 5 years of 83.6% (78.2-89.4) and 35.1% (24.9-49.6), respectively. CONCLUSIONS: Primary larynx-preserving surgery remains a valuable option for the management of CEC, with similar survival outcomes compared to primary chemoradiotherapy (CRT). On the other hand, larynx non-preserving surgery showed a significantly reduced survival, that may reflect the more advanced T classification of these tumors. Further studies are mandatory to directly compare primary surgery and primary CRT, distinguishing larynx preserving and non-preserving surgery.

Evaluation of plan complexity and dosimetric plan quality of total marrow and lymphoid irradiation using volumetric modulated arc therapy.

PURPOSE: To assess the impact of the planner's experience and optimization algorithm on the plan quality and complexity of total marrow and lymphoid irradiation (TMLI) delivered by means of volumetric modulated arc therapy (VMAT) over 2010-2022 at our institute. METHODS: Eighty-two consecutive TMLI plans were considered. Three complexity indices were computed to characterize the plans in terms of leaf gap size, irregularity of beam apertures, and modulation complexity. Dosimetric points of the target volume (D2%) and organs at risk (OAR) (Dmean) were automatically extracted to combine them with plan complexity and obtain a global quality score (GQS). The analysis was stratified based on the different optimization algorithms used over the years, including a knowledge-based (KB) model. Patient-specific quality assurance (QA) using Portal Dosimetry was performed retrospectively, and the gamma agreement index (GAI) was investigated in conjunction with plan complexity. RESULTS: Plan complexity significantly reduced over the years (r = -0.50, p < 0.01). Significant differences in plan complexity and plan dosimetric quality among the different algorithms were observed. Moreover, the KB model allowed to achieve significantly better dosimetric results to the OARs. The plan quality remained similar or even improved during the years and when moving to a newer algorithm, with GQS increasing from 0.019 ± 0.002 to 0.025 ± 0.003 (p < 0.01). The significant correlation between GQS and time (r = 0.33, p = 0.01) indicated that the planner's experience was relevant to improve the plan quality of TMLI plans. Significant correlations between the GAI and the complexity metrics (r = -0.71, p < 0.01) were also found. CONCLUSION: Both the planner's experience and algorithm version are crucial to achieve an optimal plan quality in TMLI plans. Thus, the impact of the optimization algorithm should be carefully evaluated when a new algorithm is introduced and in system upgrades. Knowledge-based strategies can be useful to increase standardization and improve plan quality of TMLI treatments.

Accelerated hypofractionated radiation for elderly or frail patients with a newly diagnosed glioblastoma: A pooled analysis of patient-level data from 4 prospective trials.

BACKGROUND: The standard of care for elderly or frail patients with glioblastoma (GBM) is 40 Gy in 15 fractions of radiotherapy. However, this regimen has a lower biological effective dose (BED) compared with the Stupp regimen of 60 Gy in 30 fractions. It is hypothesized that accelerated hypofractionated radiation of 52.5 Gy in 15 fractions (BED equivalent to Stupp) is safe and efficacious. METHODS: Elderly or frail patients with GBM treated with 52.5 Gy in 15 fractions were pooled from 3 phase 1/2 studies and a prospective observational study. Overall survival (OS) and progression-free survival (PFS) were defined time elapsing between surgery/biopsy and death from any cause or progression of disease. RESULTS: Sixty-two newly diagnosed patients were eligible for this pooled analysis of individual patient data. The majority (66%) had a Karnofsky performance status (KPS) score <70. The median age was 73 years. The median OS and PFS were 10.3 and 6.9 months, respectively. Patients with KPS scores ≥70 and <70 had a median OS of 15.3 and 9.5 months, respectively. Concurrent chemotherapy was an independent prognostic factor for improved PFS and OS. Grade 3 neurologic toxicity was seen in 2 patients (3.2%). There was no grade 4/5 toxicity. CONCLUSIONS: This is the only analysis of elderly/frail patients with GBM prospectively treated with a hypofractionated radiation regimen that is isoeffective to the Stupp regimen. Treatment was well tolerated and demonstrated excellent OS and PFS compared with historical studies. This regimen gives the elderly/frail population an alternative to regimens with a lower BED. Randomized trials are needed to validate these results.

Preservation of Axillary Lymph Nodes Compared with Complete Dissection in T1-2 Breast Cancer Patients Presenting One or Two Metastatic Sentinel Lymph Nodes: The SINODAR-ONE Multicenter Randomized Clinical Trial.

BACKGROUND: The SINODAR-ONE trial is a prospective noninferiority multicenter randomized study aimed at assessing the role of axillary lymph node dissection (ALND) in patients undergoing either breast-conserving surgery or mastectomy for T1-2 breast cancer (BC) and presenting one or two macrometastatic sentinel lymph nodes (SLNs). The endpoints were to evaluate whether SLN biopsy (SLNB) only was associated with worsening of the prognosis compared with ALND in terms of overall survival (OS) and relapse. METHODS: Patients were randomly assigned (1:1 ratio) to either removal of ≥ 10 axillary level I/II non-SLNs followed by adjuvant therapy (standard arm) or no further axillary treatment (experimental arm). RESULTS: The trial started in April 2015 and ceased in April 2020, involving 889 patients. Median follow-up was 34.0 months. There were eight deaths (ALND, 4; SNLB only, 4), with 5-year cumulative mortality of 5.8% and 2.1% in the standard and experimental arm, respectively (p = 0.984). There were 26 recurrences (ALND 11; SNLB only, 15), with 5-year cumulative incidence of recurrence of 6.9% and 3.3% in the standard and experimental arm, respectively (p = 0.444). Only one axillary lymph node recurrence was observed in each arm. The 5-year OS rates were 98.9% and 98.8%, in the ALND and SNLB-only arm, respectively (p = 0.936). CONCLUSIONS: The 3-year survival and relapse rates of T1-2 BC patients with one or two macrometastatic SLNs treated with SLNB only, and adjuvant therapy, were not inferior to those of patients treated with ALND. These results do not support the use of routine ALND.

Radiomics-based prognosis classification for high-risk prostate cancer treated with radiotherapy.

OBJECTIVE: The present study aimed to investigate if CT-based radiomics features could correlate to the risk of metastatic progression in high-risk prostate cancer patients treated with radical RT and long-term androgen deprivation therapy (ADT). MATERIALS AND METHODS: A total of 157 patients were investigated and radiomics features extracted from the contrast-free treatment planning CT series. Three volumes were segmented: the prostate gland only (CTV_p), the prostate gland with seminal vesicles (CTV_psv), and the seminal vesicles only (CTV_sv). The patients were split into two subgroups of 100 and 57 patients for training and validation. Five clinical and 62 radiomics features were included in the analysis. Considering metastases-free survival (MFS) as an endpoint, the predictive model was used to identify the subgroups with favorable or unfavorable prognoses (separated by a threshold selected according to the Youden method). Pure clinical, pure radiomic, and combined predictive models were investigated. RESULTS: With a median follow-up of 30.7 months, the MFS at 1 and 3 years was 97.2% ± 1.5 and 92.1% ± 2.0, respectively. Univariate analysis identified seven potential predictors for MFS in the CTV_p group, 11 in the CTV_psv group, and 9 in the CTV_sv group. After elastic net reduction, these were 4 predictors for MFS in the CTV_p group (positive lymph nodes, Gleason score, H_Skewness, and NGLDM_Contrast), 5 in the CTV_psv group (positive lymph nodes, Gleason score, H_Skewnesss, Shape_Surface, and NGLDM_Contrast), and 6 in the CTV_sv group (positive lymph nodes, Gleason score, H_Kurtosis, GLCM_Correlation, GLRLM_LRHGE, and GLZLM_SZLGE). The patients' group of the training and validation cohorts were stratified into favorable and unfavorable prognosis subgroups. For the combined model, for CTV_p, the mean MFS was 134 ± 14.5 vs. 96.9 ± 22.2 months for the favorable and unfavorable subgroups, respectively, and 136.5 ± 14.6 vs. 70.5 ± 4.3 months for CTV_psv and 150.0 ± 4.2 vs. 91.1 ± 8.6 months for CTV_sv, respectively. CONCLUSION: Radiomic features were able to predict the risk of metastatic progression in high-risk prostate cancer. Combining the radiomic features and clinical characteristics can classify high-risk patients into favorable and unfavorable prognostic groups.

Oligoscore: a clinical score to predict overall survival in patients with oligometastatic disease treated with stereotactic body radiotherapy.

BACKGROUND: to find clinical features that can predict prognosis in patients with oligometastatic disease treated with stereotactic body radiotherapy (SBRT). MATERIAL AND METHODS: Patients with less than 5 metastases in less than 3 different body sites were included in the analysis. Various clinical and treatment parameters were analyzed to create a Cox proportional hazard model for Overall Survival (OS). Subsequently, significant variables were used to create a score. RESULTS: 997 patients were analyzed. Median OS was 2.61 years, 1 and 3 years OS was respectively 85% and 43%. Location of the primary tumor, performance status, site of irradiated metastases, presence of extratarget non irradiated lesions and RT dose were significant prognostic factors for OS. These parameters were used to create a score and to distinguish three different classes, with median OS of 5.67 years in low risk, 2.47 years in intermediate risk and 1.82 years in high risk group. CONCLUSION: moving from easily accessible clinical parameters, a score was created to help the physician's decision about the better treatment or combination of treatments for the individual patient.

Metastatic salivary gland carcinoma: A role for stereotactic body radiation therapy? A study of AIRO-Head and Neck working group.

OBJECTIVES: The role of radiotherapy (RT) for oligometastases is currently established in different oncological settings but data on salivary gland cancer (SGC) are lacking. We evaluated the role of RT in oligometastatic SGC patients, focusing on stereotactic body radiation therapy (SBRT). MATERIALS AND METHODS: We performed a retrospective, multicentric study of oligometastatic SGC treated with palliative RT or SBRT. Endpoints included response evaluation and local control (LC). RESULTS: Between 2006 and 2016, 64 patients were collected from 9 Italian Cancer Centers, on behalf of the Italian Association of Radiotherapy and Clinical Oncology (AIRO) Head and Neck Working Group. 37 patients (57.8%) were suffering from adenoid cystic carcinoma (ACC) and 27 patients (42.2%) had non-ACC. Thirty-four patients underwent palliative RT (53,1%), and 30 received SBRT (46,9%). Most common metastatic sites were bone for palliative RT and lung for SBRT. Among patients treated with SBRT, an objective response or a stability was observed in all treated lesions. After a median follow-up of 29.2 months (range 2.3-117.1), LC at 12 months was 57.5% for patients treated with SBRT and was higher in ACC subgroup. CONCLUSION: We confirmed the potential role of SBRT in the management of oligometastatic SGC patients to control limited burden of disease considering the absence of effective systemic therapies.

Discrepancies between UICC and AJCC TNM classifications for oral cavity tumors in the 8th editions and following versions.

PURPOSE: To underline discrepancies between the Union for International Cancer Control (UICC) and the American Joint Committee on Cancer (AJCC) Tumor-Node-Metastasis (TNM) classifications in oral cavity cancer. METHODS: Comparison between the UICC and AJCC TNM classifications of oral cavity cancer in their 8th editions and following versions. RESULTS: The most important update was the introduction of the depth of infiltration (DOI), which reflects the proximity of the tumor to the underlying lymphovascular tissues and was associated to the presence of nodal metastases. Since the first publication of the 8th edition of the AJCC Cancer Staging Manual on March 30, 2017, two further versions have been published, while the UICC TNM classification was left unchanged until a document containing modifications to the 8th edition of the UICC TNM Classification of Malignant Tumours was published online on October 6, 2020. CONCLUSION: Different versions of the TNM classification can be confounding for the scientific community. Citing the 8th edition of the UICC TNM Classification of Malignant Tumours or the AJCC Cancer Staging Manual without specifying the precise version used for classification may be insufficient. Clinicians and researchers are invited to always refer to the latest update of each classification.

Moderate hypofractionated radiotherapy for post-operative treatment of prostate cancer: long-term outcome and pattern of toxicity.

OBJECTIVE: Postoperative radiotherapy (RT) is an established treatment for prostate cancer (PC). Though hypofractionation is commonly used for radical treatments, open issues still remain in the postoperative setting due to the lack of long-term data. Aim of this study was to evaluate long-term results of postoperative moderately hypofractionated RT (MHRT). METHODS: We conducted a retrospective analysis including PC patients treated with prostatectomy and postoperative MHRT delivered with volumetric modulated arc therapy (VMAT). Endpoints of the analysis included biochemical relapse-free survival (BRFS), distant metastases free-survival (DMFS), overall survival (OS), and pattern of acute and late toxicity. RESULTS: 181 patients were included. Pathological stage was classified as pT3a in 33.6% and pT3b in 30%. Median PSA value before RT was 0.23 ng/ml and median RT total dose was 70 Gy (65-74.2 Gy) in 25/28 fractions. With a median follow-up of 54.5 months, rates of BRFS at 3 and 5 years were 80.7 and 72.3%. ISUP grade group (HR 1.44, p = 0.015), pathological T stage (HR 2.03; p = 0.009), and pre-RT PSA >0.2 ng/ml (HR 2.64; p = 0.015) were correlated with BRFS. Three and 5­year DMFS were 87.4 and 80.8%. ISUP grade group (HR 1.50; p = 0.011) and pre-RT PSA (HR 5.34; p = 0.001) were correlated with DMFS. Five (2.7%) and 3 (1.6%) patients reported late grade 3 GU and GI toxicity, respectively. CONCLUSION: Our results confirm the long-term safety and efficacy of postoperative MHRT for PC. ADVANCES IN KNOWLEDGE: The present paper demonstrates the long-term safety and efficacy of MHRT for postoperative prostate cancer. Reduction of treatment time in long-course radiotherapy has advantages in terms of both patients' quality of life and departmental organization.

Dose coverage impacts local control in ultra-central lung oligometastases treated with stereotactic radiotherapy.

INTRODUCTION: The use of Stereotactic Body Radiotherapy (SBRT) is controversial in Ultra-Central lung tumors, a subset of central lung tumors characterized by proximity to critical mediastinal structures. This is of interest in oligometastatic (≤3 metastases) patients, who can yield survival benefit from local treatments. The aim of our study is to assess the determinants of efficacy and toxicity in this setting. MATERIALS AND METHODS: Clinical and dosimetric parameters were reviewed in a cohort of oligometastatic patients treated with SBRT for ultra-central tumors. Local control rate (LC) and toxicity were assessed. Statistical Analysis was carried out to assess the impact of those predictors on local recurrence and adverse events. RESULTS: One-hundred-nine consecutive patients were included. A median Biologic Effective Dose (BED) of 105 (75-132) Gy10 was prescribed. At a median follow-up of 17 (range 3-78) months, 2-year LC was 87%. Improved LC was correlated to Planning Treatment Volume (PTV) covered by 95% of the prescription dose (V95% PTV) > 85% (HR 0.15, 95%CI 0.05-0.49, p = 0.0017) and to Gross Tumor Volume (GTV) < 90 cm3 (HR 0.2, 95%CI 0.07-0.56, p = 0.0021). Overall and grade ≥ 3 toxicity incidence was 20% and 5%, respectively. Patients experiencing acute and late toxicities received significantly higher dose to 1 cm3 (D1cm3) of esophagus and lung volume receiving ≥5 Gy (V5Gy) (p = 0.016 and p = 0.013), and higher dose to 0.1 cm3 (D0.1cm3) of heart (p = 0.036), respectively. CONCLUSION: V95% PTV > 85% and GTV < 90 cm3 are independent predictors of LC. Dose to esophagus, lung and heart should be carefully assessed to minimize treatment-related toxicities.