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Introduction: The historically feared radiation-induced secondary cancers and cardiac toxicities observed among mediastinal classical Hodgkin Lymphoma (cHL) patients may still negatively burden the benefit of radiotherapy among long-term survivors. Modern radiotherapy (RT) delivery techniques, including intensity-modulated RT (IMRT) and deep inspiration breath-hold (DIBH) solutions, are drastically changing this scenario. Results of a literature overview are reported and discussed in this paper., Materials and Methods: Key references were derived from a PubMed query. Hand searching and clinicaltrials.gov were also used., Results: This paper contains a narrative report and a critical discussion of organs-at-risk dose-volume metrics linked with radiation-induced toxicities in cHL patients., Conclusions: The scenario of early-stage cHL presents long-life expectancies, thus the goal of treatment should aim at maintaining high cure rates and limiting the onset of late complications. Further evaluations of dosimetric measures and clinical outcomes are warranted to identify patients at higher risk to target treatment tailoring., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Aim: Aim of this analysis is to review the role of RT in the management of several rare tumors for adult patients., Methods: Collection data regarding RT and rare tumors was made by Pubmed., Results: For mucosal melanomas, RT is prescribed, being associated with lower local recurrence rate. For trachea tumors, RT was used as adjuvant or salvage treatment for unresectable disease. For pNET, RT can be a suitable option for post-surgical or unresectable/borderline. For bronchopulmonary neuroendocrine tumors the role of adjuvant treatments is uncertain. For hepatobiliary and ovarian malignancy, stereotactic body RT (SBRT) is a promising approach. For soft tissue sarcoma, perioperative treatments are indicated, and a growing role of SBRT in oligometastatic disease is recognized. For endocrine tumors, adjuvant RT has demonstrated benefits through reducing recurrence risk., Conclusion: The radiotherapy is a frequent indication in adult rare cancers; thus the role of Radiation Oncologist must not be neglected., (Copyright © 2021 Elsevier B.V. All rights reserved.)

In case of circumscribed recurrent glioblastoma (rec-GBM), a second surgery (Re-S) and reirradiation (Re-RT) are local strategies to consider. The aim is to provide an algorithm to use in the daily clinical practice. The first step is to consider the life expectancy in order to establish whether the patient should be a candidate for active treatment. In case of a relatively good life expectancy (>3 months) and a confirmed circumscribed disease(i.e. without multiple lesions that are in different lobes/hemispheres), the next step is the assessment of the prognostic factors for local treatments. Based on the existing prognostic score systems, patients who should be excluded from local treatments may be identified; based on the validated prognostic factors, one or the other local treatment may be preferred. The last point is the estimation of expected toxicity, considering patient-related, tumor-related and treatment-related factors impacting on side effects. Lastly, patients with very good prognostic factors may be considered for receiving a combined treatment., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Introduction: Local failure (LF) following stereotactic radiosurgery (SRS) of brain metastases (BM) may be treated with a second course of SRS (SRS2), though this procedure may increase the risk of symptomatic radionecrosis (RN)., Methods: A literature search was conducted according to PRISMA to identify studies reporting LF, overall survival (OS) and RN rates following SRS2. Meta-analysis was performed to identify predictors of RN., Results: Analysis included 11 studies (335 patients,389 metastases). Pooled 1-year LF was 24 %(CI95 % 19-30 %): heterogeneity was acceptable (I2 = 21.4 %). Median pooled OS was 14 months (Confidence Interval 95 %, CI95 % 8.8-22.0 months). Cumulative crude RN rate was 13 % (95 %CI 8 %-19 %), with acceptable heterogeneity (I2 = 40.3 %). Subgroup analysis showed higher RN incidence in studies with median patient age ≥59 years (13 % [95 %CI 8 %-19 %] vs 7 %[95 %CI 3 %-12 %], p = 0.004) and lower incidence following prior Whole Brain Radiotherapy (WBRT, 19 %[95 %CI 13 %-25 %] vs 7%[95 %CI 3 %-13 %], p = 0.004)., Conclusions: SRS2 is an effective strategy for in-site recurrence of BM previously treated with SRS., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Aim: Functional and molecular imaging, including positron emission tomography with computed tomography imaging (PET/CT) is increasing for radiotherapy (RT) definition of the target volume. This expert review summarizes existing data of functional imaging modalities and RT management, in terms of target volume delineation, for the following anatomical districts: brain (for primary and secondary tumors), head/neck and lung., Materials and Methods: A collection of available published data was made, by PubMed a search. Only original articles were carefully and critically revised., Results: For primary and secondary brain tumors, amino acid PET radiotracers could be useful to identify microscopic residual areas and to differ between recurrence and treatment-related alterations in case of re-irradiation. As for head and neck neoplasms may benefit from precise PET/CT-based target delineation, due to the major capability to identify high-risk RT areas. In primary and secondary lung cancer, PET/CT could be useful both to delimit a tumor and collapsed lungs and as a predictive parameter of treatment response., Conclusion: Taken together, molecular and functional imaging approaches offer a major step to individualize radiotherapeutic care going forward. Nevertheless, several uncertainties remain on the standard method to properly assess the target volume definition including PET information for primary and secondary brain tumors., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Aim: Positron Emission Tomography with Computed Tomography (PET/CT) has been proven to be useful in the definition of Radiotherapy (RT) target volume. In this regard, the present expert review summarizes existing data for pancreas, prostate, gynecological and rectum/anal cancer., Methods: A comprehensive search of published original article was made, based on SCOPUS and PubMed database, selecting the paper that evaluated the role of PET/CT in the definition of RT volume., Results: FDG-PET has an important and promising role for pancreatic cancer. Choline PET/CT could be useful for identifying high-risk volumes for prostate cancer; while PSMA PET/CT is still under evaluation. FDG PET/CT in gynecological cancers has been shown to impact external-beam RT planning. The role of FDG-PET for Gross Tumor volume identification is crucial, representing a useful and powerful tool for anal and rectal cancer., Conclusion: Taken together, molecular and functional imaging approaches offer a major step to individualize radiotherapeutic approach., (Copyright © 2019 Elsevier B.V. All rights reserved.)

A diagnosis of breast cancer at a young age, defined per guidelines as ≤ 40 years, represents a challenging situation requiring additional attention by the treating physicians including radiation oncologists and surgeons involved in the local treatment of these tumors. The present review aims at providing updated evidence on the state of the art about the available techniques and indications for radiation therapy in patients with early breast cancer, specifically focusing on young women. In addition, future perspectives including the ongoing trials and the potential impact of combined approaches with systemic therapies (such as immunotherapy) are reviewed. Major conclusions from this overview are that young women affected by invasive breast cancer seem to receive the greatest benefit from the boost on the tumor bed. Most young patients affected by ductal carcinoma in situ should receive postoperative whole breast irradiation (WBI). When regional node irradiation is considered, young age should be considered as a high-risk factor. Partial breast irradiation is not suitable for young patients and should be recommended within the context of a clinical trial. Importantly, robust data have already supported the efficacy and safety of hypofractionated-WBI schedules that should now replace standard fractionated-WBI as gold standard for all patients irrespective of their age. Finally, organs-at-risk sparing systems as strategy for prevention of radiation-related long-term toxicities should be strongly considered for these patients. Considering the lack of inclusion of young patients in several published trials as well as in some of the ongoing ones, robust evidence to counsel young breast cancer patients on the optimal radiation therapy approach is still lacking. Further studies and ad hoc subgroup analyses in this specific patient population are strongly warranted., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Purpose: Aim of the present review is to assess present data about the use of the association of Radiotherapy (RT) and targeted therapy/immunotherapy (TT/IT) in elderly people., Design: PubMed database was searched for English literature published up to December 2017 using the keywords "radiotherapy" combined with "bevacizumab", "cetuximab", "trastuzumab", "erlotinib", "gefitinib", "sorafenib", "sunitinib", "vismodegib", "sonidegib", "ipilimumab", "pembrolizumab", "nivolumab". Studies performing RT and TT/IT in people aged >65-years were evaluated focusing on safety, toxicity and efficacy. Studies eligible for inclusion were: case reports, retrospective/prospective studies in which RT and new drugs were used concomitantly or sequentially, focusing on elderly sub-group., Results: The systematic search identified 626 records. After exclusion of duplicates, full-text review, cross-referencing and paper that did not respect the inclusion criteria, 81 studies were included in this review. In elderly patients the combination of RT with cetuximab or bevacizumab seems feasible but with higher reported side effects. Patients' age should not limit the association of trastuzumab and RT in HER2 positive breast cancer. The concurrent administration of TKIs and RT appears to be feasible and effective. Regarding the Immune Check Point inhibitors and RT, tolerance seems similar among older and younger people but definitive data are lacking. Instead, the association of RT and vismodegib/sonidegib remains investigational., Conclusion: TT/IT in association of RT seems to be safe, but in elderly patients data concerning safety and toxicity are limited. Specific clinical trials on this population are encouraged., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Stereotactic body radiotherapy (SBRT) is characterized by the delivery of high doses of ionizing radiation in few fractions. It is highly effective in achieving local control, and, due to the high biological effective dose administered, it seems to overcome the radioresistance of renal cell carcinoma (RCC). Thus, SBRT could constitute a treatment option for the management of localized RCC in patients who are not surgical candidates. In this paper, we report an overview about data from the current evidence about SBRT in patients affected by localized RCC., Materials and Methods: A non-systematic review was performed, including data from both retrospective and prospective studies focusing on the use of SBRT for localized RCC and its biological rationale. Furthermore, ongoing trials on this issue are reported., Conclusion: Currently, SBRT might be considered a treatment alternative in inoperable patients affected by primary RCC. Currently, dose-escalation to 48 Gy in 3-4 fractions are effective and well tolerated. Emerging role of immune therapies in RCC patients warrant further studies to explore interactions between SBRT and immune response., (Copyright © 2018 Elsevier B.V. All rights reserved.)

The primary aim of this review is to provide practical recommendations in terms of fractionation, dose, constraints and selection criteria to be used in the daily clinical routine. Based on the analysis of the literature reviewed, in order to keep the risk of severe side effects ≤3,5%, patients should be stratified according to the target volume. Thus, patients should be treated with different fractionation and total EQD2 (<12.5 ml: EQD2 < 65 Gy with radiosurgery; >12.5 ml and <35 ml: EQD2 < 50 Gy with hypofractionated stereotactic radiotherapy; >35 ml and <50 ml: EQD2 < 36 Gy with conventionally fractionated radiotherapy). Concurrent approaches with temozolomide or bevacizumab do not seem to improve the outcomes of reirradiation and may lead to a higher risk of toxicity but these findings need to be confirmed in prospective series., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Purpose: Radiotherapy plus cetuximab is an effective combination therapy for locally advanced head and neck squamous cell carcinoma. The aim of our study was to determine the frequency of skin toxicity in patients receiving the combined treatment., Results: Forty-eight studies were included in our analysis, for a total of 2152 patients. The mean rates of G3/G4 radiation dermatitis and acneiform rash were 32.5% (SD: 20.4; 95% CI: 28.5-36.5) and 13.4% (SD: 11.5; 95% CI: 11.2-15.6), respectively. The majority of studies referred to CTCAE scales for reporting both side effects (85.7% and 92.1%, respectively). Data on the management of skin toxicity were available in only 35.4% of the reviewed literature., Conclusions: severe radiation dermatitis is a frequent side effect induced by the combination of radiotherapy and cetuximab in head and neck cancer. The lack of predictive biomarkers of toxicity hampers the possibilty to design preventive measures on a personalized basis., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Major advances in the knowledge of cancer biology and its interactions with tumor immune environment led to the emergence, in the last five years of new immunotherapy-based treatment strategies in cancer patients. At the same time, improvement in radiation technique and progress in radiobiology allowed in the last decade to expand the applications of radiotherapy in a growing number of settings. At present, there are strong theoretical basis to propose immune-enhanced radiation therapy that may represent in the future a new paradigm of treatment, combining the intrinsic power of radiotherapy to elicit a specific, systemic, tumor-directed immune response with modern highly conformal and precise dose delivery, in order to maximize response at the major site of disease and obtain durable disease control. The aim of this review is to describe the principal mechanisms of immune modulation of response to radiation and investigational strategies to harness the potential of radiation-inducible immune response: radiation therapy is expected to be not just a local treatment but the cornerstone of a multimodal strategy that might achieve long-lasting tumor remission at the primary site and systemic efficacy metastatic lesions., (Copyright © 2017 Elsevier B.V. All rights reserved.)