Delphi consensus on stereotactic ablative radiotherapy for oligometastatic and oligoprogressive renal cell carcinoma-a European Society for Radiotherapy and Oncology study endorsed by the European Association of Urology.

The purpose of this European Society for Radiotherapy and Oncology (ESTRO) project, endorsed by the European Association of Urology, is to explore expert opinion on the management of patients with oligometastatic and oligoprogressive renal cell carcinoma by means of stereotactic ablative radiotherapy (SABR) on extracranial metastases, with the aim of developing consensus recommendations for patient selection, treatment doses, and concurrent systemic therapy. A questionnaire on SABR in oligometastatic renal cell carcinoma was prepared by a core group and reviewed by a panel of ten prominent experts in the field. The Delphi consensus methodology was applied, sending three rounds of questionnaires to clinicians identified as key opinion leaders in the field. At the end of the third round, participants were able to find consensus on eight of the 37 questions. Specifically, panellists agreed to apply no restrictions regarding age (25 [100%) of 25) and primary renal cell carcinoma histology (23 [92%] of 25) for SABR candidates, on the upper threshold of three lesions to offer ablative treatment in patients with oligoprogression, and on the concomitant administration of immune checkpoint inhibitor. SABR was indicated as the treatment modality of choice for renal cell carcinoma bone oligometatasis (20 [80%] of 25) and for adrenal oligometastases 22 (88%). No consensus or major agreement was reached regarding the appropriate schedule, but the majority of the poll (54%-58%) retained the every-other-day schedule as the optimal choice for all the investigated sites. The current ESTRO Delphi consensus might provide useful direction for the application of SABR in oligometastatic renal cell carcinoma and highlight the key areas of ongoing debate, perhaps directing future research efforts to close knowledge gaps.

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.

Dose-intensified stereotactic body radiotherapy for painful vertebral metastases: A randomized phase 3 trial.

BACKGROUND: The purpose of this randomised study was to determine whether dose-intensified stereotactic body radiotherapy (SBRT) for painful vertebral metastases results in increased rates of pain improvement compared with conventional external beam radiotherapy (cEBRT) (control) 6 months after treatment. METHODS: This randomized, controlled phase 3 trial was conducted between November 2016 and January 2023, when it was stopped early. Patients were eligible if they were aged 18 years or older; had one or two painful, stable, or potentially unstable vertebral metastases; and had a life expectancy of 1 year or longer according to the investigator's estimates. Patients received 48.5 grays (Gy) in 10 fractions (with epidural involvement) or 40 Gy in five fractions (without epidural involvement) in the SBRT group and 30 Gy in 10 fractions or 20 Gy in five fractions in the cEBRT group, respectively. The primary end point was an improvement in the pain score at the treated site by at least 2 points (on a visual analog scale from 0 to 10 points) at 6-month follow-up. Data were analyzed on an intention-to-treat and per-protocol basis. RESULTS: Of 214 patients who were screened for eligibility, 63 were randomized 1:1 between SBRT (33 patients with 36 metastases) and cEBRT (30 patients with 31 metastases). The median age of all patients was 66 years, and 40 patients were men (63.5%). In the intention-to-treat analysis, the 6-month proportion of patients who had metastases with pain reduction by 2 or more points was significantly higher in the SBRT group versus the control group (69.4% vs. 41.9%, respectively; two-sided p = .02). Changes in opioid medication intake relative to baseline were nonsignificant between the groups. No differences were observed in vertebral compression fracture or adverse event rates between the groups. CONCLUSIONS: Dose-intensified SBRT improved pain score more effectively than cEBRT at 6 months.

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.

Management of radiation-induced oral mucositis in head and neck cancer patients: a real-life survey among 25 Italian radiation oncology centers.

AIM: Radiation-induced oral mucositis (RIOM) is the most frequent side effect in head and neck cancer (HNC) patients treated with curative radiotherapy (RT). A standardized strategy for preventing and treating RIOM has not been defined. Aim of this study was to perform a real-life survey on RIOM management among Italian RT centers. METHODS: A 40-question survey was administered to 25 radiation oncologists working in 25 different RT centers across Italy. RESULTS: A total of 1554 HNC patients have been treated in the participating centers in 2021, the majority (median across the centers 91%) with curative intent. Median treatment time was 41 days, with a mean percentage of interruption due to toxicity of 14.5%. Eighty percent of responders provide written oral cavity hygiene recommendations. Regarding RIOM prevention, sodium bicarbonate mouthwashes, oral mucosa barrier agents, and hyaluronic acid-based mouthwashes were the most frequent topic agents used. Regarding RIOM treatment, 14 (56%) centers relied on literature evidence, while internal guidelines were available in 13 centers (44%). Grade (G)1 mucositis is mostly treated with sodium bicarbonate mouthwashes, oral mucosa barrier agents, and steroids, while hyaluronic acid-based agents, local anesthetics, and benzydamine were the most used in mucositis G2/G3. Steroids, painkillers, and anti-inflammatory drugs were the most frequent systemic agents used independently from the RIOM severity. CONCLUSION: Great variety of strategies exist among Italian centers in RIOM management for HNC patients. Whether different strategies could impact patients' compliance and overall treatment time of the radiation course is still unclear and needs further investigation.

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.

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.

A Propensity Score Matching Study on the Effect of OnabotulinumtoxinA Alone versus Short-Term Psychodynamic Psychotherapy Plus Drug-of-Choice as Preventive Therapy in Chronic Migraine: Effects and Predictive Factors.

OBJECTIVE: The objective of this study was to test the superiority of multidisciplinary approach, that is, Short-Term Psychodynamic Psychotherapy (STPP) plus drug of choice, versus monotherapy, that is, OnabotulinumtoxinA (OnaBoNT-A). METHOD: We consecutively recorded data from chronic migraine (CM) patients, with or without medication overuse headache (MOH), who underwent STPP or OnaBoNT-A, with a 3-month follow-up schedule. Headache days and analgesics intake were monitored as primary outcome measures. Propensity score matching (PSM) was used to eliminate discrepancies between groups. Discriminant function analysis (DFA) was used to pinpoint predictive factors associated with the clinical response. RESULTS: 96 patients with CM (64% with MOH) were treated with STPP and 54 (59% with MOH) with OnaBoNT-A. At baseline, OnaBoNT-A patients had more failed preventive therapies, more years of illness and chronicity, and were older; STPP patients were more depressed and had a higher HIT-6. Both STPP and OnaBoNT-A patients showed a significant reduction of headache days (STPP: -14 vs. OnaBoNT-A:-14.3) and analgesics intake (STPP: -12,3 vs. OnaBoNT-A -13.5 pills/month), respectively. MOH diminished more in STPP, adherence was higher in OnaBoNT-A. Results were confirmed after PSM balancing of the groups for those variables that resulted as different (but age). CONCLUSION: OnaBoNT-A monotherapy produced similar results to psychotherapy plus medication, after correcting for baseline differences.

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.

Stereotactic radiotherapy for liver oligometastases.

The liver is the first metastatic site in 15-25% of colorectal cancer patients and one of the first metastatic sites for lung and breast cancer patients. A computed tomography (CT ) scan with contrast medium is a standard procedure for assessing liver lesions but magnetic resonance imaging (MRI) characterizes small lesions better thanks to its high soft-tissue contrast. Positron emission tomography with computed tomography (PET-CT ) plays a complementary role in the diagnosis of liver metastases. Triphasic (arterial, venous and time-delayed) acquisition of contrast-medium CT images is the first step in treatment planning. Since the liver exhibits a relatively wide mobility due to respiratory movements and bowel filling, appropriate techniques are needed for target identification and motion management. Contouring requires precise recognition of target lesion edges. Information from contrast MRI and/or PET-CT is crucial as they best visualize metastatic disease in the parenchyma. Even though different fractionation schedules were reported, doses and fractionation schedules for liver stereotactic radiotherapy (SRT ) have not yet been established. The best local control rates were obtained with BED10 values over 100 Gy. Local control rates from most retrospective studies, which were limited by short follow-ups and included different primary tumors with intrinsic heterogeneity, ranged from 60% to 90% at 1 and 2 years. The most common SRT-related toxicities are increases in liver enzymes, hyperbilirubinemia and hypoalbuminemia. Overall, late toxicity is mild even in long-term follow-ups.

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.

Radiotherapy role in non-seminomatous germ cell tumors, radiobiological and technical issues of an unexplored scenario.

Historically, non-seminomatous germ cell tumor (NSGCT) has been considered a radio-resistant disease, excluding radiotherapy (RT) from curative strategies. However, case series exploring the use of radiation treatment in this setting are often outdated, and prospective ongoing studies testing new radiotherapeutic approaches in NSGCT are lacking. Considering that tremendous advances in radiotherapy technology have enabled improved precision in RT delivery as well as dose escalation while decreasing treatment-related morbidity, we overviewed the currently available literature to explore the radiobiological basis, the technical issues, and potential strategies for implementation of RT in the management of this clinical entity. The purpose of the present overview is to provide insight for future research in this unexplored scenario. In summary, the biological rationale for RT use and potential implementation with systemic therapies exist, especially considering the advantage of new technologies, which were unavailable in the era of early literature reports. The NSGCT radioresistance paradigm could be based only on the fact that effective treatment schedules were simply undeliverable with older RT techniques due to toxicity issues, but the availability of actual techniques may prompt further exploration to offer treatment alternatives to these patients. Ongoing trials on this issue are lacking, but potential areas of research are platinum-refractory disease and consolidation therapy for residual masses after PST.

Dosimetric impact of volumetric modulated arc therapy for nasopharyngeal cancer treatment.

BACKGROUND: The purpose of the study was to evaluate the toxicity and outcome of nasopharyngeal carcinoma patients treated using 3-dimensional conformal radiotherapy (3DCRT) or volumetric modulated arc therapy (VMAT) technique. MATERIALS AND METHODS: 68 patients treated between 2006 and 2018 were retrospectively analysed. Since 2009 patients received 3DCRT with 50/70 Gy to the elective/boost volumes in 35 fractions; from then, VMAT with simultaneous integrated boost (SIB) with 54.45/69.96 Gy in 33, or 54/66 Gy in 30 fractions. Induction chemotherapy was administered in 74% of the patients, concomitant cisplatinum in 87%. Acute and late toxicity data, progression-free survival PSF and overall survival OS, and toxicity correlations with dose metrics were reported. RESULTS: With a median follow-up of 64 months, complete remission at the last evaluation was in 68% of the patients, while 28% and 9% had locoregional relapse and distant disease, respectively. The 5- and 10-year progression free survival (PFS) rates were 62.7 ± 6.5% and 53.2 ± 8.7%, respectively. The 5- and 10-year OS rates were 78.9 ± 5.5% and 61.4 ± 9.2%, respectively. At the multivariate Cox analysis TNM stage (p = 0.02) and concomitant chemotherapy (p = 0.01) resulted significant for PFS, concomitant chemotherapy (p = 0.04) for OS.Improvements in acute toxicity were presented for VMAT patients due to its ability to spare OARs. Odds ratio (OR) for acute salivary toxicity, between VMAT and 3DCRT, was 4.67 (p = 0.02). Dosimetrically, salivary toxicity correlated with mean parotid dose (p = 0.05), dysphagia with laryngeal (p = 0.04) and mean oral cavity (p = 0.06) doses, when dose-volume histograms (DVHs) are corrected for fractionation. CONCLUSION: This study is a proof of a significant benefit of the VMAT technique compared with 3DCRT in terms of side effects in nasopharynx patients, and adds dosimetric correlations.

Recurrence pattern of stereotactic body radiotherapy in oligometastatic prostate cancer: a multi-institutional analysis.

PURPOSE: For patients with oligometastatic/oligorecurrent/oligoprogressive lymph node metastases from PCa, metastases-directed therapy is an emerging strategy. The aim of this retrospective study was to evaluate the oncological outcome and pattern of recurrence in patients treated with stereotactic body radiation therapy (SBRT) to lymph node metastases. METHODS: In this multi-institutional analysis, patients with a maximum of five lymph node metastases from PCa treated with SBRT were included. Primary endpoints of the analysis were local control (LC), out-of-field nodal progression-free survival (NPFS), overall progression-free survival (PFS), and overall survival (OS). RESULTS: 109 patients and 155 lymph node metastases were evaluated. Patients' median age was 70.8 years (range 51-84) and median PSA before SBRT was 1.88 ng/ml (range 0.3-45.5 ng/ml). The dose delivered to the target ranged from 25 to 48 Gy in 4-7 fractions; median BED1.5 Gy was 198 Gy (range 108.3-432 Gy). With a median follow-up of 16 months, LC rates at 1 and 3 years were 93% and 86%, respectively. In-field progression of disease was observed in 11 (7%) lesions. One- and 3­year NPFS was 59% and 29%, and median NPFS was 15 months. Rates of OS at 1 and 3 years were 100% and 95%. The median time to administration of a systemic treatment after SBRT was 7.8 months (1.7-54.8). CONCLUSION: SBRT is an effective and well-tolerated treatment option in the management of lymph node metastases from PCa. Prospective trials are necessary to better select patients who benefit most from this ablative focal treatment and better define the recurrence patterns.

A radiomic approach to predicting nodal relapse and disease-specific survival in patients treated with stereotactic body radiation therapy for early-stage non-small cell lung cancer.

PURPOSE: To describe the possibility of building a classifier for patients at risk of lymph node relapse and a predictive model for disease-specific survival in patients with early stage non-small cell lung cancer. METHODS: A cohort of 102 patients who received stereotactic body radiation treatment was retrospectively investigated. A set of 45 textural features was computed for the tumor volumes on the treatment planning CT images. Patients were split into two independent cohorts (70 patients, 68.9%, for training; and 32 patients, 31.4%, for validation). Three different models were built in the study. A stepwise backward linear discriminant analysis was applied to identify patients at risk of lymph node progression. The performance of the model was assessed by means of standard metrics derived from the confusion matrix. Furthermore, all textural features were correlated to survival data to build two separate predictive models for progression-free survival (PFS) and disease-specific survival (DS-OS). These models were built from the features/predictors found significant in univariate analysis and elastic net regularization by means of a multivarate Cox regression with backward selection. Low- and high-risk groups were identified by maximizing the separation by means of the Youden method. RESULTS: In the total cohort (77, 75.5%, males; and 25, 24.5%, females; median age 76.6 years), 15 patients presented nodal progression at the time of analysis; 19 patients (18.6%) died because of disease-specific causes, 25 (24.5%) died from other reasons, 28 (27.5%) were alive without disease, and 30 (29.4%) with either local or distant progression. The specificity, sensitivity, and accuracy of the classifier resulted 83.1 ± 24.5, 87.4 ± 1.2, and 85.4 ± 12.5 in the validation group (coherent with the findings in the training). The area under the curve for the classifier resulted in 0.84 ± 0.04 and 0.73 ± 0.05 for training and validation, respectively. The mean time for DS-OS and PFS for the low- and high-risk subgroups of patients (in the validation groups) were 88.2 month ± 9.0 month vs. 84.1 month ± 7.8 month (low risk) and 52.7 month ± 5.9 month vs. 44.6 month ± 9.2 month (high risk), respectively. CONCLUSION: Radiomics analysis based on planning CT images allowed a classifier and predictive models capable of identifying patients at risk of nodal relapse and high-risk of bad prognosis to be built. The radiomics signatures identified were mostly related to tumor heterogeneity.

Linac-based stereotactic body radiation therapy for low and intermediate-risk prostate cancer : Long-term results and factors predictive for outcome and toxicity.

INTRODUCTION: Stereotactic body radiation therapy (SBRT) is considered an effective and safe treatment in patients with low- and intermediate-risk prostate cancer (PC). However, due to a lack of long-term follow-up and late toxicity data, this treatment is not universally accepted. The present study aimed to evaluate outcome and early and late toxicity in a cohort of patients with low- and intermediate-risk PC treated prospectively with linear accelerator (linac)-based SBRT. PATIENTS AND METHODS: Patients with low- or intermediate-risk (NCCN criteria) PC were included. All patients received linac-based SBRT to 35 Gy in 5 fractions delivered on alternate days. Endpoints were toxicity, biochemical relapse-free survival (BRFS), metastatic progression-free survival (mPFS), and overall survival (OS). RESULTS: From 2012 to 2018, 178 patients were treated. Median baseline prostate-specific antigen (iPSA) was 6.37 ng/ml (range 1.78-20). Previous transurethral resection of the prostate (TURP) was present in 23 (12.9%) patients. Median follow-up was 58.9 months (range 9.7-89.9). BRFS rates at 1, 3, and 5 years were 98.3 (95% confidence interval, CI, 94.7-99.4%), 94.4 (95%CI 89.4-97), and 91.6% (95%CI 85.4-95.2), respectively. In univariate analysis, performance status (PS), iPSA, and nadir PSA (nPSA) were correlated with BRFS. In multivariable analysis iPSA and nPSA remained significant. BRFS rates at 5 years were 94.9% (95%CI 86.8-98) for International Society of Urological Pathology (ISUP) grade group 1, 93.2% (95%CI 80.5-97.7) for ISUP group 2, and 74.8% (95%CI 47.1-89.5) for ISUP group 3. At 1, 3, and 5 years, mPFS rates were 98.8 (95%CI 95.5-99.7), 96.2 (95%CI 91.9-98.3), and 92.9% (95%CI 87.2-96.2), respectively; OS rates were 100, 97.2 (95%CI 92.9-98.9), and 95.1% (95%CI 90-97.6), respectively. One (0.56%) case of grade 3 acute genitourinary (GU), one case of acute gastrointestinal (GI), and one case of grade 3 late GU toxicity were observed. GI toxicity positively correlated with prostate volume. CONCLUSION: At long-term follow-up, linac-based SBRT continues to be a valid option for the management localized PC. Biochemical control remains high at 5 years, albeit with some concerns regarding the optimal schedule for unfavorable intermediate-risk PC. Considering the excellent prognosis, patient selection is crucial for prevention of severe late toxicity.

Role of stereotactic body radiation therapy in the treatment of liver metastases: clinical results and prognostic factors.

PURPOSE: To evaluate feasibility and efficacy of Stereotactic Body Radiation Therapy (SBRT) for unresectable liver metastasis in oligometastatic patients. METHODS: Oligometastatic patients with up to three liver metastases of a maximum diameter of 6 cm were treated with SBRT. Total dose was 75 Gy in three consecutive fractions. Study endpoints were efficacy of this fractionation in terms of local control (LC), overall survival (OS), toxicity, and prognostic factors affecting OS and LC. RESULTS: Between February 2010 and December 2016, we enrolled 202 patients, with a total of 268 unresectable liver metastases. Median follow-up time from SBRT was 33 months (5-87 months). One-, 3­, and 5­year LC rates were 92%, 84%, and 84%, respectively. In univariate analysis, the primary histology and previous local ablative therapies were significant. Median OS was 21 months and the survival rates were 79%, 27%, and 15% at 1, 3, and 5 years after SBRT, respectively. At univariate analysis, sex, primary disease histology, intra-, and extra-hepatic progression were significant prognostic factors. This analysis confirmed the absence of late toxicity >G3. CONCLUSION: This study confirms the efficacy and safety of SBRT for unresectable liver metastases. Selection of cases may improve survival and LC.