Dosimetric Correlation of Acute Radiation Dermatitis in Patients With Breast Cancer Undergoing Hypofractionated Proton Beam Therapy Using Pencil Beam Scanning.

PURPOSE: Pencil-beam scanning (PBS) is a modern delivery technique used in proton beam therapy (PBT) to reduce normal tissue reactions. No dosimetric correlation between dermatitis and PBS has been reported for breast cancer. The current study aimed to investigate the factors associated with grade 2 or higher dermatitis in patients with breast cancer undergoing PBT using PBS. METHODS: The medical data of 42 patients with breast cancer who underwent adjuvant radiotherapy between December 2019 and September 2023 were reviewed. All patients received hypofractionated radiotherapy (HFRT), either 26 Gy (relative biological effectiveness [RBE])/five fractions or 40.05 or 43.5 Gy (RBE)/15 fractions, for the whole breast/chest wall with or without nodal irradiation. The duration of acute radiation dermatitis was defined as within 90 days from the start of radiotherapy. The Kaplan-Meier method and Cox proportional hazards model were used for univariate and multivariate analyses of the actuarial rates of grade 2-3 dermatitis. RESULTS: Twenty-two (52.4%) and 20 (47.6%) patients were diagnosed with grade 1 and 2 dermatitis, respectively. Multivariate analysis revealed a clinical target volume (CTV) ≥ of 320 cc (p = 0.035) and a skin dose of D10cc ≥ 38.3 Gy (RBE) (p = 0.009) as independent factors of grade 2 dermatitis. The 10-week cumulative grade 2 dermatitis rates were 88.2%, 39.4%, and 8.3% (p < 0.001) for patients with both high, either high, and neither high CTV and D10cc, respectively. CONCLUSION: To the best of our knowledge, this is the first study on dosimetric correlations for dermatitis in patients with breast cancer who underwent hypofractionated PBT using PBS. In the era of HFRT, skin dose modulation using PBS may reduce the incidence of dermatitis.

Patient-reported outcomes after personalised dose-escalation for stage II-III non-small-cell lung cancer patients: Results from the randomised ARTFORCE PET-Boost trial.

BACKGROUND AND PURPOSE: The ultimate challenge in dose-escalation trials lies in finding the balance between benefit and toxicity. We examined patient-reported outcomes (PROs), including health-related quality of life (HRQoL) in patients with locally advanced non-small cell lung cancer (LA-NSCLC), treated with dose-escalated radiotherapy. MATERIALS AND METHODS: The international, randomised, phase 2 ARTFORCE PET-Boost study (NCT01024829) aimed to improve 1-year freedom from local failure rates in patients with stage II-III NSCLC, with a ≥ 4 cm primary tumour. Treatment consisted of an individualised, escalated fraction dose, either to the primary tumour as a whole or to its most FDG-avid subvolume (24 x 3.0-5.4 Gy). Patients received sequential or concurrent chemoradiotherapy, or radiotherapy only. Patients were asked to complete the EORTC QLQ-C30, QLQ-LC13, and the EuroQol-5D at eight timepoints. We assessed the effect of dose-escalation on C30 sum score through mixed-modelling and evaluated clinically meaningful changes for all outcomes. RESULTS: Between Apr-2010 and Sep-2017, 107 patients were randomised; 102 were included in the current analysis. Compliance rates: baseline 86.3%, 3-months 85.3%, 12-months 80.3%; lowest during radiation treatment 35.0%. A linear mixed-effect (LME) model revealed no significant change in overall HRQoL over time, and no significant difference between the two treatment groups. Physical functioning showed a gradual decline in both groups during treatment and at 18-months follow-up, while clinically meaningful worsening of dyspnoea was seen mainly at 3- and 6-months. CONCLUSION: In patients with LA-NSCLC treated with two dose-escalation strategies, the average patient-reported HRQoL remained stable in both groups, despite frequent patient-reported symptoms, including dyspnoea, dysphagia, and fatigue.

A Novel Treatment Planning Design for Intraoperative Electron Radiation Therapy (IOERT) using an Electronic Board.

Background: Intraoperative Irradiation Therapy (IORT) refers to the delivery of radiation during surgery and needs the computed- thickness of the target as one of the most significant factors. Objective: This paper aimed to compute target thickness and design a radiation pattern distributing the irradiation uniformly throughout the target. Material and Methods: The Monte Carlo code was used to simulate the experimental setup in this simulation study. The electron flux variations on an electronic board's metallic layer were studied for different thicknesses of the target tissue and validated with experimental data of the electronic board. Results: Based on the electron number for different Poly Methyl Methacrylate (PMMA) phantom thicknesses at various energies, 6 MeV electrons are suitable to determine the target thickness. Uniformity in radiation and corresponding time for each target were investigated. The iso-dose and percentage depth dose curves show that higher energies are suitable for treatment and distribute uniform radiation throughout the target. Increasing the phantom thickness leads to rising radiation time based on the radiation time corresponding to these energies. The tissue thickness of each section is determined, and the radiation time is managed by scanning the target. Conclusion: Calculation of the thickness of the remaining tissue and irradiation time are needed after incomplete tumor removal in IORT for various remaining tissues. The patients should be protected from overexposure to uniform irradiation of tissues since the radiation dose is prescribed and checked by an oncologist.

Outcome of dose-escalated intensity-modulated radiotherapy for limited disease small cell lung cancer.

PURPOSE: An optimal once-daily radiotherapy (RT) regimen is under investigation for definitive concurrent chemoradiotherapy (CCRT) in limited disease small cell lung cancer (LD-SCLC). We compared the efficacy and safety of dose escalation with intensity-modulated radiotherapy (IMRT). MATERIALS AND METHODS: Between January 2016 and March 2021, patients treated with definitive CCRT for LD-SCLC with IMRT were retrospectively reviewed. Patients who received a total dose <50 Gy or those with a history of thoracic RT or surgery were excluded. The patients were divided into two groups (standard and dose-escalated) based on the total biologically effective dose (BED, α/ß = 10) of 70 Gy. The chemotherapeutic regimen comprised four cycles of etoposide and cisplatin. RESULTS: One hundred and twenty-two patients were analyzed and the median follow-up was 27.8 months (range, 4.4 to 76.9 months). The median age of the patients was 63 years (range, 35 to 78 years) and the majority had a history of smoking (86.0%). The 1- and 3-year overall survival rates of the escalated dose group were significantly higher than those of the standard group (93.5% and 50.5% vs. 76.7% and 33.3%, respectively; p = 0.008), as were the 1- and 3-year freedom from in-field failure rates (91.4% and 66.5% vs. 73.8% and 46.9%, respectively; p = 0.018). The incidence of grade 2 or higher acute and late pneumonitis was not significantly different between the two groups (p = 0.062, 0.185). CONCLUSION: Dose-escalated once-daily CCRT with IMRT led to improved locoregional control and survival, with no increase in toxicity.

Safety and efficacy of salvage conventional re-irradiation following stereotactic radiosurgery for spine metastases.

PURPOSE: There has been limited work assessing the use of re-irradiation (re-RT) for local failure following stereotactic spinal radiosurgery (SSRS). We reviewed our institutional experience of conventionally-fractionated external beam radiation (cEBRT) for salvage therapy following SSRS local failure. MATERIALS AND METHODS: We performed a retrospective review of 54 patients that underwent salvage conventional re-RT at previously SSRS-treated sites. Local control following re-RT was defined as the absence of progression at the treated site as determined by magnetic resonance imaging. RESULTS: Competing risk analysis for local failure was performed using a Fine-Gray model. The median follow-up time was 25 months and median overall survival (OS) was 16 months (95% confidence interval [CI], 10.8-24.9 months) following cEBRT re-RT. Multivariable Cox proportional-hazards analysis revealed Karnofsky performance score prior to re-RT (hazard ratio [HR] = 0.95; 95% CI, 0.93-0.98; p = 0.003) and time to local failure (HR = 0.97; 95% CI, 0.94-1.00; p = 0.04) were associated with longer OS, while male sex (HR = 3.92; 95% CI, 1.64-9.33; p = 0.002) was associated with shorter OS. Local control at 12 months was 81% (95% CI, 69.3-94.0). Competing risk multivariable regression revealed radioresistant tumors (subhazard ratio [subHR] = 0.36; 95% CI, 0.15-0.90; p = 0.028) and epidural disease (subHR = 0.31; 95% CI, 0.12-0.78; p =0.013) were associated with increased risk of local failure. At 12 months, 91% of patients maintained ambulatory function. CONCLUSION: Our data suggest that cEBRT following SSRS local failure can be used safely and effectively. Further investigation is needed into optimal patient selection for cEBRT in the retreatment setting.

A Monte Carlo study on dose distribution of an orthovoltage radiation therapy system.

It is important to plan radiotherapy treatment and establish optimal dose distribution to reduce the chances of side effects and injury. Because there are no commercially available tools for calculating dose distribution in orthovoltage radiotherapy in companion animals, we developed an algorithm to accomplish this and verified its characteristics using tumor disease cases. First, we used the Monte Carlo method to develop an algorithm to calculate the dose distribution of orthovoltage radiotherapy (280 kVp; MBR-320, Hitachi Medical Corporation, Tokyo, Japan) using BEAMnrc at our clinic. Using development of Monte Carlo method, dose distribution for tumor and normal organs were evaluated in brain tumors, squamous cell carcinomas of the head, and feline nasal lymphomas. In all cases of brain tumors, the mean dose delivered to the GTV ranged from 36.2 to 76.1% of the prescribed dose due to the decrease through the skull. In the nasal lymphoma in cats, the eyes with covered a 2 mm-thick lead plate, the respective average dose to the eyes was 71.8% and 89.9% less than that to the uncovered eyes. The findings may be useful for informed decision making in orthovoltage radiotherapy with more effective and targeted irradiation and data collection allowing detailed informed consent.

Radiation safety measures in diagnostic nuclear medicine, based on the potential radiation dose emitted by radioactive patients.

Objective: To measure the potential radiation dose emitted by patients who have recently undergone diagnostic nuclear medicine procedures, in order to establish optimal radiation safety measures for such procedures. Materials and Methods: We evaluated the radiation doses emitted by 175 adult patients in whom technetium-99m, iodine-131, and fluorine-18 radionuclides were administered for bone, kidney, heart, brain, and whole-body scans, as measured with a radiation detector. Those values served as the basis for evaluating whole-body radiopharmaceutical clearance, as well as the risk for the exposure of others to radiation, depending on the time elapsed since administration of the radiopharmaceutical. Results: The mean time to clearance of the radiopharmaceuticals administered, expressed as the effective half-life, ranged from 1.18 ± 0.30 h to 11.41 ± 0.02 h, and the mean maximum cumulative radiation dose at 1.0 m from the patients was 149.74 ± 56.72 µSv. Even at a distance of 0.5 m, the cumulative dose was found to be only half and one tenth of the limits established for exposure of the general public and family members/caregivers (1.0 mSv and 5.0 mSv per episode, respectively). Conclusion: Cumulative radiation doses emitted by patients immediately after diagnostic nuclear medicine procedures are considerably lower than the limits established by the International Commission on Radiological Protection and the International Atomic Energy Agency, and precautionary measures to avoid radiation exposure are therefore not required after such procedures.

Objetivo: O objetivo deste trabalho foi levantar o potencial de dose de radiação emitida por pacientes em procedimentos diagnósticos, visando a estabelecer cuidados de radioproteção mais otimizados. Materiais e Métodos: Taxas de dose de radiação emitidas por 175 pacientes administrados com os radionuclídeos 99mTc, 131I e 18F para cintilografias óssea, renal, cardíaca, cerebral e corpo inteiro, foram mensuradas com um detector de radiação, servindo para avaliar o clareamento do radiofármaco no organismo e risco de exposição após administração dos radiofármacos. Resultados: O clareamento, representado pela meia-vida efetiva, variou de 1,18 ± 0,30 h até 11,41 ± 0,02 h e a dose de radiação máxima acumulada oferecida pelos pacientes a 1,0 m foi de 149,74 ± 56,72 µSv. Mesmo para distâncias de 0,5 m, as doses estimadas foram, respectivamente, duas e dez vezes inferiores ao nível de restrição para o público geral (1,0 mSv) e exposição médica (5,0 mSv/episódio). Conclusão: Doses de radiação oferecidas por pacientes em procedimentos diagnósticos são inferiores aos níveis de restrição recomendados pela International Commission on Radiological Protection e International Atomic Energy Agency, e assim, cuidados de radioproteção são geralmente desnecessários.

Radiation safety measures in diagnostic nuclear medicine, based on the potential radiation dose emitted by radioactive patients / Cuidados de radioproteção em medicina nuclear diagnóstica baseados no potencial de dose de radiação emitida por pacientes radioativos

Abstract Objective: To measure the potential radiation dose emitted by patients who have recently undergone diagnostic nuclear medicine procedures, in order to establish optimal radiation safety measures for such procedures. Materials and Methods: We evaluated the radiation doses emitted by 175 adult patients in whom technetium-99m, iodine-131, and fluorine-18 radionuclides were administered for bone, kidney, heart, brain, and whole-body scans, as measured with a radiation detector. Those values served as the basis for evaluating whole-body radiopharmaceutical clearance, as well as the risk for the exposure of others to radiation, depending on the time elapsed since administration of the radiopharmaceutical. Results: The mean time to clearance of the radiopharmaceuticals administered, expressed as the effective half-life, ranged from 1.18 ± 0.30 h to 11.41 ± 0.02 h, and the mean maximum cumulative radiation dose at 1.0 m from the patients was 149.74 ± 56.72 µSv. Even at a distance of 0.5 m, the cumulative dose was found to be only half and one tenth of the limits established for exposure of the general public and family members/caregivers (1.0 mSv and 5.0 mSv per episode, respectively). Conclusion: Cumulative radiation doses emitted by patients immediately after diagnostic nuclear medicine procedures are considerably lower than the limits established by the International Commission on Radiological Protection and the International Atomic Energy Agency, and precautionary measures to avoid radiation exposure are therefore not required after such procedures.

Resumo Objetivo: O objetivo deste trabalho foi levantar o potencial de dose de radiação emitida por pacientes em procedimentos diagnósticos, visando a estabelecer cuidados de radioproteção mais otimizados. Materiais e Métodos: Taxas de dose de radiação emitidas por 175 pacientes administrados com os radionuclídeos 99mTc, 131I e 18F para cintilografias óssea, renal, cardíaca, cerebral e corpo inteiro, foram mensuradas com um detector de radiação, servindo para avaliar o clareamento do radiofármaco no organismo e risco de exposição após administração dos radiofármacos. Resultados: O clareamento, representado pela meia-vida efetiva, variou de 1,18 ± 0,30 h até 11,41 ± 0,02 h e a dose de radiação máxima acumulada oferecida pelos pacientes a 1,0 m foi de 149,74 ± 56,72 µSv. Mesmo para distâncias de 0,5 m, as doses estimadas foram, respectivamente, duas e dez vezes inferiores ao nível de restrição para o público geral (1,0 mSv) e exposição médica (5,0 mSv/episódio). Conclusão: Doses de radiação oferecidas por pacientes em procedimentos diagnósticos são inferiores aos níveis de restrição recomendados pela International Commission on Radiological Protection e International Atomic Energy Agency, e assim, cuidados de radioproteção são geralmente desnecessários.

Thyroid volume changes following adjuvant radiation therapy for breast cancer.

Background and purpose: Incidental thyroid gland irradiation frequently occurs in breast cancer patients who receive regional nodal irradiation (RNI) to the supraclavicular (SCV) region. Recent studies suggest hypothyroidism (HT) is a complication of radiation therapy (RT) that includes SCV fields. We retrospectively analyzed patients who received RNI to evaluate thyroid gland evolution following RT as well as its association with the development of HT. Materials and methods: 61 breast cancer patients received SCV-directed RT between 2007 and 2019 and met inclusion criteria. Thyroid glands were retrospectively contoured on CT simulation and follow-up images. Individual dose-volume histograms were analyzed to determine thyroid volume within and outside specific isodose lines. Relative thyroid volume changes based on different radiation doses were estimated by fusing post-RT scans with CT simulation. Logistic regression was performed to assess thyroid volume changes as a factor in the development of HT. Results: Median pre-treatment thyroid volume was 11.8 cc (range: 6.3-74.1 cc) with a median of 42.2 % within the 20 Gy and 23.2 % within the 40 Gy isodose lines. A significant decrease in thyroid volume was noted by 1-year post-treatment (p < 0.0001) and thereafter. By 4 years post-treatment, average thyroid volume was decreased by 29.7 % (range: 2.3-64.4 %). Thyroid volume receiving 40 Gy or higher demonstrated a greater decrease compared to those receiving lower irradiation dosage. HT occurred in 17 patients (27.9 %). Patients who developed HT displayed a larger decrease in the thyroid volume receiving between 20 and 40 Gy at 12 months (p = 0.033). Conclusion: Our study demonstrates for the first time that a reduction in thyroid volume may be seen as early as 6 months after SCV-directed RT for breast cancer, which correlates with development of clinical and subclinical HT. Furthermore, a dose-dependent correlation exists between thyroid subvolume reduction and SCV-directed RT in breast cancer patients. As feasible, efforts should be made to reduce the dose to the thyroid in patients who undergo RNI for breast cancer.

Blood-brain barrier permeability following conventional photon radiotherapy - A systematic review and meta-analysis of clinical and preclinical studies.

Radiotherapy (RT) is a cornerstone treatment strategy for brain tumours. Besides cytotoxicity, RT can cause disruption of the blood-brain barrier (BBB), resulting in an increased permeability into the surrounding brain parenchyma. Although this effect is generally acknowledged, it remains unclear how and to what extent different radiation schemes affect BBB integrity. The aim of this systematic review and meta-analysis is to investigate the effect of photon RT regimens on BBB permeability, including its reversibility, in clinical and preclinical studies. We systematically reviewed relevant clinical and preclinical literature in PubMed, Embase, and Cochrane search engines. A total of 69 included studies (20 clinical, 49 preclinical) were qualitatively and quantitatively analysed by meta-analysis and evaluated on key determinants of RT-induced BBB permeability in different disease types and RT protocols. Qualitative data synthesis showed that 35% of the included clinical studies reported BBB disruption following RT, whereas 30% were inconclusive. Interestingly, no compelling differences were observed between studies with different calculated biological effective doses based on the fractionation schemes and cumulative doses; however, increased BBB disruption was noted during patient follow-up after treatment. Qualitative analysis of preclinical studies showed RT BBB disruption in 78% of the included studies, which was significantly confirmed by meta-analysis (p < 0.01). Of note, a high risk of bias, publication bias and a high heterogeneity across the studies was observed. This systematic review and meta-analysis sheds light on the impact of RT protocols on BBB integrity and opens the discussion for integrating this factor in the decision-making process of future RT, with better study of its occurrence and influence on concomitant or adjuvant therapies.

Image-guided brachytherapy in cervical cancer including fractionation.

Image-guided brachytherapy in cervical cancer has been developed to be a feasible and very efficient component of the treatment of locally advanced cervical cancer in addition to concurrent chemoradiation treatment. This technique allows effective dose coverage of the target while sparing the organs at risk through adjustment of the implants (intracavitary and interstitial needles) and multi-pararametric three-dimensional treatment planning. Emerging evidence from prospective studies shows a high rate of local control throughout all stages, superior to two-dimensional brachytherapy, with limited toxicity for each organ site. This is associated with a high rate of pelvic control and overall survival. Based on clinical evidence, there is a dose-effect relationship for both disease and morbidity endpoints from which clear dose constraints for the target and organs at risk were derived. This review gives an overview of the major milestones that occurred in the development of image-guided adaptive brachytherapy in the last two decades, including outcome data and a summary of the hard and soft dose constraints recommended for targets and organs at risk.

Highly hypofractionated schedules for localized prostate cancer: Recommendations of the GETUG radiation oncology group.

Stereotactic body radiotherapy (SBRT) has become treatment option for localized prostate cancer but the evidence base remains incomplete. Several clinical studies, both prospective and retrospective, have been published. However, treatment techniques, target volumes and dose constraints lack consistency between studies. Based on the current available literature, the French Genito-Urinary Group (GETUG) suggests that.

Stereotactic body radiotherapy in oligometastatic cervical cancer (MITO-RT2/RAD study): a collaboration of MITO, AIRO GYN, and MaNGO groups.

OBJECTIVE: This retrospective, multicenter study analyzes the efficacy and safety of stereotactic body radiotherapy in a large cohort of patients with oligometastatic/persistent/recurrent cervical cancer. METHODS: A standardized data collection from several radiotherapy centers that treated patients by stereotactic body radiotherapy between March 2006 and February 2021 was set up. Clinical and stereotactic body radiotherapy parameters were collected. Objective response rate was defined as a composite of complete and partial response, while clinical benefit included objective response rate plus stable disease. Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer and Common Terminology Criteria for Adverse Events scales were used to grade toxicities. The primary endpoints were the rate of complete response to stereotactic body radiotherapy, and the 2 year actuarial local control rate on a 'per lesion' basis. The secondary end points were progression-free survival and overall survival, as well as toxicity. RESULTS: A total of 83 patients with oligometastatic/persistent/recurrent cervical cancer bearing 125 lesions treated by stereotactic body radiotherapy at 15 different centers were selected for analysis. Of the sites of metastatic disease, lymph node metastases were most common (55.2%), followed by parenchyma lesions (44.8%). Median total dose was 35 Gy (range 10-60), in five fractions (range 1-10), with a median dose/fraction of 7 Gy (range 4-26). Complete, partial, and stable response were found in 73 (58.4%), 29 (23.2%), and 16 (12.8%) lesions, respectively, reaching 94.4% of the clinical benefit rate. Forty-six (55.4%) patients had a complete response. Patients achieving complete response on a 'per lesion' basis experienced a 2 year actuarial local control rate of 89.0% versus 22.1% in lesions not achieving complete response (p<0.001). The 2 year actuarial progression-free survival rate was 42.5% in patients with complete response versus 7.8% in patients with partial response or stable or progressive disease (p=0.001). The 2 year actuarial overall survival rate was 68.9% in patients with complete response versus 44.3% in patients with partial response or stable or progressive disease (p=0.015). Fifteen patients (18.1%) had mild acute toxicity, totaling 29 side events. Late toxicity was documented in four patients (4.8%) totaling seven adverse events. CONCLUSION: Our analysis confirmed the efficacy of stereotactic body radiotherapy in oligometastatic/persistent/recurrent cervical cancer patients. The low toxicity profile encourages the wider use of stereotactic body radiotherapy in this setting.

Single-isocenter versus multiple-isocenters for multiple lung metastases: Evaluation of lung dose.

BACKGROUND AND PURPOSE: A potential challenge in single-isocenter multi-lesion lung stereotactic body radiotherapy (SBRT) is that patient positioning is not based on each lesion individually, but on the average position of all lesions. This may lead to larger margins compared to treating with one isocenter per lesion, but increases workflow efficiency. The aim of this study was to investigate whether a single-isocenter technique leads to increased normal lung dose compared to a conventional multiple-isocenters technique. MATERIALS AND METHODS: A cohort of 15 NSCLC patients with two or three lesions previously treated with SBRT was subjected to treatment planning with a multiple-isocenter technique and a single-isocenter technique. For the latter, two margin approaches were evaluated: (1) identical margins for each internal target volume (ITV), assuming an average registration for all lesions in cone-beam CT (CBCT) positioning verification and (2) a smaller margin for the largest lesion, assuming an optimal registration for that lesion. For all 45 treatment plans, mean lung dose (MLD) and lungs-V20Gy were evaluated. The study was performed following RATING guidelines. RESULTS: The MLD was 4.9 ± 1.9 Gy (mean ± SD) for multiple-isocenters and 5.4 ± 2.1 Gy and 5.3 ± 2.2 Gy for single-isocenter approach 1 and 2, respectively. V20Gy was 5.5 ± 3.7%, 5.5 ± 3.2% and 5.4 ± 3.3%. A median [range] increase in MLD of 11.6% [-14.9 - 26.8] was observed when comparing single-isocenter treatment plans to those with multiple isocenters. V20Gy increased by 0.2 [-3.4 - 1.3] percentage points. CONCLUSION: A single-isocenter SBRT technique for lung patients with multiple targets results in clinically acceptable increases in normal lung dose.

Efficacy and safety of stereotactic body radiotherapy (SBRT) in oligometastatic/persistent/recurrent ovarian cancer: a prospective, multicenter phase II study (MITO-RT3/RAD).

BACKGROUND: Stereotactic body radiotherapy (SBRT) has shown promising results in the clinical setting of oligometastatic, persistent, or recurrent disease in several malignancies including ovarian cancer. PRIMARY OBJECTIVE: The MITO-RT3/RAD trial is a prospective, multicenter phase II study aimed at identifying potential predictors of response and clinical outcome after SBRT treatment. STUDY HYPOTHESIS: Radiotherapy delivered by pre-defined SBRT treatment schedules and shared constraints could improve the rate of complete response. TRIAL DESIGN: All patients accrued will be treated with a radiotherapy dose in the range of 30-50 Gy by 1, 3, or 5 SBRT daily fractions to all sites of active metastatic disease according to diagnostic imaging. Schedules of treatment and dose prescription have been established before considering target sites and healthy organ dose constraints. Follow-up and monitoring of side effects will be carried out every 3 months for the first year with imaging and clinical evalutation, and every 4 months within the second year; thereafter, surveillance will be carried out every 6 months. The best response on a per lesion basis will be evaluated by computed tomographic (CT) scan, positron emission tomography/CT, or magnetic resonance imaging in case of brain lesions, every 3 months. MAJOR INCLUSION/EXCLUSION CRITERIA: The study includes patients with oligometastatic, persistent, or recurrent ovarian cancer for which salvage surgery or other local therapies are not feasible due to any relative contra-indication to further systemic therapy because of serious co-morbidities, previous severe toxicity, unavailability of potentially active systemic therapy, or patient refusal. PRIMARY ENDPOINT: The primary endpoint of the study is the clinical complete response rate to SBRT by imaging on a per lesion basis. SAMPLE SIZE: Approximately 205 lesions will be treated (90 lymph nodes and 115 parenchyma lesions). ESTIMATED DATES FOR COMPLETING ACCRUAL AND PRESENTING RESULTS: Fifty-two centers have expressed their intention to participate. Enrollment should be completed by March 2023 and analysis will be completed in September 2023. TRIAL REGISTRATION: NCT04593381.

Incidental axillary dose delivery to axillary lymph node levels I-III by different techniques of whole-breast irradiation: a systematic literature review.

BACKGROUND AND OBJECTIVE: In breast cancer treatment, radiotherapy is an essential component for locoregional management. Axillary recurrence in patients with invasive breast carcinoma remains an issue. The question of whether breast irradiation may unintentionally include levels I, II, and III, and may decrease the risk of axillary recurrence, remains a topic of discussion. PATIENTS AND METHODS: A literature search was performed in PubMed and the Cochrane Library to identify articles that have published data regarding dose-volume analysis of axillary levels in breast irradiation. The following MESH terms were used: "breast cancer/lymph nodes" AND "radiotherapy dosage." RESULTS: Thirteen articles were identified. The irradiation technique, initial dose prescribed to the breast, delineated volumes, and dose received at axillary levels were heterogeneous. The average dose delivered to axilla levels I, II, and III with three-dimensional conformal radiotherapy using standard fields (ST) ranged between 22 and 43.5 Gy, 3 and 35.6 Gy, and 1.0 and 20.5 Gy, respectively. The average doses delivered to axilla levels I, II, and III with three-dimensional conformal radiotherapy using "high tangential" fields (HT) ranged between 38 and 49.7 Gy, 11 and 47.1 Gy, and 5 and 44.7 Gy, respectively. Finally, the average doses delivered to axilla levels I, II, and III using intensity-modulated radiation therapy (IMRT) were between 14.5 and 42.6 Gy, 3.4 and 35 Gy, and 1.2 and 25.5 Gy, respectively. CONCLUSION: Our literature review suggests that the incidental dose delivered to the axilla during whole-breast irradiation is heterogenous and dependent on the irradiation technique used. However, whether this observation can be translated into a therapeutic effect is still a matter of debate.

Quantification of the uncertainties within the radiotherapy dosimetry chain and their impact on tumour control.

BACKGROUND AND PURPOSE: Dose delivered during radiotherapy has uncertainty arising from a number of sources including machine calibration, treatment planning and delivery and can impact outcomes. Any systematic uncertainties will impact all patients and can continue for extended periods. The impact on tumour control probability (TCP) of the uncertainties within the radiotherapy calibration process has been assessed. MATERIALS AND METHODS: The linear-quadratic model was used to simulate the TCP from two prostate cancer and a head and neck (H&N) clinical trial. The uncertainty was separated into four components; 1) initial calibration, 2) systematic shift due to output drift, 3) drift during treatment and 4) daily fluctuations. Simulations were performed for each clinical case to model the variation in TCP present at the end of treatment arising from the different components. RESULTS: Overall uncertainty in delivered dose was +/-2.1% (95% confidence interval (CI)), consisting of uncertainty standard deviations of 0.7% in initial calibration, 0.8% due to subsequent calibration shift due to output drift, 0.1% due to drift during treatment, and 0.2% from daily variations. The overall uncertainty of TCP (95% CI) for a population of patients treated on different machines was +/-3%, +/-5%, and +/-3% for simulations based on the two prostate trials and H&N trial respectively. CONCLUSION: The greatest variation in delivered target volume dose arose from calibration shift due to output drift. Careful monitoring of beam output following initial calibration remains vital and may have a significant impact on clinical outcomes.

Optimal stereotactic body radiotherapy dosage for hepatocellular carcinoma: a multicenter study.

BACKGROUND: The optimal dose and fractionation scheme of stereotactic body radiation therapy (SBRT) for hepatocellular carcinoma (HCC) remains unclear due to different tolerated liver volumes and degrees of cirrhosis. In this study, we aimed to verify the dose-survival relationship to optimize dose selection for treatment of HCC. METHODS: This multicenter retrospective study included 602 patients with HCC, treated with SBRT between January 2011 and March 2017. The SBRT dosage was classified into high dose, moderate dose, and low dose levels: SaRT (BED10 ≥ 100 Gy), SbRT (EQD2 > 74 Gy to BED10 < 100 Gy), and ScRT (EQD2 < 74 Gy). Overall survival (OS), progression-free survival (PFS), local control (LC), and intrahepatic control (IC) were evaluated in univariable and multivariable analyses. RESULTS: The median tumor size was 5.6 cm (interquartile range [IQR] 1.1-21.0 cm). The median follow-up time was 50.0 months (IQR 6-100 months). High radiotherapy dose correlated with better outcomes. After classifying into the SaRT, SbRT, and ScRT groups, three notably different curves were obtained for long-term post-SBRT survival and intrahepatic control. On multivariate analysis, higher radiation dose was associated with improved OS, PFS, and intrahepatic control. CONCLUSIONS: If tolerated by normal tissue, we recommend SaRT (BED10 ≥ 100 Gy) as a first-line ablative dose or SbRT (EQD2 ≥ 74 Gy) as a second-line radical dose. Otherwise, ScRT (EQD2 < 74 Gy) is recommended as palliative irradiation.

Assessment of Thyroid Lobe Dose in Breast Cancer Intraoperative Radiotherapy.

BACKGROUND: Breast cancer is the most common cancer among women. Considering the fact that a high dose is delivered in a single fraction of IORT, the evaluation of the dose at sensitive organs like thyroid is necessary. OBJECTIVE: The current study has aimed to evaluate the received dose to thyroid lobes in the breast IORT technique. MATERIAL AND METHODS: A total of 49 women with breast cancer undergoing IORT were enrolled in this cross-sectional study with census sampling. Immediately after tumor resection, a single dose of 20 Gray at the applicator surface was delivered using 50KV X-ray by an Intrabeam machine. The thyroid dose was detected using thermoluminescent detectors (TLD) 100 at the mid-thyroid line, left and right lobes. RESULTS: The dose at the right and left lobes of the thyroid gland as well as the mid-thyroid line was found to be 40.18±35.44 mGy, 35.50±27.32 mGy, and 40.61±32.47 mGy, respectively. The right lobe received a significantly higher absorbed dose compared to the left lobe when the right breast was under IORT treatment. The same trend was seen with the left lobe and left breast under IORT treatment (P=0.0001 and P=0.018, respectively). The applicator size showed non-significant effects on the absorbed dose at the thyroid gland. Also, the applicator depth had a non-significant inverse effect on thyroid dose. CONCLUSION: According to our findings, the absorbed dose at each thyroid lobe depends on the under-treatment side as well as the applicator size and depth (applicator upper surface distance from the skin).

Radiotherapy dose escalation on pelvic lymph node control in patients with cervical cancer.

OBJECTIVE: Data supporting dose escalation for node-positive cervical cancer are currently limited to small retrospective studies. The goal of this study was to assess whether radiation dose was associated with lymph node control or gastrointestinal toxicity in patients with node-positive cervical cancer. METHODS: A total of 390 patients with carcinoma of the uterine cervix were treated between October 1997 and October 2017. Patients included in our analysis were those with squamous cell carcinoma or adenocarcinoma who were node-positive, treated definitively, and with at least one follow-up visit and post-treatment imaging scan. We excluded those without follow-up and those treated with palliative intent. All patients were treated with external beam radiation to pelvic±para-aortic fields with concurrent weekly cisplatin. All lymph nodes present at the time of treatment were stratified by size as <2 cm or ≥2 cm. Acute and late gastrointestinal toxicity were recorded for all patients. RESULTS: A total of 77 patients with 206 lymph nodes were identified. Median stage at presentation was FIGO IIB. Thirteen patients underwent definitive surgical resection followed by adjuvant radiation, of which 12 were treated to doses ≤5040 (range 2700-5940) cGy. Sixty-four patients were treated with definitive chemoradiation, of which 42 (66%) received ≤5040 (range 4500-5040) cGy and 22 (34%) received >5040 (range 5300-6640) cGy. Patients with pre-chemoradiation lymph nodes ≥2 cm had inferior lymph node control compared with patients with pre-chemoradiation lymph node <2 cm at 12 months (77% vs 100%, p=0.002). Radiation dose >5040 cGy was not significantly associated with improved lymph node control compared with ≤5040 cGy when analyzing all patients (12 months, 100% vs 89%, p=0.112). In patients with pre-chemoradiation lymph nodes ≥2 cm, radiation dose >5040 cGy was associated with improved lymph node control (12 months, 100% vs 60%, p=0.020). Acute grade ≥2 gastrointestinal toxicity was not associated with radiation dose >5040 cGy (20% vs 13%, p=0.424). Two patients developed grade ≥2 late gastrointestinal toxicity, both of whom were treated to ≤5040 cGy. CONCLUSIONS: This series supports the role of dose escalation for patients with lymph nodes ≥2 cm. Dose escalation is associated with improved control in patients with larger lymph nodes, and is not associated with greater gastrointestinal toxicity.