BACKGROUND: A predictive assay for late radiation toxicity would allow more personalized treatment planning, reducing the burden of toxicity for the more sensitive minority, and improving the therapeutic index for the majority. In a previous study in prostate cancer patients, the γ-H2AX foci decay ratio (γ-FDR) was the strongest predictor of late radiation toxicity. The current study aimed to validate this finding in a more varied group of patients with pelvic cancer. Additionally, the potential correlation between the γ-FDR and patient-reported outcomes was investigated.
METHODS: Prostate and gynecological cancer patients with ≥ 24 months of follow-up were included in the current analysis. Toxicity was evaluated by physician (CTCAE version 4) and patient (EORTC questionnaires). γ-FDRs were determined in ex vivo irradiated lymphocytes. Correlation between γ-FDR and toxicity was assessed using both linear and logistic regression analyses. The highest toxicity grade recorded during follow-up was used. The association between global quality of life and γ-FDR was tested by comparing the change in quality of life over time in patients with γ-FDR < or ≥ 3.41, a previously established threshold.
RESULTS: Eighty-eight patients were included. Physician-assessed and patient-reported cumulative grade ≥ 2 toxicity was 25% and 29%, respectively; which is much lower than in the previous cohort (i.e., 51% CTCAE grade ≥ 2). Patients with toxicity exhibited less favorable dose-volume parameters. In men, these parameters showed significant improvement compared to the previous cohort. The proportion of patients with a low γ-FDR increased with severity of toxicity, but this trend was not statistically significant. In addition, a γ-FDR < 3.41 was not correlated with the development of moderate to severe toxicity. Post-treatment decline in global quality of life was minimal, and similar for patients with γ-FDR < or ≥ 3.41.
CONCLUSIONS: In the present study, the γ-H2AX foci decay ratio could not be validated as a predictor of late radiation toxicity in patients with pelvic cancer. Improved radiotherapy techniques with smaller irradiated bladder and bowel volumes have probably resulted in less toxicities. Future studies on genetic markers of toxicity should be powered on these lower incidences. We further recommend taking persistency, next to severity, into consideration.

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.

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.

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.

UNASSIGNED: The purpose of this study is to compare the performance of the Photon Optimizer (PO) version 16.1 algorithm with its earlier version PO v13.6 and with Progressive Resolution Optimizer (PRO) version 13.6 algorithms.
UNASSIGNED: 20 patients with single brain lesions treated with the stereotactic radiosurgery (SRS) technique were retrospectively selected for this study. Initially, for all patients volumetric modulated arc therapy (VMAT) SRS plans were generated with the PRO v 13.6 algorithm. Then, all the plans were re-generated with two versions 13.6 and 16.1 of PO algorithm using the same setup and dose-volume optimization objectives as that of PRO with a similar planning approach. The quality of the generated plans was analysed using ICRU 91 plan evaluation parameters and also using dice similarity co-efficient (DSC), centre of mass distance (CMD) between target and prescription isodose line, Monitor units (MU) and brain-gross tumor volume (GTV) 12 Gy volume. Paired Student t-test was used for statistical analysis with 0.05 as a significant value.
UNASSIGNED: PO v16.1 improved all the dosimetric parameters studied compared to PO 13.6, the difference is statistically significant for all the parameters (p < 0.05), except for median dose and brain-GTV 12 Gy volume. PO v16.1 also showed statistically significant improvement for all the dosimetric parameters evaluated, except DSC and conformity index (CI), compared to PRO v13.6.
UNASSIGNED: The PO v16.1 generated plans are dosimetrically superior to PO v13.6 and PRO v13.6 in terms of target dose coverage and dose gradient with lesser beam modulation and plan complexity for single brain lesion SRS.

UNASSIGNED: This case report demonstrates the possibility of successful eye and vision-sparing therapy for caruncular melanoma.
UNASSIGNED: We present an atypical presentation of a caruncular melanoma. After excisional biopsy, residual flat conjunctival melanosis resolved using topical chemotherapy (5-fluorouracil), which was well tolerated. Relapse of the melanoma was treated with external beam radiotherapy, but the tumor grew despite treatment. Eighteen months after complete excision of the relapsed melanoma, the patient remains tumor-free while the eye and its function remain preserved.
UNASSIGNED: This case report suggests that aggressive eye-sparing therapy for caruncular melanoma combining surgery, adjuvant topical chemotherapy, and external beam radiotherapy, can be an alternative for primary orbital exenteration.

Although many patients who receive definitive radiotherapy (RT) for localised prostate cancer (CaP) experience long-term disease-free survival and better quality of life, some also have biochemical progression during follow-up. Oftentimes this implies additional treatment for patients with the accompanying challenges of cumulative treatment side effects, inconvenience and financial toxicity. This study retrospectively assessed the clinicopathological characteristics and biochemical outcomes of patients treated for localised CaP with external beam radiotherapy (EBRT) between 2015 and 2020 at a major cancer treatment centre in Accra, Ghana. Patients\' socio-demographic and clinical data were collected from their hospital records and analysed with the Statistical Package for Social Sciences version 26. Biochemical failure (BCF) was defined as an increase in the level of serum prostate-specific antigen (PSA) >2 ng/mL above the nadir after curative therapy based on the Phoenix definition. The mean age was 67.6 years (SD ± 6.2). The majority of the study participants (n = 79, 64.8%) had initial PSA >20 ng/mL, with the highest recorded value of 705 ng/mL. All the patients had biopsy-proven adenocarcinoma of the prostate gland. Some patients received 3-dimensional conformal radiotherapy (3DCRT) on a cobalt-60 teletherapy machine whereas others were treated with either 3DCRT or intensity-modulated radiotherapy (IMRT) on a 6 MV Linac. In all, 13.1% of the patients experienced BCF after receiving EBRT after an average follow-up of 31.3 months. This study demonstrated a low rate of BCF among patients treated with EBRT for localised CaP in Ghana. Strong prognostic factors of biochemical outcome demonstrated in this study were the percentage of cores positive, grade group, and risk stratification. Diarrhaea and desquamation experienced by treated CaP patients were exclusively attributable to EBRT. RT produced a complete resolution of symptoms in some of the patients.