The new and increasingly studied concept of immunogenic cell death (ICD) revealed a previously unknown perspective of the various regulated cell death (RCD) modalities, elucidating their immunogenic properties and rendering obsolete the notion that immune stimulation is solely the outcome of necrosis. A distinct characteristic of ICD is the release of danger-associated molecular patterns (DAMPs) by dying and/or dead cells. Thus, several members of the DAMP family, such as the well-characterized heat shock proteins (HSPs) HSP70 and HSP90, the high-mobility group box 1 protein and calreticulin, and the thymic polypeptide prothymosin α (proTα) and its immunoreactive fragment proTα(100–109), are being studied as potential diagnostic tools and/or possible therapeutic agents. Here, we present the basic aspects and mechanisms of both ICD and other immunogenic RCD forms; denote the role of DAMPs in ICD; and further exploit the relevance of human proTα and proTα(100–109) in ICD, highlighting their possible clinical applications. Furthermore, we present the preliminary results of our in vitro studies, which show a direct correlation between the concentration of proTα/proTα(100–109) and the levels of cancer cell apoptosis, induced by anticancer agents and γ-radiation.

Purpose: The current review aims to summarize the international experience of the impact of adaptive radiotherapy on dosimetry and clinical and toxicity outcomes. Additionally, it might trigger Radiation Oncologists to use ART and evaluate whether ART improves target volume coverage and/or normal tissue sparing and, consequently, therapeutic results. Materials and methods: We conducted an electronic literature search of PubMed/MEDLINE and ScienceDirect from January 2007 to January 2023. The search adhered to the PRISMA guidelines and employed keywords such as ART, HNC, parotid gland, and target volume. Furthermore, we examined the reference lists for studies pertinent to the present review. This study included both retrospective and prospective studies that were considered for inclusion. Conclusion: ART replanning appears to be a sustainable strategy to minimize toxicity by improving normal tissue sparing. Furthermore, it can enhance target volume coverage by correctly determining the specific dose to be delivered to the tumor. In conclusion, this review confirmed that ART benefits dosimetric, clinical/therapeutic, and toxicity outcomes.

Radiation therapy is an integral part of management in breast carcinoma treatment. Standard curative schedules of radiotherapy to the breast deliver 25 fractions of 2.0 Gy per day over 5–6 weeks. Considerable recent literature suggests that hypo-fractionation may be advisory in breast cancer. The use of fewer fractions of more than 2 Gy per day (hypo-fractionation) is based on data suggesting that breast carcinoma is more sensitive to fraction size than squamous carcinomas and therefore could have similar fractionation sensitivity to the dose-limiting healthy tissues, including skin, subcutaneous tissues, muscle and ribs. In this article, a review of published studies and currently ongoing trials, which may provide evidence for the use of hypo-fractionated radiotherapy in breast cancer patients, is presented. Also, for all these different hypo-fractionation regimens found in literature, biologically effective dose (BED) values are calculated and compared. Data from studies and randomised trials seem to support the concept that modest hypo-fractionation can be used to treat the whole breast after breast-conserving surgery with similar rates of local control and radiation morbidity as seen with conventional fractionation.

To evaluate the impact of intermediate time between chemotherapy and radiotherapy (ITCR) to skin toxicity for a hypofractionated irradiation schedule. Forty-four patients with stage I-II invasive breast cancer receiving postoperative radiotherapy (RT) after lumpectomy and axillary dissection were studied. All patients received RT with 6 MV linear accelerator (LINAC) with a total tumor dose of 53 Gy (Equivalent dose-EQD2- 60 Gy), 2.65 Gy per fraction, in 20 fractions. All patients received six cycles of cyclophosphamide methotrexate fluorouracil chemotherapy i.v. every 21 days. Acute and late effects and cosmetic results were assessed using the European Organization for Research and Treatment of Cancer and Radiation Therapy Oncology Group (EORTC/RTOG) Rating System. The mean follow-up was 7 years. The spearman rho test showed that there was a significant correlation between short ITCR and acute skin toxicity 3 months post RT, by means of acute radiation induced morbidity. None of the related late-toxicity parameters was correlated with the ITCR. However, there was significantly higher acute toxicity when the ITCR was less than 20 days (p < 0.05). We may suggest that when a hypofractionated irradiation schedule is used for breast cancer patients, then the ITCR should be more than 20 days from chemotherapy.

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.

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.