OBJECTIVE: to evaluate the outcome of partial breast re-irradiation (re-PBI) with intensity modulated RT (IMRT), using a hypofractionated scheme for breast cancer (BC) local recurrence (LR) operated on with repeat breast-conserving surgery (re-BCS).
METHODS: IMRT-based re-PBI was performed using either helical or step-and-shoot modality to deliver 37.05 Gy in 13 fractions in 2.5 weeks. Cumulative incidence (CumI) of 2ndLR, toxicity, disease-free (DFS), BC specific (BCSS), and overall (OS) survival were evaluated.
RESULTS: Between 5/2012 and 5/2021, 70 patients had re-PBI. Median follow-up (FU) was 6.3 years (Q1-Q3, 4.0-8.1.). Median age at 1stLR was 62. The median primary BC-1stLR interval was 12.4 years (range: 1.6-26.7). Luminal A-like 1stLR accounted for 41% of the cases and median size was 0.8 cm. During FU, 18 (26%) patients showed a subsequent event: three 2snLRs (corresponding to 8-y Cumulative rate of 4%), 3 regional nodal recurrences, 7 distant metastases, and 5 other primary tumors. At 8 years, DFS, BCSS and OS were 76%, 90%, and 90%, respectively. At multivariate analysis, Grade 3 and extensive intraductal component were independent predictors for DFS. For 51 and 46 patients, chronic toxicity and cosmesis were evaluated, respectively: 4% had grade 3 fibrosis and cosmesis was deemed good/excellent in just over 60% of the cases.
CONCLUSIONS: Re-PBI after re-BCS represents a feasible alternative to mastectomy with regard to local control, showing an acceptable toxicity profile. A long-term FU is crucial to better understand the pattern of relapse and consolidate the position of re-PBI in clinical practice.

Peptide receptor radionuclide therapy (PRRT) using 177Lu-DOTA-TATE has recently been evaluated for the treatment of meningioma patients. However, current knowledge of the underlying radiation biology is limited, in part due to the lack of appropriate in vitro models. Here, we demonstrate proof-of-concept of a meningioma patient-derived 3D culture model to assess the short-term response to radiation therapies such as PRRT and external beam radiotherapy (EBRT). We established short-term cultures (1 week) for 16 meningiomas with high efficiency and yield. In general, meningioma spheroids retained characteristics of the parental tumor during the initial days of culturing. For a subset of tumors, clear changes towards a more aggressive phenotype were visible over time, indicating that the culture method induced dedifferentiation of meningioma cells. To assess PRRT efficacy, we demonstrated specific uptake of 177Lu-DOTA-TATE via somatostatin receptor subtype 2 (SSTR2), which was highly overexpressed in the majority of tumor samples. PRRT induced DNA damage which was detectable for an extended timeframe as compared to EBRT. Interestingly, levels of DNA damage in spheroids after PRRT correlated with SSTR2-expression levels of parental tumors. Our patient-derived meningioma culture model can be used to assess the short-term response to PRRT and EBRT in radiobiological studies. Further improvement of this model should pave the way towards the development of a relevant culture model for assessment of the long-term response to radiation and, potentially, individual patient responses to PRRT and EBRT.

BACKGROUND: The management of locally recurrent gynecological carcinoma remains a challenge due to the limited availability of data. This study aims to share our institutional experience in using definitive radiotherapy (RT) for the treatment of locally recurrent cervical and endometrial carcinoma.
METHODS: The study retrospectively reviewed 20 patients in our hospital completing salvage 3D image-based HDR brachytherapy, with or without EBRT, for locally recurrent cervical and endometrial carcinoma after surgery. The Kaplan-Meier method was applied to estimate the disease-free survival (DFS) and overall survival (OS). The toxicities were assessed by CTCAEv5.
RESULTS: During a median observation period of 21 months, the study reported a tumor objective response rate of 95%. The 3-year DFS and OS rates were 89.4% and 90.9%, respectively. The EBRT combined with brachytherapy achieved a median cumulative dose of 88 Gy to CTV D90. 14 patients received concurrent and/or systemic chemotherapy. Two patients suffered locoregional recurrence after salvage treatment, one of whom only received salvage brachytherapy for prior RT history. The analysis identified significant predictors for DFS, including tumor histology and FIGO stage. 5 patients observed acute grade 1-2 rectal (15%) or genitourinary (10%) toxicities. Late toxicities including grade 1-2 rectal bleeding (10%) and grade 2 pelvic fracture (5%) were seen in 3 patients.
CONCLUSIONS: 3D image-guided brachytherapy combined with EBRT shows effective tumor control and acceptable toxicity profile for women with locally recurrent gynecologic cancer. The success in managing vaginal recurrence is notably influenced by histologic subtype and FIGO staging.

OBJECTIVE: The occurrence of genitourinary (GU) toxicity is a common adverse event observed after external beam radiation therapy (EBRT) for prostate cancer (PCa). Recent findings suggest that the dose delivered to specific urinary organs at risk (OARs) such as the ureters, bladder trigone, and urethra is involved in the development of GU toxicity.
METHODS: A multidisciplinary task force including 3 radiation oncologists, a uroradiologist, and a urologist was created in 2022. First, OARs potentially involved in GU toxicity were identified and discussed. A literature review was performed, addressing several questions relative to urinary OARs: anatomic and radiological definition, radiation-induced injury, and dose-volume parameters. Second, results were presented and discussed with a panel of radiation oncologists and members of the \"Francophone Group of Urological Radiation Therapy.\" Thereafter, the \"Francophone Group of Urological Radiation Therapy\" experts were asked to answer a dedicated questionnaire, including 35 questions on the controversial issues related to the delineation of urinary OARs.
RESULTS: The following structures were identified as critical for PCa EBRT: ureters, bladder, bladder neck, bladder trigone, urethra (intraprostatic, membranous, and spongious), striated sphincter, and postenucleation or posttransurethral resection of the prostate cavity. A consensus was obtained for 32 out of 35 items.
CONCLUSIONS: This consensus highlights contemporary urinary structures in both the upper and lower urinary tract to be considered for EBRT treatment planning of PCa. The current recommendations also propose a standardized definition of urinary OARs for both daily practice and future clinical trials.

BACKGROUND: Adjuvant radiotherapy after mastectomy or breast conserving surgery (BCS) is the standard of care for majority of patients with breast cancer. This is however associated with mucosal and epidermal toxicity of organs at risk (OARs). Breast cancer patients are exposed to a plethora of wrong perceptions, misinformation and myths concerning the usefulness and adverse effects of radiotherapy. There is paucity of literature on the incidence and severity of radiation-induced acute toxicities experienced by patients with breast cancer in Ghana.
OBJECTIVE: To assess the occurrence and severity of four main acute radiation-induced toxicities among female breast cancer patients treated with external beam radiotherapy at a major cancer treatment centre in Ghana.
METHODS: Data on the occurrence of acute toxicities among patients was collected from patients\' medical records, through a semi-structured questionnaire and via weekly clinical assessments. The Common Terminology Criteria for Adverse Events (CTCAE) grading scale (version 4.0) was used to grade the severity of these toxicities. Descriptive and inferential statistics using an independent two-sampled t-test (two-tailed), one-way analysis of variance (ANOVA), Pearson\'s Chi-square and Fisher\'s exact tests were performed.
RESULTS: Dermatitis, fatigue, pharyngitis, and breast (chest) pain were the radiation toxicities found among the breast cancer patients undergoing treatment on the two machines. The mean predominant radiation doses associated with the onset of dermatitis, fatigue, pharyngitis, and chest pain in the breast cancer patients were 22.32 Gy, 22.48 Gy, 13.59 Gy, and 19.27 Gy respectively for treatment with a statistically significant (p = 0.0173). Radiation dermatitis was the most dominant acute radiation toxicity recorded, and its incidence and severity. The range of Fisher\'s p-values (0.689-0.999) between the acute radiation toxicities with both machines revealed no statistical significance.
CONCLUSIONS: Radiation dermatitis was the dominant acute toxicity, both in incidence and severity for patients treated. There was no statistical significance in the incidence and severity of acute radiation side effects.

OBJECTIVE: To investigate the efficacy of 125I seed brachytherapy for non-central pelvic recurrence of cervical cancer after external beam radiotherapy, and to analyze the clinical influential factors.
METHODS: Between June 2015 and April 2022, 32 patients with 41 lesions were treated with 125I seed brachytherapy. The seeds were implanted under the guidance of CT and/or 3D-printed template images at a median dose of 100 Gy (range, 80-120 Gy), and the local control rate (LCR) and survival rates were calculated. We used multivariate logistic regression to identify prognosis predictors, and receiver operating characteristic (ROC) curve analysis to determine the optimal cut-off values.
RESULTS: The median follow-up was 48.52 months (range, 4-86 months), and the 6-, 12-, and 24-month LCR was 88.0%, 63.2%, and 42.1%, respectively. The 1- and 2-year survival rates were 36% and 33%, respectively, and the median survival time was 13.26 months. No significant adverse events occurred. Multivariate regression analysis showed that tumor diameter, tumor stage, and LCR were independent factors influencing survival. ROC curve analysis showed that the area under the curve for tumor diameter and D90 were 0.765 and 0.542, respectively, with cut-off values of 5.3 cm and 108.5 Gy.
CONCLUSIONS: The present findings indicate that 125I seed brachytherapy is feasible for treating non-central pelvic recurrence of cervical cancer after external beam radiotherapy. Further, tumor diameter < 5.3 cm and immediate postoperative D90 > 108.5 Gy were associated with better efficacy.

This work builds upon a prior study, examining the dosimetric utility of pencil lead and thin graphitic sheets, focusing upon the measurement of skin doses within the mammographic regime. In recognizing the near soft-tissue equivalence of graphite and the earlier-observed favourable thermoluminescence yield of thin sheets of graphite, this has led to present study of 50 μm thick graphite for parameters typical of external beam fractionated radiotherapy and skin dose evaluations. The graphite layers were annealed and then stacked to form an assembly of 0.5 mm nominal thickness. Using a 6 MV photon beam and delivering doses from 2- to 60 Gy, irradiations were conducted, the assembly first forming a superficial layer to a solid water phantom and subsequently underlying a 1.5 cm bolus, seeking to circumvent the build-up to electronic equilibrium for skin treatments. Investigations were made of several dosimetric properties arising from the thermoluminescence yield of the 50 μm thick graphite slabs, in particular proportionality and sensitivity to dose. The results show excellent sensitivity within the dose range of interest, the thermoluminescence response varying with increasing depth through the stacked graphite layers, obtaining a coefficient of determination of 90%. Acknowledging there to be considerable challenge in accurately matching skin thickness with dose, the graphite sheets have nevertheless shown considerable promise as dosimeters of skin, sensitive in determination of dose from the surface of the graphite through to sub-dermal depth thicknesses.

OBJECTIVE: To evaluate the real-world added value of androgen deprivation therapy (ADT) in addition to external beam radiotherapy (EBRT) in men with high-risk non-metastatic prostate cancer, in view of advances in radiotherapy and diagnostics.
METHODS: All Dutch men diagnosed with high-risk non-metastatic prostate cancer (defined as: ≥cT2c-T3b N0M0, PSA ≥20-50 ng/ml, and/or Gleason score ≥8 (International Society of Urological Pathology [ISUP] grade ≥4)) from 2009 through 2019 and treated with EBRT with or without ADT were identified in the population-based Netherlands Cancer Registry. Propensity scores were used to match (1:1) men that received ADT to men that did not receive ADT. Subsequently, OS was compared. Analyses were also stratified by number of high-risk features, 1 (either ≥cT2c, PSA >20 ng/ml or Gleason score ≥8) versus ≥2 (out of ≥cT2c, PSA >20 ng/ml and Gleason score ≥8).
RESULTS: A total of 14,773 men with high-risk non-metastatic prostate cancer were identified, 3,958 (27%) of which received EBRT alone. After matching, 3,427 men remained in both groups and baseline characteristics were well-balanced. After a median follow-up of 92 months, OS was better in men treated with EBRT and ADT compared to men treated with EBRT alone (10-year OS: 66.4% versus 61.8%; HR 0.88 [95%CI: 0.80-0.96]). There was no statistically significant difference in OS in the subgroup of men with only 1 high-risk feature (10-year OS 67.7% versus 64.9%; HR 0.95 [95%CI: 0.85-1.07]).
CONCLUSIONS: In a contemporary cohort of men treated for high-risk non-metastatic prostate cancer with EBRT, an OS benefit of adding ADT was only observed in men with at least 2 high-risk features. These results suggest that improvements in diagnostics and treatment in recent decades have resulted in a stage shift of men benefiting from the addition of ADT to EBRT.

Management of prostate cancer (PC) might be improved by combining external beam radiotherapy (EBRT) and prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (RLT) with lutetium-177 (177Lu)-labeled PSMA inhibitors. We hypothesized a higher efficacy of the combination due to augmentation of the radiation dose to the tumor and interactions of EBRT with PSMA expression potentially increasing radiopharmaceutical uptake. Therefore, this study analyzed the influence of radiation on PSMA expression levels in vitro. The results were translated to evaluate the efficacy of the combination of photon EBRT and [177Lu]Lu-PSMA-617 in a murine PC xenograft model. Finally, a clinical case report on a combined elective field EBRT with RLT dose escalation illustrates a proof-of-concept. Methods: PSMA gene and protein expression were assessed in human PSMA-overexpressing LNCaP cells after irradiation using reverse transcription quantitative polymerase chain reaction (RT-qPCR), flow cytometry and On-Cell Western assays. In the in vivo therapy study, LNCaP tumor-bearing BALB/c nu/nu mice were irradiated once with 2 Gy X-ray EBRT and injected with 40 MBq [177Lu]Lu-PSMA-617 after 4 h or received single or no treatment (n = 10 each). Tumor-absorbed doses by [177Lu]Lu-PSMA-617 were calculated according to the Medical Internal Radiation Dosimetry (MIRD) formalism after deriving time-activity curves using a gamma probe. An exemplified patient case is demonstrated where fractionated EBRT (54 Gy to prostate; 45 Gy to pelvic lymphatics) and three cycles of [177Lu]Lu-PSMA-617 (3.4-6.0 GBq per cycle) were sequentially combined under concurrent androgen deprivation for treating locally advanced PC. Results: At 4 h following irradiation with 2-8 Gy, LNCaP cells displayed a PSMA protein upregulation by around 18% relative to non-irradiated cells, and a stronger upregulation on mRNA level (up to 2.6-fold). This effect was reversed by 24 h when PSMA protein levels were downregulated by up to 22%. Mice treated with the combination therapy showed significantly improved outcomes regarding tumor control and median survival (p < 0.0001) as compared to single or no treatment. Relative to monotherapy with PSMA-RLT or EBRT, the tumor doubling time was prolonged 1.7- or 2.7-fold and the median survival was extended by 24% or 60% with the combination, respectively. Additionally, tumors treated with EBRT exhibited a 14% higher uptake of the radiopharmaceutical as evident from the calculated tumor-absorbed dose, albeit with high variability in the data. Concerning the patient case, the tri-modality treatment was well tolerated and the patient responded with a long-lasting complete biochemical remission for five years following end of PSMA-RLT. The patient then developed a biochemical relapse with oligo-recurrent disease on follow-up imaging. Conclusion: The present preclinical and clinical data demonstrate that the combination of EBRT with dose escalation by PSMA-RLT improves tumor control and potentially prolongs survival. This may pave the way for further clinical investigations of this approach to explore the curative potential of the combination therapy.

UNASSIGNED: Data on the carbon footprint of external beam radiotherapy (EBRT) are scarce. Reliable and exhaustive data, including a detailed carbon inventory, are needed to determine effective mitigation strategies.
UNASSIGNED: This study proposes a methodology for calculating the carbon footprint of EBRT and applies it to a single center. Mitigation strategies are derived from the carbon inventory, and their potential reductions are quantified whenever possible.
UNASSIGNED: The average emission per treatment and fraction delivered was 489 kg CO₂eq and 27 kg CO₂eq, respectively. Patient transportation (43 %) and the construction and maintenance of linear accelerators (LINACs) and scanners (17 %) represented the most significant components. Electricity, the only energy source used, accounted for only 2 % of emissions.Derived mitigation strategies include a data deletion policy (reducing emissions in 30 years by 12.5 %), geographical appropriateness (-12.2 %), transportation mode appropriateness (-9.3 %), hypofractionation (-5.9 %), decrease in manufacturers\' carbon footprint (-5.2 %), and an increase in machine durability (-3.5 %).
UNASSIGNED: Our findings indicate that a significant reduction in the carbon footprint of a radiotherapy unit can be achieved without compromising the quality of care.This study provides a methodology and a starting point for comparison and proposes and quantifies mitigation strategies, paving the way for others to follow.