Background/Objectives: Precise staging and tumor delineation are essential for optimizing treatment and enhancing outcomes of radiotherapy (RT). While computed tomography (CT)-based RT remains standard, fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) offers improved detection of primary and nodal disease. This study investigates the role of PET/CT in RT planning of HNSCC. Methods: Fifty-one HNSCC patients underwent radical volumetric modulated arc RT with concurrent cisplatin chemotherapy in a prospective study. Two RT plans per patient were sequentially created by a single oncologist using CT-only and PET/CT data, respectively. Planning target volumes (PTVs) for primary and nodal regions were independently defined, and dose–volume histograms were analyzed and compared. Results: PET/CT significantly affected TNM staging, increasing the T-stage in 11.8% of patients and the N-stage in 33.3%. Distant metastases were found in 9.8% of patients, leading to a redefinition of the overall treatment policy. PET/CT-based planning improved primary tumor PTV coverage (PTV4) in 37.2% (19/51) of cases. The tumor areas excluded from the CT-based planning received an average of 85.6% of the prescribed PTV4 dose (range 18–93%), while in PET/CT planning, they received 95.4% (range 93–99%) (p < 0.0001). Nodal PTV areas requiring a booster dose (PTV2) were adjusted in 33.3% (17/51) of patients during PET-CT planning. These nodal areas received an average of 85.6% of the prescribed dose for PTV2 (range 18–93%) during CT planning, compared to 95.4% (range 93–99%) during PET/CT planning. There was no statistically significant difference in the dose received by organs at risk between CT- and PET/CT-RT planning. Conclusions: PET/CT improves target delineation for primary tumors and lymph nodes, also allowing for dose escalation in metabolically highly active lesions in patients with HNSCC. The method also reveals occult distant metastases in a subset of patients, enabling personalized treatment strategies.

Radiotherapy (RT)-induced lymphopenia may hinder the anti-tumor immune response. Preoperative RT or chemo-RT (CRT) for locally advanced rectal cancer is a standard therapeutic approach, while immunotherapy has been approved for mismatch repair-deficient rectal tumors. We retrospectively analyzed 98 rectal adenocarcinoma patients undergoing neoadjuvant CRT with VMAT (groups A, B, C) or IMRT (group D) techniques, with four different RT schemes: group A (n = 24): 25 Gy/5 Gy/fraction plus a 0.2 Gy/fraction rectal tumor boost; group B (n = 22): 34 Gy/3.4 Gy/fraction, with a 1-week treatment break after the first five RT fractions; group C (n = 20): 46 Gy/2 Gy/fraction plus a 0.2 Gy/fraction rectal tumor boost; group D (n = 32): 45 Gy/1.8 Gy/fraction followed by 5.4 Gy/1.8 Gy/fraction to the rectal tumor. We examined the effect of the time-corrected normalized total dose (NTD-T) to the BM on lymphopenia. Groups A and B (hypofractionated RT) had significantly higher lymphocyte counts (LCs) after RT than groups C and D (p < 0.03). An inverse association between the LCs after RT and NTD-T was demonstrated (p = 0.01). An NTD-T threshold of 30 Gy delivered to 30% of the BM volume emerged as a potential constraint for RT planning, which could be successfully integrated in the RT plan. Hypofractionated and accelerated RT schemes, and BM-sparing techniques may reduce lymphocytic damage and prove critical for immuno-RT clinical trials.

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.

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.

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.

This study provides an accurate assessment of radiotherapy-induced tissue changes in prostate cancer when relying solely on serum prostate-specific antigen kinetics. The current study aims to explore the role of quantitative magnetic resonance imaging and radiomic analyses. In this exploratory prospective study, 22 patients with histologically confirmed prostate cancer underwent multiparametric magnetic resonance imaging at three time points: pre-treatment, mid-treatment, and two months post-radiotherapy. Quantitative imaging analysis included total prostate volume, T2, apparent diffusion coefficient—ADC, and T2* mapping, alongside T2-weighted and diffusion-weighted radiomic feature extraction. Longitudinal changes and dose correlations were analyzed using repeated-measures ANOVA and linear mixed-effects models. Prostate volume increased from 44.22 ± 21.26 cm³ at baseline to 51.11 ± 22.36 cm³ mid-treatment (p < 0.001) and decreased to 37.98 ± 15.5626 cm³ post-treatment (p = 0.034), indicative of temporary radiation-induced glandular edema. T2 relaxation times decreased from 106.00 ± 23.74 ms to 93.33 ± 9.50 ms after therapy (p = 0.023), with androgen deprivation therapy influencing overall values (partial η² = 0.228, p = 0.028), while ADC and T2* remained largely stable (p > 0.05). Radiomic features, particularly from DWI, exhibited subtle time- and dose-dependent variations. Radiation dose was significantly associated with volume and T2, but not with ADC or T2*. These findings suggest that quantitative MRI biomarkers combined with radiomic analysis may provide objective, non-invasive measures of early prostate cancer radiotherapy-induced changes. These imaging-derived metrics may capture early treatment-related tissue alterations and could provide exploratory signals for early treatment evaluation in prostate cancer, although their relationship with biochemical markers requires further validation.