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Background/Objectives : The lung is the most common site of metastases, regardless of the cancer subtype. Treating oligometastatic disease with surgery or stereotactic ablative radiotherapy (SABR) may improve patient survival. Methods : We retrospectively analyzed 41 patients with limited (one or two lesions, max dimension <3 cm) lung-only metastatic disease that were treated with the CK M6 robotic radiosurgery system in our Department, in terms of treatment efficacy and toxicity. Results : Acute and late toxicity was negligible (4 out of 41 patients developed grade 2 or 3 lung fibrosis). Six months post-SABR, complete response was achieved in 18 out of 41 patients (43.9%), while the rest of the cases exhibited major responses. A biological effective dose (BED α/β=10 ) in the range of 100 Gy appears to be equally effective with higher doses. Within a median follow-up of 34 months, only three patients (7.3%) progressed locally, while three patients progressed to distal sites. Two-year local progression-free survival (LPFS) rates were 92.6% (95% CI 78.5-97%). Conclusions : SABR for low-burden lung oligometastases is an effective treatment modality that yields high local control and survival rates. Toxicity is negligible, regardless of the performance status of patients. Early referral of such patients to radiation oncology departments may be critical for patient survival and quality of life.

The approval of tyrosine kinase inhibitors (TKIs) as first-line agents has revolutionised treatment of patients diagnosed with advanced non-small cell lung cancer (NSCLC) harboring targetable mutations, adding substantial overall survival (OS) benefit, compared to chemotherapy. However, the efficacy of these agents is inevitably diminished at a point in the disease course, either because of cellular resistance-mechanisms or due to affected pharmacokinetics, like low-central nervous system penetration. The aim of this article is to review existing evidence on the combined use of EGFR (epidermal growth factor)- or ALK (anaplastic lymphoma kinase)-specific TKIs and radiotherapy (RT) in advanced NSCLC setting, as an attempt to delay or overcome TKI-resistance and thus, to expand the time period during which patients derive benefit from a given line of targeted therapy. At present, combining RT with EGFR- or ALK-TKIs in the management of advanced, oncodriver-mutated NSCLC has shown quite promising results, with regards to PFS and OS, rendering prolongation of the TKI-derived benefit feasible, with generally tolerable toxicity. Future studies to confirm the observed efficacy and clarify possible safety issues as well as the appropriate treatment sequence and target volumes are needed, especially in the rapidly-evolving era of newer-generation TKIs., 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 © 2024 Elsevier B.V. All rights reserved.)

Purpose: Neoadjuvant radiotherapy (RT) or chemoradiotherapy (CRT) is the standard treatment for locally advanced rectal adenocarcinoma. The recent emerging data on preoperative immunotherapy as an effective therapeutic modality for mismatch repair deficient rectal carcinomas suggests that the immune system plays a significant role in tumor eradication. Although RT has been shown to stimulate anti-tumor immunity, it also leads to substantial lymphopenia, hindering the effect of immune response., Materials and Methods: We retrospectively analyzed 33 rectal adenocarcinoma patients who underwent CRT in our department, aiming to identify the effects of CRT on the peripheral blood lymphocyte counts (LC) and the potential impact of CRT-induced lymphopenia on tumor response and prognosis of patients., Results: A statistically significant decrease in the LC of patients was observed after CRT (median values of 2,184/μL and 517/μL before and after treatment, respectively; p < 0.001). While no correlation between ypT-stage, ypN status, and LC was found, poor tumor regression grade was significantly associated with lower LC (p = 0.036). Moreover, lymphopenia was associated with poorer distant metastasis-free survival (p = 0.003). Distant metastases were documented in 0% of patients with post-CRT LC above 518/μL vs. 44.5% of patients with lower LC values., Conclusion: Although further investigation is demanded, given the limited number of patients analyzed in the study, lymphopenia emerges as a significant adverse event that rectal adenocarcinoma patients face during treatment with neoadjuvant CRT, with subsequent implications on tumor response and prognosis. Protection of the immune system during CRT emerges as an important target for clinical research.

Background/objectives: Surgery is the primary treatment for early-stage lung cancer. Patients with medically inoperable lung carcinomas and patients who refuse to undergo surgery are treated with definite radiotherapy. Stereotactic ablative radiotherapy (SABR) is a compelling non-invasive therapeutic modality for this group of patients that confers promising results., Methods: We report an interim analysis of an ongoing trial. Eighty-one patients with medically inoperable early-stage (T1,2N0) lung cancer underwent SABR in our institution. SABR was delivered via the CyberKnife M6 robotic radiosurgery system. The endpoints of the analysis were treatment efficacy and tolerance., Results: There were no acute or late toxicities from the skin or the connective tissue of the thorax. A grade 2/3 lung injury of non-clinical significance was noted in 6% of patients, which was directly related to a higher biologically effective dose (BED α/β = 3 ) and larger irradiation lung volumes in both univariate and multivariate analyses. A local control (LC) was achieved in 100% of the patients at the first follow-up, and the projected 24-month local progression-free survival (LPFS) rate was 95%. The projected 24-month disease-specific overall survival (OS) was 94%., Conclusions: High LC and OS rates can be achieved with SABR for early-stage lung cancer, with minimal toxicity. This study continues to recruit patients.

This comprehensive review explores the existing literature on the effects of radiotherapy on testicular function, focusing mainly on spermatogenic effects, but also with a brief report on endocrine abnormalities. Data from animal experiments as well as results on humans either from clinical studies or from accidental radiation exposure are included to demonstrate a complete perspective on the level of vulnerability of the testes and their various cellular components to irradiation. Even relatively low doses of radiation, produced either from direct testicular irradiation or more commonly from scattered doses, may often lead to detrimental effects on sperm count and quality. Leydig cells are more radioresistant; however, they can still be influenced by the doses used in clinical practice. The potential resultant fertility complications of cancer radiotherapy should be always discussed with the patient before treatment initiation, and all available and appropriate fertility preservation measures should be taken to ensure the future reproductive potential of the patient. The topic of potential hereditary effects of germ cell irradiation remains a controversial field with ethical implications, requiring future research.

Neoadjuvant chemotherapy (NACT) for certain breast cancer (BC) subtypes confers significant tumor regression rates and a survival benefit for patients with a complete pathologic response. Clinical and preclinical studies have demonstrated that immune-related factors are responsible for better treatment outcomes, and thus, neoadjuvant immunotherapy (IO) has emerged as a means to further improve patient survival rates. Innate immunological "coldness", however, of specific BC subtypes, especially of the luminal ones, due to their immunosuppressive tumor microenvironment, hinders the efficacy of immune checkpoint inhibitors. Treatment policies aiming to reverse this immunological inertia are, therefore, needed. Moreover, radiotherapy (RT) has been proven to have a significant interplay with the immune system and promote anti-tumor immunity. This "radiovaccination" effect could be exploited in the neoadjuvant setting of BC and significantly enhance the effects of the already established clinical practice. Modern stereotactic irradiation techniques directed to the primary tumor and involved lymph nodes may prove important for the RT-NACT-IO combination. In this review, we provide an overview and critically discuss the biological rationale, clinical experience, and ongoing research underlying the interplay between neoadjuvant chemotherapy, anti-tumor immune response, and the emerging role of RT as a preoperative adjunct with immunological therapeutic implications in BC.

Chemo-radiotherapy is the standard treatment for locally advanced head-neck cancer (LA-HNC). However, about 30% of tumors do not respond or even progress shortly after the completion of radiotherapy. We investigated whether anti-PD1 immunotherapy can eradicate the irradiated tumor and reverse the ominous prognosis of these patients. We retrospectively analyzed a small series of 9 patients with LA-HNC who did not respond (6/9) or showed local disease progression (3/9) during chemo-radiotherapy and were treated with nivolumab anti-PD1 immunotherapy. Immunotherapy started 1.5 months after the end of radiotherapy. Out of 9 patients, 3 (33.3%) had a complete response and 3 (33.3%) partial response at 6 months after the onset of immunotherapy. Two patients are alive with no evidence of disease at 36 months. One more patient with partial response and without disease progression survived 16 months after therapy when he died from intercurrent disease. Immunotherapy showed an excellent tolerance profile. One patient developed an extensive skin rash on the 16th cycle. Anti-PD-1 immunotherapy after radiotherapy can lead to clearance of the remnant tumor and ameliorate the prognosis of patients. Randomized trials are necessary to establish post-irradiation immunotherapy as a standard of care in this ill-fated subgroup of HNC patients., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)