Radiotherapy Fractionation Research Articles

Privacy-friendly evaluation of patient data with secure multiparty computation in a European pilot study

In multicentric studies, data sharing between institutions might negatively impact patient privacy or data security. An alternative is federated analysis by secure multiparty computation. This pilot study demonstrates an architecture and implementation addressing both technical challenges and legal difficulties in the particularly demanding setting of clinical research on cancer patients within the strict European regulation on patient privacy and data protection: 24 patients from LMU University Hospital in Munich, Germany, and 24 patients from Policlinico Universitario Fondazione Agostino Gemelli, Rome, Italy, were treated for adrenal gland metastasis with typically 40 Gy in 3 or 5 fractions of online-adaptive radiotherapy guided by real-time MR. High local control (21% complete remission, 27% partial remission, 40% stable disease) and low toxicity (73% reporting no toxicity) were observed. Median overall survival was 19 months. Federated analysis was found to improve clinical science through privacy-friendly evaluation of patient data in the European health data space.

Hypofractionated versus standard fractionation radiotherapy for merkel cell carcinoma

Purpose/Objective(s)Merkel cell carcinoma (MCC) radiation treatment has historically consisted of standard 1.8–2 Gy fractions treated daily over 4–6 weeks. Hypofractionated treatment regimens have demonstrated tumor control and toxicity equivalence to standard fractionation regimens for common cutaneous malignancies such as basal cell and squamous cell carcinomas. Herein we report the outcomes of hypofractionated versus standard fractionation radiotherapy for MCC at our institution.Materials/MethodsThe study involved a retrospective review of MCC patients treated with radiotherapy. Treatment characteristics and patient outcomes, including acute toxicities, disease recurrence and survival data were collected. The cumulative incidence of local and distant failures was estimated, with death as a competing risk.ResultsA total of 29 treatment courses for 24 patients were included, of which 13 involved standard fractionation with curative intent, 10 involved hypofractionated radiotherapy with curative intent, and 6 involved single fraction (8 Gy) palliative radiation. Half the patients were treated to a head/neck site. A subset of patients treated adjuvantly with curative intent included 8 standard fractionation and 8 hypofractionated radiotherapy patients. No statistically significant differences in local and/or distant failure or overall survival was observed between the patient groups.ConclusionHypofractionated radiotherapy for MCC was associated with similar treatment outcomes relative to standard fractionation. In our limited patient sample, hypofractionated radiation treatment achieved similar results with similar toxicity and fewer treatments. Further analysis of a larger patient population with longer follow up is needed to confirm treatment tolerability and efficacy.

Phase-change ultrasound contrast agents for proton range verification: towards an in vivo application

Objective.In proton therapy, range uncertainties prevent optimal benefit from the superior depth-dose characteristics of proton beams over conventional photon-based radiotherapy. To reduce these uncertainties we recently proposed the use of phase-change ultrasound contrast agents as an affordable and effective range verification tool. In particular, superheated nanodroplets can convert into echogenic microbubbles upon proton irradiation, whereby the resulting ultrasound contrast relates to the proton range with high reproducibility. Here, we provide a firstin vivoproof-of-concept of this technology.Approach.First, thein vitrobiocompatibility of radiation-sensitive poly(vinyl alcohol) perfluorobutane nanodroplets was investigated using several colorimetric assays. Then,in vivoultrasound contrast was characterized using acoustic droplet vaporization (ADV) and later using proton beam irradiations at varying energies (49.7 MeV and 62 MeV) in healthy Sprague Dawley rats. A preliminary evaluation of thein vivobiocompatibility was performed using ADV and a combination of physiology monitoring and histology.Main results.Nanodroplets were non-toxic over a wide concentration range (<1 mM). In healthy rats, intravenously injected nanodroplets primarily accumulated in the organs of the reticuloendothelial system, where the lifetime of the generated ultrasound contrast (<30 min) was compatible with a typical radiotherapy fraction (<5 min). Spontaneous droplet vaporization did not result in significant background signals. Online ultrasound imaging of the liver of droplet-injected rats demonstrated an energy-dependent proton response, which can be tuned by varying the nanodroplet concentration. However, caution is warranted when deciding on the exact nanodroplet dose regimen as a mild physiological response (drop in cardiac rate, granuloma formation) was observed after ADV.Significance.These findings underline the potential of phase-change ultrasound contrast agents forin vivoproton range verification and provide the next step towards eventual clinical applications.

State opioid prescribing laws and associations with radiotherapy delays and radiotherapy completion.

122 Background: In July 2018, Missouri introduced a 7-day limit for initial opioid prescriptions, though there was an exemption for cancer-related pain. However, some worry that the exemptions may be inadequate for patients with cancer who experience cancer-related pain. Since some courses of radiotherapy can cause pain (eg, mucositis, esophagitis), appropriate opioid access is important for helping patients complete radiotherapy in a timely manner, which is associated with oncologic outcomes. Methods: Patients with cancer of all ages treated with radiotherapy from 2018-2019 at a large academic institution in Missouri were identified. More recent data were excluded due to the COVID-19 pandemic and Missouri Medicaid expansion. Trends over time in the proportion of missed/delayed radiotherapy fractions, incomplete radiotherapy courses, and a composite measure of excessive delays (≥5 days) or incomplete course were evaluated in linear and linear probability models. Additional analyses included patients from Illinois, an adjacent state without opioid prescribing legislation, and we subsequently performed difference-in-differences analyses comparing the outcomes from pre- to post- Missouri opioid legislation between the states. We conducted unadjusted analyses as well as analyses adjusted for age, sex, site, radiotherapy modality and fractions, as well as other covariates that could impact access to radiotherapy (ZIP code deprivation, distance from the facility, insurance status, and social work referral for unmet needs). Subgroup analyses focused on patients with head and neck cancer and lung cancer receiving definitive radiotherapy, who are at high risk of radiotherapy-related pain. Results: A total of 2613 and 1518 patients from Missouri and Illinois were identified, respectively. 4.7% of fractions were missed/delayed, 3.7% of patients did not complete treatment, and 8.1% of patients had either an incomplete course or excessive delays. There were no statistically significant increases (ie, worsening) in any outcome in any quarter after opioid policy implementation, and there were significant decreases in the composite outcome in multiple post-policy quarters in both unadjusted and adjusted analyses. In difference-in-differences analyses comparing trends over time with patients from Illinois, there were no significant associations of policy implementation with any of the outcomes. Results were similar in subgroup analyses for patients with head and neck and lung cancers. Conclusions: Missouri legislation limiting opioid prescribing for non-cancer-related pain was not associated with significant changes in a patient’s ability to undergo radiotherapy. Limitations of the study include evaluation of a single center in a single state and the lack of other intermediate outcomes important to patients including access to opioid medication itself, which we will examine in future work.

Response Of Radiation Therapy Between 30 Gy In 10 Fractions Versus 20 Gy In 5 Fractions In The Management Of Bony Metastasis

Background: Bone metastases are a common complication of advanced-stage cancers, particularly affecting patients with lung, breast, and prostate cancers. Palliative radiotherapy is a primary modality used to alleviate pain and improve quality of life. This study aimed to compare the efficacy and toxicity of two radiotherapy fractionation schedules—20 Gy in 5 fractions versus 30 Gy in 10 fractions—in managing bone metastases in a resource-limited setting. Methods: This prospective, quasi-experimental study was conducted at the National Institute of Cancer Research and Hospital in Dhaka, Bangladesh, from July 2014 to December 2014. A total of 60 patients were divided into two arms: Arm A received 20 Gy in 5 fractions, and Arm B received 30 Gy in 10 fractions. Radiological and laboratory investigations were conducted pre- and post-treatment, and toxicity was monitored. Patient responses were assessed using RECIST version 2.0 criteria. Results: Complete response was achieved in 60.00% of Arm A patients and 66.67% of Arm B patients. Partial responses were observed in 36.67% of patients in Arm A and 33.33% in Arm B. Genitourinary toxicity was significantly higher in Arm A (p = 0.003), while skin toxicity resolved in all patients after 3 months. SGPT levels were significantly higher in Arm B both after 1 month (p = 0.001) and 3 months (p = 0.001). Conclusion: Both fractionation schedules were effective in managing bone metastases, with comparable pain relief and response rates. However, toxicity profiles differed, highlighting the importance of individualized treatment planning, especially in resource-limited settings.

Radiotherapy-associated Sensorineural Hearing Loss in Pediatric Oncology Patients.

During the radiotherapeutic treatment of pediatric oncology patients, they would be at a latent risk of developing ionizing radiation-induced ototoxicity when the cochlea or auditory nerve is located within the radiation field. Sensorineural hearing loss (SNHL) is an irreversible late complication of radiotherapy, and its incidence depends on various factors such as the patient's hearing sensitivity, total radiation dose to the cochlea, radiotherapy fractionation regimen, age and chemoradiation. Importantly, this complication exhibits serious challenges to adult survivors of childhood cancer, as it has been linked to impairments in academic achievement, psychosocial development, independent living skills, and employment in the survivor population. Therefore, early detection and proper management can alleviate academic, speech, language, social, and psychological morbidity arising from hearing deficits. In the present review, we have addressed issues such as underlying mechanisms of radiation-induced SNHL, audiometric findings of pediatric cancer patients treated with radiotherapy, and management and protection measures against radiation-induced ototoxicity.

Lymphopenia Induced by Different Neoadjuvant Chemo-Radiotherapy Schedules in Patients with Rectal Cancer: Bone Marrow as an Organ at Risk.

Radiotherapy (RT)-induced lymphopenia may hinder the anti-tumor immune response. Preoperative RT or chemo-RT (CRT) for locally advanced rectal cancer is a standard therapeutic approach, while immunotherapy has been approved for mismatch repair-deficient rectal tumors. We retrospectively analyzed 98 rectal adenocarcinoma patients undergoing neoadjuvant CRT with VMAT (groups A, B, C) or IMRT (group D) techniques, with four different RT schemes: group A (n = 24): 25 Gy/5 Gy/fraction plus a 0.2 Gy/fraction rectal tumor boost; group B (n = 22): 34 Gy/3.4 Gy/fraction, with a 1-week treatment break after the first five RT fractions; group C (n = 20): 46 Gy/2 Gy/fraction plus a 0.2 Gy/fraction rectal tumor boost; group D (n = 32): 45 Gy/1.8 Gy/fraction followed by 5.4 Gy/1.8 Gy/fraction to the rectal tumor. We examined the effect of the time-corrected normalized total dose (NTD-T) to the BM on lymphopenia. Groups A and B (hypofractionated RT) had significantly higher lymphocyte counts (LCs) after RT than groups C and D (p < 0.03). An inverse association between the LCs after RT and NTD-T was demonstrated (p = 0.01). An NTD-T threshold of 30 Gy delivered to 30% of the BM volume emerged as a potential constraint for RT planning, which could be successfully integrated in the RT plan. Hypofractionated and accelerated RT schemes, and BM-sparing techniques may reduce lymphocytic damage and prove critical for immuno-RT clinical trials.

Localized Radiotherapy for Classic Kaposi's Sarcoma: An Analysis of Lesion Characteristics and Treatment Response.

Classic Kaposi's sarcoma (CKS) is a rare malignancy with diverse clinical presentations, lacking a standard treatment. While localized therapies are commonly used for symptomatic lesions, radiotherapy (RT) has demonstrated effectiveness. This study aims to evaluate the efficacy of RT for treating skin lesions in CKS. A retrospective analysis was conducted on patients with KS treated between April 2012 and January 2024. In total, 69 lesions in 16 patients were included. Treatment response was defined as follows: complete response (CR) indicated the absence of clinically detectable skin lesions and symptoms; partial response (PR) was a reduction in lesion height by more than half or a lighter lesion color compared to before treatment. In-field recurrence was the appearance of new lesions within a previously irradiated field. Logistic regression analysis was used to investigate factors influencing response and in-field recurrence. The median follow-up period was 52 months (range, 3-138 months). The overall response rate was 100%, with 92.8% of the patients achieving CR and 7.2% receiving PR. PR was observed in three patients with five lesions, all of which remained stable. In-field recurrence occurred in two patients with initially advanced disease, and all recurrent lesions responded to RT. No variables were significantly associated with response or in-field recurrence. RT for CKS showed a 100% response rate, with complete symptom relief in all cases. The effectiveness of RT was evident, even in cases involving disseminated lesions. Further research is needed to determine the optimal RT dose and fractionation.

Impact of kV-cone beam computed tomography dose on DNA repair mechanisms: A pilot study

PurposeIn head and neck squamous cell carcinoma (HNSCC), early complications of the radiotherapy (RT) are observed from the beginning of the treatment to a few months after its end. During external radiotherapy treatment, several patient-dependent parameters can cause a modification of the dose distribution compared to the planned distribution due to variation in patient positioning, anatomy, or intra-fractional movements for example. To verify these parameters during treatment sessions, one of the most commonly used solutions is the cone-beam computed tomography (CBCT). Nowadays, the use of CBCT may constitutes a significant part of the total dose at the end of treatment (up to 10 cGy per session) and more often the volume irradiated by imaging is larger than the one irradiated by the treatment, leading to unintentional irradiation of nearby organs.In this study, we asked whether the imaging low dose added to a following fraction dose (2Gy) may affect the biological response in terms of DNA repair. Material and methodsUsing an IVInomad dosimeter and scintillating fiber probes specially designed for this exploratory study, we exposed fibroblasts cells from head and neck cancer (HNC) patients to a CBCT dose followed by a radiotherapy fraction dose. DNA double strand breaks and DNA repair were assessed by immunofluorescence using the biomarkers gamma H2AX (γH2AX) and pATM. ResultsThe median dose of CBCT was measured between 17 to 21 mGy per session. The kinetics of both biomarkers were found to be strongly dependent on the individual factor in radiosensitive patients. For HNC patients, a prior CBCT dose applied few minutes before the 2Gy dose may have a sublinear effect on the DNA repair mechanisms and potentially on observed health tissue toxicity. ConclusionThe preliminary results obtained highlight the importance of individual and tissue factors for recognizing and repairing DSB during a treatment by radiotherapy using CBCT.

Is intensive training with atime interval between instruction and planning CT necessary for deep inspiration breath-hold radiotherapy in breast cancer?

Breathing instruction and exercises and atime gap between training and planning CT scans (pCT) is recommended as part of deep inspiration breath-hold (DIBH) assisted radiotherapy (RT). However, this is associated with additional time expenditure. In two of the authors' treatment centers (TC), patient training took place before the planning CT of DIBH-assisted therapy. In TC1, afurther appointment was made with aminimum interval of 2days to perform the planning CT. At TC2, the planning CT was performed immediately after the first patient instruction. Aretrospective evaluation of the clinical parameters of the therapy was carried out to investigate the relevance of the time gap between DIBH exercises and pCT. Atotal of 72patients were included, 35 of whom were treated in TC1 and37 in TC2. In TC1, an average interval of ~4 days was observed between patient training and planning CT, while in TC2, training and CT were performed immediately after each other. No significant differences in radiation dose exposure of the lung on the treated side, the whole lung, or the heart were found between the two centers. Furthermore, there was no significant difference in the application of the daily RT fraction. The requirement for daily positioning checks was also the same at both treatment centers. This study does not show any advantages for atime gap between instruction/training and pCT. Skipping the time break does not deteriorate any clinically relevant endpoints.

Cherenkov imaging combined with scintillation dosimetry provides real-time positional and dose monitoring for radiotherapy patients with cardiac implanted electronic devices

Background and purposeCardiac implanted electronic devices (CIED) require dose monitoring during each fraction of radiotherapy, which can be time consuming and may have delayed read-out times. This study explores the potential of Cherenkov imaging combined with scintillation dosimetry as an alternative verification system. Methods and materialsTime-gated, complementary metal–oxide–semiconductor (iCMOS) cameras were used to collect video images of anthropomorphic phantoms and patients undergoing radiation treatment near chest wall cardiac devices. Scintillator discs and optically stimulated luminescence dosimeters (OSLDs) were used for dose measurement. Accuracy of spatial delivery was assessed by overlaying predicted surface dose outlines derived from the treatment planning system (TPS) with the Cherenkov images. Dose measurements from OSLDs and scintillators were compared. ResultsIn phantom studies, Cherenkov images visibly indicated when dose was delivered to the CIED as compared to non-overlapping dose deliveries. Comparison with dose overlays revealed congruence at the planned position and non-congruence when the phantom was shifted from the initial position. Absolute doses derived from scintillator discs aligned well with the OSLD measurements and TPS predictions for three different positions, measuring within 10 % for in-field positions and within 5 % for out-of-field positions. For two patients with CIEDs imaged over 18 fractions, Cherenkov imaging confirmed positional accuracy for all fractions, and dose measured by scintillator discs deviated by <0.015 Gy from the OSLD measurements. ConclusionsCherenkov imaging combined with scintillation dosimetry presents an alternative methodology for CIED monitoring with the added benefit of instantly detecting deviations, enabling timely corrective actions or proper patient triage.

An “Older Old” Woman with Large Squamous Cell Carcinoma of the Nasal Pyramid: Excellent Response to Ultra-Hypofractionated Radiation Therapy

A 98-year-old patient with cognitive impairment and a history of squamous cell carcinoma of the nasal pyramid was referred to the radiation oncology department of our institution’s hospital given that surgery was not recommended. The lesion was sized 6 × 6 cm, ulcerated, and bleeding; was significantly impairing the patient’s health-related quality of life, causing pain; and was not responsive to analgesics, including opioids. The patient experienced deterioration of her general conditions, with a Karnofsky performance status of 40. A single radiotherapy (RT) fraction was delivered on a weekly basis for 3 weeks, up to a total dose of 21 Gy, using a VMAT technique (7 Gy/fraction). The patient was given three fractions of radiotherapy, during which she received continuous assistance due to episodes of mental disorientation and an altered sense of consciousness. One month after the conclusion of the treatment, the patient exhibited a nearly complete clinical response, with full pain relief and an improved health-related quality of life. This favourable clinical outcome was maintained for a period of four months following the conclusion of RT. A brief review was performed on the role of hypofractionated radiation therapy in elderly patients with locally advanced skin cancer of the head and neck region.

High-dose hyperfractionated simultaneous integrated boost radiotherapy versus standard-dose radiotherapy for limited-stage small-cell lung cancer in China: a multicentre, open-label, randomised, phase 3 trial

For the past 20 years, twice-daily thoracic radiotherapy with concurrent chemotherapy has been the treatment of choice for limited-stage small-cell lung cancer (LS-SCLC), which has a poor prognosis. We aimed to assess the efficacy and safety of high-dose, accelerated, hyperfractionated, twice-daily thoracic radiotherapy (54 Gy in 30 fractions) versus standard-dose radiotherapy (45 Gy in 30 fractions) as a first-line treatment for LS-SCLC. This open-label, randomised, phase 3 trial was performed at 16 public hospitals in China. The key inclusion criteria were patients aged 18-70 years, with histologically or cytologically confirmed LS-SCLC, who had an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, and who were previously untreated or had received one course of cisplatin or carboplatin and etoposide. Eligible patients were randomly assigned (1:1) to receive volumetric-modulated arc radiotherapy (VMAT) of 45 Gy in 30 fractions to the gross tumour volume or VMAT with a simultaneous integrated boost of 54 Gy in 30 fractions to the gross tumour volume starting 0-42 days after the first chemotherapy course. Both groups received 10 fractions of twice-daily thoracic radiotherapy per week. The planning target volume was 45 Gy in 30 fractions in both groups. Patients with responsive disease received prophylactic cranial radiotherapy (25 Gy in 10 fractions). Randomisation was performed using a centralised interactive web response system, stratified by ECOG performance status, disease stage, previous chemotherapy course, and chemotherapy choice. The primary outcome was overall survival in the intention-to-treat population. Safety was analysed in the as-treated population. This study was registered at ClinicalTrials.gov, NCT03214003. From June 30, 2017, to April 6, 2021, 224 patients (102 [46%] females and 122 [54%] males; median age 64 years [IQR 58-68]) were enrolled and randomly assigned to the 54 Gy group (n=108) or 45 Gy (n=116) group. The median follow-up was 46 months (IQR 33-56). The median overall survival was significantly longer in the 54 Gy group (60·7 months [95% CI 49·2-62·0]) than in the 45 Gy group (39·5 months [27·5-51·4]; hazard ratio 0·55 [95% CI 0·37-0·72]; p=0·003). Treatment was tolerable, and the chemotherapy-related and radiotherapy-related toxicities were similar between the groups. The grade 3-4 radiotherapy toxicities were oesophagitis (14 [13%] of 108 patients in the 54 Gy group vs 14 [12%] of 116 patients in the 45 Gy group; p=0·84) and pneumonitis (five [5%] of 108 patients vs seven [6%] of 116 patients; p=0·663). Only one treatment-related death occurred in the 54 Gy group (myocardial infarction). The study was prematurely terminated by an independent data safety monitoring board on April 30, 2021, based on evidence of sufficient clinical benefit. Compared with standard-dose thoracic radiotherapy (45 Gy), high-dose radiotherapy (54 Gy) improved overall survival without increasing toxicity in a cohort of patients aged 18-70 years with LS-SCLC. Our results support the use of twice-daily accelerated thoracic radiotherapy (54 Gy) with concurrent chemotherapy as an alternative first-line LS-SCLC treatment option. Chinese Society of Clinical Oncology-Linghang Cancer Research, the Wu Jieping Medical Foundation, and Clinical Research Fund For Distinguished Young Scholars of Peking University Cancer Hospital and Beijing Municipal Administration of Hospitals Incubating Program.

First implementation of artificial intelligence empowered all-in-one radiotherapy workflow for nasopharyngeal carcinoma.

134 Background: To establish an artificial intelligence (AI)-empowered All-In-One (AIO) workflow for providing one-stop radiotherapy to patients with nasopharyngeal carcinoma (NPC), and evaluate its feasibility and performance. Methods: The NPC-specific AIO workflow operates on a CT-integrated linac and integrates AI contouring and AI planning modules. A 3D U-net was employed for contours generation and 3D dose distribution. Knowledge-based planning approach and a protocol-based approach were used for plan optimization. MRI datasets with contours of primary gross tumors, CT datasets with contours of targets and organs at risk, and radiotherapy treatment planning datasets were collected from 877, 139, and 243 patients, respectively, for the training, validation, and testing of AI contouring and planning models. The NPC-specific AIO workflow underwent real-world clinical testing with an end-to-end evaluation involving 120 patients with NPC. The technical characteristics, implementation procedures and performance of AIO workflow were described and evaluated. Results: From March 2022 to October 2023, 120 patients with newly-diagnosed, non-metastatic NPC underwent AIO workflow, and 117 patients completed it in a median time of 23.2 min (range: 16.3 to 45.8 min). Median translation motions were 0.2 mm (CT scan to planning approval) and 0.1 mm (during beam delivery). AI-generated contours required little revision for clinical target volume (CTV1) and organs at risk (OARs), minor revision for cervical lymph nodes (GTVn) and clinical target volume (CTV2), with median Dice similarity coefficients (DSCs) of 0.98 and 0.94, respectively; more revision for GTVp, with a median DSC of 0.84. Of the 117 AI-generated plannings, 108 (92.3%) passed after initial auto-optimization. Volumes receiving ≥ 100% of the prescribed dose for all planning target volumes was ≥ 97.8%. Mean dosimetric parameters met dose constraints for all OARs except the thyroid and submandibulars. One patient died from acute renal failure after 10 fractions of radiotherapy. At week 12 after radiotherapy completion, 115 patients achieved complete response;1 had stable disease. Grade 3-4 acute effects were reported by 54 of 115 patients (36%). Conclusions: We successfully established an AI-empowered AIO workflow for initial radiotherapy of NPC, confirming its feasibility and safety for clinical application.

Correlation between dose-volume parameters and rectal bleeding after 12 fractions of carbon ion radiotherapy for prostate cancer.

Carbon ion radiotherapy (CIRT) is currently used to treat prostate cancer. Rectal bleeding is a major cause of toxicity even with CIRT. However, to date, a correlation between the dose and volume parameters of the 12 fractions of CIRT for prostate cancer and rectal bleeding has not been shown. Similarly, the clinical risk factors for rectal bleeding were absent after 12 fractions of CIRT. To identify the risk factors for rectal bleeding in 12 fractions of CIRT for prostate cancer. Among 259 patients who received 51.6 Gy [relative biological effectiveness (RBE)], in 12 fractions of CIRT, 15 had grade 1 (5.8%) and nine had grade 2 rectal bleeding (3.5%). The dose-volume parameters included the volume (cc) of the rectum irradiated with at least x Gy (RBE) (Vx) and the minimum dose in the most irradiated x cc normal rectal volume (Dx). The mean values of D6cc, D2cc, V10 Gy (RBE), V20 Gy (RBE), V30 Gy (RBE), and V40 Gy (RBE) were significantly higher in the patients with rectal bleeding than in those without. The cutoff values were D6cc = 34.34 Gy (RBE), D2cc = 46.46 Gy (RBE), V10 Gy (RBE) = 9.85 cc, V20 Gy (RBE) = 7.00 cc, V30 Gy (RBE) = 6.91 cc, and V40 Gy (RBE) = 4.26 cc. The D2cc, V10 Gy (RBE), and V20 Gy (RBE) cutoff values were significant predictors of grade 2 rectal bleeding. The above dose-volume parameters may serve as guidelines for preventing rectal bleeding after 12 fractions of CIRT for prostate cancer.

Mechanistic in silico explorations of the immunogenic and synergistic effects of radiotherapy and immunotherapy: a critical review.

Immunotherapy is a rapidly evolving field, with many models attempting to describe its impact on the immune system, especially when paired with radiotherapy. Tumor response to this combination involves a complex spatiotemporal dynamic which makes either clinical or pre-clinical in vivo investigation across the resulting extensive solution space extremely difficult. In this review, several in silico models of the interaction between radiotherapy, immunotherapy, and the patient's immune system are examined. The study included only mathematical models published in English that investigated the effects of radiotherapy on the immune system, or the effect of immuno-radiotherapy with immune checkpoint inhibitors. The findings indicate that treatment efficacy was predicted to improve when both radiotherapy and immunotherapy were administered, compared to radiotherapy or immunotherapy alone. However, the models do not agree on the optimal schedule and fractionation of radiotherapy and immunotherapy. This corresponds to relevant clinical trials, which report an improved treatment efficacy with combination therapy, however, the optimal scheduling varies between clinical trials. This discrepancy between the models can be attributed to the variation in model approach and the specific cancer types modeled, making the determination of the optimum general treatment schedule and model challenging. Further research needs to be conducted with similar data sets to evaluate the best model and treatment schedule for a specific cancer type and stage.

Long-Term Analysis of NRG Oncology RTOG 0415: A Randomized Phase III Noninferiority Study Comparing Two Fractionation Schedules in Patients With Low-Risk Prostate Cancer.

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.NRG Oncology RTOG 0415 is a randomized phase III noninferiority (NI) clinical trial comparing conventional fractionation (73.8 Gy in 41 fractions) radiotherapy (C-RT) with hypofractionation (H-RT; 70 Gy in 28) in patients with low-risk prostate cancer. The study included 1,092 protocol-eligible patients initially reported in 2016 with a median follow-up of 5.8 years. Updated results with median follow-up of 12.8 years are now presented. The estimated 12-year disease-free survival (DFS) is 56.1% (95% CI, 51.5 to 60.5) for C-RT and 61.8% (95% CI, 57.2 to 66.0) for H-RT. The DFS hazard ratio (H-RT/C-RT) is 0.85 (95% CI, 0.71 to 1.03), confirming NI (P < .001). Twelve-year cumulative incidence of biochemical failure (BF) was 17.0% (95% CI, 13.8 to 20.5) for C-RT and 9.9% (95% CI, 7.5 to 12.6) for H-RT. The HR (H-RT/C-RT) comparing biochemical recurrence between the two arms was 0.55 (95% CI, 0.39 to 0.78). Late grade ≥3 GI adverse event (AE) incidence is 3.2% (C-RT) versus 4.4% (H-RT), with relative risk (RR) for H-RT versus C-RT 1.39 (95% CI, 0.75 to 2.55). Late grade ≥3 genitourinary (GU) AE incidence is 3.4% (C-RT) versus 4.2% (H-RT), RR 1.26 (95% CI, 0.69 to 2.30). Long-term DFS is noninferior with H-RT compared with C-RT. BF is less with H-RT. No significant differences in late grade ≥3 GI/GU AEs were observed between assignments (ClinicalTrials.gov identifier: NCT00331773).

Tumor-Localized Interleukin-2 and Interleukin-12 Combine with Radiation Therapy to Safely Potentiate Regression of Advanced Malignant Melanoma in Pet Dogs.

Cytokines IL2 and IL12 exhibit potent anticancer activity but suffer a narrow therapeutic window due to off-tumor immune cell activation. Engineering cytokines with the ability to bind and associate with tumor collagen after intratumoral injection potentiated response without toxicity in mice and was previously safe in pet dogs with sarcoma. Here, we sought to test the efficacy of this approach in dogs with advanced melanoma. This study examined 15 client-owned dogs with histologically or cytologically confirmed malignant melanoma that received a single 9-Gy fraction of radiotherapy, followed by six cycles of combined collagen-anchored IL2 and IL12 therapy every 2 weeks. Cytokine dosing followed a 3 + 3 dose escalation design, with the initial cytokine dose chosen from prior evaluation in canine sarcomas. No exclusion criteria for tumor stage or metastatic burden, age, weight, or neuter status were applied for this trial. Median survival regardless of the tumor stage or dose level was 256 days, and 10/13 (76.9%) dogs that completed treatment had CT-measured tumor regression at the treated lesion. In dogs with metastatic disease, 8/13 (61.5%) had partial responses across their combined lesions, which is evidence of locoregional response. Profiling by NanoString of treatment-resistant dogs revealed that B2m loss was predictive of poor response to this therapy. Collectively, these results confirm the ability of locally administered tumor-anchored cytokines to potentiate responses at regional disease sites when combined with radiation. This evidence supports the clinical translation of this approach and highlights the utility of comparative investigation in canine cancers.

Evidence-based clinical recommendations for hypofractionated radiotherapy: exploring efficacy and safety - Part 3. Genitourinary and gynecological cancers.

Hypofractionated radiotherapy (RT) has become a trend in the modern era, as advances in RT techniques, including intensity-modulated RT and image-guided RT, enable the precise and safe delivery of high-dose radiation. Hypofractionated RT offers convenience and can reduce the financial burden on patients by decreasing the number of fractions. Furthermore, hypofractionated RT is potentially more beneficial for tumors with a low α/β ratio compared with conventional fractionation RT. Therefore, hypofractionated RT has been investigated for various primary cancers and has gained status as a standard treatment recommended in the guidelines. In genitourinary (GU) cancer, especially prostate cancer, the efficacy, and safety of various hypofractionated dose schemes have been evaluated in numerous prospective clinical studies, establishing the standard hypofractionated RT regimen. Hypofractionated RT has also been explored for gynecological (GY) cancer, yielding relevant evidence in recent years. In this review, we aimed to summarize the representative evidence and current trends in clinical studies on hypofractionated RT for GU and GY cancers addressing several key questions. In addition, the objective is to offer suggestions for the available dose regimens for hypofractionated RT by reviewing protocols from previous clinical studies.

Preclinical photon minibeam radiotherapy using a custom collimator: Dosimetry characterization and preliminary in-vivo results on a glioma model

PurposeThe purpose of this study is to investigate the dosimetric characteristics of a collimator for minibeam radiotherapy (MBRT) with film dosimetry and Monte Carlo (MC) simulations. The outcome of MBRT with respect to conventional RT using a glioma preclinical model was also evaluated. MethodsA multi-slit collimator was designed to be used with commercial small animal irradiator. The collimator was built by aligning 0.6 mm wide and 5 mm thick parallel lead leaves at 0.4 mm intervals. Dosimetry characteristics were evaluated by Gafchromic (CG) films and TOPAS Monte Carlo (MC) code.An in vivo experiment was performed using a glioma preclinical model by injecting two million GL261cells subcutaneously and treating with 25 Gy, single fraction, with MBRT and conventional RT. Survival curves and acute radiation damage were measured to compare both treatments. ResultsA satisfactory agreement between experimental results and MC simulations were obtained, the measured FWHM and distance between the peaks were respectively 0.431 and 1.098 mm.In vivo results show that MBRT can provide local tumor control for three weeks after RT treatment and a similar survival fraction of open beam radiotherapy. No severe acute effects were seen for the MBRT group. ConclusionsWe developed a minibeam collimator and presented its dosimetric features. Satisfactory agreement between MC and GC films was found with differences consistent with uncertainties due to fabrication and set-up errors. The survival curves of MBRT and open field RT are similar while atoxicity is dramatically lower with MBRT, preliminarily confirming the expected effect.