Radiotherapy Fractionation Research Articles

Preliminary results of the ALTER-E009 study: Efficacy and safety of anlotinib combined with radiotherapy in patients with locally advanced or metastatic esophageal squamous cell carcinoma (ESCC)—A multicenter, multi-cohort retrospective exploratory study.

361 Background: Therapeutic options for metastatic esophageal squamous cell carcinoma (ESCC) primarily involve immunotherapy combined with chemotherapy. For locally advanced ESCC, concurrent chemoradiotherapy (CRT) or radiotherapy is the standard, though outcomes remain suboptimal. Targeted therapies, particularly anti-angiogenic agents, hold promise to enhance CRT efficacy. Anlotinib, a multi-target anti-angiogenic agent inhibiting VEGFR, PDGFR, FGFR, and c-KIT, has shown potential to enhance radiotherapy by alleviating tumor hypoxia. This multicenter, retrospective study evaluates the efficacy and safety of anlotinib combined with radiotherapy in locally advanced or metastatic ESCC. Methods: This study screened patients (pts) with locally advanced or metastatic ESCC treated with anlotinib (8-12 mg, p.o., qd, d1-14, q3w) and radiotherapy from June 2018 to June 2024. Two cohorts were included: Cohort 1 (metastatic ESCC) and Cohort 2 (locally advanced ESCC). Cohort 2 was divided into an observational group (OG, anlotinib + radiotherapy ± chemotherapy) and a control group (CG, radiotherapy ± chemotherapy). Radiotherapy doses for primary lesions were 45-60 Gy (1.8-2.2 Gy per fraction), while metastatic lesions received either standard fractionation (≥45 Gy) or stereotactic body radiotherapy (SBRT, ≥3 Gy per fraction, total dose ≥30 Gy). Chemotherapy regimens were not restricted. Cohort 1 aimed to enroll 50 pts, while Cohort 2 included 100 in the OG and 200 in the CG. The primary endpoint was overall survival (OS), with secondary endpoints including objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), duration of response (DoR), and safety. Results: By September 10, 2024, 128 pts had been enrolled: 34 in Cohort 1 and 94 in the OG of Cohort 2. In Cohort 1, all 34 pts (100%) were stage IVB, with a median OS of 24.0 months (95% CI: 12.44-35.60) and a median PFS of 9.2 months (95% CI: 7.60-10.80). The 24-month OS and PFS rates were 54.0% (95% CI: 27.20-74.73) and 30.8% (95% CI: 10.21-54.53), respectively. ORR was 52.9% (95% CI: 35.1-70.2), with 1 complete response (CR) and 17 partial responses (PR), DCR was 88.2% (95% CI: 72.5-96.7). In Cohort 2, 50 pts (53.2%) were stage III, and 28 (29.8%) were stage IVA. The median OS is not yet mature, but the median PFS was 20.1 months. The 36-month OS and PFS rates were 61.9% (95% CI: 46.12-74.34) and 48.4% (95% CI: 29.58-64.87). ORR was 46.8% (95% CI: 36.4-57.4), with 6 CRs and 38 PRs, DCR was 95.7% (95% CI: 89.5-98.8). Safety data collection is ongoing. Conclusions: Anlotinib combined with radiotherapy exhibited promising efficacy in locally advanced or metastatic ESCC, though further data are needed to confirm these preliminary findings.

Using ultrasound sequential images processing to predict radiotherapy-induced sternocleidomastoid muscle fibrosis

Purpose The purpose of this study was to evaluate the thickness and biomechanical parameters of the sternocleidomastoid muscle (SCM) before, during, and after radiotherapy using ultrasound elastography to predict radiotherapy-induced muscle fibrosis. Materials and methods The mean daily absorbed doses of 20 SCMs were determined. To find out the Young and shear modulus, shear wave elastography (SWE) and the B-mode sequential images processing method were implemented. In the B-mode sequential images processing method, by administering dynamic stress, the Young and shear modulus were estimated utilizing the maximum gradient and the block-matching algorithms, respectively. The imaging was done before, during the third and sixth weeks of treatment, and 3 months after radiotherapy. Results There was a statistically significant increase in the maximum thickness during the sixth week compared to before radiotherapy (p = .043). However, this parameter did not change significantly 3 months later (p = .095). The Young modulus (p = .611) derived from SWE did not differ significantly throughout any of the weeks of radiotherapy. But Young and shear modulus increased significantly in the B-mode sequential images processing method before and during the third and sixth weeks of treatment (p = .001). The outcomes observed 3 months after radiotherapy revealed a statistically significant increase in both Young modulus (p = .029) and shear modulus (p = .004) compared to pre-radiotherapy. Conclusion The Young modulus and shear modulus are introduced as biological markers used to detect the onset of the fibrosis process during the initial radiotherapy fractions.

Review of presentations and radiotherapy outcomes of patients with malignant spinal cord compression

Background: Malignant spinal cord compression (MSCC) is the commonest radiotherapy emergency. A high index of suspicion, prompt diagnosis, early referral and treatment is important to restore quality of life and improve survival in patients with MSCC.Aim: This study aimed to evaluate the clinical and treatment characteristics of patients presenting with MSCC at the Radiation Oncology department.Setting: The study was conducted at Steve Biko Academic Hospital, Radiation Oncology.Methods: This is a retrospective review of 110 patients who were treated for MSCC between January 2022 and November 2023. Information on patients’ characteristics, disease characteristics, imaging findings, radiotherapy dose prescription, clinical response and survival was extracted from clinical records.Results: Breast and prostate cancer were the most frequent primary disease sites. Most patients presented in a poor Eastern Cooperative Oncology Group (ECOG) performance status (PS 4), de novo disease (63%) and multilevel vertebral involvement (70%). Eighty-four patients (76.4%) received a single fraction treatment (6 Gy – 8 Gy). The median overall survival was 145 days. Patients with a Rades score of 32–37 points had a statistically significant better overall survival at 1 year compared with those with a score of 22–31 points. There was no difference in survival between single versus multiple fraction treatment.Conclusion: A single fraction radiotherapy schedule is acceptable in this setting where most patients present with extensive disease and non-ambulatory baseline function.Contribution: The findings from this study could be used to establish protocols for treatment strategies in facilities with limited resources.

Survival and toxicity outcomes of hypofractionated conformal radiotherapy compared to conventionally fractionated radiotherapy in the treatment of diffuse intrinsic pontine gliomas.

Diffuse intrinsic pontine gliomas are associated with dismal survival outcomes. Conventional fractionation radiation to a dose of 60Gy is the standard of treatment. This retrospective review aims to compare survival and toxicity outcomes of patients treated with conventional fractionation (CF) and hypofractionation (HF) radiotherapy. Treatment-naïve diffuse intrinsic pontine glioma patients undergoing radical radiation were analyzed. CF was delivered to a dose of 50-60Gy in 25-30 fractions, while HF was delivered as 38-40Gy in 12-15 fractions. All patients were planned via the volumetric modulated arc therapy (VMAT) technique. A total of 64 patients were eligible for analysis. The median age of presentation was 10years. Motor deficit was the most common presenting complaint in 51.6% of the patients, with a median symptom duration of 2months. The pons was the most frequent site of disease epicenter in 71.8% of the patients. After a median follow-up of 9.45months (range 0.23-72.63months), 23 patients died, and 28 patients experienced disease progression. The unadjusted hazard ratio (HR) for death in patients treated with HF as compared to CF was 1.330 (95% CI 0.522-3.386) (p-value 0.550, by Cox regression analysis). The median OS for the entire cohort was 13.9months, while it was 9.7months (95% CI 5.65-13.74) and 15.1months (95% CI 9.02-21.18) (p-value = 0.547) with CF and HF, respectively. On multivariate analysis, disease epicenter in the pons was the only significant factor associated with PFS. Hypofractionation was associated with a significantly higher aspiration rate and Ryle's tube requirement (p-value 0.027). Hypofractionated radiation can be considered for diffuse intrinsic pontine glioma with optimum supportive care.

Correlation of microRNAs-10b/21/34a expression levels with IDH1-mutation status in patients with glioblastoma

Introduction/Objective. Isocitrate dehydrogenase mutations play a significant role in gliomagenesis. Specific microRNAs such as miR-10b/21 act as oncogenic microRNAs, while miR-34a acts as tumor suppressors in glioblastoma. Our study aimed to investigate the mutation status of IDH correlate with microRNAs-10b/21/34a expression levels in patients with glioblastoma. Methods. The study included 43 patients diagnosed with glioblastoma. We examined microRNA-10b, microRNA-21 and microRNA-34a expression levels in peripheral blood mononuclear cells after surgery and prior to concurrent radiotherapy with temozolomide, at the 15th and 30th fractions of radiotherapy with temozolomide. The data on IDH1 mutation status were gathered from medical history and histopathology. Results. Two groups were created to assess the association of microRNAs-10b/21/34a expression levels: glio-blastoma IDH1-wild type and glioblastoma IDH1-mutant + Not Other Specified (NOS). The median microRNA-10b expression level before the initiation of concurrent radiotherapy with temozolomide was 130.44 (52.20 - 622.53) in the IDH1-wildtype glioblastoma group and 94.61 (2.13 - 816.89) in the IDH1-mutant + glioblastoma NOS group. The median microRNA-21 expression level was 57.16 (2.68 - 278.98) in the IDH1-wildtype glioblastoma group and 69.74 (4.60 - 825.43) in the IDH1-mutant + glioblastoma NOS group. The median microRNA-34a expression level was 13.52 (3.16 - 105.20) in the IDH1-wildtype glioblastoma group and 10.11 (1.00 - 210.55) in the IDH1-mutant + glioblastoma NOS group. The results showed no statistically significant difference in the expression levels of miR-10b/21/34a between the two groups (p > 0.05). Conclusion. Our results suggest that the IDH1 mutation status may not be a critical factor for altered expression of microRNAs-10b/21/34a in glioblastoma patients.

Multicentric Cross-Sectional Survey to Assess the Variation of Fractionation Strategies Used in the Management of Head and Neck Cancers in the Asian Region (INNOCENCE-ASIA).

Head and neck cancers (HNCs) are in general treated with conventional fractionation regimen of 1.8-2 Gy per fraction. Altered fractionation (ALFT) strategies such as hypofractionation radiotherapy (HYPO-RT), accelerated fractionation radiotherapy (AFRT), and hyperfractionation radiotherapy (HFRT) have not been practiced uniformly across centers in different parts of the world. Countries in Asia share common cancer demographics, and we designed this survey for Federation of Asian Radiation Oncology (FARO) member countries to understand the usage and challenges in the delivery of ALFT in HNCs. A 21-point electronic survey (Federation of Asian Radiation Oncology Research Network [FERN]-S-005) was designed by the FERN and was circulated through the FARO research secretariat to the FARO council member countries and the responses were collected between August and November 2023. Twelve of 14 member countries (85.7%) responded to the survey. Twenty-seven responses were received and 78% of the respondents belonged to government/teaching academic institute. 4/27 (14.8%) reported never using HYPO-RT for any of the clinical subsite of HNCs, while the majority (85.2%) used it for glottic cancers and 22% also used it for postoperative setting. Majority (77.7%) used a fractionation schedule with dose per fraction ranging between 2.2 and 2.5 Gy. 6/27 (22.2%) used AFRT for definitive setting and five of these also used concurrent chemoradiotherapy. 4/27 (14.8%) centers reported using HFRT. The most common reason (62.9%) for the limited usage of AFRT/HFRT was reported to be logistical, such as unavailability of machine slots, patient load, and so on. The result of the survey suggests that among the ALFT strategies for HNCs, HYPO-RT schedules have common interest and feasibility among the FARO member countries and also highlights the challenges in the delivery of AFRT/HFRT in the Asian region.

Comparative Study of Cardiac Radiation Dose With Different Types of Surgery in Breast Cancer Patients

Background: It has been demonstrated that radiation therapy lowers both the death rate from breast cancer and its recurrence. Precise calculation of the radiation dose is crucial for treating the target site as well as protecting vital organs like the heart since large doses of radiation therapy significantly increase patient morbidity and death. Objective: To compare the mean heart dose of radiation in breast cancer patients between breast-conserving surgery versus mastectomy, between different radiotherapy doses and fractionation schedules, and between right and left breast cancer irradiation. Patients and Methods: This is a cross-sectional descriptive retrospective comparative study that was conducted in Baghdad Radiotherapy Center from January 2018 to June 2018, carried on 174 breast cancer patients of different age groups selected randomly and their mean heart dose data collected from their files and database in Baghdad Radiotherapy Center. Results: The overall average of the mean dose was 372 cGy (range from 76.4 to 716.2). The greatest difference in the mean heart dose was between (BCS) patients who received 5000 cGy with regional nodal irradiation and (BCS) patients who received 4005 cGy also with regional nodal irradiation (difference in the mean is 639.8, the P – value <0.001). Regarding the side of breast cancer, the greatest difference in mean heart dose was seen between left and right breast cancer patients who did the same type of surgery (MRM) and received the same dose of radiotherapy (4256 cGy) (difference in the mean is 565cGy and the P – value <0.001). No statistically significant difference in the mean dose between breast-conserving surgery and mastectomy was recorded. Conclusion: The mean heart dose of radiotherapy is significantly increased in left-sided breast cancer irradiation as compared to the right side. A dose of 5000 cGy has the greatest effect on the dose received by the heart, especially in left breast cancer. The type of surgery whether breast-conserving surgery or mastectomy did not affect the mean dose received by the heart. Keywords: Breast cancer, cardiac radiation dose, breast cancer surgery, breast cancer treatment.

Prognostic value of lymphocyte subset levels in hepatocellular carcinoma following conventionally fractionated vs. stereotactic body radiotherapy

Aim: The aim of this study was to compare the effects of conventionally fractionated radiotherapy (CFRT) and stereotactic body radiotherapy (SBRT) on peripheral lymphocyte subset levels in patients with hepatocellular carcinoma (HCC), and to assess the association between radiotherapy (RT)-induced lymphopenia and patient prognosis. Methods: A retrospective analysis was conducted on 137 HCC patients who underwent either CFRT or SBRT between July 2011 and January 2018. Variables were obtained within 1 week before RT, and 1 day and 2 months post-RT, respectively. Peripheral lymphocyte subsets, including CD4+, CD8+, CD19+, and NK cells, were measured using flow cytometry. Univariate and multivariate Cox regression analyses were conducted to investigate independent prognostic factors for overall survival (OS). Results: The one-year and two-year OS rates were 80.0% and 55.0%, respectively. Multivariate analysis identified tumor size > 4.5 cm, multiple tumors, and post-RT CD4+ T cell count < 231/μL and CD8+ T cell count < 179/μL as independent factors associated with inferior OS in HCC patients. Severe lymphopenia (< 0.5 × 109/L) occurred in 70.0% of patients following CFRT compared to 23.0% in SBRT patients. Patients who received SBRT exhibited higher total lymphocyte counts and subset levels 1 day and 2 months post-treatment compared to those receiving CFRT (P < 0.05). Logistic regression analysis identified the number of RT fractions as an independent factor for severe lymphopenia. Further analysis revealed that CD19+ B cells were predominantly depleted and recovered more slowly than other populations, whereas CD8+ T cells demonstrated rapid recovery. Among SBRT patients, higher levels of CD4+ and CD8+ T cells post-treatment were associated with longer OS (P < 0.05). Conclusion: SBRT may induce less severe lymphopenia than CFRT. Decreases in CD4+ and CD8+ T cell levels post-SBRT may independently predict worse OS in HCC patients.

Radiation-Induced Tumor-Derived Extracellular Vesicles Combined with Tyrosine Kinase Inhibitors: An Effective and Safe Therapeutic Approach for Lung Adenocarcinoma with EGFR19Del.

Combining radiotherapy with targeted therapy benefits patients with advanced epidermal growth factor receptor-mutated non-small cell lung cancer (EGFRm NSCLC). However, the optimal strategy to combine EGFR tyrosine kinase inhibitors (TKIs) with radiotherapy for maximum efficacy and minimal toxicity is still uncertain. Notably, EVs, which serve as communication mediators among tumor cells, play a crucial role in the anti-tumor immune response. Methods To exploit the role of EVs in the delivery of tumor antigens, we formulated a therapeutic strategy that involves the use of radiation-induced tumor-derived EVs (TEXs) loaded onto dendritic cells (DCs) as a kind of vaccine in conjunction with EGFR TKIs and assessed the efficacy and safety of this approach in the treatment of EGFRm NSCLC. Results In our study, we characterized the release of immunogens as influenced by various modes of cell death, examining the impact of different levels of cell death under diverse irradiation modalities. Our results demonstrated that a radiation mode of 6Gy*3f exhibited the most promising potential to stimulate anti-tumor immune responses. This radiotherapy fraction, combined with TKIs, showed promising results in a tumor-bearing mouse model with an EGFR mutation, although there is a risk of radiation-associated pneumonitis. Furthermore, we found that 6Gy*3f-TEXs in vitro activate DCs and promote T cell proliferation as well as cytotoxic T lymphocyte-mediated tumor cell destruction. The administration of EGFR-TKIs combined DCs loaded with 6Gy*3f-TEXs exhibited the potential to inhibit tumor growth and mitigate the risk of pneumonitis. Together, the research shows that TEXs from high-dose fractionation radiation can mature DCs and boost the killing of cytotoxic T lymphocytes. Combining these DC vaccines with Osimertinib offers a promising and safe treatment for EGFRm NSCLC.

Impact of radiotherapy dose, fractionation and immunotherapeutic partner in a mouse model of HR+ mammary carcinogenesis.

Hormone receptor (HR)+ breast cancer is poorly responsive to immune checkpoint inhibitors (ICIs). In some settings, radiation therapy (RT) has been shown to mediate immunostimulatory effects and promote ICI sensitivity. We investigated whether hypofractionated RT may be successfully combined with ICIs in a mouse model of multifocal, metachronous HR+ mammary carcinogenesis. We hypothesized that focal RT targeting the first detectable (primary) tumor combined with ICIs may generate effective immunity, hence delaying the development of new lesions. Focal RT in various doses and fractionations limited primary tumor growth, with an optimum for a 20 Gy X 2 regimen (ablative in ∼90% of mice). The degree of primary disease control, however, did not necessarily correlate with overall survival (OS) extension, owing to changes in the development of new neoplastic lesions contributing to global tumor burden. Adding a PD-1 blocker to focal RT delivered in a 10 Gy X 3, 20 Gy X 2 or 8 Gy X 6 regimen failed to alter OS extension enabled by RT alone. Similar results were obtained with a CTLA4 blocker, an IL1B inhibitor, and a PD-1 blocker plus recombinant FLT3LG when combined with the 10 Gy X 3 regimen. In this model of HR+ mammary carcinogenesis, RT to the primary tumor ameliorates OS (to an extent depending on dose and fractionation). Increasing local control by RT alone or RT plus immunotherapy beyond a hitherto undefined threshold, however, does not necessarily inhibit the development of subsequent non-irradiated neoplasms and hence does not necessarily provide extra OS benefits.

Outcomes of Intraoperative Radiotherapy for Locally Advanced Adenocarcinoma of the Esophagogastric Junction After Neoadjuvant Therapy: A Single-Arm, Phase 1 Trial Fromthe Chinese National Cancer Center.

The role of intraoperative radiotherapy (IORT) for adenocarcinoma of the esophagogastric junction (AEG) remains uncertain. Therefore, a prospective phase 1 trial was conducted to assess the safety and feasibility of IORT for locally advanced AEG. The study enrolled patients with AEG at stages II-IVA from January 2019 to September 2019. Eligible patients received esophagectomy and a single fraction of electron beam radiotherapy. The primary endpoint of the study was a safety profile for IORT. Additionally, survival outcomes and the locoregional recurrence rate (LRR) were compared between the non-IORT and IORT cohorts using propensity score-matching. For 15 (93.8 %) of the 16 patients in the study, R0 resection was successfully achieved, with only one patient undergoing R1 resection. A total postoperative complication morbidity rate of 43.8 % (7/16) was observed, with major complications (Clavien-Dindo classification ≥3) in 12.5 % of the cases (2/16). Total treatment-related adverse events were reported for seven patients (43.8 %, 7/16). After matching, a lower LRR was observed in the IORT group than in the non-IORT group (0 % [0/12] vs 33.3 % [4/12]; p = 0.028). However, the two groups did not differ significantly in 3-year progression-free survival (PFS: IORT [50.9 %] vs non-IORT [53.4 %]; p = 0.93) or 3-year overall survival (OS: IORT [58.3 %] vs IORT [72.9 %]; p = 0.23). The current study demonstrated favorable feasibility and safety of IORT for locally advanced AEG. Although IORT is beneficial for improving local control, it may not prolong PFS or OS for patients with locally advanced AEG. A phase 2 trial is warranted for further validation of these outcomes.

Efficacy and safety of consolidative thoracic radiotherapy after first-line chemoimmunotherapy in patients with extensive-stage small-cell lung cancer: a retrospective cohort study.

Thoracic radiotherapy (TRT) has shown potential benefits in improving local control and overall survival (OS) in chemotherapy-responsive small-cell lung cancer (SCLC) cases. However, its role in the era of chemoimmunotherapy remains underexplored. In the current era of immunotherapy, this study evaluated the efficacy and safety of consolidative TRT (cTRT) in patients with extensive-stage SCLC (ES-SCLC) and assessed its impact on OS. Additionally, the optimal radiotherapy dose and fractionation schemes were also explored. In this retrospective cohort study, 124 patients with ES-SCLC diagnosed at Taizhou Cancer Hospital between January 2019 and November 2023 were categorized into cTRT and non-cTRT groups. We compared the baseline characteristics, treatment processes, and survival outcomes between the two groups. Moreover, cTRT subgroups of different radiotherapy doses and fractionation schemes were formed and compared in terms of baseline characteristics, radiotherapy efficacy and safety, patterns of recurrence after radiotherapy, and survival outcomes. OS was selected as the primary endpoint for observation. Differences in OS between the groups were analyzed using log-rank tests. Univariable and multivariable Cox regression analyses were performed to identify factors correlated with OS in the overall patient cohort. The baseline characteristics between the two groups (cTRT and non-cTRT) were generally comparable, with the following significant differences: the cTRT group had a lower proportion of females (1.7% vs. 15.2%, P=0.02), lower levels of neuron-specific enolase (NSE, median: 15.87 vs. 32.00 ng/mL, P=0.009), and higher sodium concentrations (median: 140.50 vs. 138.25 mmol/L, P=0.01). Additionally, the cTRT group underwent more first-line treatment cycles (median: 4.00 vs. 3.00, P=0.001). Compared with the non-cTRT group, the cTRT group had a longer OS [median survival 15.5 vs. 10.5 months; hazard ratio (HR) =2.0497; 95% confidence interval (CI): 1.3548-3.1010; P<0.001]. There were no significant differences in survival outcomes associated with the different radiotherapy dosage or fractionation schedules. The most common adverse event was neutropenia, but no severe treatment-related deaths occurred. Multivariable Cox analysis revealed that the sodium concentration (HR =0.8751; 95% CI: 0.7944-0.9642; P=0.007), initial treatment response (HR =0.7022; 95% CI: 0.4949-0.9964; P=0.048), total number of systemic treatment cycles (HR =0.5501; 95% CI: 0.3618-0.8364; P=0.005), and whether to receive cTRT (HR =1.7484; 95% CI: 1.1033-2.7708; P=0.02) were independent prognostic factors for OS. cTRT improved the OS of patients with ES-SCLC and exhibited manageable associated toxicity. Further research is needed to confirm the effect of radiotherapy dose and fractionation scheme selection on treatment outcomes.

Comparison of Conventional Palliative Radiotherapy Fractionation Schedule with Quad Shot Regimen in Locally Advanced Head and Neck Cancer Patients: A Randomised Clinical Trial

Introduction: Head and Neck Cancer (HNC) accounts for 14.3% of all cancers in India and 4.8% of all cancers worldwide. In India, the most common sites are the lip and oral cavity (&gt;80%), which are more prevalent in men than in women. Histologically, most cases are Squamous Cell Carcinomas (SCC). The majority of patients present with locally advanced stages, where surgery and definitive chemoradiation therapy are not possible and palliative Radiotherapy (RT) is considered a treatment option for better symptomatic relief and improved Quality of Life (QoL). The Quad Shot (QS) palliative regimen has shortened treatment time, reduced toxicity and increased compliance. Aim: To compare the QS regimen administered over two consecutive days versus the Conventional Palliative Regimen in the treatment of locally advanced HNC, in terms of treatment response, acute toxicities and QoL. Materials and Methods: In this prospective randomised clinical trial conducted from May 2023 to July 2024 in the Department of Radiation Oncology at King George's Medical University (KGMU), Lucknow, Uttar Pradesh, India, patients with biopsyproven locally advanced carcinoma of the head and neck were recruited, with a sample size of 50 in each of the study Group B and control Group A arms. Patients in the control arm received 30 Gray (Gy) in 10 fractions, 5 fractions per week over two weeks (Conventional palliative arm). In the study arm, patients received 14 Gy in 4 fractions delivered in two daily sessions, six to eight hours apart, for two consecutive days over three cycles (QS arm). The Response Evaluation Criteria in Solid Tumours (RECIST) Criteria 1.1 was used to assess the tumour response objectively three months post-RT. Health-related QoL was assessed using questionnaires developed by the European Organisation for Research and Treatment of Cancer (EORTC), specifically the EORTC Quality of Life Questionnaire (QLQ). Continuous data were compared using the t-test for nominal data and the Mann-Whitney U test was used otherwise. Results: The mean age was 39.66±12.05 years in Group A and 42.76±11.65 years in Group B. The QS and conventional palliative arms each had 47 and 49 patients recruited, respectively. The QS arm exhibited fewer instances of skin toxicity, with 25 (53.2%) experiencing Grade I and 7 (14.9%) experiencing Grade II toxicity, compared to the conventional palliative arm, where 30 (61.2%) had Grade I and 12 (24.5%) had Grade II toxicity. Mucositis in the QS arm included 22 (46.9%) cases, with 14 (29.7%) classified as Grade I and Grade II, whereas the conventional arm had 12 (24.5%) Grade I cases, 29 (59.5%) Grade II cases and 3 (6.1%) Grade III cases. The treatment response, in terms of partial and stable disease combined, was observed in 61.2% of the conventional arm compared to 78.7% in the QS arm. QoL was reported to be better in the QS regimen post-treatment. Conclusion: Given the total number of patients recruited, the QS arm, with its shorter treatment time, demonstrated better benefits in terms of reduced toxicities and improved treatment response, as well as enhanced QoL compared to the conventional palliative arm.

SMILE—stereotactic multiple fraction radiotherapy for non-spine bone metastases: study protocol for a multicenter, open-label phase III randomized controlled trial

BackgroundThe SMILE study addresses a significant need in palliative oncology by evaluating the non-inferiority of a shortened, 3-fraction stereotactic body radiotherapy (SBRT) schedule against the traditional 5-fraction approach for non-spine bone metastases in terms of pain control. Optimizing SBRT could significantly enhance the quality of life for patients by providing effective pain relief while minimizing treatment sessions.MethodsThis international, multicenter phase III trial will randomize 162 patients to receive either a 3-fraction regimen (9 Gy per fraction) or a standard 5-fraction regimen (7 Gy per fraction). Outcomes, assessed at 3 months post-treatment, will focus on pain response, quality of life, and control of metastasis. With a hypothesis-driven design, the study will incorporate intent-to-treat and per-protocol analyses, incorporating appropriate measures for data integrity and handling of missing information.DiscussionIf the 3-fraction SBRT regimen demonstrates non-inferiority, it could streamline palliative care protocols, reduce patient burden, and set a new standard for treatment, reflecting a patient-centered approach in palliative radiation oncology.Trial registrationThe trial has been registered prospectively on ClinicalTrials.gov under the identifier NCT05406063, as of May 3, 2022.

RBIO-10. RADIATION FRACTION SIZE DIFFERENTIALLY AFFECTS MYELOID-DERIVED SUPPRESSOR CELL (MDSC) SUBSETS IN WHO GRADE 1 MENINGIOMA

Abstract Meningiomas are often cured after focal therapy with surgical resection and/or radiotherapy (RT); however, a small proportion still recur. RT dose can be used to modulate anti-tumor immune responses, potentially through regulating immunosuppressive MDSCs. Here, we investigate the effect of a single fraction of RT (2Gy vs. 15Gy) on frequency and activation status of MDSC subsets in patients with WHO grade 1 meningioma. We hypothesize that 2Gy will promote immunosuppressive MDSC activity more than 15Gy. Fresh tumor cells from patients with a presumed diagnosis of meningioma were digested into primary cell cultures and treated with a single fraction of 2 or 15 Gy or were sham irradiated using a XRAD 320 Biological Irradiator. Cells were incubated for 18hrs prior to flow cytometric analysis. MDSC populations were identified as Live/Dead-CD11b+CD33+HLA-DR-. MDSC subsets were then divided into M-MDSC (CD14+CD15-) or G-MDSC (CD15+CD14-). Five WHO grade 1 meningiomas were analyzed. The total frequency of MDSCs in tumors increased from 3% with sham RT to 4% after irradiation with 2Gy (p=0.03). This was driven by a 2-fold increase in frequency of total M-MDSCs, as G-MDSCs decreased by half after 2Gy (p=0.03). After irradiation with 15Gy, M-MDSC frequency was nearly half that of 2Gy. The frequency of TGF-β+MDSCs increased after 15 Gy (p=0.02). The frequency of IL-10+G-MDSCs increased in response to 2Gy (p =0.03) but decreased 4-fold after 15Gy. 18hrs after 2Gy, IFN-γ+M-MDSCs increased compared to sham (p=0.01). In this small cohort of grade 1 meningiomas, a 2Gy fraction of RT appeared to support expansion of the M-MDSC subset. RT at both fraction sizes increased immunosuppressive cytokine producing-MDSCs: M-MDSC-IL-10; G-MDSC-TGF-β. These findings indicate the need for further studies to understand the subset-specific impact of RT on MDSC, a key immune cell type in brain cancers.

DNAR-10. PHASE I CLINICAL TRIAL OF PEPOSERTIB PLUS RADIOTHERAPY IN ADULTS WITH NEWLY-DIAGNOSED MGMT-UNMETHYLATED GLIOBLASTOMA

Abstract BACKGROUND DNA-dependent protein kinase (DNA-PK) is an attractive target in GBM because it promotes unwanted DNA repair and renders cancer cells less vulnerable to DNA damaging agents, such as radiotherapy (RT). Peposertib, a small molecule inhibitor of DNA-PK, has demonstrated pre-clinical efficacy in sensitizing GBM to RT, resulting in tumor regression. METHODS 21 patients with newly-diagnosed MGMT-unmethylated GBM received peposertib plus 6-weeks of RT to determine the maximum-tolerated dose (MTD) based on the Bayesian Optimal Interval design. The dose-limiting toxicity (DLT) period was 10-weeks. Patients received at least 6-cycles of adjuvant temozolomide (NCT04555577). Single-nuclei RNA-sequencing (snRNA-Seq) and spatial transcriptomics (Visium, 10x Genomics) were performed on matched pair primary-recurrent tumors and controls, incorporating tumor cell state and cell type definitions by automated cluster classification and differential expression of marker genes. RESULTS The MTD of peposertib in combination with RT was 300mg per RT fraction day. One DLT (G3 radiation necrosis @300mg) was observed. After a median follow-up of 15.4 months (interquartile-range 8.9-18.5), mPFS was 10.8 months (95%CI 8.33-NR) and mOS was 22.9 months (95%CI 16-NR). 6/21 (29%) patients have undergone re-resection to date. snRNA-Seq on 102,709 cells from 12 primary and 3 recurrent tumors revealed that pre-treatment tumor cell states were progenitor-like, while treatment with peposertib plus RT was associated with differentiated and inflammatory malignant cell states, along with macrophage infiltration. Spatial transcriptomics of 8 matched primary-recurrent tumors (20,793 transcriptomes) confirmed malignant cell differentiation and enrichment of pro-inflammatory macrophages after inhibition of DNA-PK. 5 patients will be enrolled into a window-of-opportunity expansion cohort to evaluate intratumoral drug concentration. CONCLUSION The combination of peposertib and intracranial RT was safe. Survival data for this MGMT-unmethylated GBM population was promising. Single nuclei and spatial transcriptomic analyses revealed enrichment of pro-inflammatory macrophages in the tumor microenvironmentafter DNA-PK inhibition. The study was supported by EMD-Serono (CrossRef Funder ID: 10.13039/100004755).

Magnetic resonance imaging-guided single-fraction preoperative radiotherapy for early-stage breast cancer (the RICE trial): feasibility study

BackgroundOver the past decade, the adoption of screening programs, digital mammography, and magnetic resonance imaging (MRI) has increased early-stage breast cancer diagnosis rates. Mortality rates have decreased due to early detection and improved treatments, including personalized therapies. Accelerated partial-breast irradiation (APBI) is emerging as a convenient and effective treatment for some patients, with studies exploring its preoperative use. Preoperative APBI, especially with MRI guidance, offers improved tumor targeting and potentially reduced side effects. Magnetic Resonance Imaging-Guided Single-Fraction Pre-Operative Radiotherapy for Early-Stage Breast Cancer (RICE trial) aims to assess the feasibility and efficacy of MRI-guided single-dose radiotherapy (RT) for early-stage breast cancer.MethodsThe RICE study is a prospective, single-arm study evaluating single-fraction preoperative, APBI treatment for patients with early-stage breast cancer using a magnetic resonance imaging linear accelerator (MRI linac). Eligible patients enrolled in this study will have a core biopsy to confirm estrogen receptor-positive and HER2-negative sub-type. RT planning will use a planning computed tomography (CT) co-registered with a MRI with the patient in either the supine or prone position. For the diagnostic workup, [18F] fluorodeoxyglucose positron emission tomography/CT ([18F] FDG PET/CT) and [18F] fluoroestradiol positron emission tomography/CT ([18F] FES PET/CT) will be performed prior to treatment. Thirty patients will receive a single ablative RT dose of 21 Gray to the tumor. Pre-treatment and post-treatment MRI scans will be acquired at baseline and 5 weeks post-RT respectively. Breast-conserving surgery will be scheduled for 6 weeks after APBI treatment using the MRI linac.The primary study endpoint is the successful administration of a single fraction of preoperative breast RT under the guidance of an MRI linac. Secondary endpoints include evaluating the utility of MRI, [18F] FDG PET/CT, and [18F] FES PET/CT as a non-invasive method for assessing treatment response in patients undergoing single-fraction preoperative APBI.ConclusionThe RICE trial represents a significant step in breast cancer treatment, offering insights that could lead to treatment protocols with minimized RT appointments and enhanced patient outcomes.Trial registrationThis trial is registered with the Australian New Zealand Clinical Trials Registry (ANZCTR). Registered 31st of May 2021. Registration number: ACTRN12621000659808.

CBCT-based online adaptive radiotherapy of the prostate bed: first clinical experience and comparison to nonadaptive conventional IGRT.

Conventional image-guided radiotherapy (IGRT) of the prostate bed is challenged by the varying anatomy due to dynamic changes of surrounding organs such as the bladder and rectum. This leads to changed dose coverage of target and surrounding tissue. The novel online adaptive radiotherapy (oART) aims to improve target coverage as well as reduce dose exposure to surrounding healthy tissues by daily reoptimization of treatment plans. Here we set out to quantify the resulting changes of this adaptation for patients and treatment team. Atotal of 198 fractions of radiotherapy of the prostate bed (6patients) were treated using oART with the Ethos accelerator (Varian Medical Systems, Palo Alto, CA, USA). For each fraction, volumes and several dose-volume parameters of target volumes and organs at risk were recorded for the scheduled plan (initial plan, recalculated based on daily cone beam computed tomography [CBCT]), the adapted plan, and the verification plan, which is the dose distribution of the applied plan recalculated on the closing CBCT after the adaptation process. Clinical acceptability for all plans was determined using given dose-volume parameters of target volumes. Additionally, the time needed for the adaptation process was registered and compared to the time required for the daily treatment of five conventional IGRT patients. Volumes of target and organs at risk (OAR) exhibited broad variation from day to day. The differences in dose coverage D98% of the clinical target volume (CTV) were significant through adaptation (p < 0.0001; median D98% 97.1-98.0%) and further after verification CBCT (p < 0.001; median D98% 98.1%). Similarly, differences in D98% of the planning target volume (PTV) were significant with adaptation (p < 0.0001; median D98% 91.8-96.5%) and after verification CBCT (p < 0.001; median D98% 96.4%) with decreasing interquartile ranges (IQR). Dose to OAR varied extensively and did not show aconsistent benefit from oART but decreased in IQR. Clinical acceptability increased significantly from 19.2% for scheduled plans to 76.8% for adapted plans and decreased to 70.7% for verification plans. The scheduled plan was never chosen for treatment. The median time needed for oART was 25 min compared to 8 min for IGRT. Target dose coverage was significantly improved using oART. IQR decreased for target coverage as well as OAR doses indicating higher repeatability of dose delivery using oART. Differences in doses after verification CBCT for targets as well as OAR were significant compared to adapted plans but did not offset the overall dosimetric gain of oART. The median time required is three times higher for oART compared to IGRT.

Once-a-Week Ablative Radiotherapy as Replacement of Prolonged Fractionation in Frail Patients: Feasibility and Toxicity Results

Introduction The aim of this work was to explore the use of an original once-weekly radiotherapy fractionation in elderly or frail patients with recurrence or metastasis from different solid malignancies. Material and Methods A retrospective analysis was conducted on 29 patients treated from 2011 to 2019 with a once-weekly radiotherapy schedule. Patients received a median dose of 27.5 Gy, with weekly fractions of 4-5 Gy over 7-10 weeks. The treatment aimed at both palliative and cytoreductive objectives. Primary endpoints were feasibility and compliance, secondary outcome was acute toxicity. Results All patients completed the planned radiotherapy without interruptions. Acute toxicity was mild, with only one patient developing grade 3 toxicity (bowel perforation). Three months post-treatment, 74% of patients experienced symptom relief and tumor response. One-year local control rates were 26.7%, and treatment was generally well-tolerated. Conclusion This once-weekly hypofractionated radiotherapy regimen demonstrated feasibility, good tolerance, and promising tumor response in frail and elderly patients. Although limited by a small sample size, the approach offers a practical alternative for patients unable to undergo conventional daily radiotherapy. Further studies on larger cohorts are required to validate these findings.

Cross-Sectional National Survey of Practice Patterns in Radiotherapy for Rectal Cancer: A Snapshot of India.

The information on the practice of radiotherapy, including intensity-modulated radiotherapy (IMRT) use for rectal cancer in India, is lacking. This national survey was planned to understand the current status of knowledge, attitudes, and practice among radiation oncologists, specifically concerning the practice of IMRT for rectal cancers. A national survey was sent to radiation oncologists through e-mail or a WhatsApp message, where feasible, with a request letter containing the link to the survey questionnaire. The survey questionnaire was adapted from the UK IMRT survey with permission from the authors. It explored rectal cancer management, IMRT use, reasons for nonadoption, total neoadjuvant therapy (TNT), dose fractionation schedules and radiotherapy processes like radiotherapy simulation, target volume/organ at risk definition, and treatment planning, evaluation, and verification. Descriptive statistics is used to present the results. Over 300 radiation oncologists were approached, and 182 (60.6%) of the 153 institutes responded. Around 88% (160 of 182) indicated using IMRT or volumetric modulated arc therapy (VMAT) to treat rectal cancer, of whom 32% used exclusively IMRT/VMAT in all their patients. The reasons for not adopting IMRT were affordability/lack of insurance, resource constraints, and lack of guidelines. Long-course chemoradiation (capecitabine-based) followed by surgery was the most common neoadjuvant approach, with short course and TNT in less than a third of patients. Daily verification feasibility was reported by 60%. Seventy-three percent emphasized the need for a national IMRT guidance document. This national survey from India indicates a scope of routine implementation of IMRT in rectal cancer, highlighting the urgent need for a national IMRT guidance document, which could significantly enhance the quality of care for patients with rectal cancer in India.