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Objectives: The improvements in survival with expansion of the survivors' population, along with evolution of endoscopically-based treatment modalities, have contributed to emphasize the clinical relevance of recurrences in sinonasal cancers. However, at present, literature is scant regarding the pattern of recurrences and the therapeutic strategies available to manage long survivors who experienced single or multiple failures. The aim of the present study was to analyze sinonasal cancers recurrences to provide data regarding rates and patterns of relapse, predictors of failure and prognostic impact of the recurrence., Materials and Methods: All patients receiving multimodal treatments including endoscopic surgery between 1995 and 2021 in three European referral centers were included. Statistical analysis of survival was performed through univariable, multivariable and unidirectional multistate models. Survival after recurrence analysis was implemented for patients experiencing at least one recurrence., Results: The 5- and 10-year recurrence free survival rates were 34.1% and 38.4% for the whole population. With a mean follow-up time of 60 months, a global recurrence rate of 32.9% was observed. The 5- and 10-year survival after recurrence rates were 27.2% and 21.7%, respectively. Incidence and rates of recurrences were significantly associated with histology subtypes., Conclusion: This study provides valuable oncologic outcomes regarding a large homogenous cohort of patients affected by sinonasal malignances treated within a multimodal framework, emphasizing the strong correlation of histologic type with prognosis, as well as with pattern of recurrences., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: immunotherapy (IT), including checkpoint inhibitors (CIs) and Chimeric Antigen Receptor T cell therapy (CAR-T) revolutionized the treatment of relapsing or refractory (r/r) lymphoma. Several preliminary experiences evaluated concomitant administration of radiotherapy and IT., Methods: we performed a systematic review of current literature as of March 30, 2020. A total of 1090 records was retrieved, 42 articles were selected on the basis of title and abstract and, after the removal of analyses with no original data or insufficient clinical information, 28 papers were included in the review., Results: previous studies were mostly represented by case reports/series or small cohorts. Nonetheless, combination of radiotherapy and CIs or CAR-T led to promising outcomes, resulting in extremely high rates of complete response and improving progression free and overall survival compared with data from recent clinical trials. Combination of RT and CIs had a fair toxicity profile with no reports of severe side effects. Within the limits of the small cohorts retrieved, RT seems a superior option compared with systemic treatment as a 'bridge' to CAR-T and could as well reduce severe complications rates. Radiotherapy could elicit immune response against lymphoma, as demonstrated by multiple cases of abscopal effect and its inclusion in anti-neoplastic vaccines protocols., Conclusion: The results of this review warrant the evaluation of combination of RT and immunotherapy in larger and preferably prospective and randomized cohorts to confirm these preliminary impressive outcomes. The optimal dose, fractionation and timing of RT still have to be clarified., Competing Interests: Disclosure Conflicts of interest/Competing interests: none to declare, (Copyright © 2021 Elsevier Inc. All rights reserved.)

Introduction: In this observational, retrospective, multicenter study, we aimed to assess the safety of the combination of local metastasis-directed radiotherapy (RT) and immunotherapy (IT) in a cohort of advanced non-small-cell lung cancer (aNSCLC) patients., Material and Methods: We collected clinical data of aNSCLC patients who received concomitant RT and anti-PD-1/PD-L1 inhibitors in seven Italian centers from September 2015 to June 2019. Concomitant RT was defined as delivered ≤4 weeks before or after the first or last administration of immunotherapy, or within two consecutive cycles of ICI. All adverse events apparently related to RT and/or IT were graded according to the Common Terminology Criteria for Adverse Events, version 4.0, and reported in terms of incidence and severity as immune related or RT related, or combined., Results: We analyzed the clinical charts of 187 patients. Median follow-up time was 23 months, and median overall survival was 16.5 months (range, 3-162). Thirteen patients developed pure RT-related side effects, and 43 patients (23.9%) developed immune-related side effects. No additive toxic effects were observed. A case of grade 5 pulmonary toxicity was recorded as a possible consequence of a combined effect., Conclusion: This analysis suggests that the combination of concomitant RT and anti-PD-1/PD-L1 agents is safe, and the two toxicity profiles are independent., (Published by Elsevier Inc.)

Background: The present analysis aims to compare the impact of 18F-fluorocholine ( 18 F-choline) and gallium-68 prostate-specific membrane antigen ( 68 Ga-PSMA) positron emission tomography (PET)-computed tomography (CT)-guided metastases-directed therapies (MDTs) in patients with castration-sensitive oligorecurrent prostate cancer (PC)., Materials and Methods: Inclusion criteria were: (1) histologically proven prostate adenocarcinoma; (2) evidence of biochemical relapse after primary tumor treatment; (3) ≤ 3 hypermetabolic oligorecurrent lesions detected by 18 F-choline or 68 Ga-PSMA PET-CT; (4) PET-CT imaging performed in a single nuclear medicine department; (5) patients treated with upfront stereotactic body radiotherapy (SBRT) without hormone therapy; and (6) SBRT delivered with a dose per fraction ≥ 5 Gy. In the case of oligoprogression (≤ 3 lesions outside the previous RT field) after MTD, a further course of SBRT was proposed; otherwise, androgen deprivation therapy (ADT) was administered., Results: A total of 118 lesions in 88 patients were analyzed. Forty-four (50%) patients underwent 68 Ga-PSMA PET-guided SBRT, and the remaining underwent choline PET-based SBRT. The median follow-up was 25 months (range, 5-87 months) for the entire cohort. Overall survival and local control were both 100%. Distant progression occurred in 48 (54.5%) patients, for a median distant progression-free survival of 22.8 months (range, 14.4-28.8 months). The median pre-SBRT prostate-specific antigen was 2.04 ng/mL in the choline PET cohort and 0.58 ng/mL in the PSMA-PET arm. Disease-free survival rates were 63.6% and 34%, respectively, in the 68 Ga-PSMA and choline PET group (P = .06). The ADT administration rate was higher after choline-PET-guided SBRT (P = .00) owing to the higher incidence of polymetastatic disease after first-course SBRT compared with 68 Ga-PSMA-based SBRT., Conclusion: In the setting of oligorecurrent castration-sensitive PC, PSMA-PET-guided SBRT produced a higher rate of ADT-free patients when compared with the 18 F-choline-PET cohort. Randomized trials are advocated., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: To perform a meta-analysis to determine the effect of loco-regional radiation therapy (RT) compared to no loco-regional RT for operated patients in clinical stage cN2 breast cancer at diagnosis and ypN0 after preoperative chemotherapy (PST)., Material and Methods: Eligible studies were identified through a systematic search of the medical literature performed independently by two researchers using a validated search strategy. An electronic search of Medline via PubMed and Embase (Breast cancer AND preoperative chemotherapy AND radiation therapy) was conducted with no language or publication status restrictions. The effect of loco-regional RT on overall (OS), disease free (DFS), loco-regional recurrence-free (LRRFS) survival and local recurrence was evaluated. An electronic search of Medline via PubMed and Embase (Toxicity AND radiation therapy breast cancer AND preoperative therapy; toxicity AND breast surgery AND preoperative chemotherapy) was conducted for outcomes of harm: major acute and late skin toxicity, lymphedema and cardiac events., Results: Of 333 studies identified, 4 retrospective studies reporting on a total of 1107 patients were included in the meta-analysis. Six and 3 reported data of acute and late skin toxicity, while 2 studies provided information on cardiac events. Pooled results showed no difference in terms of hazard ratio for loco-regional RT versus no loco-regional RT [hazard ratio (HR) = 0.82, 95% confidence interval (CI) 0.63-1.68]. Loco-regional RT was associated with an OS benefit in the subgroup analysis: IIIB-C (loco-regional RT 79.3% vs no loco-regional RT 71.2%, p = 0.027) and T3-T4 (loco-regional RT 82.6% vs no loco-regional RT 76.6%, p = 0.025). No difference was shown in terms of 5-year DFS (loco-regional RT 91.2% vs no loco-regional RT 83%, p = 0.441) and LRRFS (loco-regional RT 98.1% vs no loco-regional RT 92.3%, p = 0.148). There was no significant difference between the groups in terms of acute and late skin toxicities, lymphedema and cardiac events., Conclusions: Because of the limitations due to the small number of studies and heterogeneity in the analysis, the present study does not allow to draw any definitive conclusion, highlighting the need for well-controlled trials to determine the effect of loco-regional RT in patients with cN2 having a pathological complete response in the axillary nodes after preoperative chemotherapy., Competing Interests: Declaration of competing interest None., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The aim of this review is to present the available radiobiological, technical and clinical data about extreme hypofractionation in primary prostate cancer radiotherapy. The interest in this technique is based on the favourable radiobiological characteristics of prostate cancer and supported by advantageous logistic aspects deriving from short overall treatment time. The clinical validity of short-term treatment schedule is proven by a body of non-randomised studies, using both isocentric (LINAC-based) or non-isocentric (CyberKnife ® -based) stereotactic body irradiation techniques. Twenty clinical studies, each enrolling more than 40 patients for a total of 1874 treated patients, were revised in terms of technological setting, toxicity, outcome and quality of life assessment. The implemented strategies for the tracking of the prostate and the sparing of the rectal wall have been investigated with particular attention. The urinary toxicity after prostate stereotactic body irradiation seems slightly more pronounced as compared to rectal adverse events, and this is more evident for late occurring events, but no worse as respect to conventional fractionation schemes. As far as the rate of severe acute toxicity is concerned, in all the available studies the treatment was globally well tolerated. While awaiting long-term data on efficacy and toxicity, the analysed studies suggest that the outcome profile of this approach, alongside the patient convenience and reduced costs, is promising. Forty-eight ongoing clinical trials are also presented as a preview of the expectation from the near future., (Copyright © 2016. Published by Elsevier Ltd.)

Background: Tailoring treatment intensity is critical in Hodgkin's lymphoma (HL). Ongoing prognostic parameters may be an useful adjunct to pretreatment stratification. We used the kinetics of computed tomography (CT) scan response and residual gallium (Ga)-67 uptake to better stratify risk., Materials and Methods: Patients received 4-8 adriamycin, bleomycin, vinblastine and dacarbazine courses according to stage. Disease was reassessed evaluating late computed tomography scan response improvement (CTRI) and Ga-67 uptake. Patients received no further treatment, radiotherapy (RT) or additional chemotherapy + RT according to the presence of none (low risk), one (intermediate risk) and both parameters (high risk). Patients with bulky mediastinum received RT anyhow., Results: Among 102 assessable patients, 35 showed late CTRI and 9 residual Ga-67 uptake. In 30 patients with bulky mediastinum, the 3-year progression-free survival (PFS) was significantly better when neither parameter was present (100% versus 69%; P = 0.02). In 72 patients without bulky mediastinum, treatment was tailored according to risk assignment. Relapses occurred in 5 of 47 low-risk and 3 of 21 intermediate-risk patients, with no differences between the two groups, and in 3 of 4 high-risk patients., Conclusion: This study shows that two on-treatment parameters, late CTRI and residual Ga-67 uptake, can predict PFS in HL and identify patients in which RT can be spared without apparently affecting the outcome.

Purpose: To quantify the possible advantages arising from the use of 'conformal' radiotherapy of localized prostate cancer, and to compare the dose distributions obtained with two different 'conformal' techniques., Patients and Methods: Twelve patients with localized prostate cancer were enrolled in the study. For each patient, three techniques were planned: the standard 'box technique' (A), a four-fields 'conformal' technique (B), and a 6-fields conformal technique (C). For each of the 36 3D plans, dose-volume histograms (DVH) were obtained, along with the mean, maximum and minimum doses for the clinical and planning target volumes (CTV, PTV) for the rectum, the bladder, and the femoral heads. The resulting data were compared., Results: On average, the standard technique resulted in the exposure of a significantly larger bladder volume to the higher doses; a similar, but less remarkable difference has been observed for the rectal volume. The coverage of the PTV appears to be significantly more homogeneous with the two conformal techniques., Conclusions: The results presented here add to the evidence available in the literature and suggest a possible advantage of both the conformal techniques over the standard 'box technique' for the treatment of localized prostate cancer. The 6-field conformal technique does not seem superior to the four field one.

Purpose: This retrospective study aims to define the effects of different radiation dose levels on survival, local control and toxicity in a series of 208 patients with localised prostate cancer consecutively treated with radical radiation therapy., Patients and Methods: From 1982 through 1996, 365 patients with prostate cancer have been consecutively treated with radical radiotherapy in Florence (n = 306) and Arezzo (n = 59). The 208 cases treated until January 1994 with Stage B (125/208, 60%) and C (83/208, 40%) are the objects of the present study. The treatment was most often limited to the prostatic area (81%), using a four-field "box technique" and 25 MV photon beams, up to a total dose of 60-65 Gy (21% of the patients), of 66-69 Gy (26%) and of 70 Gy (53%); conventional fractionation was used (fractional dose: 2 Gy; five fractions/week). Hormonal therapy was also given to 39% of the cases. The possible relationship between dose, stage, grading and survival has been analysed. The survival figures and the types of relapse observed (prostatic, lymphnodal or "biochemical") have been analysed also according to the extent of the target volume and to the prostate-specific antigen (PSA) value at diagnosis, in the entire series or in selected subgroups., Results: In the whole series and also after radiation alone, the patients with Stage B, with more differentiated tumours and those treated with higher doses to the prostate obtained significantly better survival results. Multivariate analysis confirmed that the dose level has an independent prognostic value. The use of a limited target volume did not produce an excess of pelvic lymphnodal failures. Among the patients more recently treated with radiation alone, the PSA level at diagnosis is strongly related with the risk of local and "biochemical" failure, and also with the relapse-free survival. Toxicity was acceptable, also for the patients treated with higher doses, but late treatment-related damage is more frequent in patients treated on larger volumes., Conclusion: The results of this retrospective analysis confirm the good results of small volume, high dose radiation therapy of prostatic cancer, even taking into account the possible biases due to the retrospective nature of the study, and the relevance of the PSA level at diagnosis to define the risk of local failure.

In early stage Hodgkin's disease the optimal choice of treatment for the individual patient is still an unresolved issue. So far, twenty-two randomized trials of radiotherapy alone versus radiotherapy plus combination chemotherapy have been carried out worldwide. The preliminary results of a global metaanalysis of these trials indicate that we still do not definitively know whether or not the addition of prophylactic chemotherapy up front improves survival. Arguments in favour of the addition of chemotherapy up front are: that laparotomy may be avoided, that radiation fields and doses may perhaps be reduced, and that the stress of experiencing a relapse is avoided in many patients. The major argument against the use of chemotherapy up front is: that by careful staging and selection of patients and by careful radiotherapy techniques the number of patients exposed to potentially toxic chemotherapy may be kept at a minimum. Recently, trials have been carried out testing chemotherapy alone. The results of these trials are however conflicting. In order not to jeopardize the good results achieved with the standard treatments developed over the last three decades, newer treatment approaches should be carefully tested in large randomized trials before being implemented for general clinical use.