BACKGROUND:There are limited data comparing the effect of different radiotherapy techniques on healthy cells in the same patient group. Furthermore, assessing radiotherapy-induced T-lymphocyte damage may be important given the increasing use of immunotherapy. We aimed to measure and compare DNA damage in T-lymphocytes after four types of radiotherapy for low- and intermediate-risk prostate cancer and monitor their persistence for five years. METHODS:A prospective comparison of patients receiving conventional LINAC (linear accelerator) (70-78 Gy), CyberKnife teletherapy (37.5-40 Gy), low-dose-rate brachytherapy (LDR; 145 Gy) and high-dose-rate brachytherapy (HDR; 19-21 Gy was performed using the chromosome aberration technique (at 3, 6, 9, 12, 24, 36, 48, and 60 months, 192 patients). Multivariate regression analyses were conducted to assess the predictive potential of chromosome aberrations for toxicities. RESULTS:We found that teletherapy techniques (conventional LINAC and CyberKnife therapy) caused 1.6-3.6-fold more chromosomal aberrations than brachytherapy. At three months, 4.4-13.1% of T-lymphocytes were damaged. Five years after treatment, the total aberration values of conventional LINAC and LDR brachytherapy patients were still significantly higher than those before treatment (p < 0.001 for LINAC and p = 0.011 for LDR). Significant regression models suggested that total aberrations or aberrant cell frequency might predict toxicities in addition to the biologically effective dose (BED) and the irradiated volume (V100%) (p = 0.020 for the model including total aberrations, p = 0.010 for the model including aberrant cell frequency). CONCLUSIONS:We observed a lower chromosome aberration frequency and fewer toxicities in brachytherapy patients. We also demonstrated that long-term T-lymphocyte damage depends on the type of radiotherapy.

Purpose To update recommendations on patient selection criteria for accelerated partial breast irradiation (APBI) based on available clinical evidence supplemented by expert opinions. Methods and materials Between 2010 and 2024, a systematic search of the PubMed, Medline, Scopus and Cochrane database identified 618 articles using the keywords “accelerated partial breast irradiation” and “APBI”. This search was complemented by reviewing the reference lists of articles and manual reviewing of relevant conference abstracts and book chapters. Of these, ten prospective randomized clinical trials and seven retrospective comparative studies with a minimum median follow-up time of five years were identified. The authors reviewed the clinical evidence published on APBI, supplemented it with relevant clinical and pathological studies on breast-conserving therapy, and then formulated the recommendations presented in this manuscript. Results Based on published new clinical evidence, the GEC-ESTRO Breast Cancer Working Group recommends two categories as guidelines for selecting patients eligible for APBI: (1) low-risk group representing good candidates for APBI including patients ageing > 40 years with unifocal or multifocal within 2 cm, pTis,T1-2 (≤30 mm) pN0 or pN1mi, all histology types of breast cancer without the presence of an extensive intraductal component (EIC), without extensive lympho-vascular invasion (LVI) and with negative surgical margins for invasive tumors (≥2 mm for DCIS), (2) high-risk group, for whom APBI is considered contraindicated including patients with BRCA 1–2 mutations or ageing < 40 years; having positive margins for invasive tumor (<2 mm for DCIS), and/or multicentric or large (>30 mm), and/or triple negative tumours, and/or EIC positive, and/or extensive lympho-vascular invasion (LVI) or macrometastatic positive lymph nodes (≥pN1a) or unknown axillary status (pNx). Conclusions Based on emerging clinical evidence, the 2010 GEC-ESTRO APBI patient selection criteria can be significantly expanded, meaning that in the future, more patients may receive APBI as a part of routine clinical practice.

PURPOSE:To report the 30-year updated results of accelerated partial breast irradiation (APBI) using multicatheter interstitial high-dose-rate (HDR) brachytherapy (BT). METHODS AND MATERIALS:Forty-five prospectively selected patients with T1N0-N1mi, nonlobular breast cancer without the presence of an extensive intraductal component and with negative surgical margins were treated with APBI after breast-conserving surgery (BCS) using interstitial HDR BT. A total dose of 30.3 Gy (n = 8) and 36.4 Gy (n = 37) in 7 fractions within 4 days was delivered to the tumor bed plus a 1-2 cm margin. The median follow-up time was 28.8 years for surviving patients. Local control, disease-free (DFS), cancer-specific (CSS), and overall survival (OS), as well as late side effects, and cosmetic results were assessed. RESULTS:Five (11.1%) ipsilateral breast tumor recurrences were observed, for a 10-year and 30-year actuarial rate of 9.4%, and 12.6%, respectively. The 30-year DFS, CSS, and OS were 72.6%, 81.3%, and 46.6%, respectively. Fat necrosis requiring surgical intervention occurred in 1 woman (2.2%). Grade 3 fibrosis was observed in 1 patient (2.2%). No patient developed grade 3 late skin toxicity. Cosmetic results were rated excellent or good in 34 patients (75.6%). CONCLUSIONS:Thirty-year results with APBI using HDR multicatheter interstitial implants continue to demonstrate excellent long-term local tumor control, survival, and cosmetic results with a low rate of late side effects.

Despite their undeniable effectiveness, the spectacular increase in the number of antitumor immunotherapies (IT) in recent years has resulted in a substantial organizational and financial challenge on healthcare systems, and prolonged treatments can be burdensome for patients as well. There is an ongoing debate about how long it is optimal to continue palliative IT, or it can be discontinued after 2 years without an increased risk of relapse. Conclusively, it could be especially justified in complete tumor remission, however stable disease does not preclude it, and the decision may be strengthened by chronic complications, comorbidity state, patient preference, and PET/CT negativity, double IT, and lack of prior oligo- progression. Nevertheless, all this requires individual consideration, tumor-board discussion, and it is recommended to gradually prepare patients psychologically. In summary, while maintaining the possibility of reinduction, the discontinuation of palliative IT should always be considered after 2 years application (even after 1 year in melanoma), aiming for the longest treatment-free survival of our patients and minimizing the feeling of having a chronic and incurable disease.

Management of second ipsilateral breast cancer events (iBCEs) remains controversial, and there is a need to collate existing evidence and international guidance on patient selection and local treatment strategies. This project, endorsed by US and European surgical and radiation oncology societies, aimed to gather expert consensus on these issues. A questionnaire on second iBCE local treatment was developed and reviewed by a core group of eight experts, and Delphi methodology was applied over two rounds to 36 panellists, including radiation oncologists, breast surgeons, a plastic surgeon, and medical physicists. Consensus was predefined as agreement of 75% or higher. After two rounds, consensus was reached for 78 (80%) of 97 items. Panellists agreed that patient preferences are central to decision making (100%) and that a second breast-conserving therapy represents a reasonable option for selected patients (100%). Criteria associated with greater suitability for second breast-conserving therapy included an interval between surgeries of at least 60 months, low-risk accelerated partial breast irradiation classification, luminal molecular profile, and no grade 3 late toxicity related to the first breast-conserving therapy. HER2 (also known as ERBB2)-positive or triple negative subtypes were not viewed as absolute contraindications. Strong consensus was also observed regarding the importance of tumour-to-breast volume ratio, clear surgical margins, and tumour bed reirradiation. For patients undergoing mastectomy, immediate autologous reconstruction was preferred (94%) over implant-based approaches (75%). This international Delphi consensus offers structured guidance for the local management of second iBCE and supports shared decision making and individualised treatment planning.

The radiotherapy (RT) expert panel revised and updated the RT guidelines accepted in 2020 at the 4th Hungarian Breast Cancer Consensus Conference, based on new scientific evidence. Radiotherapy after breast-conserving surgery (BCS) is indicated in ductal carcinoma in situ (St. 0), as RT decreases the risk of local recurrence (LR) by 50-60%. In early stage (St. I-II) invasive breast cancer RT remains a standard treatment following BCS. However, in elderly (≥70 years) patients with stage I, hormone receptor positive tumour hormonal therapy without RT can be considered. Hypofractionated (15×2,67 Gy) or ultra-hypofractionated (5×5,2 Gy) whole breast irradiation (WBI) and for selected cases accelerated partial breast irradiation are validated treatment alternatives of conventional WBI. Following mastectomy RT significantly decreases the risk of LR and improves overall survival of patients having 1 to 3 or ≥4 positive axillary lymph nodes. In selected cases of patients with 1 to 2 positive sentinel lymph nodes, meeting the ACOSOG Z0011 study criteria, axillary dissection can be substituted with axillary RT. After neoadjuvant chemotherapy (NAC) followed by BCS WBI is mandatory, while after NAC followed by mastectomy RT should be given in cases of initial stage IIB-IV, and locoregional RT indicated in cases of ypN1-2-3 axillary status.

Background As the assessment of lymphocyte damage caused by radiotherapy gains importance as immunotherapies are used more frequently. Furthermore, there is scarce data to compare the biological dose of radiotherapy techniques in the same patient group. Methods Applying chromosome aberration technique, a five-year long (at 3, 6, 9, 12, 24, 36, 48, 60 months) prospective comparison of the biological impact of four different types of treatments for low- and intermediate-risk prostate cancer was performed (195 patients): conventional LINAC (linear accelerator) (70-78 Gy) and Cyberknife (40-37.5 Gy) teletherapy, LDR (low dose rate brachytherapy, 145 Gy) and HDR (high dose rate brachytherapy 19/21 Gy). Multivariate regression analyses were performed to analyze the predictive potential of the chromosome aberrations on side effects. The median follow-up was 48-60 months. Results We have found that teletherapy techniques (conv. LINAC and Cyberknife therapy) caused 1.7–3.2-fold more chromosomal aberrations than brachytherapies. At three months, 4.6%– 12.7% of the lymphocytes were damaged. Five years after treatment, the total aberration values of conventional LINAC and LDR brachytherapy patients were still significantly higher than before the therapy (p=0.035 for LINAC and p=0.003 for LDR BT). We found significant regression models suggesting chromosome aberration might predict side effects beside radiation dose and irradiated volumes (V100%): Late genitourinary (GU) side effects were dependent of chromosome fragments directly after conv. LINAC therapy (p=0.005). Conclusions We demonstrated long-term lymphocyte damage dependent on the type of radiotherapy. We also found less biological dose and side effects in brachytherapy patients. Highlights ### Competing Interest Statement The authors have declared no competing interest. * BT : brachytherapy CTV : clinical target volume EORTC-RTOG : European Organization for Research and Treatment of Cancer-Radiation Therapy Oncology Group FBS : fetal bovine serum GI : gastrointestinal GU : genitourinary GS : gleason score HDR : high dose rate HT : hormone therapy IPSS : International prostate symptom score LDR : low dose rate LINAC : linear accelerator PROM : patient-reported outcome measure PTV : planning target volume SIB : simultaneous integrated boost QoL : quality of life V100% : volume, which received the 100% of the prescribed dose the National Research, Development and Innovation Fund of the Ministry of Culture and Innovation, 2022-2.1.1-NL-2022-00010, TKP2021-EGA-44, 2020-1.1.6-JÖVŐ-2021-00008

Due to the better survival of patients with tumorous diseases, it is increasingly important to predict the side effects of radiotherapy, for which the Radiation-Induced Lymphocyte Apoptosis (RILA) method is proving to be effective in multicentric studies. Prostate cancer is the leading cause of cancer-related deaths among men worldwide, which is usually treated with radiotherapy. We recruited 49 patients with localized prostate cancer and performed RILA measurements before radiotherapy. Patients were treated with CyberKnife (35–40 Gy) or high-dose-rate brachytherapy (1 × 21 Gy). We performed chromosome aberration test for five years and graded side effects, IPSS and QoL questionnaire scores were recorded. We found that RILA% correlated with the IPSS increase (p = 0.0016, r=-0.44), which was confirmed with negative binomial regression (p = 0.0013). The negative predictive value for severe urinary side effects according to the IPSS questionnaire was 87.9% at the lower tertile of RILA values. Chromosome aberrations also correlated with side effects, but when we built models including variables of baseline and treatment characteristics of the patients, RILA, and chromosome aberrations, only RILA predicted a late increase in IPSS score (p < 0.0001, adjusted R2 = 68%). The RILA method was shown to be predictive of urinary side effects especially of patient-reported outcomes.

OBJECTIVES:Hungary is among the countries with the highest cancer mortality burden in Europe, consequently there is a crucial need to monitor changes in death rates in the population using appropriate surveillance tools. The Lexis diagram provides a means to depict age, period and cohort influences on long-term cancer mortality trends. METHODS:Age-specific mortality rates for six cancer localizations were constructed based on the Deaths Register of the Hungarian Central Statistical Office and the Human Mortality Database, then smoothed (p-splines) within the cells of the Lexis diagram assuming Poisson distribution. After calculating the annual percentage change in mortality rates, the results were visualized using heat maps. RESULTS:Substantial reduction in mortality was observable from the mid-1990s in both sexes as a strong period effect, depicting two distinct epidemiological eras in Hungary. Since 2010, breast cancer mortality in women among ages 70-90 (those born between 1930 and 1950) has been rising. Women born between 1940 and 50 experienced two plateaus in lung cancer mortality, unlike men, emphasizing the delayed nature of the smoking epidemic. CONCLUSIONS:The results align with cancer transition patterns observed in similarly developed countries and emphasize a critical need to expand the implementation of effective primary and secondary prevention measures. This includes sustaining organized screening and anti-smoking programs, as well as introducing lung cancer screening with low-dose CT.

AIM:Daily online adaptive radiation therapy (OART) allows the creation of individualized safety margins based on daily optimized treatment planning, taking into account daily anatomy variations. The goal of our work was to compare the protocols and safety margins of a non-adapted, image- guided radiation therapy (IGRT), a published Danish and the National Institute of Oncology of Hungary (NIO) protocol in the first eight bladder cancer patients treated with OART. METHODS:Three cone beam CTs (CBCT) were taken during the first three fractions: after patient positioning, after adaptation, and at the end of treatment. Bladder contours, extensions and margins were established on all CT images (n=512). Intraadaptational, intrafractional and interfractional changes were examined. RESULTS:Regarding PTV, a mean reduction of 12.2% could be achieved using the Danish, and 34.1% using the NIO protocol compared to IGRT. Healthy tissue irradiated by the prescribed dose could be reduced. The target volume miss is decreased as well. CONCLUSIONS:PTV could be reduced and optimized, increasing healthy tissue protection using OART.

Introduction:In the treatment of node-negative, non-metastatic high-risk (HR) and very high-risk (VHR) prostate cancer, the necessity of elective pelvic irradiation is controversial. According to our in-house treatment protocol - elective pelvic irradiation is generally omitted for HR and VHR patients over the age of 70 or those in poor general health due to its toxicity. Objective:To retrospectively examine the outcome for HR and VHR prostate cancer patients treated with elective whole pelvic radiotherapy (WPRT) versus prostate-only radiotherapy (PORT). Materials and Methods:The study included 434 patients treated with definitive radiotherapy, 203 patients received PORT (HR: 127, VHR: 76) and 231 WPRT (HR: 113, VHR: 118) with a boost to the prostate. Patients also received 2-3 years of androgen deprivation. Patients' average age who received PORT vs. WPRT was 73.9 ± 4.3 years vs. 66.4 ± 5.4 years respectively. An inverse propensity score weighting method was utilized to create homogeneous WPRT and PORT treatment groups that are balanced for T stage, PSA, and Gleason score, but not for age. The survival outcomes for HR and VHR subgroups were examined depending on whether they received WPRT or PORT. Biochemical- (BRFS), local- (LRFS) and regional relapse-free survival (RRFS), distant metastasis-free- (DMFS), disease-free- (DFS), failure-free- (FFS), and overall survival (OS) were compared using the Kaplan -Meier method and Cox regression analysis. Results:The median follow-up time was 76 months (3-134 months). In the VHR subgroup five-year outcomes showed a significant advantage for patients receiving WPRT vs. PORT in BRFS (82.2 % vs. 73 %; p = 0.028), in DMFS (87.5 % vs. 73.6 %; p = 0.025), in DFS (86.1 % vs. 70.5 %; p = 0.012), and in FFS (82.3 % vs. 68.9 %; p = 0.005), respectively. The OS (92.8 % vs. 81.8 %; p = 0.056) showed a trend favoring the WPRT group. There was no significant difference between WPRT vs. PORT in LRFS (95.8 % vs. 96.4 %; p = 0.763) and RRFS (95.8 % vs. 89.9 %; p = 0.099). On the contrary, in the HR group, no significant survival differences were observed between WPRT vs. PORT groups: BRFS 93.0 % vs. 93.3 % (p = 0.978), LRFS 99.0 % vs. 100 % (p = 0.120), RRFS 98.2 % vs. 95.1 % (p = 0.813), DMFS 93.5 % vs. 95.5 % (p = 0.793), DFS 91.7 % vs. 92.9 % (p = 0.691), FFS 89.5 % vs. 90.9 % (p = 0.853), OS 91.0 % vs. 87.7 % (p = 0.407). Conclusion:Based on our retrospective data elective pelvic irradiation can be omitted in HR patients, especially over the age of 70. For VHR patients, elective pelvic irradiation should be considered even for the subgroup of elderly patients.