The Immunomodulatory Potential of Concurrent High-Dose Radiotherapy and Immune Checkpoint Inhibitor Cemiplimab in Advanced Cutaneous Squamous Cell Carcinoma: Initial Results.

In this retrospective case series, we investigate the synergistic effect and the immunomodulatory potential of combination radiotherapy and immunotherapy on 11 patients affected by locally advanced or metastatic cutaneous squamous cell carcinoma (CSCC), treated at our institution between 2020 and 2023. The primary endpoints of this study are objective tumor response, assessed by Immunotherapy Response Evaluation Criteria in Solid Tumors (iRECIST), and time to treatment failure (disease progression). In all patients, surgery was deemed not amenable, due to its potential functional and aesthetic impact. Therefore, upon multidisciplinary agreement, radiotherapy and immunotherapy with cemiplimab were alternatively administered. After 6 months, an early objective tumor response was observed in 9/11 patients, with 17/20 cutaneous lesions (85%) presenting either a complete or partial response. Only 2/11 patients, with a total of 3/20 cutaneous lesions (15%), had stable disease. These benefits persisted at a longer follow-up (21.4 ± 9.7 months), with no patients presenting disease progression. Despite the retrospective nature of this study and small sample size, our experience highlights the ability of concomitant radiotherapy and cemiplimab to promote an early objective response in patients with advanced CSCC. Moreover, in our population, the clinical benefits were also related to a longer progression-free survival, without any safety alert reported.

Radiotherapy of Orbital and Ocular Adnexa Lymphoma: Literature Review and University of Catania Experience.

Orbital and ocular adnexa lymphomas are rare neoplasms confined to the orbital region. The prognosis is generally favorable, with a high proportion of localized disease, indolent clinical course, prolonged disease-free intervals, and low lymphoma-related mortality rate. We report our experience on eleven patients with confirmed histological diagnosis of lymphoma stage IE-IIE, treated between 2010 and 2021 with radiotherapy alone or in association with chemotherapy or immunotherapy. Eight patients were treated with primary radiotherapy only, while three received previous systemic treatments. Six patients were treated with Proton beam therapy (PBT), and five with external beam radiotherapy (EBRT). The five-year local control rate was 98%; only one patient developed an out-of-field recurrence. We also conducted a comprehensive literature review using electronic databases (PubMed, EMBASE, and Cochrane Library). Articles were selected based on their pertinence to treatment of the ocular and adnexal lymphoma focusing on radiotherapy techniques (electron beam radiotherapy, photon beam radiotherapy, or proton beam radiotherapy), treatment total dose, fractionation schedule, early and late radio-induced toxicities, and patient's clinical outcome. Radiotherapy is an effective treatment option for orbital lymphoma, especially as standard treatment in the early stage of orbital lymphoma, with excellent local control rate and low rates of toxicity.

The role of interventional radiotherapy (brachytherapy) in nasopharynx tumors: A systematic review.

Purpose: Nasopharyngeal cancers (NPC) are very aggressive, and the recurrence rate after radical therapy is high. This study aimed to evaluate the efficacy of brachytherapy (BT) also called interventional radiotherapy (IRT) in primary NPC in comparison with external beam radiotherapy (EBRT) alone. Material and methods: A systematic search was performed in Scopus, Cochrane, and PubMed databases. Clinical query based on PICO framework was as follows: In patients with NPC (P), is EBRT plus IRT (I) superior to EBRT alone (C) in terms of local control (LC) and toxicity (O)? Full articles evaluating the efficacy of IRT as a boost after EBRT in patients with NPC were considered. Results: Eight papers, including 1,320 patients fulfilled the inclusion criteria. The median 5-year LC for IRT group and no-IRT group was 98% (range, 95.8-100%) and 86% (range, 80.2-91%), respectively; the median 5-year overall survival (OS) for IRT group and no-IRT group was 93.3% (range, 89.2-97.5%) and 82.9% (range, 74.8-91.1%), respectively; the median 5-year DFS for IRT group and no-IRT group was 94.2% (range, 92.5-96%) and 83.9% (range, 73.3-94.6%), respectively; the median 5-year cancer-specific survival (CSS) for IRT group and no-IRT group was 96% (range, 94.5-97.5%) and 88.2% (range, 83.4-93.1%), respectively. G1-2 and G3-4 toxicities were similar in some articles, or significantly lower in patients treated with IRT in other papers. Conclusions: Data suggest that IRT may improve results of external beam radiotherapy in primary NPCs, especially when using new technologies.

The Role of Reirradiation in Childhood Progressive Diffuse Intrinsic Pontine Glioma (DIPG): An Ongoing Challenge beyond Radiobiology.

To investigate the clinical impact of multiple courses of irradiation on pediatric patients with progressive diffuse intrinsic pontine glioma (DIPG), we conducted a retrospective case series on three children treated at our institution from 2018 to 2022. All children were candidates to receive systemic therapy with vinorelbine and nimotuzumab. Radiotherapy was administered to a total dose of 54 Gy. At any disease progression, our local tumor board evaluated the possibility of offering a new course of radiotherapy. To determine feasibility and assess toxicity rates, all children underwent clinical and hematological evaluation both during and after the treatment. To assess efficacy, all children performed contrast-enhanced MRI almost quarterly after the end of the treatment. In all children, following any treatment course, neurological improvement (>80%) was associated with a radiological response (41.7-46%). The longest overall survival (24 months) was observed in the child who underwent three courses of radiotherapy, without experiencing significant side effects. Even though it goes beyond the understanding of conventional radiobiology, first and second reirradiation in pediatric patients with progressive DIPG may represent a feasible and safe approach, capable of increasing overall survival and disease-free survival in selected patients and improving their quality of life.

Hypofractionated Radiotherapy in Localized, Low-Intermediate-Risk Prostate Cancer: Current and Future Prospectives.

At the time of diagnosis, the vast majority of prostate carcinoma patients have a clinically localized form of the disease, with most of them presenting with low- or intermediate-risk prostate cancer. In this setting, various curative-intent alternatives are available, including surgery, external beam radiotherapy and brachytherapy. Randomized clinical trials have demonstrated that moderate hypofractionated radiotherapy can be considered as a valid alternative strategy for localized prostate cancer. High-dose-rate brachytherapy can be administered according to different schedules. Proton beam radiotherapy represents a promising strategy, but further studies are needed to make it more affordable and accessible. At the moment, new technologies such as MRI-guided radiotherapy remain in early stages, but their potential abilities are very promising.

Integrated Intensified Chemoradiation in the Setting of Total Neoadjuvant Therapy (TNT) in Patients with Locally Advanced Rectal Cancer: A Retrospective Single-Arm Study on Feasibility and Efficacy.

While surgery is considered the main treatment for early-stage rectal cancer, locally advanced rectal cancer needs to be handled with a multidisciplinary approach. Based on literature data suggesting promising advantages of total neoadjuvant therapy (TNT), we performed a retrospective, single-arm, single-center study on 45 patients affected by histologically and radiologically proven locally advanced rectal cancer, with the aim of analyzing the feasibility and short-term efficacy of an integrated intensified treatment in the setting of TNT. Each analyzed patient performed three cycles of FOLFOX4 or De Gramont induction chemotherapy (iCT), followed by concurrent chemoradiotherapy (CRT) with long course radiotherapy (LCRT) plus concomitant boost and continuous 5-FU infusion, followed by three cycles of FOLFOX4 or De Gramont consolidation chemotherapy (conCT) and then surgery with total mesorectal excision. At a median follow-up of 30 months, this strategy has shown to be feasible and effective in terms of pathological complete response (pCR) and short-term disease-free survival (DFS).

Relapsing High-Grade Glioma from Peritumoral Zone: Critical Review of Radiotherapy Treatment Options.

Glioblastoma (GBM) is the most common and aggressive brain tumor in adults, with a median survival of about 15 months. After the prior treatment, GBM tends to relapse within the high dose radiation field, defined as the peritumoral brain zone (PTZ), needing a second treatment. In the present review, the primary role of ionizing radiation in recurrent GBM is discussed, and the current literature knowledge about the different radiation modalities, doses and fractionation options at our disposal is summarized. Therefore, the focus is on the necessity of tailoring the treatment approach to every single patient and using radiomics and PET/MRI imaging to have a relatively good outcome and avoid severe toxicity. The use of charged particle therapy and radiosensitizers to overcome GBM radioresistance is considered, even if further studies are necessary to evaluate the effectiveness in the setting of reirradiation.

Histopathologic and MR Imaging Appearance of Spontaneous and Radiation-Induced Necrosis in Uveal Melanomas: Initial Results.

Necrosis in uveal melanomas can be spontaneous or induced by radiotherapy. The purpose of our study was to compare the histopathologic and MRI findings of radiation-induced necrosis of a group of proton beam-irradiated uveal melanomas with those of spontaneous necrosis of a control group of patients undergoing primary enucleation. 11 uveal melanomas who had undergone proton beam radiotherapy, MRI and secondary enucleation, and a control group of 15 untreated uveal melanomas who had undergone MRI and primary enucleation were retrospectively identified. Within the irradiated and nonirradiated group, 7 and 6 eyes with histological evidence of necrosis respectively, were furtherly selected for the final analysis; the appearance of necrosis was assessed at histopathologic examination and MRI. Irradiated melanomas showed a higher degree of necrosis as compared with nonirradiated tumors. Irradiated and nonirradiated lesions differed based on the appearance and distribution of necrosis. Irradiated tumors showed large necrotic foci, sharply demarcated from the viable neoplastic tissue; nonirradiated tumors demonstrated small, distinct foci of necrosis. Radiation-induced necrosis, more pigmented than surrounding viable tumor, displayed high signal intensity on T1-weighted and low signal intensity on T2-weighted images. The hemorrhagic/coagulative necrosis, more prevalent in nonirradiated tumors (4 out of 6 vs. 1 out of 7 cases), appeared hyperintense on T2-weighted and hypointense on T1-weighted images. Our study boosts the capability to recognize radiation-induced alterations in uveal melanomas at MRI and may improve the accuracy of radiologists in the evaluation of follow-up MR examination after radiotherapy.

Diagnostic methods and therapeutic options of uveal melanoma with emphasis on MR imaging-Part II: treatment indications and complications.

Therapy of uveal melanoma aims to preserve the eye and its function and to avoid metastatic dissemination. The treatment choice is difficult and must keep into account several factors; the therapeutic strategy of uveal melanoma should therefore be personalized, sometimes requiring to combine different treatment techniques. Nowadays globe-sparing radiotherapy techniques are often preferred to enucleation. Plaque brachytherapy, the most commonly used eye-preserving therapy, is suitable for small- and medium-sized uveal melanomas. Proton beam radiotherapy is indicated for tumours with noticeable size, challenging shape and location, but is more expensive and less available than brachytherapy. Enucleation is currently restricted to advanced tumours, uveal melanomas with orbital or optic nerve involvement, blind and painful eyes because of treatment-related complications (neovascular glaucoma, chronic inflammatory processes). The effect of proton beam therapy on neoplastic tissue is related to direct cytotoxic action of the radiations, impairment of neoplastic vascular supply and immunologic response. Complications after radiotherapy are frequent and numerous and mainly related to tumour thickness, radiation dose and distance between the tumour and optic nerve. The purpose of this pictorial review is to provide the radiologists with awareness about diagnostic methods and therapeutic options of uveal melanoma. In the present second section, we discuss the therapeutic management of uveal melanoma, describing the main ocular-conserving radiotherapic techniques. We subsequently present an overview of the effects of radiations on neoplastic tissue. Lastly, we review ocular complications following radiotherapy that should be evaluated by radiologists during follow-up MRI examinations.

Adenoid cystic carcinoma of trachea: long-term disease control after endoscopic surgery and radiotherapy.

Aim: Adenoid cystic carcinoma is a rare tumor of head and neck region and its development in the thoracic region is even less frequent. This implies the absence of guidelines for therapeutic management and a consequent case-by-case approach. The role of radiotherapy is not yet clearly defined, but intensity-modulated radiotherapy allows for improved organ-at-risk sparing. Materials & methods: We have collected the cases of four patients treated at our institutions by the means of intensity-modulated radiotherapy, after endoscopic resection. Results & conclusion: Patients treated achieved long-term disease control of about 5 years, with a minimal acute toxicity. Longer follow-up is needed to drain conclusion on the impact of this treatment on overall survival.

Trends in combined radio-chemotherapy for locally advanced rectal cancer: a survey among radiation oncology centers of Sicily region on behalf of AIRO.

AIM: To conduct a survey among Sicilian centers of radiation oncology belonging to Associazione Italiana di Radioterapia ed Oncologia Clinica (AIRO), to record the different methods of integration of radio-chemotherapy both in neoadjuvant and adjuvant settings, to evaluate surgical procedures in relation to the sphincter preservation and to report the different toxicity profiles of the treatment strategies. METHODS: A questionnaire was sent at the end of 2017 to all the radiation oncology centers of Sicily region in order to collect the data from individual centers and the treatment characteristics retrospectively over the previous 5 years, from 2012 to 2016. The required data were collected from 13 centers out of 17 which, in relation to the single catchment areas, correspond to approximately 85% of the Sicilian population. The requested data concerned the type of integrated treatment (neoadjuvant vs adjuvant vs radical), combination with chemotherapy (induction, concomitant, adjuvant), type of surgical intervention (sphincter-saving vs abdomino-perineal resection), disease stage, schedule and radiotherapy technique adopted, as well as toxicity detected over the treatment period. RESULTS: A total of 784 pts (M/F: 509/275) were treated between 2012 and 2016, with a median age of 67 years (range 25-92). The majority of patients was treated in the neoadjuvant phase (62% of the total) compared to the adjuvant phase (31%) and to those treated radically (7%). Twenty-five percent of patients did not receive combination chemotherapy mainly for cardiovascular problems. Chemotherapy used concomitantly to radiotherapy was single-agent capecitabine (73% of patients) or 5-fluorouracil (27%). The use of chemotherapy alone before concomitant treatment is more common for patients treated in the adjuvant phase (64% of this subgroup), while 14% of patients treated in the neoadjuvant phase received induction chemotherapy before the concomitant phase; in both cases of chemotherapy alone, the majority of patients (91%) received oxaliplatin-based protocols (FOLFOX/XELOX/CAPOX). Few patients (3%) received chemotherapy alone after the concomitant phase. Information on the surgical treatment received is available for 88% of the sample. Of these, 93% received a surgical treatment. The overall rate of sphincter-saving surgery (anterior resection) was 72%, but the contribution of neoadjuvant treatment allowed to reach a rate of 83% in this subgroup (against 65% found in the subgroup of patients treated in adjuvant phase). Traditional radiotherapy schedule (45-50 Gy in 25-28 fractions) was used in 90% of patients, of which an intensified treatment in neoadjuvant phase (45 Gy + boost of 9-10 Gy) was used in 11% of patients. A short-course regimen (25 Gy in 5 fraction) in neoadjuvant setting was opted rarely (7%). Three-dimensional conformal technique was preferred over intensity-modulated ones (73% vs 27%). Toxicity was mainly of grade I-II CTCAE (skin 23%, gastrointestinal 39%, genitourinary 14%) compared to grade III (gastrointestinal 4%, genitourinary and hematological < 1%). Interestingly, the toxicity rates were significantly higher in the adjuvant group compared to the neoadjuvant (GI: 58% vs 31%, GU: 21% vs 10%). CONCLUSION: The present survey shows that in the Sicily region integrated therapies for rectal cancer have allowed a neoadjuvant approach in the majority of patients, thus resulting in a greater use of sphincter conservative surgery. The toxicity has also been reported to be significantly less in this treatment setting.

Combined taxane-based chemotherapy and intensity-modulated radiotherapy with simultaneous integrated boost for gastroesophageal junction adenocarcinoma.

We describe our experience, gained over the past 3 years, in the treatment of gastroesophageal junction adenocarcinoma, whose incidence has been increasing in recent years. In our series, we present the results to a follow-up of about 2 years for a total of 18 patients, treated with a particularly intensive combination treatment. It consists of neoadjuvant induction chemotherapy with the protocol docetaxel-cisplatin-5-fluorouracil for four cycles, before a concomitant chemoradiotherapy treatment. During combined phase, patients received an intensity-modulated radiotherapy and a weekly cisplatin. We will present the data to a long follow-up time and we will discuss the literature, the integration with thoracoabdominal surgery and other specific issues of this pathology.

Intensity-modulated radiotherapy for relapsed malignant pleural mesothelioma.

The use of novel radiotherapy techniques is widely increasing, allowing clinicians to treat diseases that were previously difficult to treat with radiation therapy. Malignant pleural mesothelioma is a clear example of this clinical challenge. We describe our first experience with intensity-modulated radiotherapy technique which was used to treat a 73-year-old patient with multiple relapsing malignant pleural mesothelioma. Intensity-modulated radiation therapy has allowed to respect the QUANTEC (quantitative analyses of normal tissue effects in the clinic) dose constraints, patient has experienced a 14 months progression-free time, without relevant subacute or late lung toxicity.

Role, timing and technique of radiotherapy in pediatric pleuropulmonary synovial sarcoma.

The management of pediatric thoracic synovial sarcoma remains a matter of debate in clinical oncology, especially as regard to the local control of the disease. Surgery remains the gold standard, while the role and timing of radiotherapy is still controversial. We report a 14-year-old male, who has not received proper treatment at the time of diagnosis and initial management. Intensity-modulated irradiation was performed only at relapse, as a salvage treatment and, at 10-month follow-up, the young patient was free from relapse, without significant acute and subacute toxicity. We discuss the role and timing of radiotherapy in thoracic synovial sarcoma, a disease in which the need to increase local control should be placed in the foreground.

The utilization of imaging features in the management of intraductal papillary mucinous neoplasms.

Intraductal papillary mucinous neoplasms (IPMNs) represent a group of cystic pancreatic neoplasms with large range of clinical behaviours, ranging from low-grade dysplasia or borderline lesions to invasive carcinomas. They can be grouped into lesions originating from the main pancreatic duct, main duct IPMNs (MD-IPMNs), and lesions which arise from secondary branches of parenchyma, denominated branch-duct IPMNs (BD-IPMNs). Management of these cystic lesions is essentially based on clinical and radiological features. The latter have been very well described in the last fifteen years, with many studies published in literature showing the main radiological features of IPMNs. Currently, the goal of imaging modalities is to identify "high-risk stigmata" or "worrisome feature" in the evaluation of pancreatic cysts. Marked dilatation of the main duct (>1 cm), large size (3-5 cm), and intramural nodules have been associated with increased risk of degeneration. BD-IPMNs could be observed as microcystic or macrocystic in appearance, with or without communication with main duct. Their imaging features are frequently overlapped with cystic neoplasms. The risk of progression for secondary IPMNs is lower, and subsequently an imaging based follow-up is very often proposed for these lesions.