Radiation Fractionation Schedules Research Articles

Alpha/beta values in pediatric medulloblastoma: implications for tailored approaches in radiation oncology

BackgroundMedulloblastoma is the most common malignant pediatric brain tumor, typically treated with normofractionated craniospinal irradiation (CSI) with an additional boost over about 6 weeks in children older than 3 years. This study investigates the sensitivity of pediatric medulloblastoma cell lines to different radiation fractionation schedules. While extensively studied in adult tumors, these ratios remain unknown in pediatric cases due to the rarity of the disease.Materials and methodsFive distinct medulloblastoma cell lines (ONS76, UW228-3, DAOY, D283, D425) were exposed to varying radiation doses and fractionation schemes. In addition, ONS76 and UW228-3 stably overexpressing MYC were analyzed. Alpha/beta values, representing fractionation sensitivity, were quantified using the linear-quadratic model of radiation survival.ResultsThe study unveiled elevated alpha/beta ratios across diverse medulloblastoma cell lines, with a weighted mean alpha/beta value of 11.01 Gy (CI: 5.23–16.79 Gy). Neither TP53 status nor the levels of MYC expression influenced fractionated radiosensitivity. Furthermore, differences in alpha/beta values cannot be correlated with molecular subgroups (p = 0.07) or radiosensitivity (SF2).ConclusionThese in vitro findings strongly recommend normofractionated or hyperfractionated radiotherapy for paediatric medulloblastoma cases due to consistently high alpha/beta values across subgroups. Conversely, hypofractionated radiotherapy is not advisable within a curative approach. This study presents significant potential by enabling the estimation of radiobiological fractionations and dose effects in young, vulnerable patients, highlighting its importance for advancing patient-specific therapeutic strategies.

Abstract P016: Optimizing macrophage-mediated abscopal effects for enhanced clinical translation: Radiation therapy combined with CD47 blockade

Abstract Radiation therapy (RT) can activate both innate and adaptive immune responses, and the combination of RT and immunotherapy may produce synergistic anti-tumor responses. We found that the “don’t-eat-me” molecule CD47 is highly expressed on the surface of small cell lung cancer (SCLC) cells, a highly metastatic form of lung cancer, and that blockade of CD47 can enhance phagocytosis of SCLC cells by macrophages. In this study, we investigated whether combining CD47 blockade and RT could synergize to inhibit the tumor growth of SCLC as well as other cancer types in preclinical models. We evaluated the immune responses induced by RT and CD47 blockade and their efficacy in controlling tumors in preclinical models of SCLC as well as colon cancer, breast cancer and lymphoma. Cancer cells were engrafted into both flanks of recipient mice and one side was irradiated, with or without CD47 antibodies, to investigate local and systemic effects of RT and CD47 blockade. We also used liver metastases models and endogenous lung tumor models to investigate anti-tumor effects and immune responses in physiological tumor microenvironments. Various radiation doses and fractionation schedules were evaluated to determine the optimal conditions for inducing anti-tumor responses. We found CD47 blockade potently enhances the local anti-tumor effects of RT in all the preclinical models of SCLC we tested. Strikingly, CD47 blockade also stimulates systemic “abscopal” effects inhibiting non-irradiated SCLC tumors in mice receiving RT. These effects are observed in liver metastases, endogenous lung tumors, and subcutaneous tumor models. Surprisingly, these abscopal effects are independent of T cells but require macrophages that migrate into non-irradiated tumor sites in response to inflammatory signals produced by RT and are locally activated by CD47 blockade to phagocytose cancer cells. Similar abscopal anti-tumor effects were observed in other cancer models treated with RT and CD47 blockade. Additionally, we observed that RT increases tumor infiltrating macrophages in human cancer patients. Interestingly, these abscopal anti-tumor effects can be enhanced when combined with PD-1 blockade. Furthermore, we found that a wide range of radiation doses, from 2 Gy to 20 Gy, can induce abscopal responses, with fractionated doses (24 Gy in 3 fractions) inducing stronger abscopal effects than single doses. Our data demonstrate macrophage-mediated abscopal responses following RT when combined with CD47 blockade across multiple cancer models. This systemic activation of anti-tumor macrophages following RT and CD47 blockade may be particularly impactful for cancer patients who suffer from metastatic disease. Given that RT is a standard-of-care treatment and CD47-blocking strategies are undergoing clinical trials, our findings hold significant translational potential for cancer patients. Citation Format: Yoko Nishiga, Edward Graves, Julien Sage.Optimizing macrophage-mediated abscopal effects for enhanced clinical translation: Radiation therapy combined with CD47 blockade.[abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Translating Targeted Therapies in Combination with Radiotherapy; 2025 Jan 26-29; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(2_Suppl):Abstract nr P016

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.

Radioimmunotherapy: a game-changer for advanced non-small cell lung cancer.

Lung cancer, particularly non-small cell lung cancer (NSCLC), remains a leading cause of cancer-related deaths, with conventional treatments offering limited effectiveness in advanced stages, due to distant metastases and treatment resistance. Recent advancements in immunotherapy, specifically immune checkpoint inhibitors (ICIs), have shown promise, but their efficacy as standalone therapies are often insufficient. This has led to increased interest in combining ICIs with radiotherapy, known as radioimmunotherapy (iRT), to enhance treatment outcomes. This review explores the mechanisms that underlie the synergy between radiotherapy and immunotherapy. Radiotherapy can induce the "abscopal effect", eliciting systemic immune responses that reduce tumor burdens outside the treated area. It also increases the expression of major histocompatibility complex class I (MHC-I) on tumor cells, improving immune recognition. Furthermore, radiotherapy can modify the tumor microenvironment by inducing metabolic reprogramming to bolster anti-tumor immunity. We discuss strategies for optimizing iRT, including considerations of radiation doses, fractionation schedules, and treatment site selection, which significantly influence immune responses by enhancing MHC-I expression or promoting T-cell infiltration. Clinical evidence supports the efficacy of iRT in NSCLC and other cancers, though challenges in standardizing treatment protocols and managing side effects persist. Overall, radioimmunotherapy presents a promising approach to improving NSCLC treatment outcomes. Ongoing research into its mechanisms and the refinement of treatment may reshape clinical practice, offering more effective and personalized options for patients with advanced lung cancer. Further studies are essential to validate these findings and optimize therapeutic protocols.

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.

Activation of Stimulator of Interferon Genes (STING): Promising Strategy to Overcome Immune Resistance in Prostate Cancer.

Prostate cancer (PCa) is the most frequent and second-lethal cancer among men. Despite considerable efforts to explore treatments like autologous cellular immunotherapy and immune checkpoint inhibitors, their success remains limited. The intricate tumor microenvironment (TME) and its interaction with the immune system pose significant challenges in PCa treatment. Consequently, researchers have directed their focus on augmenting the immune system's anti-tumor response by targeting the STimulator of the Interferon Genes (STING) pathway. The STING pathway is activated when foreign DNA is detected in the cytoplasm of innate immune cells, resulting in the activation of endoplasmic reticulum (ER) STING. This, in turn, triggers an augmentation of signaling, leading to the production of type I interferon (IFN) and other pro-inflammatory cytokines. Numerous studies have demonstrated that activation of the STING pathway induces immune system rejection and targeted elimination of PCa cells. Researchers have been exploring various methods to activate the STING pathway, including the use of bacterial vectors to deliver STING agonists and the combination of radiation therapy with STING agonists. Achieving effective radiation therapy with minimal side effects and optimal anti-tumor immune responses necessitates precise adjustments to radiation dosing and fractionation schedules. This comprehensive review discusses promising findings from studies focusing on activating the STING pathway to combat PCa. The STING pathway exhibits the potential to serve as an effective treatment modality for PCa, offering new hope for improving the lives of those affected by this devastating disease.

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.

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.

Palliative Thoracic Radiotherapy in the Era of Modern Cancer Care for NSCLC.

Palliative thoracic radiotherapy provides rapid and effective symptom relief in approximately two-thirds of NSCLC patients treated. In patients with poor performance status, the degree of palliation appears unrelated to the radiation dose or fractionation schedule. Conversely, in patients with good performance status, higher radiation doses administered over longer periods have shown modest survival benefits. These findings stem from studies conducted before the advent of immunotherapy and targeted therapy in clinical practice. Currently, there are no large prospective studies specifically dedicated to palliative radiotherapy conducted in this new treatment era. Modern radiotherapy technologies are now widely available and are increasingly used for palliative purposes in selected patients, reflecting the expanded array of therapeutic options for disseminated NSCLC and improved prognosis. Some traditional tenets of palliative thoracic radiotherapy, such as the improvement of overall survival with a protracted radiation schedule and the use of simple, cost-effective radiation techniques for palliative purposes, may no longer hold true for patients receiving immunotherapy or targeted therapy. The application of IMRT or SBRT in the context of palliative radiotherapy for NSCLC is not yet sufficiently explored, and this is addressed in this review. Moreover, new risks associated with combining palliative radiotherapy with these systemic treatments are being explored and are discussed within the context of palliative care. The optimal timing, doses, fractionation schedules, and treatment volumes for radiotherapy combined with immunotherapy or targeted therapy are currently subjects of investigation. In emergencies, radiotherapy should be used as a life-saving measure without delay. However, for other indications of palliative thoracic radiotherapy, decisions regarding doses, timing relative to systemic treatments, and treatment volumes should be made in a multidisciplinary context, considering the patient's prognosis, anticipated outcomes, and access to potentially effective treatments. We still lack robust data from prospective studies on this matter. This review examines and discusses available evidence on the use of palliative thoracic radiotherapy within the framework of modern treatment strategies for NSCLC.

Targeting the Tumor Vascular Supply to Enhance Radiation Therapy Administered in Single or Clinically Relevant Fractionated Schedules.

This pre-clinical study was designed to demonstrate how vascular disrupting agents (VDAs) should be administered, either alone or when combined with radiation in clinically relevant fractionated radiation schedules, for the optimal anti-tumor effect. CDF1 mice, implanted in the right rear foot with a 200 mm3 murine C3H mammary carcinoma, were injected with various doses of the most potent VDA drug, combretastatin A-1 phosphate (CA1P), under different schedules. Tumors were also locally irradiated with single-dose, or stereotactic (3 × 5-20 Gy) or conventional (30 × 2 Gy) fractionation schedules. Tumor growth and control were the endpoints used. Untreated tumors had a tumor growth time (TGT5; time to grow to 5 times the original treatment volume) of around 6 days. This increased with increasing drug doses (5-100 mg/kg). However, with single-drug treatments, the maximum TGT5 was only 10 days, yet this increased to 19 days when injecting the drug on a weekly basis or as three treatments in one week. CA1P enhanced radiation response regardless of the schedule or interval between the VDA and radiation. There was a dose-dependent increase in radiation response when the combined with a single, stereotactic, or conventional fractionated irradiation, but these enhancements plateaued at around a drug dose of 25 mg/kg. This pre-clinical study demonstrated how VDAs should be combined with clinically applicable fractionated radiation schedules for the optimal anti-tumor effect, thus suggesting the necessary pre-clinical testing required to ultimately establish VDAs in clinical practice.

Salvage Breast-Conserving Surgery and Reirradiation With Intraoperative Electrons for Recurrent Breast Cancer: A Multicentric Study on Behalf of Italian Association of Radiotherapy and Clinical Oncology (AIRO)

AimIntraoperative radiotherapy with electrons (IOERT) may represent a viable choice for partial breast re-irradiation (rePBI) after repeat quadrantectomy for local recurrence (LR) for primary breast cancer (BC) in lieu of mastectomy. Materials and MethodsA database collecting data on rePBI with IOERT from 8 Italian centres was set up in 2016- 2018, providing data on cumulative incidence (CumI) of 2nd LR nd survival with a long follow-up (FU) ResultsFrom 2002 to 2015, 109 patients underwent the conservative retreatment.The median primary BC -1stLR interval was 11.1 years (range: 2.4-27.7). The median 1stLR size was 0.9 cm (range: 0.3-3.0) and 43.6% were Luminal A. Median IOERT dose was 18 Gy (range: 12-21) and median collimator was 4 cm (range: 3-6). Median FU was 11.7 years (interquartile range: 7.7-14.6). The 2ndLR CumI was 12.2% (95% CI: 6.8-19.2) at 5 years and 32.3% at 10 years (95% CI: 22.8-42.2), occurring in the same site as the 1stLR in about half of the cases. HER2 status and collimator size were independent LR predictors. The 5- and 10-year overall survival were 95.2% and 88.3%, respectively, while 5- and 10-year BC specific survival were 98% and 94.5%. The development of a 2ndLR significantly reduced BCSS (HR=9.40, P<0.001). Grade ≥3 fibrosis was 18.9%. Patient-reported cosmesis was good/excellent in 59.7% of the cases. Conclusion2ndLR CumI was within the range of the literature, but higher than expected, opening questions on radiation field extension and fractionation schedule. Since a 2ndLR worsened the outcome, salvage modality must be carefully planned.

Osteolytic Bone Metastasis: Different Radiotherapy Fractionation Schedules Compared Clinically and Radiographically.

The purpose of this study is to compare three commonly used radiotherapy fractionation schedules for bone metastasis in terms of clinical and radiological effectiveness. A total of 93 patients with osteolytic bone metastasis were randomized to receive 8 Gyin a single fraction (group A), 20 Gy in 5 fractions (group B) and 30 Gy in 10 fractions (group C). Changes in bone density were measured using the Relative Electron Density (RED) type corrected by Thomas (pe = HU/1.950 + 1.0), where HU is Hounsfield Units. Pain response was assessed according to the Brief Pain Inventory tool. Quality of life was estimated using the EORTC QLQ-C30 and the MD Anderson Symptom (MDAS) tools.After RT, RED, together with the parameters of EORTC QLQ-C30, MDAS and SAT, significantly increased in all groups (p < 0.001).Specifically, the increase of RED was higher in group C compared to group Athree months post-RT (p = 0.014). Group C was also superior to group A in terms of QoL and BPI three months post-treatment. Multifractionated radiotherapy for osteolytic bone metastasis is superior to single fraction radiotherapy in terms of improvement in quality of life and bone remineralization three months post-RT.

HDAC-Mediated Glial Crosstalk Mediates Radiation Induced Memory Changes from Whole Brain Radiation in a Mouse Model

Prior work demonstrated radiation sensitivity can be regulated via Class III HDAC-mediated intracellular DNA damage response coordinated with Wnt-beta catenin signaling. We hypothesized that radiation induced functional alterations in HDAC mediated glial crosstalk in the CNS produce intercellular signaling alterations leading to phenotypic changes in cognition following whole brain radiation exposure. Primary human astrocytes, human astrocytoma (U251), and immortalized human microglia (HMC3) were examined in vitro in response to treatment with conditioned media isolated from irradiated glial cells. Prior to treatment with either single-dose or fractionated radiation schedules, cells were transfected with siRNA expression vector for Sirt2, a class III HDAC, versus scrambled controls. Quantitative PCR and immunoblots for neurotransmitters, metabolism, and inflammatory markers were obtained. Cells exposed to conditioned media were examined by immunofluorescence for cytoskeletal alterations and changes in junctional proteins. The findings were correlated with in vivo qPCR and immunohistochemical changes in brain tissue and functional memory changes in Sirt2 knockout versus wild type mice after whole brain radiation using novel object recognition testing at 2 weeks and 6 month post radiation timepoints. Statistical analysis was performed using paired Students T test between treated and control groups. Cells treated with conditioned media produced from irradiated U251, astrocytes and microglia produced increased expression of inflammatory cytokines IL-6, IL-8, GM-CSF and VEGF. However, immunofluorescence of cells treated with conditioned media from irradiated Sirt2 knockdown microglia and primary astrocytes demonstrated qualitative disruptions in glutamate neurotransmitter metabolism and actin cytoskeletal alterations with changes in pseudopodia and lamellipodia after staining with phalloidin and neurofilament L, suggesting altered intercellular communication. Connexin 43 in gap junctions was increased >2-fold (p<0.05) after exposure to conditioned media, whereas E-cadherin in adherens junctions was not significantly affected. Novel object recognition testing of Sirt2 knockout mice demonstrated resistance to radiation induced memory decline from whole brain radiation at pre radiation day 5 versus post radiation days 5 and 185 compared to controls (p<0.05). Glial crosstalk can be mediated via elimination of a Class III HDAC and appears to be a key mediator of radiation induced disruptions of intercellular communication in the CNS, connecting radiation to structural changes on the cell surface to synaptic activity and neurotransmitter metabolism, leading to functional disputations in recognition memory similar to what is experienced by patients receiving brain radiotherapy. These data suggest glial cross talk as a new therapeutic avenue to combat radiation induced cognitive dysfunction.

Quantitative and Qualitative Impact of CT-Based Radiotherapy Dose Maps on Radiologists' Interpretation of Post-treatment Thoracic Surveillance Imaging

For diagnostic radiologists, interpretation of surveillance imaging for oncology patients treated with radiation therapy (RT) can be challenging because (1) the imaging order may not adequately describe the radiation fields and (2) RT treatment effect and progression can appear similar. Volumetric dose visualization used for plan review is often inaccessible to radiologists. We hypothesize that displaying RT dose would improve radiologists' confidence and ability to correctly identify and distinguish irradiated targets and treatment effects. CT images were read by a board-certified cardiothoracic radiologist and a diagnostic radiology resident. The readers interpreted pre-RT, treatment planning, and 3-4 month post-RT CT images in anonymized software sessions first without, then-after a 1 month "washout" period-with access to RT dose overlay. Six color-coded isodose lines ranging from 25% to 110% represented in absolute cGy were displayed along with a brief clinical history. RT fractionation schedules ranged in BED10 from 39 to 112.5 Gy. Readers were asked to label the treated lesion(s) and treatment effect(s), and record their confidence using a Likert scale of 1-5 and agreement with statements using yes/no responses. Two readersindependently interpreted imaging for 32 patients who received thoracic RT to 1-5 lesion(s) for primary (24) or metastatic (8) cancer. Nineteen patients had 1 lesion and 13 patients had >1 lesion. Correct identification of all treated lesions significantly increased with the addition of dose visualization (61% to 81%; McNemar test, p = 0.00079), with the largest increase noted for cases with >1 lesion (15% to 54%; McNemar test, p = 0.0039). With the addition of dose information, the number of false negatives attributable to missed extranodal targets fell from 52% to 18%. Without dose information, 13% of labeled lesions and treatment effects fell outside of the 25% isodose lines, representing false positives. With the addition of dose information, false positives fell below 2% for both lesions and treatment effects. The readers' confidence that they had identified treated lesion(s) increased from a rating of 4.1 to 4.8 on a scale of 1-5 (Paired two-tail t test; p = 0.000005). Whendiagnostic radiologists have access to dose visualization, correct identification rate of irradiated lesions and treatment effects, as well as confidence in these identifications significantly increased. The decrease in false negatives could reduce potential missed identification of tumor progression while the decrease in false positives could reduce inaccurate identification of treatment failure in a new or stable lesion. Our results demonstrate that adding volumetric visualization of dose to imaging could improve quality of surveillance care for patients with irradiated thoracic malignancies.

Precision radiation oncology in head and neck cancer: beyond physical precision - a narrative review

Radiotherapy is an integral part of the management of head and neck cancers, both in radical and adjuvant settings. Traditionally, similar radiation dose and fractionation schedules have been used based on tumor stage with variable outcomes indicating “one size does not fit all”. In the era of precision medicine, though we have achieved physical precision with technological advancements, we have yet to attain biologic precision. In the current review, we have highlighted the different aspects of precision oncology such as hypoxia targeting, radiomics and radiogenomics, radiobiologic targeting, and big data. The review also discusses various potential therapeutic targets and approaches in head and neck cancer management that might help to increase radiosensitization, which in turn increase survival, and quality of life. This can be incorporated into the armamentarium of radiation oncology in all the phases of radiation planning, from diagnosis to treatment to the prognosis and management of long-term side effects. Biologic precision can be applied in the clinic to provide individualized, personalized treatment in the future.

Effect of Radiation Schedule on Transportation-Related Carbon Emissions: A Case Study in Rectal Cancer

The health care sector is a major contributor of worldwide greenhouse gas (GHG) emissions. Indirect emissions, including those associated with transportation, make up 82% of the US health care sector's environmental footprint. Radiation therapy (RT) treatment regimens present an opportunity for environmental health care-based stewardship owing to the high incidence of cancer diagnosis, significant utilization of RT, and myriad treatment days required for curative regimens. Because the use of short-course RT (SCRT) in the treatment of rectal cancer has demonstrated noninferior clinical outcomes compared with conventional, long-course RT (LCRT), we investigate the environmental and health equity-related outcomes. Patients treated with curative, preoperative RT for newly diagnosed rectal cancer at our institution between 2004 and 2022 and living in-state were included. Travel distance was estimated using patients' reported home address. Associated GHG emissions were calculated and reported in carbon dioxide equivalents (CO2e). Of 334 patients included, the total distance traveled for the treatment course was significantly greater in patients treated with LCRT versus SCRT (median, 1417 vs 319 miles; P < .001). Total CO2e emissions for those undergoing LCRT (n=261) and SCRT (n=73) were 665.3 kg CO2e and 149.9 kg CO2e, respectively, per treatment course (P < .001), with a net difference of 515.4 kg CO2e. Relatively, this suggests that LCRT is associated with 4.5 times greater GHG emissions from patient transportation. Using treatment of rectal cancer as proof-of-principle, we advocate for the inclusion of environmental considerations in the creation of climate-resilient oncologic RT practices, especially in the context of equivocal clinical outcomes between RT fractionation schedules.

A comparative and prospective study of two different radiation fractionation schedules with concurrent chemotherapy in locally advanced head-and-neck squamous cell carcinoma

Background: Accelerated fractionation radiotherapy has radiobiological advantage of preventing accelerated tumor repopulation and logistic advantage of treating more patients than conventionally fractionated radiotherapy because of its relatively shorter treatment duration. Aims and Objectives: In this study, we compared accelerated fractionation with conventionally fractionated radiotherapy in terms of tumor response and acute toxicities for the treatment of locally advanced head-and-neck carcinomas. Materials and Methods: Patients with Stage III and IVA carcinoma of head-and-neck region were randomized into two groups. The study group patients received accelerated radiotherapy to a total dose of 66Gy in 33 fractions, 2Gy/fraction, 6 fractions/week over a time period of 5.5 weeks. Control group received conventionally fractionated radiotherapy to same total dose and fraction size but 5 fractions/week, over a time period of 6.5 weeks. Both groups received concurrent weekly Cisplatin. All patients were followed up weekly for treatment related acute toxicity during the treatment and then at every month for 6 months after completion of treatment. Results: About 26.6% patients of study arm achieved complete response in comparison to 25.6% of control arm, but the difference was not statistically significant (P=0.957). Although statistically not significant, higher grade of skin toxicity (60%vs.35%, P=0.179) and xerostomia (46% vs. 29%, P=0.155) was also numerically higher in accelerated fractionation. Conclusion: For locally advanced head-and-neck carcinoma, accelerated fractionation radiotherapy with concurrent chemotherapy can be considered as an acceptable and effective alternative of conventionally fractionated concurrent chemoradiotherapy in terms of treatment response and acute toxicity profile.

A PROSPECTIVE INTERVENTIONAL STUDY TO COMPARE THE TREATMENT OUTCOMES IN PATIENTS WITH TWO DIFFERENT FRACTIONATION SCHEDULE OF WHOLE BRAIN RADIOTHERAPY WITH MULTIPLE BRAIN METASTASES

Purpose of study : To compare the treatment outcomes in patients with brain metastasis treated with two different fractionation schedules of whole brain radiotherapy. A prospective randomised study was carried out on newly diagnosed cancer patients with MRIMaterials and methods: diagnosis of brain metastasis. Patients with multiple bm with Eastern Cooperative Oncology Group performance status 0-4 were included. In Arm A, patients received whole brain radiotherapy (WBRT) of total dose 30 GY , 3Gy/fraction/10# over 2 weeks ,whereas , in Arm-B patients received total dose of 20 GY in 4Gy/fraction/5# over 1 week. Assessment of improvement in clinical symptoms was done using BARTHEL'S ADJUSTED DAILY LIVE (ADL)14 Score before treatment, just after treatment and 6 week of treatment and improvement was analysed. At three months follow up , radiological response was carried out by MRI scan of brain. Acute toxicities were assessed during treatment and follow up ( up to 90 days post EBRT ) using clinical status, laboratory investigations and radiological test and graded according to RTOG/EORTC criteria. Results: Signicant improvement in terms of ADL score was observed in both arms , however when both arms were compared , no signicant difference was found out. There was no statistically signicant difference in response or morbidity between the two treatment arms. In theConclusions: palliative setting short duration of treatment with minimum discomfort to the patient is desirable. 20 Gy in 5 fractions is equally effective as 30 Gy in 10 fractions, with slight advantage in terms of toxicity. Thus 20 Gy in 5 fractions can be preferred in brain metastasis patients, especially those with poor performance status.

Radiation doses and fractionation schedules in non-low-risk ductal carcinoma in situ in the breast (BIG 3–07/TROG 07.01): a randomised, factorial, multicentre, open-label, phase 3 study

Whole breast irradiation (WBI) after conservative surgery for ductal carcinoma in situ (DCIS) reduces local recurrence. We investigated whether a tumour bed boost after WBI improved outcomes, and examined radiation dose fractionation sensitivity for non-low-risk DCIS. The study was an international, randomised, unmasked, phase 3 trial involving 136 participating centres of six clinical trials organisations in 11 countries (Australia, New Zealand, Singapore, Canada, the Netherlands, Belgium, France, Switzerland, Italy, Ireland, and the UK). Eligible patients were women aged 18 years or older with unilateral, histologically proven, non-low-risk DCIS treated by breast-conserving surgery with at least 1 mm of clear radial resection margins. They were assigned to one of four groups (1:1:1:1) of no tumour bed boost versus boost after conventional versus hypofractionated WBI, or randomly assigned to one of two groups (1:1) of no boost versus boost after each centre prespecified conventional or hypofractionated WBI. The conventional WBI used was 50 Gy in 25 fractions, and hypofractionated WBI was 42·5 Gy in 16 fractions. A boost dose of 16 Gy in eight fractions, if allocated, was delivered after WBI. Patients and clinicians were not masked to treatment allocation. The primary endpoint was time to local recurrence. This trial is registered with ClinicalTrials.gov (NCT00470236). Between June 25, 2007, and June 30, 2014, 1608 patients were randomly assigned to have no boost (805 patients) or boost (803 patients). Conventional WBI was given to 831 patients, and hypofractionated WBI was given to 777 patients. Median follow-up was 6·6 years. The 5-year free-from-local-recurrence rates were 92·7% (95% CI 90·6-94·4%) in the no-boost group and 97·1% (95·6-98·1%) in the boost group (hazard ratio 0·47; 0·31-0·72; p<0·001). The boost group had higher rates of grade 2 or higher breast pain (10% [8-12%] vs 14% [12-17%], p=0·003) and induration (6% [5-8%] vs 14% [11-16%], p<0·001). In patients with resected non-low-risk DCIS, a tumour bed boost after WBI reduced local recurrence with an increase in grade 2 or greater toxicity. The results provide the first randomised trial data to support the use of boost radiation after postoperative WBI in these patients to improve local control. The international scale of the study supports the generalisability of the results. National Health and Medical Research Council of Australia, Susan G Komen for the Cure, Breast Cancer Now, OncoSuisse, Dutch Cancer Society, Canadian Cancer Trials Group.

Low-dose localised electron radiotherapy in a case of refractory mycosis fungoides

We present a case of refractory mycosis fungoides (MF) that responded to low-dose localised electron radiotherapy. A 59-year-old man presented with a 5-year history of a generalised, pruritic, scaly, red skin rash that had recently become more nodular. Skin biopsy confirmed MF. After a variable initial response to topical steroids and oral methotrexate, progressive tumours were treated with low-dose electron radiotherapy. We describe the clinical effect of different radiation doses and fractionation schedules applied over a 2-year period. Our experience in this case of MF suggests that low-dose localised electron radiotherapy offers excellent palliation by effectively resolving tumorous lesions, improving quality of life and allowing for retreatment of refractory lesions.