Fractionation Regimens Research Articles

Optimum radiation dose for palliation in head and neck squamous cell carcinoma (OpRAH) – A phase 3 randomized controlled trial

PurposeRadiotherapy is frequently employed for palliative treatment in locally advanced head and neck squamous cell carcinoma (HNSCC) but radiation dose fractionation regimens are not well-defined. We designed this phase 3 randomized controlled trial to compare two weekly hypo fractionated regimes and study the effect on progression-free survival (PFS) in this subset of patients. Materials and MethodsNon-metastatic locally advanced HNSCC patients (n = 305) who were not suitable for curative treatment were randomized to Arm A (20 Gy/5#/5 days) and Arm B (30 Gy/5#/5 days). PFS and OS were recorded along with acute toxicity using patient-reported quality of life HN QLQ 43. ResultsFrom April 2020 to August 2023, 390 patients were randomized, of which 305 were eligible for final analysis. At a median follow-up of 13.9 months, PFS and median overall survival (OS) for the entire cohort was 7.4 and 10.03 months, respectively. PFS (p-0.553) and OS (p-0.203) did not differ significantly between the two groups. Toxicity rates were similar between the two arms and dose escalation was well tolerated. Patients with a better PS were found to have significantly better OS. No significant benefit in OS or PFS was observed in patients who received neoadjuvant chemotherapy (NACT), underwent definitive conversion, or received palliative chemotherapy at progression. ConclusionThis is the largest phase 3 RCT to analyze the safety and efficacy of weekly palliative radiotherapy regimens and has not demonstrated further improvement with dose escalation

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.

Technical feasibility of delivering a simultaneous integrated boost in partial breast irradiation

Feasibility of volumetric modulated arc therapy (VMAT) for partial breast irradiation (PBI) with simultaneous integrated boost (SIB) to tumour bed was investigated. Four plans were created for 10 patients: 30 Gy/5 fractions, 26 Gy/5 fractions with 30 Gy SIB, 40.05 Gy/15 fractions, and 40.05 Gy/15 fractions with 48 Gy SIB. SIB in the 5 fraction arm had reduced ipsilateral breast dose relative to uniform dose. SIB in the 15 fraction arm had noninferior conformity compared to uniform dose. Addition of SIB did not increase other organ-at-risk doses or plan complexity. VMAT PBI with SIB was feasible for both fractionation regimens.

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.

Palliative Radiation Treatment in Patients Managed With Advanced/Interventional Pain Therapy such as Pump-delivered Continuous Opioids.

The study aim was to analyze the feasibility and efficacy of palliative radiotherapy in patients receiving advanced/interventional pain therapy, such as epidural or spinal anesthesia or subcutaneous pump delivery of opioids. Endpoints such as pain relief, treatment in the last month of life and survival were evaluated. Different baseline parameters including but not limited to age and Eastern Cooperative Oncology Group performance status (ECOG PS) were assessed. Outcomes were abstracted from electronic health records. The Edmonton Symptom Assessment System (ESAS) was utilized to score pain intensity. The study included 48 patients, 44 of whom completed radiotherapy as prescribed. Device malfunction was not observed. Overall, 31 patients (65%) had journal notes available allowing for evaluation of pain relief. Twenty-six of 31 experienced pain relief (54% in the intention-to-treat population of 48 study patients). Twelve patients (25%) stopped interventional pain therapy and were converted to transdermal or oral drugs. Median survival was 1.6 months. Forty-four percent had received radiotherapy during the last month of life. Sixty-four percent of patients with ECOG PS 3-4 had received radiotherapy during the last month of life, compared to 22% of those with ECOG PS <3, p=0.004. Palliative radiotherapy was feasible in this setting, but given the short median survival and high likelihood of treatment during the last month of life, patient selection and choice of fractionation regimen should be optimized. The record review identified several patients who experienced worthwhile pain relief, sometimes leading to conversion of pain therapy back to non-invasive oral or transdermal application.

Effect of consolidation radiation therapy on treatment outcomes of early-stage favorable Hodgkin lymphoma

Background. Early (stage I–II) classical Hodgkin lymphoma is a highly treatable malignant neoplasm. For many years, the standard treatment of early Hodgkin lymphoma has been combination therapy: polychemotherapy with subsequent consolidating radiation therapy. Aim. To retrospectively evaluate the results of treatment of stage I–II classical Hodgkin lymphoma in a favorable prognosis group using monotherapy and combination therapy (chemotherapy followed by consolidating radiotherapy). Materials and methods. The study included 58 patients aged 19–81 years (median age 36 years) diagnosed with stage I–II classical Hodgkin lymphoma with favorable prognosis; 23 (39.7 %) patients were men, 35 (60.3 %) were women. Depending on the treatment received, the patients were divided into two groups: 40 (69 %) patients received ABVD polychemotherapy, and 18 (31 %) patients received polychemotherapy followed by consolidating radiation therapy to the initial lesion zones with standard fractionation regimen (total dose 30 Gy). The Kaplan–Mayer method was used to evaluate overall, progression-free, recurrence-free, and event-free survival. Odds ratios and their 95 % confidence intervals were also calculated. The statistical significance of differences in survival was assessed using the log-rank test. The level of statistical significance was 0.05. Statistical data processing was carried out using the IBM SPSS Statistics 27 software and Microsoft Excel. Results. According to the results of our study, while in the total patient group a clear numerical advantage in survival (overall, progression-free, relapse-free and event-free survival) was observed in the combination therapy group compared to chemotherapy group (5.5, 13.2, 9.2 and 23.9 %, respectively), no preferred tactics were identified in the total patient group. However, considering a subgroup of patients with mediastinum involved in the tumor process, a statistically significant advantage of combined treatment over single-mode chemotherapy was determined for 2-year event-free survival (92.9 ± 6.9 % vs. 62.5 ± 9.9 %, respectively, p = 0.046). The risk of an adverse event is reduced by &gt;80 % (odds ratio 0.197; 95 % confidence interval 0.036–0.977) when using consolidating radiation therapy after chemotherapy.

1134: Search for the ideal palliative fractionation regimen in HNC : a single institutional experience.

1134: Search for the ideal palliative fractionation regimen in HNC : a single institutional experience.

Impact of Fractionation Regimen on Local Control Following Frameless Linear Accelerator-Based Image-Guided Stereotactic Radiosurgery and Radiotherapy for Intracranial Meningioma

ObjectivesStereotactic radiosurgery (SRS) is an established treatment for intracranial meningioma, yet this approach is often precluded by tumor size or proximity to critical structures. Fractionated radiotherapy may be employed to address these limitations. We performed a comparison of local control (LC) outcomes between three stereotactic techniques. MethodsA retrospective review was performed of 543 consecutive patients with 613 histologically-proven WHO grade I or radiographically-defined benign intracranial meningioma treated with SRS (median dose: 1250cGy) (n=211), fractionated SRS (FSRS) (2500cGy in 500cGy fractions) (n=170), or conventionally fractionated stereotactic radiotherapy (FSRT) (median dose: 5022cGy in <200cGy fractions) (n=232) in the definitive (n=475) or post-operative (n=138) setting between January 2008 and December 2021. Post-operative treatment was delivered upfront after a subtotal resection (n=43) or for recurrent disease (n=95). ResultsMedian follow-up per lesion was 8.0 years. LC for all lesions at 5/10/14 years was 97.4%/86.8%/86.8%. Base of skull location (p=0.01), tumor volume >5cc (p=0.01), and recurrent disease (p=0.02) were associated with inferior LC. No difference was observed in LC by fractionation regimen; LC at 5/10 years was 97.3%/85.7% for SRS, 97.5%/89.1% for FSRS, and 97.5%/86.3% for FSRT. Dose escalation above 1250cGy for SRS or above 5040cGy for FSRT did not result in improved LC. ConclusionsDurable LC was observed at long-term follow-up of intracranial meningioma treated with stereotactic radiosurgery and radiotherapy. LC outcomes were similar across the three fractionation regimens, suggesting that clinicians may tailor radiotherapy recommendations based on clinical factors without concern for reduced efficacy.

Hemostatic radiotherapy: a narrative review of the literature.

In locally advanced cancer, bleeding is a common clinical presentation and radiotherapy (RT) provides a noninvasive, well-tolerated, cost-effective treatment. However, the choice for fractionation dose and schedule seem to merely depend on physician's preference rather than specific guidelines. We reviewed the available literature on palliative hemostatic RT for response rate (RR) and bleeding duration in relation with the given dose. The PubMed database was used to search for articles, which were assessed by predetermined inclusion and exclusion criteria. A total of 54 articles, published over the last 20 years until December 2023 were analyzed for dose and/or fractionation regimen and their relation to the RR. A variety of fractionation schedules are used for palliative symptom control, including hemostasis. Research focusing on hemostatic irradiation specifically and prospective studies are rare. Moreover, to our knowledge, there are no specific (prospective) studies ongoing. Both external beam radiotherapy (EBRT) and brachytherapy lead to bleeding control and daily or weekly hypofractionated irradiation is safe and effective for both high and low biological equivalent dose (BED) regimens. If feasible, based on patient condition, some studies favor higher BED regimens to obtain more durable tumor/higher bleeding response. Higher radiation dose for thoracic irradiation may be indicative for simultaneous presentation of obstruction and/or dysphagia. Brachytherapy may be used solely or in combination with EBRT or in the setting of re-irradiation. Short-course regimens are preferred in patients in with low performance index scores. For future studies, multivariate analysis, including BED, can be important to assess efficacy of different fractionation schedules for a variety of tumor etiologies. Hemostatic RT, both by EBRT and brachytherapy, appears to be a safe and effective palliative treatment that clinically and statistically significantly reduces bleeding in cancer patients. The available literature is limited regarding prospective and uniform evaluation of hemostatic RT, including fractionation schedules. BED seems to be indicative for a better RR for specific indications. Current evidence suggests that treatment decisions should be tailored according to the patients' condition, tumor etiology and other clinical symptoms. More (prospective) research focusing on hemostasis is necessary to develop clear guidelines.

Randomized prospective trial comparing two schedules of hypofractionated adjuvant radiotherapy 3 weeks against 1 week fractionation regimen in females with breast cancer

Purpose Acceleration of radiotherapy in five fractions for breast cancer can improve treatment accessibility, especially in low, middle-income countries and during pandemics. We report on acute toxicity after whole breast irradiation/chest wall irradiation±nodal irradiation, radiotherapy interruption and reported acute pneumonitis with an ultra-hypofractionation schedule compared to modest hypofractionation protocol during the coronavirus disease pandemic. Patients and methods Acute toxicity assessment using the RTOG acute toxicity scoring system. One of two specified doses was administered to the breast: 15 × 2.67 Gy (40.05 Gy) or 5 × 5.2 Gy (26 Gy), tumor boost when indicated prescribed dose 5 × 200 Gy with three-dimensional conformal radiotherapy technique. Inclusion criteria were: T1–T3 invasive breast cancer, N0–N1 and N2 after breast conserving or modified radical surgery. Results A total of 101 patients were included in the study. Median age was 53 ± 10.29 years, with median follow-up time 14 months (12–20 months). A significant difference was observed for acute skin toxicity after radiotherapy in favor of better tolerability for the ultrafractionation schedule (P&lt;0.0001). None of the cases in ultra-hypofractionation had interrupted radiotherapy course for more than 2 days, on the other hand, 45.8% of the cases in modest hypofractionation had interrupted course with chest infection as the second most common cause. Regarding acute radiation pneumonitis none of the cases in both arms reported grades 3–4 acute radiation pneumonitis within the first 90 days postradiotherapy. Conclusion Regarding initial toxicity and patient adherence to the radiation course, this single institute study suggests that hypofractionated breast irradiation in 15 fractions compares favorably to accelerated breast radiotherapy in five fractions over 5 days. However, a longer time for follow-up and larger enrolled numbers are needed to confirm noninferiority of this approach.

Tumor Control and Normal Tissue Complications in High-dose-rate Brachytherapy for Cervical Cancer Patients Using Ir-192 Radioactive Source.

The purpose of the study was to calculate, tumor control probability (TCP) and normal tissue complication probability (NTCP) in cervical cancer patients and to clinically correlate the outcomes with a follow-up period of 24 months. One hundred and fifty patients were included in the present study who received 46 Gy/23 fractions/4½ weeks of external beam radiotherapy with concurrent cisplatin chemotherapy, followed by intracavitary brachytherapy of 3 different fractionations regimens, i.e., 9.5 Gy per fraction of two fractions (50 patients in Arm1), 7.5 Gy per fraction of three fractions (50 patients in Arm2), and 6.0 Gy per fraction of four fractions (50 patients in Arm3). The median TCP value for Arm1, Arm2, and Arm3 was 99.6%, 94%, and 98.1%, respectively, (P < 0.01). The median NTCP value for bladder in Arm1, Arm2, and Arm3 was 0.17%, 0.04%, and 0.07%, respectively, (P = 0.05). The median NTCP value for rectum in Arm1, Arm2, and Arm3 was 4.73%, 4.35%, and 3.17%, respectively, (P = 0.052). The overall survival (OS) of 90%, 86%, and 84% was found for Arm1, Arm2, and Arm3, respectively, at 24 months of follow-up. TCP, NTCP, and OS rates were found higher in Arm1 as compared to the other two arms. The complications found in all arms were less, low grade, and manageable. Hence, Arm1, i.e., 9.5 Gy per fraction of two fractions can be concluded as the optimum fractionation regime in terms of radiobiological parameters as well as overall patient comfort.

Radiation enhancement using focussed ultrasound-stimulated microbubbles for breast cancer: A Phase 1 clinical trial.

Preclinical studies have demonstrated that tumour cell death can be enhanced 10- to 40-fold when radiotherapy is combined with focussed ultrasound-stimulated microbubble (FUS-MB) treatment. The acoustic exposure of microbubbles (intravascular gas microspheres) within the target volume causes bubble cavitation, which induces perturbation of tumour vasculature and activates endothelial cell apoptotic pathways responsible for the ablative effect of stereotactic body radiotherapy. Subsequent irradiation of a microbubble-sensitised tumour causes rapid increased tumour death. The study here presents the mature safety and efficacy outcomes of magnetic resonance (MR)-guided FUS-MB (MRgFUS-MB) treatment, a radioenhancement therapy for breast cancer. This prospective, single-center, single-arm Phase 1 clinical trial included patients with stages I-IV breast cancer with in situ tumours for whom breast or chest wall radiotherapy was deemed adequate by a multidisciplinary team (clinicaltrials.gov identifier: NCT04431674). Patients were excluded if they had contraindications for contrast-enhanced MR or microbubble administration. Patients underwent 2 to 3 MRgFUS-MB treatments throughout radiotherapy. An MR-coupled focussed ultrasound device operating at 800 kHz and 570 kPa peak negative pressure was used to sonicate intravenously administrated microbubbles within the MR-guided target volume. The primary outcome was acute toxicity per Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Secondary outcomes were tumour response at 3 months and local control (LC). A total of 21 female patients presenting with 23 primary breast tumours were enrolled and allocated to intervention between August/2020 and November/2022. Three patients subsequently withdrew consent and, therefore, 18 patients with 20 tumours were included in the safety and LC analyses. Two patients died due to progressive metastatic disease before 3 months following treatment completion and were excluded from the tumour response analysis. The prescribed radiation doses were 20 Gy/5 fractions (40%, n = 8/20), 30 to 35 Gy/5 fractions (35%, n = 7/20), 30 to 40 Gy/10 fractions (15%, n = 3/20), and 66 Gy/33 fractions (10%, n = 2/20). The median follow-up was 9 months (range, 0.3 to 29). Radiation dermatitis was the most common acute toxicity (Grade 1 in 16/20, Grade 2 in 1/20, and Grade 3 in 2/20). One patient developed grade 1 allergic reaction possibly related to microbubbles administration. At 3 months, 18 tumours were evaluated for response: 9 exhibited complete response (50%, n = 9/18), 6 partial response (33%, n = 6/18), 2 stable disease (11%, n = 2/18), and 1 progressive disease (6%, n = 1/18). Further follow-up of responses indicated that the 6-, 12-, and 24-month LC rates were 94% (95% confidence interval [CI] [84%, 100%]), 88% (95% CI [75%, 100%]), and 76% (95% CI [54%, 100%]), respectively. The study's limitations include variable tumour sizes and dose fractionation regimens and the anticipated small sample size typical for a Phase 1 clinical trial. MRgFUS-MB is an innovative radioenhancement therapy associated with a safe profile, potentially promising responses, and durable LC. These results warrant validation in Phase 2 clinical trials. clinicaltrials.gov, identifier NCT04431674.

Abstract PO1-22-04: Cosmetic results of the breast in patients treated with Five Fraction Accelerated Partial Breast Irradiation for early stage breast cancer: retrospective review comparing Daily versus Every Other Day Treatment

Abstract Introduction: Breast cosmesis results using Accelerated Partial Breast Irradiation (APBI) with IMRT external beam in 5 fractions (6Gy x 5 fractions) has been reported as good to excellent in the literature. This retrospective review compares breast cosmesis in patients treated with Daily versus Every Other Day APBI in the community practice setting. Methods: The patient electronic medical records (EMR) were used to identify APBI patients treated at the community cancer center with the 6Gy x 5 fraction regimen. Harvard breast cosmesis four point scale results (poor, fair, good, excellent results) were extracted for each treated APBI patient from clinical notes in the EMR to rate breast cosmesis. For many patients in this review, provider reporting of cosmesis in the EMR overlapped good and excellent categories and so a “good to excellent” score was assigned. Therefore, a three point scale was utilized in statistical analysis (poor-1, fair-2, good to excellent-3). Results: There were 62 patients treated with APBI at a single institution with greater than 6 months follow up (18 patients treated daily and 44 patients treated every other day). Median follow up was 12 months (range 6- 32 months). Of all patients treated there were 0 with poor cosmesis, 3 with fair (1 every other day treatment, 2 every day treatment), 59 with good to excellent cosmesis. Univariate logistical regression analysis revealed no significant difference between daily and every other day treatment (p=0.457) Conclusion: With careful patient selection, quality planning and treatment delivery, good to excellent cosmesis is achievable in the great majority of patients undergoing breast APBI (6Gy x 5 fractions) using IMRT in the community radiation oncology clinic with either daily or every other day treatment. More study is needed, but in this review cosmetic differences seem to be minimal between daily and every other day treatment schedules. Citation Format: Alex Goss, Ellaine Haroz, Anna Voltura, Jennifer McGrath, Olivia Sloan, Matthew Jackson, Savvas Morris, Bryan Goss. Cosmetic results of the breast in patients treated with Five Fraction Accelerated Partial Breast Irradiation for early stage breast cancer: retrospective review comparing Daily versus Every Other Day Treatment [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-22-04.

2956: Comparison of two different dose and fractionation regimens of lung SBRT.

2956: Comparison of two different dose and fractionation regimens of lung SBRT.

Abstract 2879: Spatiotemporal fractionation: An innovative concept of fractionated radiotherapy

Abstract Impressive outcomes in therapeutic radiation oncology have been achieved in the past decade through the development of advanced computer technology and imaging methods, such as intensity modulated radiotherapy. Ideally, radiotherapy treatment delivers a high dose to the tumor while sparing the surrounding healthy tissues and organs at risk from radiation damage. Spatiotemporal Fractionated Radiotherapy has emerged as an innovative technique that delivers different dose distributions to different parts of the tumor in order to achieve high doses to the target while ensuring a low dose-bath in the surrounding normal tissue. Spatiotemporally fractionated regimens showed in silico up to 10 - 15% sparing of normal tissue from radiation damage, while ensuring isoeffective tumor control compared to conventionally fractionated regimens. However, prior to advancing spatiotemporal fractionation to the clinical level, it is important to probe the validity of the main assumption of spatiotemporal fractionation derived from the Biologically Effective Dose (BED) model: two different fractionation schemes that implement a high and a low dose will lead to equivalent clinical effects, regardless of dose-treatment sequence. A tumor growth delay study was performed in a subcutaneous immunocompetent murine tumor model (MC38-tumor cell derived) receiving two different fractionation regimens. Particularly, tumors belonging to the two treatment groups received the same dose combination - a high (12 Gy) and a low (6 Gy) dose fraction separated by 72 hours - with the doses delivered in opposite order in the two treatment groups. The same experimental outline was performed in a subcutaneous immunodeficient murine tumor model derived from the same tumor cells. Tumors were also characterized by immunophenotyping analysis seven days after first irradiation. Even though the two regimens deliver the same physical dose to the tumor - and would be considered equivalent according to the BED model - different tumor growth delays were observed in a time window of 30 days after first irradiation depending on the treatment group. Such differences were observed in the immunocompetent model but not in the immunodeficient model. The immunophenotyping results showed immunostimulatory vs immunosuppressive phenotypes of the tumor microenvironment depending on the order of the treatment doses. An additional tumor growth delay study including immune checkpoint inhibitors confirmed the fundamental role of the immune system with the differential efficacy outcomes of the two regimens. Overall, these intriguing results suggest that a differential radiotherapy-induced immune response to different doses of ionizing radiation plays an important role in the treatment outcome and asks for re-evaluation of the BED model taking scheduling-dependent parameters into consideration. Citation Format: Irene Vetrugno, Irma Telarovic, Nathan Torelli, Jan Unkelbach, Martin Pruschy. Spatiotemporal fractionation: An innovative concept of fractionated radiotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2879.

Optimal hypofractionated radiation therapy schemes for early-stage hepatocellular carcinoma

PurposeStereotactic body radiation therapy (SBRT) has been emerging as an efficacious and safe treatment modality for early-stage hepatocellular carcinoma (HCC), but optimal fractionation regimens are unknown. This study aims to analyze published clinical tumor control probability (TCP) data as a function of biologically effective dose (BED) and to determine radiobiological parameters and optimal fractionation schemes for SBRT and hypofractionated radiation therapy of early-stage HCC. Material and MethodsClinical 1- to 5-year TCP data of 4313 patients from 41 published papers were collected for hypofractionated radiation therapy at 2.5–4.5 Gy/fraction and SBRT of early-stage HCC. BED was calculated at isocenter using three representative radiobiological models developed per the Hypofractionated Treatment Effects in the Clinic (HyTEC) initiative. Radiobiological parameters were determined from a fit to the TCP data using the least χ2 method with one set of model parameters regardless of tumor stages or Child-Pugh scores A and B. ResultsThe fits to the clinical TCP data for SBRT of early-stage HCC found consistent α/β ratios of about 14 Gy for all three radiobiological models. TCP increases sharply with BED and reaches an asymptotic maximal plateau, which results in optimal fractionation schemes of least doses to achieve asymptotic maximal tumor control for SBRT and hypofractionated radiation therapy of early-stage HCC that are found to be model-independent. ConclusionFrom the fits to the clinical TCP data, we presented the first determination of radiobiological parameters and model-independent optimal fractionation regimens in 1–20 fractions to achieve maximal tumor control whenever safe for SBRT and hypofractionated radiation therapy of early-stage HCC. The determined optimal fractionation schemes agree well with clinical practice for SBRT of early-stage HCC. However, most existing hypofractionated radiation therapy schemes of 3–5 Gy/fraction are not optimal, higher doses are required to maximize tumor control, further validation of these findings is essential with clinical TCP data.

Single vs. multiple fraction non-inferiority trial of stereotactic ablative radiotherapy for the comprehensive treatment of oligo-metastases/progression: SIMPLIFY-SABR-COMET

BackgroundRadiotherapy delivery regimens can vary between a single fraction (SF) and multiple fractions (MF) given daily for up to several weeks depending on the location of the cancer or metastases. With limited evidence comparing fractionation regimens for oligometastases, there is support to explore toxicity levels to nearby organs at risk as a primary outcome while using SF and MF stereotactic ablative radiotherapy (SABR) as well as explore differences in patient-reported quality of life and experience.MethodsThis study will randomize 598 patients in a 1:1 ratio between the standard arm (MF SABR) and the experimental arm (SF SABR). This trial is designed as two randomized controlled trials within one patient population for resource efficiency. The primary objective of the first randomization is to determine if SF SABR is non-inferior to MF SABR, with respect to healthcare provider (HCP)-reported grade 3-5 adverse events (AEs) that are related to SABR. Primary endpoint is toxicity while secondary endpoints include lesional control rate (LCR), and progression-free survival (PFS). The second randomization (BC Cancer sites only) will allocate participants to either complete quality of life (QoL) questionnaires only; or QoL questionnaires and a symptom-specific survey with symptom-guided HCP intervention. The primary objective of the second randomization is to determine if radiation-related symptom questionnaire-guided HCP intervention results in improved reported QoL as measured by the EuroQoL-5-dimensions-5levels (EQ-5D-5L) instrument. The primary endpoint is patient-reported QoL and secondary endpoints include: persistence/resolution of symptom reporting, QoL, intervention cost effectiveness, resource utilization, and overall survival.DiscussionThis study will compare SF and MF SABR in the treatment of oligometastases and oligoprogression to determine if there is non-inferior toxicity for SF SABR in selected participants with 1-5 oligometastatic lesions. This study will also compare patient-reported QoL between participants who receive radiation-related symptom-guided HCP intervention and those who complete questionnaires alone.Trial registrationClinicaltrials.gov identifier: NCT05784428. Date of Registration: 23 March 2023.

Hypofractionated Radiotherapy for Hematologic Malignancies during the COVID-19 Pandemic and Beyond.

Radiotherapy is integral in the management of hematological malignancies (HM). Standard radiotherapy dose fractionation regimens range between 20 and 50 Gy in 10-25 fractions over 2-5 weeks. This study presents the outcomes of patients with HM treated with hypofractionation radiotherapy (HFRT) during the COVID-19 pandemic. Patients (n = 36) were treated with HFRT between January 2020 and September 2022. The outcomes measured were the overall response rate (ORR), freedom from local progression (FFLP), and overall survival (OS). The median follow-up was 13.2 months. Thirty-three patients (92%) had non-Hodgkin (NHL) or Hodgkin lymphoma (HL). Eighteen patients (50%) had aggressive and nine (25%) had indolent NHL. Nineteen patients (53%) presented with stage I/II and fifteen (42%) with stage III/IV disease. Twenty-five (69.4%) and eleven (30%) received consolidative and definitive RT, respectively. Twenty patients (56%) received treatment to the neck and/or thorax and nine (25%) to the abdomen or pelvis. The total dose ranged from 18 to 42.5 Gy in 6-17 fractions/2.67-5 Gy per fraction. The median dose in 2 Gy fractions for an alpha/beta (α/β) ratio of 10 amounted to 39 Gy (SD ± 13.86) and 43.6 Gy (SD ± 12) for an α/β of 3. The most commonly used fractionation scheme was 39 Gy in 13 fractions. ORR was 94.4% for the entire cohort, and 100, 94.4, and 83.3% for indolent NHL, aggressive NHL, and HL patients. The two-year FFLP was 76% (95% CI: 34-93%) for the entire cohort and 100, 87 (95% CI: 56.4-96.5%), and 42% (95% CI: 1.1-84.3%) for the indolent NHL, aggressive NHL, and HL patients. Two-year OS for the entire cohort was 80% (95% CI: 59.9-90.5%) and 100, 66.1 (95% CI: 36.4-84.4%), and 100% for the indolent NHL, aggressive NHL, and HL patients. Only one patient presented with grade two pulmonary toxicity. HFRT in HM provides excellent local control to be validated in a larger prospective study.

Compare Two Different Fractionated Regimes of HDR Intracavitary Brachytherapy after Concomitant Chemoradiation in Carcinoma Cervix: A Prospective Study

Background: Cervical cancer is the common cancer cause of death among women in developing countries. High Dose Rate (HDR) intracavitary brachytherapy that is given with or sequential after EBRT, is an integral component in the treatment of carcinoma of the cervix. In recent years, High Dose Rate (HDR) brachytherapy in combination with External Beam Radiotherapy (EBRT) has been popular in the management of carcinoma of the cervix. Objectives: To evaluate treatment response post 3 and 6 months after treatment completion and treatment-related toxicities during treatment in weekly v/s biweekly HDR intracavitary brachytherapy after concomitant chemoradiation in squamous cell carcinoma cervix patients. Methods: A total of 60 cervical cancer patients fulfilling the inclusion criteria were selected. Patients were randomly assigned to the weekly and Biweekly HDR ICBT using the chit-box method with replacement. Arm A (Study arm): 30 patients with concurrent EBRT (50 Gy/25 fractions with 2 Gy per fraction) with weekly cisplatin (35 mg/m2) followed by HDR-ICBT 5 Gy * 5 fractions biweekly after completion of EBRT. Arm B (Control arm): 30 patients with concurrent EBRT (50 Gy/25 fractions with 2 Gy per fraction) with weekly cisplatin (35 mg/ m2) followed by HDR - ICBT 7.5 Gy * 3 fractions weekly after completion of EBRT. Results: Patients were assessed at 3 and 6 months to determine the local disease response and the incidence of any toxicities assessed during the treatment. All responses were graded as either CR (complete response), PR (partial response), SD (stable disease), or PD (progressive disease). 30 patients were assessed for therapy response using the WHO criteria. At 3 months arm A showed 86% CR and arm B showed 90% CR. 2 patients in arm A and 1 patient in arm B had PR. In both arms 2 patients had progressive disease. At 6 months 1 patient in both arms who had progressive disease converted into partial response after taking post RT chemotherapy. Conclusions: To sum up, brachytherapy is a vital aspect of the process of treating cervical cancer. Several centers have experimented with various doses and fractionation regimes. Patients in the current trial reported no safety concerns or intolerability issues across any treatment protocol. Arm A had treatment completion before arm B with comparable disease response and toxicities. Therefore, the choice of treatment plan depends on the individual patient’s circumstances and the institution’s demands. nonetheless, longer follow-ups and a bigger patient sample are needed for a solid evaluation of disease response and toxicity.

Survival Following Palliative Radiotherapy for Head and Neck Squamous Cell Carcinoma: Examining Treatment Indications in Elderly Patients.

This study investigated the survival outcomes of patients with head and neck squamous cell carcinoma (HNSCC) undergoing palliative radiotherapy, particularly focusing on challenges and factors associated with older age, providing insights into appropriate palliative radiotherapy use in this demographic. A retrospective study was conducted using electronic medical records of 73 patients with HNSCC who were deemed unsuitable for curative therapy. Palliative radiotherapy involved a uniform dose of 30 Gy in 10 fractions. Survival analysis was performed using Kaplan-Meier method, and multivariate analysis identified significant prognostic factors. The median overall survival was 7.5 months, with no significant difference between age groups. Karnofsky performance status (KPS) >70 correlated with favorable survival. Multivariate analysis confirmed KPS as an independent prognostic factor (hazard ratio=1.949, p=0.031). The results of this study align with those of previous studies, emphasizing the importance of palliative radiotherapy for HNSCC treatment. Optimal dose fractionation regimens remain undetermined, and tailored approaches that consider factors, such as age and performance status are crucial. Individualized, comprehensive assessments and supportive care measures enhance patient well-being, reflecting palliative care principles.