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Background: The favorable role of SBRT for lymph-nodal oligometastases from prostate cancer has been reported by several retrospective and prospective experiences, suggesting a more indolent natural history of disease when compared to patients with bone oligometastases. This retrospective multicenter study evaluates the outcomes of a cohort of patients treated with stereotactic body radiotherapy for lymph-nodal oligometastases. Methods: Inclusion criteria were up to five lymph-nodal oligometastases detected either with Choline-PET or PSMA-PET in patients naïve for ADT or already ongoing with systemic therapy and at least 6 Gy per fraction for SBRT. Only patients with exclusive lymph-nodal disease were included. The primary endpoint of the study was LC; a toxicity assessment was retrospectively performed following CTCAE v4.0. Results: A total of 100 lymph-nodal oligometastases in 69 patients have been treated with SBRT between April 2015 and November 2022. The median age was 73 years (range, 60-85). Oligometastatic disease was mainly detected with Choline-PET in 47 cases, while the remaining were diagnosed using PSMA-PET, with most of the patients treated to a single lymph-nodal metastasis (48/69 cases), two in 14 cases, and three in the remaining cases. The median PSA prior to SBRT was 1.35 ng/mL (range, 0.3-23.7 ng/mL). Patients received SBRT with a median total dose of 35 Gy (range, 30-40 Gy) in a median number of 5 (range, 3-6) fractions. With a median follow-up of 16 months (range, 7-59 months), our LC rates were 95.8% and 86.3% at 1 and 2 years. DPFS rates were 90.4% and 53.4%, respectively, at 1 and 2 years, with nine patients developing a sequential oligometastatic disease treated with a second course of SBRT. Polymetastatic disease-free survival (PMFS) at 1 and 2 years was 98% and 96%. Six patients needed ADT after SBRT for a median time of ADT-free survival of 15 months (range, 6-22 months). The median OS was 16 months (range, 7-59) with 1- and 2-year rates of both 98%. In multivariate analysis, higher LC rates and the use of PSMA-PET were related to improved DPFS rates, and OS was significantly related to a lower incidence of distant progression. No G3 or higher adverse events were reported. Conclusions: In our experience, lymph-nodal SBRT for oligometastatic prostate cancer is a safe and effective option for ADT delay with no severe toxicity.

Purpose: To evaluate the role of stereotactic body radiation therapy (SBRT) delivered after external-beam fractionated irradiation in non-small-cell lung cancer (NSCLC) patients with clinical stage III A, B., Materials and Methods: All patients received three-dimensional conformal radiotherapy (3D-CRT) or intensity modulated radiation therapy (IMRT) (60-66 Gy/30-33 fractions of 2 Gy/5 days a week) with or without concomitant chemotherapy. Within 60 days from the end of irradiation, a SBRT boost (12-22 Gy in 1-3 fractions) was delivered on the residual disease., Results: Here we report the mature results of 23 patients homogeneously treated and followed up for a median time of 5.35 years (range 4.16-10.16). The rate of overall clinical response after external beam and stereotactic boost was 100%. No treatment-related mortality was recorded. Radiation-related acute toxicities with a grade ≥ 2 were observed in 6/23 patients (26.1%): 4/23 (17.4%) had esophagitis with mild esophageal pain (G2); in 2/23 (8.7%) clinical radiation pneumonitis G2 was observed. Lung fibrosis (20/23 patients, 86.95%) represented a typical late tissue damage, which was symptomatic in one patient. Median disease-free survival (DFS) and overall survival (OS) were 27.8 (95% CI, 4.2-51.3) and 56.7 months (95% CI, 34.9-78.5), respectively. Median local progression-free survival (PFS) was 17 months (range 11.6-22.4), with a median distant PFS of 18 months (range 9.6-26.4). The 5-year actuarial DFS and OS rates were 28.7% and 35.2%, respectively., Conclusions: We confirm that a stereotactic boost after radical irradiation is feasible in stage III NSCLC patients. All fit patients who have no indication to adjuvant immunotherapy and presenting residual disease after curative irradiation could benefit from stereotactic boost because outcomes seem to be better than might be historically assumed., (© 2023. Italian Society of Medical Radiology.)

High-precision image-guided radiation therapy (RT) for tumors abutting the appendicular skeleton may mean technical difficulties and concerns among practitioners. This technical note addresses the specific challenge for normofractionated image-guided RT of a tumor target in a forearm through an unconventional use of a treatment verification system usually devoted to stereotactic RT., (Copyright © 2022 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

Background/aim: One of the main limitations of standard imaging modalities is microscopic tumor extension, which is often difficult to detect on magnetic resonance imaging (MRI) and computer tomography (CT) in the early stages of the tumor. (68)Ga-DOTA(0)-Phe(1)-Tyr(3)-octreotide positron-emission tomography/computed tomography ( 68 Ga-DOTATOC PET/CT) has shown efficacy in detecting lesions previously undiagnosed by neuroimaging modalities, such as MRI or CT, and has enabled the detection of multiple benign tumors (like multiple meningiomas in a patient presenting with a single lesion on MRI) or additional secondary metastatic locations., Patients and Methods: We retrospectively reviewed data from the Cannizzaro Hospital on brain and body 68 Ga-DOTATOC PET/CT "incidentalomas", defined as tumors missed on CT or MRI scans, but detected on 68 Ga-DOTATOC PET/CT scans. "Incidentalomas" were classified into "brain" and "body" groups based on their location. The standardized uptake values (SUVs) were compared between the two groups., Results: A total of 61 patients with "incidentalomas" documented on the 68 Ga-DOTATOC PET/CT were identified: 18 patients with 25 brain lesions and 43 patients with 85 body lesions. The mean SUV at baseline was 9.01±7.66 in the brain group and 14.8±14.63 in the body group., Conclusion: We present the first series on brain and body "incidentalomas" detected on 68 Ga-DOTATOC PET/CT. Whole-body 68 Ga-DOTATOC PET/CT may be considered in selected patients with brain tumors with high expression of somatostatin receptors to assist radiosurgical or surgical planning and, simultaneously, provide accurate follow-up with early detection of potential metastases., (Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Objective: Spine hepatocellular carcinoma (HCC) metastases severely worsen quality of life and prognosis, with the role of radiotherapy being controversial. The authors systematically reviewed the literature on radiotherapy for spine metastatic HCCs., Methods: The PubMed, Scopus, Web of Science, and Cochrane databases were searched according to the PRISMA guidelines to include studies of radiotherapy for spine metastatic HCCs. Outcomes, complications, and local control were analyzed with indirect random-effect meta-analyses., Results: The authors included 12 studies comprising 713 patients. The median time interval from diagnosis of HCC to spine metastases was 12 months (range 0-105 months). Most lesions were thoracic (35.9%) or lumbar (24.7%). Radiotherapy was delivered with conventional external-beam (67.3%) or stereotactic (31.7%) techniques. The median dose was 30.3 Gy (range 12.5-52 Gy) in a median of 5 fractions (range 1-20 fractions). The median biologically effective dose was 44.8 Gy10 (range 14.4-112.5 Gy10). Actuarial rates of postradiotherapy pain relief and radiological response were 87% (95% CI 84%-90%) and 70% (95% CI 65%-75%), respectively. Radiation-related adverse events and vertebral fractures had actuarial rates of 8% (95% CI 5%-11%) and 16% (95% CI 10%-23%), respectively, with fracture rates significantly higher after stereotactic radiotherapy (p = 0.033). Fifty-eight patients (27.6%) had local recurrences after a median of 6.8 months (range 0.1-59 months), with pooled local control rates of 61.6% at 6 months and 40.8% at 12 months, and there were no significant differences based on radiotherapy type (p = 0.068). The median survival was 6 months (range 0.1-62 months), with pooled rates of 52.5% at 6 months and 23.4% at 12 months., Conclusions: Radiotherapy in spine metastatic HCCs shows favorable rates of pain relief, radiological responses, and local control. Rates of postradiotherapy vertebral fractures are higher after high-dose stereotactic radiotherapy.

Background: Craniovertebral junction (CVJ) schwannomas are rare, with surgery and stereotactic radiosurgery (SRS) being effective yet challenging options. We systematically reviewed the literature on CVJ schwannomas., Methods: PubMed, Scopus, Web-of-Science, and Cochrane were searched following the PRISMA statement to include studies reporting CVJ schwannomas. Clinical features, management, and outcomes were analyzed., Results: We collected 353 patients from 101 included articles. Presenting symptoms were mostly neck pain (30.3%) and headache (26.3%), with most cranial neuropathies involving the XII (31.2%) and X (24.4%) nerves. Most tumors originated from C2 (30.9%) and XII (29.4%) nerves, being extracranial (45.1%) and intradural-extradural (44.2%). Erosion of C1-C2 vertebrae (37.1%), the hypoglossal canal (28.3%), and/or jugular foramen (20.1%) were noted. All tumors were operated, preferably with the retrosigmoid approach (36.5%), with the far-lateral approach (29.7%) or with the posterior approach and cervical laminectomy (26.9%), far-lateral approaches (14.2%), or suboccipital craniotomy with concurrent cervical laminectomy (14.2%). Complete tumor resection was obtained most frequently (61.5%). Adjuvant post-surgery stereotactic radiosurgery was delivered in 5.9% patients. Median follow-up was 27 months (range, 12-252). Symptom improvement was noted in 88.1% of cases, and cranial neuropathies showed improvement in 10.2%. Post-surgical complications occurred in 83 patients (23.5%), mostly dysphagia (7.4%), new cranial neuropathies (6.2%), and cerebrospinal fluid leak (5.9%). A total of 16 patients (4.5%) had tumor recurrence and 7 died (2%), with median overall survival of 2.7 months (range, 0.1-252)., Conclusions: Microsurgical resection is safe and effective for CVJ schwannomas. Data on SRS efficacy and indications are still lacking, and its role deserves further evaluation.

Purpose: Gamma Knife radiosurgery (GKRS) is feasible for pituitary adenomas, but post-surgery GKRS may cause severe hormone deficits. We reviewed the literature on primary GKRS for pituitary adenoma focusing on radiation-induced hormone deficiencies., Methods: PubMed, Web-of-Science, Scopus, and Cochrane were searched upon the PRISMA guidelines to include studies describing primary GKRS for pituitary adenomas. Pooled-rates of GKRS-induced hormone deficiencies and clinical-radiological responses were analyzed with a random-effect model meta-analysis., Results: We included 24 studies comprising 1381 patients. Prolactinomas were the most common (34.2%), and 289 patients had non-functioning adenomas (20.9%). Median tumor volume was 1.6cm 3 (range, 0.01-31.3), with suprasellar extension and cavernous sinus invasion detected in 26% and 31.1% cases. GKRS was delivered with median marginal dose 22.6 Gy (range, 6-49), maximum dose 50 Gy (range, 25-90), and isodose line 50% (range, 9-100%). Median maximum point doses were 9 Gy (range, 0.5-25) to the pituitary stalk, 7 Gy (range, 1-38) to the optic apparatus, and 5 Gy (range, 0.4-12.3) to the optic chiasm. Pooled 5 year rates of endocrine normalization and local tumor control were 48% (95%CI 45-51%) and 97% (95%CI 95-98%). 158 patients (11.4%) experienced endocrinopathies at a median of 45 months (range, 4-187.3) after GKRS, with pooled 5-year rates of 8% (95%CI 6-9%). GKRS-induced hormone deficiencies comprised secondary hypothyroidism (42.4%) and hypogonadotropic hypogonadism (33.5%), with panhypopituitarism reported in 31 cases (19.6%)., Conclusion: Primary GKRS for pituitary adenoma may correlate with lower rates of radiation-induced hypopituitarism (11.4%) than post-surgery GKRS (18-32%). Minimal doses to normal pituitary structures and long-term endocrine follow-up are of primary importance., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background/aim: We investigated the treatment outcomes and complications associated with hypofractionated GKRS for the treatment of benign and malignant intracranial tumors., Patients and Methods: Patients with intracranial tumors not candidate or refusing surgery were evaluated to assess eligibility to undergo hypofractionated Gamma Knife radiosurgery (GKRS). Targeted volumes were calculated using the GammaPlan ® workstation, and GKRS protocols were delivered with 3 or 5 daily fractions and a maximal total dose of 25 Gy. The thermoplastic mask was used to immobilize the patient's head without pin-based fixation frames., Results: A total of 41 patients, affected with 6 different histologies, were treated and followed-up for a median of 12 months (range=4-24 months). Meningiomas were the most common tumors (33, 80.5%), followed by brain metastases (4, 9.7%). At last follow-up, 33 patients (80.5%) had stable disease, 8 tumor regression (19.5%), and 0 tumor progression. No acute radiation toxicity was observed. Death was reported in 3 patients (7.3%) due to malignant tumor progression., Conclusion: Our hypofractionated GKRS protocol proved to be effective and safe in the treatment of patients with benign and malignant intracranial tumors. Local tumor control was achieved in all patients, with 8 patients showing tumor regression and no cases of acute radiation toxicity., (Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

In this short report we present a series of thirteen patients with locally advanced, unresectable, pancreatic cancer treated with a COMBO-Therapy consisting of: STEP-1: induction chemotherapy; STEP-2: concomitant chemoradiotherapy; STEP-3: stereotactic body radiotherapy boost. After four weeks from the end of each step all patients had a re-staging and a surgical re-evaluation. All patients completed STEP-1 and STEP-2. STEP-3 has been successfully delivered to 8/13 patients with a median dose of 12 Gy (range 10-21 Gy) in 1-3 fractions. The median LC was 20 months (range 10-32) with a 2-year LC of 72.9%, and none of the patients developed G3 acute or late toxicities. The median OS was 21.5 months (range 12-34), and the 2-year OS was 53.9%; the median PFS was 17.5 months (range 10-27). Our non-surgical COMBO-Therapy has demonstrated a feasible profile with good tolerance. Further prospective protocols are needed to confirm our preliminary results., (© 2022. Italian Society of Medical Radiology.)

Stereotactic body radiation therapy in patients with spine metastases maximizes local tumor control and preserves neurologic function. A novel approach could be the use of stereotactic body radiation therapy with simultaneous integrated boost delivering modality. The aim of the present study is to report our experience in the treatment of spine metastases using a frameless radiosurgery system delivering stereotactic body radiation therapy-simultaneous integrated boost technique. The primary endpoints were the pain control and the time to local progression; the secondary ones were the overall survival and toxicity. A total of 20 patients with spine metastases and 22 metastatic sites were treated in our center with stereotactic body radiation therapy-simultaneous integrated boost between December 2007 and July 2018. Stereotactic body radiation therapy-simultaneous integrated boost treatments were delivered doses of 8 to 10 Gy in 1 fraction to isodose line of 50%. The median follow-up was 35 months (range: 12-110). The median time to local progression for all patients was not reached and the actuarial 1-, 2-, and 3-years local free progression rate was 86.36%. In 17 of 20 patients, a complete pain remission was observed and 3 of 20 patients had a partial pain remission (complete pain remission + partial pain remission: 100%). The median overall survival was 38 months (range 12-83). None of the patients experienced neither radiation adverse events (grade 1-4) nor reported pain flair reaction. None of the patients included in our series experienced vertebral compression fracture. Spine radiosurgery with stereotactic body radiation therapy-simultaneous integrated boost is safe. The use of this modality in spine metastases patients provides an excellent local control.