Linac-based stereotactic salvage reirradiation for intraprostatic prostate cancer recurrence: toxicity and outcomes.

BACKGROUND: The rates of local failure after curative radiotherapy for prostate cancer (PC) remain high despite more accurate locoregional treatments available, with one third of patients experiencing biochemical failure and clinical relapse occurring in 30-47% of cases. Today, androgen deprivation therapy (ADT) is the treatment of choice in this setting, but with not negligible toxicity and low effects on local disease. Therefore, the treatment of intraprostatic PC recurrence represents a challenge for radiation oncologists. Prostate reirradiation (Re-I) might be a therapeutic possibility. We present our series of patients treated with salvage stereotactic Re­I for intraprostatic recurrence of PC after radical radiotherapy, with the aim of evaluating feasibility and safety of linac-based prostate Re­I. MATERIALS AND METHODS: We retrospectively evaluated toxicities and outcomes of patients who underwent salvage reirradiation using volumetric modulated arc therapy (VMAT) for intraprostatic PC recurrence. Inclusion criteria were age ≥ 18 years, histologically proven diagnosis of PC, salvage Re­I for intraprostatic recurrence after primary radiotherapy for PC with curative intent, concurrent/adjuvant ADT with stereotactic body radiation therapy (SBRT) allowed, performance status ECOG 0-2, restaging choline/PSMA-PET/TC and prostate MRI after biochemical recurrence, and signed informed consent. RESULTS: From January 2019 to April 2022, 20 patients were recruited. Median follow-up was 26.7 months (range 7-50). After SBRT, no patients were lost at follow-up and all are still alive. One- and 2­year progression free survival (PFS) was 100% and 81.5%, respectively, while 2­year biochemical progression-free survival (bFFS) was 88.9%. Four patients (20%) experienced locoregional lymph node progression and were treated with a further course of SBRT. Prostate reirradiation allowed the ADT start to be postponed for 12-39 months. Re­I was well tolerated by all patients and none discontinued the treatment. No cases of ≥ G3 genitourinary (GU) or gastrointestinal (GI) toxicity were reported. Seven (35%) and 2 (10%) patients experienced acute G1 and G2 GU toxicity, respectively. Late GU toxicity was recorded in 10 (50%) patients, including 8 (40%) G1 and 2 (10%) G2. ADT-related side effects were found in 7 patients (hot flashes and asthenia). CONCLUSION: Linac-based SBRT is a safe technique for performing Re­I for intraprostatic recurrence after primary curative radiotherapy for PC. Future prospective, randomized studies are desirable to better understand the effectiveness of reirradiation and the still open questions in this field.

Prognostic factors, efficacy, and toxicity of involved-node stereotactic body radiation therapy for lymph node oligorecurrent prostate cancer : An investigation of 117 pelvic lymph nodes.

BACKGROUND: The optimal radiotherapy regimen is not yet defined in the setting of oligorecurrent prostate cancer (oligorPC). There is evidence of high variability in treatment protocols among different centers worldwide, and no international consensus guidelines on treatment volumes, radiation schedules, and techniques. The purpose of the present retrospective study is to evaluate the efficacy and safety of involved-pelvic-node stereotactic body radiotherapy (SBRT) for oligorPC. MATERIALS AND METHODS: Patients with pelvic node oligorPC following primary surgery, radical radiotherapy, or salvage radiotherapy for biochemical or local relapse of prostate cancer who underwent involved-node SBRT with biological effective dose (BED) > 100 Gy, with or without concurrent and adjuvant androgen deprivation therapy (ADT), were retrospectively evaluated. Biochemical progression-free survival (bPFS), distant progression-free survival (DPFS), overall survival (OS), possible prognostic factors, and toxicity outcomes were investigated. RESULTS: From November 2012 to December 2019, 74 patients fitted the selection criteria. A total of 117 lesions were treated. Median follow-up was 31 months (range 6-89). Concurrent ADT was administered in 58.1% of patients. The 1­year, 2­year, and 3­year DPFS was 77%, 37%, and 19%, respectively; the 1­year, 2­year, and 3­year OS was 98%, 98%, and 95%, respectively. The presence of a single target lesion was associated with a statistically significant impact on OS. No in-field recurrence occurred. Patients who reached early prostate-specific antigen (PSA) nadir (< 3 months after SBRT) had a lower 3­year survival (p = 0.004). The value of PSA nadir after SBRT and the time between primary treatment and SBRT had an impact on bPFS. Concomitant ADT was associated with improved DPFS. No acute or early late (> 6 months) genitourinary and gastrointestinal adverse events of any grade were reported, albeit with relatively short median follow-up. CONCLUSION: SBRT is a safe and effective treatment for oligorPC, with a 100% local control rate in our series. It is not possible to clearly assess the opportunity to postpone ADT prescription in patients with two or more nodal metastases. The number of secondary lesions, time-to-nadir PSA, PSA nadir value, and the time interval between primary treatment and SBRT were identified as prognostic factors. Future prospective randomized studies are desirable to better understand the still open questions regarding the oligorecurrent prostate cancer state.

Dose-dense ABVD as first-line therapy in early-stage unfavorable Hodgkin lymphoma: results of a prospective, multicenter double-step phase II study by Fondazione Italiana Linfomi.

We investigated the feasibility and activity of an intensified dose-dense ABVD (dd-ABVD) regimen in patients with early-stage unfavorable Hodgkin lymphoma (HL). This prospective, multicenter, phase II study enrolled 96 patients with newly diagnosed, unfavorable stage I or II classical HL. The patients received four cycles of dd-ABVD followed by radiotherapy. Interim PET (PET-2) was mandatory after two courses. Primary endpoints were the evaluation of dd-ABVD feasibility and activity (incidence of PET-2 negativity). The feasibility endpoint was achieved with 48/52 (92.3%) patients receiving > 85% of the programmed dose. The mean dose intensity in the overall patient population (n = 96) was 93.7%, and the median duration of dd-ABVD was 85 days (range, 14-115) versus an expected duration of 84 days. PET-2 was available for 92/96 (95.8%) patients, of whom 79 were PET-2 negative (85.9%). In total, 90 (93.8%) patients showed complete response at the end of treatment. With a follow-up of 80.9 months (3.3-103.2), the median progression-free survival (PFS) and overall survival (OS) were not reached. At 84 months, PFS and OS rates were 88.4% and 95.7%, respectively. No evidence for a difference in PFS or OS was observed for PET-2-negative and PET-2-positive patients. Infections were documented in 8.3% and febrile neutropenia in 6.2% of cases. Four patients died: one had alveolitis at cycle 3, one death was unrelated to treatment, and two died from a secondary cancer. dd-ABVD is feasible and demonstrates activity in early-stage unfavorable HL. The predictive role of PET-2 positivity in early-stage unfavorable HL remains controversial. The study was registered in the EudraCT (reference number, 2011-003,191-36) and the ClinicalTrials.gov (reference number, NCT02247869) databases.

Radiation-induced breast angiosarcoma: report of two patients after accelerated partial breast irradiation (APBI) and review of the literature.

BACKGROUND: Angiosarcoma may rarely complicate radiotherapy of breast cancer. This so-called radiation-induced angiosarcoma (RIAS) occurs in less than 0.3% of patients that underwent breast conservation surgeries, usually years after completion of radiotherapy. CASE PRESENTATION: we introduce two cases of invasive ductal carcinoma who underwent lumpectomy and accelerated partial breast irradiation (APBI) as an alternative protocol to whole breast irradiation (WBI). They received adjuvant partial breast radiotherapy on tumor cavity for a total dose of 38.5 Gy in 10 fractions in 5 days using 3D-external-beam RT. In both cases, RIAS occurred eight years after radiotherapy, in the sub-cicatricial area in one patient and outside the irradiated area in the other one. They both underwent radical surgery and chemotherapy was performed in one patient. DISCUSSION: The underlying mechanism for development of RIAS is not well known, but its incidence seems to be increasing. RIAS after partial breast irradiation is very rare and has been reported in two cases so far. As it may be suggested in case 2, it is still a matter of debate if the risk of radiation-induced sarcoma is radiation-dose dependent. Although mastectomy is considered as a standard treatment, choice of treatment should be made according to the patient's specifications. CONCLUSION: There are very few studies in the literature that report RIAS after APBI. Present study is the only one reporting two cases after the external 3D technique APBI. Prognosis of RIAS remains poor. Only a careful evaluation in a multidisciplinary context can offer to the patients the best result in terms of local control and survival.

Extracranial metastases in secondary glioblastoma multiforme: a case report.

BACKGROUND: Glioblastoma (GBM) is known for its devastating intracranial infiltration and its unfavorable prognosis, while extracranial involvement is a very rare event, more commonly attributed to IDH wild-type (primary) GBM evolution. CASE PRESENTATION: We present a case of a young woman with a World Health Organization (WHO) grade II Astrocytoma evolved to WHO grade IV IDH mutant glioblastoma, with subsequent development of lymphatic and bone metastases, despite the favorable biomolecular pattern and the stability of the primary brain lesion. CONCLUSIONS: Our case highlights that grade II Astrocytoma may evolve to a GBM and rarely lead to a secondary metastatic diffusion, which can progress quite rapidly; any symptoms referable to a possible systemic involvement should be carefully investigated.

Re-irradiation for recurrent glioma: outcome evaluation, toxicity and prognostic factors assessment. A multicenter study of the Radiation Oncology Italian Association (AIRO).

INTRODUCTION: The prognosis of glioma is dismal, and almost all patients relapsed. At recurrence time, several treatment options are considered, but to date there is no a standard of care. The Neurooncology Study Group of the Italian Association of Radiation Oncology (AIRO) collected clinical data regarding a large series of recurrent glioma patients who underwent re-irradiation (re-RT) in Italy. METHODS: Data regarding 300 recurrent glioma patients treated from May 2002 to November 2017, were analyzed. All patients underwent re-RT. Surgical resection, followed by re-RT with concomitant and adjuvant chemotherapy was performed. Clinical outcome was evaluated by neurological examination and brain MRI performed, 1 month after radiation therapy and then every 3 months. RESULTS: Re-irradiation was performed at a median interval time (IT) of 16 months from the first RT. Surgical resection before re-RT was performed in 19% of patients, concomitant temozolomide (TMZ) in 16.3%, and maintenance chemotherapy in 29%. Total doses ranged from 9 Gy to 52.5 Gy, with a median biological effective dose of 43 Gy. The median, 1, 2 year OS were 9.7 months, 41% and 17.7%. Low grade glioma histology (p  ≪ 0.01), IT > 12 months (p = 0.001), KPS > 70 (p = 0.004), younger age (p = 0.001), high total doses delivered (p = 0.04), and combined treatment performed (p = 0.0008) were recorded as conditioning survival. CONCLUSION: our data underline re-RT as a safe and feasible treatment with limited rate of toxicity, and a combined ones as a better option for selected patients. The identification of a BED threshold able to obtain a greater benefit on OS, can help in designing future prospective studies.

Hypofractionated radiation therapy in the management of locally advanced NSCLC: a narrative review of the literature on behalf of the Italian Association of Radiation Oncology (AIRO)-Lung Working Group.

A systematic literature was performed to assess the benefit in terms of effectiveness and feasibility of hypofractionated radiotherapy (HypoRT), with or without chemotherapy (CT), in the treatment of locally advanced non-small cell lung cancer (NSCLC). We have identified all studies, published from 2007 onwards, on patients with locally advanced NSCLC treated with HypoRT with radical intent, with a minimal dose per fraction of 2.4 Gy, with or without concurrent chemotherapy. Twenty-nine studies were identified, for a total of 2614 patients. Patients were divided in the concurrent chemo-radiation therapy group (CT-RT) and radiotherapy alone (RT). In RT group, the delivered dose ranged from 45 to 85.5 Gy, with a dose/fraction from 2.4 to 4 Gy. Actuarial 2-year PFS ranged from 13 to 57.8%, and 1, 2- and 3-year overall survival (OS) ranged from 51.3 to 95%, from 22 to 68.7%, and from 7 to 32%, respectively. Acute Grade ≥ 3 esophagitis occurred in 0-15%, while late esophageal toxicity was 0-16%. Acute pneumonitis occured in 0-44%, whereas late pneumonitis occured in 0-47%, most commonly grade ≤ G3. In CT-RT group, the delivered dose ranged from 52.5 to 75 Gy, with a dose/fraction ranging from 2.4 to 3.5 Gy. Actuarial 2-year PFS ranged from 19 to 57.8%, and OS at 1, 2 and 3 years ranged from 28 to 95%, 38.6 to 68.7%, and 31 to 44%, respectively. Acute Grade 2 and 3 esophagitis occurred in 3-41.7%, while late esophageal toxicity occurred in 0-8.3%. Acute pneumonitis ranged from 0 to 23%, whereas late pneumonitis occured 0-47%. HypoRT seems to be safe in patients with locally advanced NSCLC. The encouraging survival results of several studies analyzed suggest that hypofractionated radiation schemes should be further investigated in the future.

Renewed interest for low-dose radiation therapy in follicular lymphomas: From biology to clinical applications.

Follicular lymphoma (FL) is the most common subtype of indolent non-Hodgkin lymphoproliferative disorders. Treatment strategies for FL may include several therapeutic choices, ranging from a "watchful waiting" approach to stem cell transplantation, mostly depending on staging, age, risk factors, and disease burden at diagnosis. The high radiosensitivity of FL compared with other solid tumors has been known since the beginning of radiotherapy treatment in lymphoma patients. Doses of 24 to 40 Gy were considered appropriate in first line curative treatment for localized disease (stages I-II), but several publications investigating low-dose radiotherapy (LDRT) of 4Gy (2 × 2Gy) reported an overall response rate surprisingly high. Due to its high local efficacy and negligible toxicity, LDRT might be offered to both early and advanced stage FL patients in combination with new agents, at diagnosis or after several lines of systemic therapy. The aim of this review is to summarize and discuss the current knowledge on LDRT for FL and its potential application in a curative setting in combination with new drugs for both early and advanced disease.

Radiation therapy in small cell lung cancer: a national Italian survey.

INTRODUCTION: Radiation therapy plays an important role in the management of SCLC both in curative and palliative setting, however, conflicting data from clinical trials incite debate over the appropriate use of radiation therapy regarding prophylactic cranial irradiation (PCI) and/or thoracic consolidative in extensive-stage SCLC (ES-SCLC). This survey is conducted to evaluate the current pattern of care among Italian radiation oncologists. METHODS: In June 2016, all Italian radiation oncologists were invited to a web-based survey. The survey contained 34 questions regarding the role of RT in SCLC. Questions pertaining the role of RT in the clinical management of both limited-stage (LS) and ES-SCLC were included. RESULTS: We received 48 responses from Italian radiation oncologists. More than half of respondents had been practicing for more than 10 years after completing residency training and 55% are subspecialists in lung cancer. Preferred management of LS-SCLC favored primary concurrent chemoradiotherapy (89%), even if the 36.9% usually delivered RT during or after the cycle 3 of chemotherapy, due to organizational issues. The most common dose and fractionation schedule in this setting was 60 Gy in 30 once-daily fractions. Furthermore, almost all respondents recommended PCI in patients with LS-SCLC. For ES-SCLC scenario, chemotherapy was defined the standard treatment by all respondents. PCI was recommended in ES-SCLC patients with thoracic complete remission (63% of respondents), with thoracic partial response (45%) and with thoracic stable disease (17%) after first-line chemotherapy. Lastly, the thoracic consolidative RT was recommended by 51% of respondents in patients with ES-SCLC in good response after first-line chemotherapy and a great variability was shown in clinical target volume definition, doses and fractionation schedules. CONCLUSIONS: Our analysis showed a high adherence to current guidelines among the respondents in regard to chemoradiation approach in LS-SCLC patients and to PCI indications and doses. The great variability in radiation therapy doses and volumes in the thoracic consolidative radiotherapy in ES-SCLC is concerning. Future clinical trials are needed to standardize these treatment approaches to improve treatment outcomes among patients with ES-SCLC.

Redetermination of PD-L1 expression after chemio-radiation in locally advanced PDL1 negative NSCLC patients: retrospective multicentric analysis.

Background: Chemoradiation therapy (CRT) is the treatment of choice for locally advanced non-small cell lung cancer (LA-NSCLC). Several clinical trials that combine programmed cell death 1 (PD1) axis inhibitors with radiotherapy are in development for patients with LA-NSCLC. However, the effect of CRT on tumor cells programmed cell death ligand-1 (PD-L1) expression is unknown. Methods: In this multicentric retrospective study, we analyzed paired NSCLC specimens that had been obtained pre- and post-CRT. PD-L1 expression on tumor cells was studied by immunohistochemistry. The purpose of this study was to evaluate the feasibility, risk of complications, and clinical relevance of performing re-biopsy after CRT in patients with PD-L1 negative LA-NSCLC. Results: Overall, 31 patients from 6 centers with PD-L1 negative LA-NSCLC were analyzed. The percentage of tumor cells with PD-L1 expression significantly increased between pre- and post-CRT specimens in 14 patients (45%). Nine patients had unchanged PD-L1 expression after CRT, in five patients the rebiopsy material was insufficient for PD-L1 analysis and in two patients no tumor cells at rebiopsy were found. The post-rebiopsy complication rate was very low (6%). All patients with positive PD-L1 re-biopsy received Durvalumab maintenance after CRT, except one patient who had a long hospitalization for tuberculosis reactivation. Median PFS of patients with unchanged or increased PD-L1 expression was 10 and 16.9 months, respectively. Conclusion: CRT administration can induce PD-L1 expression in a considerable fraction of PD-L1 negative patients at baseline, allowing them receiving the maintenance Durvalumab in Europe. Hence, after a definitive CRT, PD-L1 redetermination should be considered in patients with LA-NSCLC PD-L1 negative, to have a better selection of maintenance Durvalumab candidates.

Sterotactic Ablative Radiotherapy in a Multicentric Series of Oligometastatic SCLC: The SAMOS Cohort.

AIMS: SCLC is the most aggressive lung cancer histology with a 5-year OS <10%. At the diagnosis, almost two-thirds of the SCLC an Extended Disease presentation. Two randomized studies (CASPIAN and ImPower133) demonstrated an OS improvement, when immunotherapy was prescribed as maintenance therapy after standard chemotherapy. To date, SABR has had a limited indication in managing metastatic SCLC, although recent reports proposed it as a valid treatment option in selected patients. We propose a retrospective multicentric analysis of patients treated with SABR for oligometastatic SCLC. METHOD: Data of patients affected by oligometastatic-SCLC treated with SABR between 2017 and 2022 in 11 Italian centers were collected. Clinical and therapeutic variables together with OS and time to next treatment were analyzed. Univariate analysis with Kaplan-Meier curve were calculated, and log-rank test were applied. Cox proportional hazard model was used for multivariate analysis. RESULTS: Data from 93 patients and 132 metastatic lesions were analyzed. The median age was 64 years (36-86) and all but 1 had Performance Status 0 or 1. Fifty-two patients presented ED at diagnosis. The first line treatment was radiochemotherapy in 42%, CHT alone in 24% and CHT-IO in 28%, others treatment accounts for 4% and only 2% of patients underwent best supportive care. Of the 132 lesions treated with SBRT 55 were in brain, 27 in lung, 11 in liver, 10 in lymph nodes, 8 in bones and 20 in adrenal gland. Median OS was 14 months, 1 year-OS and 2 years OS were 53% and 27%, respectively. The median TtNT was 14 months for the entire population. Of all the analyzed variables only, the anatomical site of the metastases and their number showed statistical significance in the univariate analysist, confirmed in the subsequent multivariate. CONCLUSION: SABR seems to play a role in delaying further systemic lines in oligometastatic disease and to extend the use of ongoing treatment in oligoprogressive state. Prospective studies are needed to confirm these findings.

The "BUONGIORNO" project: burnout syndrome among young Italian radiation oncologists.

Few data exist about the prevalence of burnout syndrome among young radiation oncologists. A national survey to assess its prevalence among junior members (under 40 yrs of age) of the Italian Society of Radiation Oncology was conducted. One hundred and twelve young radiation oncologists completed the questionnaire: the prevalence of burnout syndrome was 35%, and it was related to the presence of different personal, organizational, and work-related aspects, with an impact also on the private life (p<.005). Burnout syndrome is relatively common among young Italian radiation oncologists, and specific educational tools to help improve the management of workload and stress are needed.

Short-course preoperative radiotherapy combined with chemotherapy in resectable locally advanced rectal cancer: local control and quality of life.

PURPOSE: The authors sought to evaluate the clinical outcome after preoperative short-course radiotherapy (SC-RT) for locally advanced resectable rectal cancer in terms of local control (LC) and quality of life (QoL). MATERIALS AND METHODS: Patients with locally advanced rectal cancer enrolled between 1997 and 2008 in an observational study of preoperative SC-RT were analysed. The treatment algorithm was neo-adjuvant chemotherapy (CT) administered for four cycles, followed by preoperative SC-RT administered 1 week after chemotherapy completion, delivering 20 Gy in five fractions over 1 week. Immediately in the following week surgery was performed. The adjuvant 5-FU-based CT was planned for pathological stage UICC≥II. LC, overall survival (OS), disease-free survival (DFS), early and late complications (RTOG scale) were analysed. All patients completed the EORTC QoL (C-30 and C-38), Faecal Incontinence QoL, and International Index of Erectile Function questionnaires (IIEF). RESULTS: A total of 67 patients were analysed. Chemotherapy and radiotherapy were well tolerated. At the pathological analysis, stable disease was obtained in 24 patients (36%), reduction of disease stage in 34 patients (50.7%), and progression in nine cases (13.3%). Adjuvant chemotherapy was indicated in 21 patients. Two locoregional recurrences, both within the radiotherapy volume, were observed, resulting in a 5-year LC of 97%. The 5-year DFS was 84%, with mean time to systemic progression of 24 months. After a mean follow-up of 114 months, the 5-year OS rate was 67%. Late toxicity >grade II was observed in 9% of patients. High anterior resection (AR) patients had significantly better scores than low AR or abdomino-perineal resection (APR). A total of 89% of the patients treated with conservative surgery had regular anal sphincter function. In male patients undergoing AR or APR, erectile dysfunction was found in 47% and 75% of the cases, respectively. CONCLUSIONS: Preoperative SC-RT combined with chemotherapy for locally advanced resectable rectal cancers was well tolerated. This treatment resulted in favourable LC, OS, low rates of toxicity and satisfying QoL.

The "PROCAINA (PROstate CAncer INdication Attitudes) Project" (Part II)--a survey among Italian radiation oncologists on radical radiotherapy in prostate cancer.

PURPOSE: Radiotherapy (RT) has an established role in the treatment of prostate cancer patients. Despite the large number of patients treated with RT, some issues about optimal techniques, doses, volumes, timing, and association with androgen deprivation are still subject of debate. The aim of this survey was to determine the patterns of choice of Italian radiation oncologists in two different clinical cases of prostate cancer patients treated with radical RT. STUDY DESIGN: During the 2010 Italian Association of Radiation Oncology (AIRO) National congress, four different clinical cases were presented to attending radiation oncologists. Two of them were prostate cancer cases that could be treated by RT +/- hormonal therapy (HT), different for T stage of primary tumour according to TNM, preoperative diagnostic procedures for staging, initial prostate specific antigen (iPSA), and Gleason Score sum of biopsy. For each clinical case, radiation oncologists were asked to: (a) give indication to pretreatment procedures for staging; (b) give indication to treatment; (c) define specifically, where indicated, total dose, type of fractionation, volumes of treatment, type of technique, type of image-guided setup control; (d) indicate if HT should be prescribed; (e) define criteria that particularly influenced prescription. A descriptive statistical analysis was performed. RESULTS: Three hundred questionnaires were given to radiation oncologists attending the congress, 128 questionnaires were completed and considered for this analysis (41%). Some important differences were shown in prescribing and delivering RT, particularly with regards to treatment volumes and fractionation. CONCLUSIONS: Despite the results of clinical trials, several differences still exist among Italian radiation oncologists in the treatment of prostate cancer patients. These patients probably deserve a more uniform approach, based on upto-date, detailed, and evidence-based recommendations.

Prostate embryonal rhabdomyosarcoma in adults: Case report and review of literature.

INTRODUCTION: Prostate embryonal rhabdomyosarcoma (ERMS) is a common tumour in infants and children, with a median occurrence age of 5 years, but it is rare in adults. It is characterized by a high degree of malignancy, both local rapid growth with formation of large pelvic masses, often leading to renal failure due to urethral obstruction, and systemic spread, commonly to the lungs, liver and bone. Several therapeutic approaches have been employed in the effort to treat prostate ERMS, but all of them have failed to gain a significant survival benefit in adult patients. CASE REPORT: We report on a case of a stage IV prostate ERMS, approached with combined-modality treatment, with the administration of 5 courses of doxorubicin, ifosfamide and 2-mercaptoethane sulfonate sodium (mesna), and, subsequent radiotherapy to the prostatic bed (60 Gy/30 fxs). The patient remained free of progression of disease for about 1 year to finally experience a systemic relapse with multiple lung metastases and pleural effusion. The patient died for metastatic disease 27 months following the initial diagnosis. CONCLUSION: While it remains questionable which therapeutic approach for prostate ERMS in adults is the most appropriate, our report demonstrates that a chemo-radiation combined treatment can control the prostate disease, reducing the symptoms and improving the quality of life of these patients, for the most part destined to die for systemic progression of disease.

Lattice Radiation Therapy in clinical practice: A systematic review.

Purpose: Lattice radiation therapy (LRT) is an innovative type of spatially fractionated radiation therapy. It aims to increase large tumors control probability by administering ablative doses without an increased toxicity. Considering the rising number of positive clinical experiences, the objective of this work is to evaluate LRT safety and efficacy. Method: Reports about LRT clinical experience were identified with a systematic review conducted on four different databases (namely, Medline, Embase, Scopus, and Cochrane Library) through the August 2022. Only LRT clinical reports published in English and with the access to the full manuscript text were considered as eligible. The 2020 update version PRISMA statement was followed. Results: Data extraction was performed from 12 eligible records encompassing 7 case reports, 1 case series, and 4 clinical studies. 81 patients (84 lesions) with a large lesion ranging from 63.2 cc to 3713.5 cc were subjected to exclusive, hybrid, and metabolism guided LRT. Excluding two very severe toxicity with a questionable relation with LRT, available clinical experience seem to confirm LRT safety. When a complete response was not achieved 3-6 months after LRT, a median lesion reduction approximately ≥50 % was registered. Conclusion: This systematic review appear to suggest LRT safety, especially for exclusive LRT. The very low level of evidence and the studies heterogeneity preclude drawing definitive conclusions on LRT efficacy, even though an interesting trend in terms of lesions reduction has been described.

Clinical Effects of Immuno-Oncology Therapy on Glioblastoma Patients: A Systematic Review.

The most prevalent and deadly primary malignant glioma in adults is glioblastoma (GBM), which has a median survival time of about 15 months. Despite the standard of care for glioblastoma, which includes gross total resection, high-dose radiation, and temozolomide chemotherapy, this tumor is still one of the most aggressive and difficult to treat. So, it is critical to find more potent therapies that can help glioblastoma patients have better clinical outcomes. Additionally, the prognosis for recurring malignant gliomas is poor, necessitating the need for innovative therapeutics. Immunotherapy is a rather new treatment for glioblastoma and its effects are not well studied when it is combined with standard chemoradiation therapy. We conducted this study to evaluate different glioblastoma immunotherapy approaches in terms of feasibility, efficacy, and safety. We conducted a computer-assisted literature search of electronic databases for essays that are unique, involve either prospective or retrospective research, and are entirely written and published in English. We examined both observational data and randomized clinical trials. Eighteen studies met the criteria for inclusion. In conclusion, combining immunotherapy with radiochemotherapy and tumor removal is generally possible and safe, and rather effective in the prolongation of survival measures.

Moderately Hypofractionated Helical Tomotherapy for Prostate Cancer: Ten-year Experience of a Mono-institutional Series of 415 Patients.

BACKGROUND/AIM: Radiotherapy represents an important therapeutic option in the management of prostate cancer (PCa). As helical tomotherapy may improve toxicity outcomes, we aimed to evaluate and report the toxicity and clinical outcomes of localized PCa patients treated with moderately hypofractionated helical tomotherapy. PATIENTS AND METHODS: We retrospectively analyzed 415 patients affected by localized PCa and treated with moderately hypofractionated helical tomotherapy in our department from January 2008 to December 2020. All patients were stratified according to the D'Amico risk classification: low-risk 21%, favorable intermediate-risk 16%, unfavorable intermediate-risk 30.4%, and high-risk 32.6%. The dose prescription for high-risk patients was 72.8 Gy to the prostate (planning tumor volume-PTV1), 61.6 Gy to the seminal vesicles (PTV2), and 50.4 Gy to the pelvic lymph nodes (PTV3) in 28 fractions; for low- and intermediate-risk patients 70 Gy for PTV1, 56 Gy for PTV2, and 50.4 Gy for PTV3 in 28 fractions. Image-guided radiation therapy was performed daily in all patients by mega-voltage computed tomography. Forty-one percent of patients received androgen deprivation therapy (ADT). Acute and late toxicity was assessed according to the National Cancer Institute's Common Terminology Criteria for Adverse Events v.5.0 (CTCAE). RESULTS: Median follow-up was 82.7 months (range=12-157 months) and the median age of patients at diagnosis was 72.5 years (range=49-84 years). The 3, 5, and 7 yr overall survival (OS) rates were 95%, 90%, and 84%, respectively, while 3, 5, and 7 yr disease-free survival (DFS) were 96%, 90%, and 87%, respectively. Acute toxicity was as follows: genitourinary (GU) G1 and G2 in 35.9% and 24%; gastrointestinal (GI) in 13.7% and 8%, with G3 or more acute toxicities less than 1%. The late GI toxicity G2 and G3 were 5.3% and 1%, respectively, and the late GU toxicity G2 and G3 were 4.8% and 2.1%, respectively, and only three patients had a G4 toxicity. CONCLUSION: Hypofractionated helical tomotherapy for PCa treatment appeared to be safe and reliable, with favorable acute and late toxicity rates and encouraging results in terms of disease control.

Good clinical practice and the use of hypofractionation radiation schedules as weapons to reduce the risk of COVID-19 infections in radiation oncology unit: A mono-institutional experience.

BACKGROUND: After coronavirus disease outbreak emerged in 2019, radiotherapy departments had to adapt quickly their health system and establish new organizations and priorities. The purpose of this work is to report our experience in dealing with COVID-19 emergency, how we have reorganized our clinical activity, changed our priorities, and stressed the use of hypofractionation in the treatment of oncological diseases. MATERIALS AND METHODS: The patients' circuit of first medical examinations and follow-up was reorganized; a more extensive use of hypofractionated schedules was applied; a daily triage of the patients and staff, use of personal protective equipment, hand washing, environment sanitization, social distancing and limitations for the patients' caregivers in the department, unless absolutely essential, were performed; patients with suspected or confirmed COVID-19 were treated at the end of the day. In addition, the total number of radiotherapy treatment courses, patients and sessions, in the period from February 15 to April 30, 2020, comparing the same time period in 2018 were retrospectively investigated. In particular, changes in hypofractionated schedules adopted for the treatment of breast and prostate cancer and palliative bone metastasis were analyzed. RESULTS: Between February 15, and April 30, 2020, an increased number of treatments was carried out: Patients treated were overall 299 compared to 284 of the same period of 2018. Stressing the use of hypofractionation, 2036 RT sessions were performed, with a mean number of fractions per course of 6.8, compared to 3566 and 12.6, respectively, in 2018. For breast cancer, the schedule in 18 fractions has been abandoned and treatment course of 13 fractions has been introduced; a 27% reduction in the use of 40.5 Gy in 15 fractions, (67 treatments in 2018-49 in 2020) was reported. An increase of 13% of stereotactic body radiation therapy for prostate cancer was showed. The use of the 20 Gy in 4 or 5 sessions for the treatment of symptomatic bone metastasis decreased of 17.5% in favor of 8 Gy-single fraction. Three patients results COVID-19 positive swab: 1 during, 2 after treatment. Only one staff member developed an asymptomatic infection. CONCLUSIONS: The careful application of triage, anti-contagion and protective measures, a more extensive use of hypofractionation allowed us to maintain an effective and continuous RT service with no delayed/deferred treatment as evidenced by the very low number of patients developing COVID-19 infection during or in the short period after radiotherapy. Our experience has shown how the reorganization of the ward priority, the identification of risk factors with the relative containment measures can guarantee the care of oncological patients, who are potentially at greater risk of contracting the infection.

Peritransplant Radiation Therapy in Patients With Refractory or Relapsed Hodgkin Lymphoma Undergoing Autologous Stem Cell Transplant: Long-Term Results of a Retrospective Study of the Fondazione Italiana Linfomi.

PURPOSE: In this multicenter collaboration, we report real-world data in the largest published series of long-term outcomes for patients with relapsed/refractory (r/r) Hodgkin lymphoma (HL) treated with peritransplant radiation therapy (pt-RT) and high-dose chemotherapy with autologous stem cell transplant (ASCT). METHODS AND MATERIALS: We conducted a retrospective analysis including data from 12 institutions. Eligibility required histologic diagnosis of HL, receipt of ASCT plus pt-RT between 2004 and 2014 for r/r HL, and age ≥18 years at the time of ASCT. All patients received salvage chemotherapy for maximum debulking before ASCT. Metabolic responses were scored according to the Lugano Classification. The primary endpoint was overall survival (OS). Univariate and multivariate Cox proportional hazards were calculated to estimate the effect of covariates on patients' outcome. RESULTS: One hundred thirty-one patients were eligible: 68 were male (52%), and median age at ASCT was 32 years (range, 18-70). At the time of diagnosis with r/r HL, 92 patients (70%) had limited (stage I-II) disease, and 10 patients (8%) had bulky disease. Pt-RT was given pre-ASCT in 32 patients (24%) and post-ASCT in 99 (76%); median prescribed dose was 30.6 Gy (range, 20-44 Gy). With median follow-up of 60 months, 3- and 5-year OS were 84% and 77%, while 3- and 5-year progression-free survival were 75% and 72%, respectively. On univariate and multivariate analysis, advanced stage at relapse (hazard ratio [HR], 2.18; P = .04), irradiation of >3 sites (HR, 3.69; P = .01), and incomplete metabolic response after salvage chemotherapy (HR, 2.24; P = .01) had a negative effect on OS. The sequencing of pt-RT (pre- vs post-ASCT) did not affect outcomes. CONCLUSIONS: Overall, the addition of pt-RT to ASCT for patients with r/r HL is associated with very good outcomes. Limited relapsed disease with ≤3 sites involved and achievement of complete metabolic response after salvage chemotherapy were predictive of more favorable prognosis.