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Androgen deprivation therapy (ADT) is the standard treatment of metastatic prostate cancer (PCa). However, metastases-directed therapies can delay the initiation or switch of systemic treatments and allow local control (LC) and prolonged progression-free survival (PFS), particularly in patients with lymph nodes (LN) oligometastases. We performed a systematic review on stereotactic body radiotherapy (SBRT) in this setting. Papers reporting LC and/or PFS were selected. Data on ADT-free survival, overall survival, and toxicity were also collected from the selected studies. Fifteen studies were eligible (414 patients), 14 of them were retrospective analyses. A high heterogeneity was observed in terms of patient selection and treatment. In one study SBRT was delivered as a single 20 Gy fraction, while in the others the median total dose ranged between 24 and 40 Gy delivered in 3-6 fractions. LC and PFS were reported in 15 and 12 papers, respectively. LC was reported as a crude percentage in 13 studies, with 100% rate in seven and 63.2-98.0% in six reports. Five studies reported actuarial LC (2-year LC: 70.0-100%). PFS was reported as a crude rate in 11 studies (range 27.3-68.8%). Actuarial 2-year PFS was reported in four studies (range 30.0-50.0%). SBRT tolerability was excellent, with only two patients with grade 3 acute toxicity and two patients with grade 3 late toxicity. SBRT for LN oligorecurrences from PCa in safe and provides optimal LC. However, the long-term effect on PFS and OS is still unclear as well as which patients are the best candidate for this approach., (© 2022. The Author(s).)

The main treatment of MM metastases are systemic therapies, surgery, limb perfusion, and intralesional talimogene laherparepvec. Electrochemotherapy (ECT) is potentially useful also due to the high response rates recorded in cancers of any histology. No randomized studies comparing ECT with other local therapies have been published on this topic. We analyzed the available evidence on efficacy and toxicity of ECT in this setting. PubMed, Scopus, and Cochrane databases were screened for paper about ECT on MM skin metastases. Data about tumor response, mainly in terms of overall response rate (ORR), toxicity (both for ECT alone and in combination with systemic treatments), local control (LC), and overall survival (OS) were collected. The methodological quality was assessed using a 20-item validated quality appraisal tool for case series. Overall, 18 studies were included in our analysis. In studies reporting "per patient" tumor response the pooled complete response (CR) was 35.7% (95%CI 26.0-46.0%), and the pooled ORR was 80.6% (95%CI 68.7-90.1%). Regarding "per lesion" response, the pooled CR was 53.5% (95%CI 42.1-64.7%) and the pooled ORR was 77.0% (95%CI 56.0-92.6%). One-year LC rate was 80%, and 1-year OS was 67-86.2%. Pain (24.2-92.0%) and erythema (16.6-42.0%) were the most frequent toxicities. Two studies reported 29.2% and 41.6% incidence of necrosis. ECT is effective in terms of tumor response and tolerated in patients with skin metastases from MM, albeit with a wide variability of reported results. Therefore, prospective trials in this setting are warranted., (© 2022. The Author(s).)

The main clinical goal for patients with advanced or metastatic thoracic cancer is palliation of tumor-related symptoms and improvement of quality of life. The aim of this phase I-II trial was to define the maximum tolerated dose (MTD) of a short-course of palliative radiotherapy (RT) and to evaluate its efficacy in terms of palliative response. A phase I trial was planned with escalating dose increments. Total doses ranged from 16 to 20 Gy delivered (BID) in two consecutive days. Dose limiting toxicity was defined as any acute grade ≥ 3 toxicity based on the RTOG scale. MTD was used in the phase II trial to evaluate the efficacy of this regimen using a two stage Simon's design. Fifty-four patients were enrolled. The upper dose level of 20 Gy was defined as the MTD. In patients treated with this dose, the overall palliative response rate was 96.5% (CI 0.95: 81.3-99.9%). Complete pain relief rate was 50.0%. Median survival without symptomatic progression was 3 months. The tested short course accelerated regimen was well tolerated and effective in the palliative setting of metastatic or locally advanced chest cancer. A phase III trial is ongoing to validate this RT schedule.Trial registration: NCT03465553.

Half-body irradiation (HBI) represented a standard treatment for multiple painful bone metastases (BMs). However, its use has progressively reduced due to the associated toxicity rates. The aim of this paper was to evaluate HBI delivered by conformal radiotherapy (RT) technique in a large patients population with widespread BMs. HBI was delivered in 3 Gy fractions, bid, ≥ 6 h apart, on 2 consecutive days (total dose: 12 Gy) using 3-dimensional conformal RT (3D-CRT) box technique. The target included pelvic bones, lumbar-sacral vertebrae and upper third of femurs. Acute and late toxicity was scored based on RTOG and EORTC-RTOG scales, respectively. Pain was evaluated using the Pain-Drug scores and the Visual Analog Scale (VAS). One hundred and eighty patients were eligible for inclusion in this retrospective analysis. Grade 3 and 4 acute toxicity rates were 1.1% and 0.0%, respectively. Mean VAS before and after HBI was 5.3 versus 2.7, respectively (p: 0.0001). Based on VAS, 37.5% of patients showed complete pain relief (VAS: 0) while 38.1% had partial response (≥ 2-point VAS reduction). Overall, Pain and Drug Score reduction was observed in 76.3% and 50.4% of patients, respectively. 1-, 2-, and 3-year pain progression free survival was 77.0%, 63.4%, and 52.7%, respectively. Thirty patients (16.7%) underwent RT retreatment on the same site with median 15.9 months interval (range 2-126 months). HBI delivered with 3D-CRT technique is safe and effective. It provides long lasting pain control in patients with multiple BMs with negligible rates of relevant toxicity.

Metastases with soft tissues invasion, impending fractures or spinal cord compression (complicated bone metastases) represent a common clinical problem in advanced cancers and frequently lead to deterioration of patients' quality of life (QoL). A phase I-II study was planned to define the maximum tolerated dose (MTD) of a short-course radiotherapy (RT) and its efficacy in palliation of complicated bone metastases. A phase I trial was designed with three dose-escalation steps: 16, 18, and 20 Gy. Total dose at each level was delivered in 2 days, twice daily. Eligibility criteria were painful complicated bone metastases and ECOG performance status ≤ 3. The presence of acute toxicity ≥ Grade 3 (RTOG scale) was considered the dose limiting toxicity. The MTD was used to plan a phase II trial with pain response as the primary outcome. Pain was recorded using a Visual Analogic Scale (VAS), and QoL using CLAS scales. Forty-five patients were enrolled in this trial. In phase I no Grade ≥ 2 acute toxicities were recorded. Thus 20 Gy was established as MTD. In phase II, with a median follow-up of 4 months, rates of complete symptom remission, partial response, no symptomatic change, and symptoms progression were 32.0%, 52.0%, 8.0%, and 8.0%, respectively. This RT protocol tested in our study is effective and tolerable with comparable results to traditional RT treatments delivered in 5-10 daily fractions.