Advanced Radiotherapy Techniques Research Articles

Radiation therapy in functioning and no functioning pituitary neuroendocrine tumor: systematic review of the recent literature after 2011

SummaryNeuroendocrine pituitary tumor, a benign cells proliferation, can cause significant morbidity due to its local invasiveness and secretory properties. Historically, radiotherapy has been employed as a second or third-line treatment option, with studies dating back to the mid-20th century. However, advancements in radiotherapy techniques, such as intensity-modulated radiation therapy (IMRT), stereotactic radiosurgery, and proton therapy, have revolutionized treatment approaches. This review aims to critically evaluate the recent literature (2011–2022) on the use of radiotherapy in both functioning and nonfunctioning neuroendocrine pituitary tumor. We employed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) methodology to systematically analyze 52 articles, focusing on local and hormonal control, radiotherapy protocols, and treatment-related side effects.

Perianal leiomyosarcoma as a rare sequela of rectal cancer radiotherapy: a case report

Radiation-induced sarcomas (RIS) are iatrogenic malignancies that arise following high-dose radiotherapy, posing a significant clinical challenge due to their poor prognosis and resistance to conventional treatments. The incidence of RIS is increasing with advancements in radiotherapy techniques. This report presents a case of a 71-year-old male diagnosed with stage III rectal adenocarcinoma treated with neoadjuvant chemoradiotherapy and curative surgery. Three years postoperatively, he developed a low-grade radiation-induced leiomyosarcoma in the perianal region. Histopathological examination confirmed a spindle cell neoplasm with notable immunohistochemical markers. RIS often presents as aggressive high-grade tumors resistant to radiotherapy and chemotherapy, necessitating surgical resection as the primary treatment. This case underscores the importance of long-term surveillance post-radiotherapy and highlights the need for innovative therapeutic strategies, including immunotherapy. Despite being rare, RIS poses a significant risk following cancer treatment, making early detection through vigilant monitoring and advancements in therapeutic approaches crucial for improving patient outcomes.

What is the incidence and non-union rate of radiation-associated fractures? – A systematic review of the literature

BackgroundRadiation-associated fractures (RAFs) are a challenging complication in oncologic patients, yet their incidence remains unknown and optimal management lacks consensus. AimThis review aimed to evaluate the incidence of RAFs in the trunk, pelvis, and extremities as well as non-union rates of surgical and non-surgical treatment. Materials and methodsA systematic review of PubMed and Embase databases was conducted. The study was registered on PROSPERO (ID: CRD42024513017). Studies were included if they reported RAFs in oncologic populations, had a sample size of at least five patients, and provided extractable data on RAF incidence or number. The STROBE checklist was utilized for evaluation of study quality. For eligible studies, quantitative analyses were conducted to determine weighted incidence of RAF and fracture non-union. ResultsThirty-five studies comprising 9,980 patients treated with radiation therapy were included. The weighted incidence of RAFs was calculated to be 6.5% across 8,061 patients. The weighted incidence of femoral RAF was 5.2%, while pelvic RAF incidence was 17.1%. Non-union rates after initial treatment varied from 4% to 100%, with an overall weighted incidence of 48%. Treatments included intramedullary nailing, fixation with screws/plate, prosthetic replacement, conservative treatment, and amputation, with varying success rates. ConclusionThis review highlights RAFs as a significant complication of radiation therapy, with a weighted incidence of 6.5% and a non-union rate of 48%. Advanced radiation techniques have reduced RAF occurrences, but non-union remains a challenge, necessitating tailored treatment strategies. Further research is needed to optimize RAF management and improve patient outcomes.

Survival and Toxicity Outcomes with Radiotherapy Technique and Timing in the Management of Wilms Tumor: a Systematic Review to Inform a National Clinical Practice Guideline Development

Purpose: Wilms tumor (WT) management has evolved into a multimodality paradigm that includes radiotherapy (RT), usually as an adjuvant or consolidative modality. Protocols are refined to maximize cure and compliance while minimizing acute toxicity and long-term effects. RT technique and timing are two factors that could improve these outcomes. We reviewed the evidence on survival and toxicity outcomes among WT patients with conventional versus advanced RT techniques and early versus delayed RT to inform a Department of Health (DOH) commissioned guideline. Materials and Methods: We systematically searched PubMed, EuropePMC, EBSCOHost, HERDIN, systematic review and clinical trial registries and official websites of scientific societies for relevant publications and grey literature. Eligibility screening, risk-of-bias assessment and data extraction were performed using a single-reviewer approach. Given the study and data heterogeneity, only a qualitative synthesis was performed. Certainty of evidence assessment was done using the GRADE approach. Results: We screened 314 studies and included seven in the review, including a phase 1/2 trial and six retrospective studies, all from first-world countries (US, France, Netherlands), except one from a newly industrialized country (Brazil). The certainty of evidence on the survival and toxicity outcomes with advanced RT techniques was very low. Moderate-certainty evidence supports that giving RT >14 days after surgery leads to increased mortality. Conclusion: Current evidence does not support the routine use of advanced RT techniques; proper contextualization is necessary. Tertiary centers managing WT should strive to administer RT within 14 days after surgery whenever possible. Keywords: Wilms tumor, nephroblastoma, radiotherapy, intensity-modulated radiotherapy, survival, toxicity

La radiothérapie des CBNPC de stade III : nouvelles techniques, nouvelles combinaisons

Defining the optimal treatment approach for patients with stage III non-small cell lung cancer, where the loco-regional disease extension renders a surgical approach obsolete, represents an important clinical challenge. In addition, many of these patients present with several comorbidities, compromising their tolerance to treatment. This article describes how innovative radiotherapy approaches try to enhance loco-regional tumour control as a first step towards improved survival, often by exploring novel avenues to dose-escalation, while at the same time focus on limiting early and long-term radiation-induced toxicity by applying the most advanced radiotherapy techniques. Moreover, the path towards new combinations with systemic agents, particularly immunotherapy building on the actual standard of combined chemo-radiotherapy with durvalumab in consolidation, is reported. This article wants to give a balanced view on the importance to investigate how we can obtain better local and metastatic disease control by intensifying our combined treatment strategies, while bearing in mind that many of our patients in daily clinical practice may not be able tolerate this. This urges us to also explore less disruptive treatment approaches for our more frail and aged patient population and define in a multidisciplinary manner the most optimal treatment strategy for each individual patient in our daily clinical practice.1877-1203/© 2024 SPLF. Published by Elsevier Masson SAS. All rights reserved.

Health care system factors associated with receipt of treatment and treatment intent in stage III non-small cell lung cancer: A population-based study in Ontario

PurposeStage III non-small cell lung cancer (NSCLC) is a heterogeneous disease, with a spectrum of anatomic extent, health status, and treatment approaches. Receipt of treatment and its intent should be independent of health system factors where care quality is optimal. We investigated the degree that modifiable health system factors are associated with receipt of treatment and treatment intent in stage III NSCLC in a large, universal health system. MethodsThis was a population-based, retrospective cohort study with health administrative data from Ontario, Canada, 2010–2018 for those aged ≥ 20 years, with AJCC 7 or 8 stage III NSCLC. We explored system factors associated with NSCLC treatment: region of residence, diagnostic interval, travel distance, advanced radiation (e.g. IMRT, VMAT) and systemic therapy treatment volumes and year of treatment. The relative risk (RR) of (1) any treatment versus no treatment, and (2) palliative versus non-palliative treatment was determined, using multivariable stepwise Poisson regression models. We adjusted for patient, disease and treatment factors. ResultsWe identified 7,093 people with stage III NSCLC between 2010 and 2018. There were no system factors associated with receipt of treatment versus no treatment in adjusted analysis. The major system factor associated with palliative intent was region of residence (RR: Region ranges from 0.88 to 1.67, p < 0.001). Stratifying by era (2010–2012 vs. 2013–2015 vs. 2016–2018), there was an increase in receipt of curative treatment and use of advanced radiotherapy techniques and immunotherapy over time, but regional variation of treatment intent was similar. ConclusionsRegion of residence emerged as the major health system factor associated with treatment intent for stage III NSCLC. This variation remained, even as advances in radiotherapy and systemic therapy were adopted. Our study suggests possible opportunities to improve care outcomes by addressing unexplained regional variation in care.

Stereotactic Body Radiotherapy for Renal Cell Carcinoma-A Review of Use in the Primary, Cytoreductive and Oligometastatic Settings.

Renal cell carcinoma (RCC) has been increasing in incidence by around 1.5% per year for several years. However, the mortality rate has been decreasing by 1.6% per year, and this can be attributed to stage migration and improvements in treatment. One treatment modality that has emerged in recent years is stereotactic body radiotherapy (SBRT), which is an advanced radiotherapy technique that allows the delivery of high-dose radiation to the tumor while minimizing doses to the organs at risk. SBRT has developed a role in the treatment of early-stage, oligometastatic and oligoprogressive RCC. In localized disease, phase II trials and meta-analyses have shown that SBRT provides a very high probability of long-term local control with a low risk of severe late toxicity. In oligometastatic (OMD) RCC, the same level of evidence has similarly shown good local control and minimal toxicity. SBRT could also delay the necessity to start or switch systemic treatments. Medical societies have started to incorporate SBRT in their guidelines in the treatment of localized disease and OMD. A possible future role of SBRT involves cytoreduction. It is theorized that SBRT can lower tumor burden and enhance immune-related response, but it cannot be recommended until the results of the phase II trials are published.

A review of diamond dosimeters in advanced radiotherapy techniques.

This review article synthesizes key findings from studies on the use of diamond dosimeters in advanced radiotherapy techniques, showcasing their applications, challenges, and contributions to enhancing dosimetric accuracy. The article explores various dosimeters, highlighting synthetic diamond dosimeters as potential candidates especially due to their high spatial resolution and negligible ion recombination effect. The clinically validated commercial dosimeter, PTW microDiamond (mD), faces limitations in small fields, proton and hadron therapy and ultra-high dose per pulse (UHDPP) conditions. Variability in reported values for field sizes 2 2 is noted, reflecting the competition between volume averaging and density perturbation effects. PTW's introduction of flashDiamond (fD) holds promise for dosimetric measurements in UHDPP conditions and is reliable for commissioning ultra-high dose rate (UHDR) electron beam systems, pending the clinical validation of the device. Other advancements in diamond detectors, such as in 3D configurations and real-time dose per pulse x-ray detectors, are considered valuable in overcoming challenges posed by modern radiotherapy techniques, alongside relative dosimetry and pre-treatment verifications. The studies discussed collectively provide a comprehensive overview of the evolving landscape of diamond dosimetry in the field of radiotherapy, and offer insights into future directions for research and development in thefield.

571. A PHASE I/II MULTICENTER STUDY EVALUATING THE EFFICACY AND SAFETY OF INDUCTION IMMUNOCHEMOTHERAPY FOLLOWED BY CONCURRENT IMMUNO-CHEMORADIOTHERAPY IN UNRESECTABLE LA-ESCC

Abstract Background Despite advances in radiotherapy techniques, the prognosis for patients undergoing definite chemoradiotherapy remains suboptimal. There exists an urgent and unmet need to enhance the efficacy of concurrent chemoradiotherapy for patients with unresectable Locally Advanced Esophageal Squamous Cell Carcinoma (LA-ESCC). Immunotherapy, when combined with chemotherapy, has emerged as the established first-line treatment for advanced esophageal cancer. Significant tumor shrinkage and reduced tumor residual observed after induction immunotherapy might provide the potential to enhance locoregional control of radiotherapy as well as better protection of critical organs and circulating lymphocytes. Methods We conducted a multicenter, phase I/II study aiming to assess the efficacy and safety of induction immunochemotherapy followed by immuno-chemoradiotherapy (ICRT) for unresectable LA-ESCC (SCR-ESCC-002, NCT06173986) (Figure 1). Eligible patients will initiate treatment with 2-3 cycles of immunochemotherapy. Within 4 weeks after completing the induction treatment, patients without disease progression will proceed to receive concurrent radiotherapy (45-50Gy in 25 fractions), weekly chemotherapy, and PD-1 inhibitor on day1,22. Following immuno-chemoradiotherapy, patients will continue with immunotherapy maintenance until disease progression or unacceptable toxicity, for a maximum duration of one year. The study's dual primary endpoints are progression-free survival and treatment completion rate. Results As of January 2024, 13 eligible patients were enrolled in our trial, with median follow-up of 7.8 months. Due to tumor shrinkage of induction immunochemotherapy, radiation doses to normal tissues were significantly reduced, particularly for the lungs, heart, and vertebrae. All 13 patients completed the planned induction treatment and radiotherapy, with 8 completing more than 4 weekly chemotherapies. During ICRT, 10 of 13 patients experienced grade 3-4 adverse events. These included lymphopenia (69.23%), myelosuppression (46.15%), hepatitis (7.69%), esophagitis (7.69%), and pneumonitis (7.69%). Nine patients achieved a complete response, and 3 partial response 4 weeks after ICRT according to RECIST v1.1. Conclusion Decreased radiation volumes due to tumor regression brought by induction immunochemotherapy diminish the occurrence of non-hematological adverse events during ICRT. Preliminary analysis suggests that this therapeutic modality exhibits favorable safety profiles and yields a superior clinical complete response rate compared to definitive chemoradiotherapy alone. The trial is presently enrolling participants, and the confirmation of efficacy and survival outcomes necessitates larger sample sizes and extended follow-up durations.

Postoperative radiotherapy for thymic epithelial tumors: a narrative review.

Thymic epithelial tumors (TETs), including thymomas and thymic carcinomas, are rare mediastinal tumors. Surgical resection is the treatment strategy for resectable TETs, and postoperative radiotherapy (PORT) is administered to improve local control in patients with a high risk of recurrence. The rarity of TETs has led to a lack of randomized controlled trials, and the current indications for PORT rely largely on retrospective studies. This review analyzes the literature on TETs, highlighting PORT, to guide current research and future investigations. Studies that focused on TETs, addressed topics on PORT, and had English abstracts accessible online were eligible for inclusion in our review. We excluded case reports or review articles, articles written in languages other than English, articles published >30 years ago, and articles concerning thymic neuroendocrine tumors. Masaoka or Masaoka-Koga staging, World Health Organization (WHO) histological subtype, and resection status indicate PORT in resected TETs. Current literature suggests that PORT does not improve overall survival in stage I-IIA TETs, with inconsistent results for stage IIB-III TETs. Patients with a higher risk, such as carcinomas or WHO type B, might benefit from PORT if they do not develop distant metastasis. Determining which patients will benefit most from PORT requires further investigation. For recurrent TETs, the significance of applying PORT is unclear because available data are limited. Given the long-term survival of TETs, late toxicities, including radiation pneumonitis, radiation-induced cardiotoxicities, and secondary malignancies, must be addressed. Proton beam radiotherapy might reduce toxicities by sparing organs at risk compared to conventional photon beam radiotherapy. The use of high-precision radiation therapy, along with emerging immunotherapy, targeted therapy, and minimally invasive surgery, could improve TET outcomes. This review consolidates the literature on PORT for TETs, factoring in the Masaoka-Koga staging, WHO histological subtypes, and resection status. Varying results regarding PORT efficacy have led to an undefined strategy for stage IIB-III TETs. Although advanced radiotherapy techniques promise to reduce radiation-induced toxicities, further research is needed to investigate the efficacy of PORT and combination therapy.

2842: Advanced radiotherapy techniques for pediatric brain tumors in a Sub-Saharan African Center.

2842: Advanced radiotherapy techniques for pediatric brain tumors in a Sub-Saharan African Center.

Challenges and Opportunities in Developing an Oncology Clinical Trial Network in the United States Veterans Affairs Health Care System: The VA STARPORT Experience.

The United States Veterans Affairs (VA) Health Care System has a strong history of conducting impactful oncology randomized clinical trials (RCTs). We developed a phase II/III RCT to test the use of metastasis-directed therapy in Veterans with oligometastatic prostate cancer (OMPC)-the first VA RCT in OMPC that leverages novel imaging and advanced radiotherapy techniques. To accomplish this, we developed a clinical trial network to conduct the study. In this manuscript, we describe several challenges we encountered in study development/conduct and our strategies to address them, with the goal of helping investigators establish robust study networks to conduct clinical trials. In the study start-up, we encountered challenges in timely site activation, and leveraged project management to maximize efficiency. Additionally, there were several changes in the clinical paradigms in imaging and treatment that led to protocol amendments to ensure maximum equipoise, recruitment, and impact of the study. Specifically, we amended the trial to add de novo OMPC patients (from initially only recurrent OMPC) and expanded the study to allow up to 10 metastases (from initially five). Finally, in order to maintain local study team engagement, we developed initiatives to maximize collaboration and add value to the overall clinical program through study participation.

A comprehensive overview of radiation therapy impacts of various cancer treatments and pivotal role in the immune system.

The cancer treatment landscape is significantly evolving, focusing on advanced radiation therapy methods to maximize effectiveness and minimize the adverse effects. Recognized as a pivotal component in cancer and disease treatment, radiation therapy (RT) has drawn attention in recent research that delves into its intricate interplay with inflammation and the immune response. This exploration unveils the underlying processes that significantly influence treatment outcomes. In this context, the potential advantages of combining bronchoscopy with RT across diverse clinical scenarios, alongside the targeted impact of brachytherapy, are explored. Concurrently, radiation treatments serve multifaceted roles such as DNA repair, cell elimination, and generating immune stress signaling molecules known as damage-associated molecular patterns, elucidating their effectiveness in treating various diseases. External beam RT introduces versatility by utilizing particles such as photons, electrons, protons, or carbon ions, each offering distinct advantages. Advanced RT techniques contribute to the evolving landscape, with emerging technologies like FLASH, spatially fractionated RT, and others poised to revolutionize the field. The comprehension of RT, striving for improved treatment outcomes, reduced side effects, and facilitating personalized and innovative treatments for cancer and noncancer patients. After navigating these advancements, the goal is fixed to usher in a new era in which RT is a cornerstone of precision and effectiveness in medical interventions. In summarizing the myriad findings, the review underscores the significance of understanding the differential impacts of radiation approaches on inflammation and immune modulation, offering valuable insights for developing innovative therapeutic interventions that harness the immune system in conjunction with RT.

Peer Review in Radiation Oncology: Where Does the Middle East, North Africa, and Türkiye Region Stand?

This study aims to assess the status of radiation oncology peer review procedures across the Middle East, North Africa, and Türkiye (MENAT) region. A cross-sectional electronic survey was conducted among radiotherapy centers in the MENAT region in March 2024. It assessed peer review practices, departmental demographics, perceived importance of peer review, and potential barriers. Data from 177 radiation oncology centers revealed varying peer review implementation across the MENAT region. Egypt had the highest participation (16.4%) among all responders. Most centers (31%) treated 500-1,000 cases annually. The majority (77.4%) implemented peer review, with varying levels between countries and across different centers. Advanced radiotherapy techniques significantly correlated with implementation of peer review (P < .05). Peer review meetings were mostly scheduled on a weekly basis (46%) and organized by radiation oncologists (84.7%). Target volume contouring (89%) and radiotherapy prescription (82%) were frequently peer-reviewed. Respondents with peer review at their institutions significantly valued peer review for education, adherence to guidelines, improving planning protocols, and reducing variation in practice institutions without peer review (P < .05). The most frequently reported barriers to peer review were having a high number of patients (56%) and shortage of time (54%). Peer review is essential for improving the quality of practice in radiation oncology. Despite some discrepancies, numerous obstacles, and challenges in implementation, it is instrumental in the improvement of patient care in most centers throughout the region. Raising awareness among radiation oncologists about the importance of peer review is paramount to lead to better outcomes.

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

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

Characterization of the First Prototype of an Angular Independent Silicon Diode Array for Quality Assurance in Stereotactic Radiosurgery

Quality assurance (QA) ensures the accurate and safe delivery of radiation treatment. However, there are several challenges for advanced radiotherapy techniques, such as stereotactic radiosurgery (SRS), where substantial doses of radiation with multi-directional beams and variable dose rates are delivered to specific areas. Current dosimeters lack high precision, exhibiting issues with dependency on the angle of measurement and the dose rate. This study investigates the characterization of a two-dimensional edgeless silicon diode array for QA in SRS. This detector underwent evaluation of its dose linearity, percentage depth dose (PDD), output factors (OFs), dose rate variability, and angular dependence with megavoltage linear accelerator beams. The edgeless array demonstrated a linear response in the direct detection of MV therapeutic X-rays with sensitivity of 6.95 × 10−3 ± 2.3 × 10−5 Gy/nC, and the percentage differences for PDD and OF measurements were found to be within 2% compared to the reference detector. A dose per pulse dependence of ±2% was demonstrated across the range of 0.12 to 0.39 mGy/pulse. The angular dependence was within 2% variation for irradiation angles greater than 80° and smaller than 120°; however, a maximum of 4% variation was observed with some diodes for angles between 80° and 120°. The improved performance of the edgeless array is likely to overcome limitations of the current dosimeters for SRS QA by operating without the need of any corrections.

Locoregional Therapy for Early and Locally Advanced Breast Cancer

Objective: The objective of this article is to conduct a comprehensive review of recent advances in locoregional therapies for early and locally advanced breast cancer, emphasizing the integration of these approaches into comprehensive treatment plans. Initially, this study explores contemporary findings related to surgical techniques, radiation therapy, and the integration of systemic treatments, such as targeted therapies and chemotherapy, as part of a cohesive treatment strategy. Theoretical Framework: Breast cancer remains a significant public health issue, with locoregional therapy playing a critical role in the management of early and locally advanced stages of the disease. The evolution of treatment strategies reflects a deepening understanding of the disease's biological behavior and the necessity for tailored therapeutic approaches. Method: A systematic review was conducted using major scientific databases to collect relevant articles on recent advances in locoregional therapy for breast cancer, from surgical innovations to advanced radiation techniques. Specific keywords were used to identify studies that address new findings and interdisciplinary approaches, facilitating the synthesis of effective strategies and the identification of gaps in current research. Results and Discussion: Recent research has improved surgical precision and radiation delivery techniques, reducing side effects and enhancing treatment efficacy. Innovations in intraoperative radiation and the growing use of neoadjuvant therapies offer promising results, optimizing tumor control and preserving patient quality of life. However, challenges remain in achieving consistent results across different patient populations, underscoring the need for personalized treatment plans tailored to individual patient characteristics and tumor biology.

Real world outcomes of patients with small cell lung cancer (SCLC) presenting with brain metastasis at diagnosis in a single institution health system.

e20136 Background: Extensive-stage small cell lung cancer (ES-SCLC) is an aggressive lung cancer subtype with high propensity for brain metastases (mets). Despite this, there is no consensus on the treatment of brain mets especially in the setting of frontline chemoimmunotherapy and advanced radiation techniques like Gamma Knife radiosurgery (GKRS). Methods: In this single-institution retrospective study, we queried the Yale Tumor registry for all patients diagnosed with ES-SCLC in 1/2016-4/2023. Patients with brain mets at the time of presentation were identified and underwent manual chart review for abstraction of clinical information specifically pertaining to brain mets and treatment modalities. Survival outcomes including median progression free survival (mPFS), median central nervous system-progression free survival (mcPFS) and median overall survival (mOS) measured in months were also captured. Results: 423 ES-SCLC patients were identified. Of those, 92 (22%) had brain mets at initial presentation and were reviewed. 44 (48%) of patients with brain mets were treated with frontline chemotherapy (platinum doublet) while 42 (46%) were treated with chemoimmunotherapy (platinum doublet with atezolizumab or durvalumab). Patients treated with upfront chemotherapy had mPFS 6.4 (95% CI -1.2, 14.1), mcPFS 7.7 (95% CI -1.2, 17.1), and mOS 9.3 (95% CI -13.7, 36.4), compared to patients treated with chemoimmunotherapy, who had mPFS 4.9 (p=0.23; 95% CI -3.5, 15.4), mcPFS 6.7 (p=0.99; 95% CI 3.3, 20.8), and mOS 7.7 (p=0.89; 95% CI -11.4, 33.9). 63 (68%) of patients underwent upfront brain radiation. 44 (48%) had whole brain radiation (WBRT) while 19 (30%) underwent GKRS. Of the patients undergoing GKRS, 8 (42%) were symptomatic. 7 patients (37%) presented with 1 brain met, and 12 (63%) patients presented with 2-5 brain mets. For patients treated with GKRS, mPFS 6.8 (95% CI 2.3, 10.4), mcPFS 7.2 (95% CI 2.9, 12.6), and mOS 11.1 (95% CI -13.0, 40.9). For patients undergoing WBRT, mPFS 6.5 (p = 1.0; 95% CI -4.5, 20.2), mcPFS 6.5 (p = 0.96; 95% CI -3.9, 21.6), and mOS 8.6 (p = 0.21; 95% CI -17.7, 39.9). Conclusions: GKRS is a viable option for SCLC patients presenting with brain metastases, especially in those with a low number of mets. Further studies are required to determine the optimal ES-SCLC candidates for upfront GKRS. [Table: see text]

Investigation of triaxial cables and microdetectors in small field dosimetry

Background. Small field dosimetry presents unique challenges with source occlusion, lateral charged particle equilibrium and detector size. As detector volume decreases, signal strength declines while noise increases, deteriorating the signal-to-noise ratio (SNR). This issue may be compounded by triaxial cables connecting detectors to electrometers. However, effects of cables, critical for precision dosimetry, are often overlooked. There is a need to evaluate triaxial cable and detector impacts on SNR in small fields. The purpose of this study is to evaluate the influence of triaxial cables and microdetectors on signal-to-noise ratios in small-field dosimetry. This study also aims to establish the importance of cable quality assurance for measurement accuracy. Methods. Six 9.1 m length triaxial cables from different manufacturers were tested with six microdetectors (microDiamond, PinPoint, EDGE, Plastic scintillator, microSilicon, SRS-Diode). A 6 MV photon beam (TrueBeam) was used, with a water phantom at 5 cm depth with 0.5 × 0.5 cm2 to 10 × 10 cm2 fields at 600 MU min−1. Readings were acquired using cable-detector permutations with a dedicated electrometer (except the scintillator which has its own). Cables had differing connector types, conductor materials, insulation, and diameters. Detectors had various sensitive volumes, materials, typical signals, and bias voltages. Results. Normalized field output correction factors (FOFs) relative differences of 13.4% and 4.6% between the highest and lowest values across triaxial cables for 0.5 × 0.5 cm2 and 1 × 1 cm2 fields, respectively. The maximum difference in FOF between any cable-detector combinations was 0.2% for the smallest field size. No consistent FOF trend was observed across all detectors when increasing cable diameter. Additionally, the non-normalized FOF differences of 0.9% and 0.3% were observed between cables for 0.5 × 0.5 cm2 and 1 × 1 cm2 fields, respectively. Conclusions. Regular triaxial cable quality assurance is critical for precision small field dosimetry. A national protocol is needed to standardize cable evaluations/calibrations, particularly for small signals (<pC) from modern detectors. This could enhance measurement accuracy and treatment delivery with advanced small-field radiotherapy techniques that promise improved patient outcomes. Further studies should expand detector and cable models tested across institutions to establish robust quality control guidelines.

Clinical Biomarkers of Tumour Radiosensitivity and Predicting Benefit from Radiotherapy: A Systematic Review.

Modern advanced radiotherapy techniques have improved the precision and accuracy of radiotherapy delivery, with resulting plans being highly personalised based on individual anatomy. Adaptation for individual tumour biology remains elusive. There is an unmet need for biomarkers of intrinsic radiosensitivity that can predict tumour response to radiation to facilitate individualised decision-making, dosing and treatment planning. Over the last few decades, the use of high throughput molecular biology technologies has led to an explosion of newly discovered cancer biomarkers. Gene expression signatures are now used routinely in clinic to aid decision-making regarding adjuvant systemic therapy. They have great potential as radiotherapy biomarkers. A previous systematic review published in 2015 reported only five studies of signatures evaluated for their ability to predict radiotherapy benefits in clinical cohorts. This updated systematic review encompasses the expanded number of studies reported in the last decade. An additional 27 studies were identified. In total, 22 distinct signatures were recognised (5 pre-2015, 17 post-2015). Seventeen signatures were 'radiosensitivity' signatures and five were breast cancer prognostic signatures aiming to identify patients at an increased risk of local recurrence and therefore were more likely to benefit from adjuvant radiation. Most signatures (15/22) had not progressed beyond the discovery phase of development, with no suitable validated clinical-grade assay for application. Very few signatures (4/17 'radiosensitivity' signatures) had undergone any laboratory-based biological validation of their ability to predict tumour radiosensitivity. No signatures have been assessed prospectively in a phase III biomarker-led trial to date and none are recommended for routine use in clinical guidelines. A phase III prospective evaluation is ongoing for two breast cancer prognostic signatures. The most promising radiosensitivity signature remains the radiosensitivity index (RSI), which is used to calculate a genomic adjusted radiation dose (GARD). There is an ongoing phase II prospective biomarker-led study of RSI/GARD in triple negative breast cancer. The results of these trials are eagerly anticipated over the coming years. Future work in this area should focus on (1) robust biological validation; (2) building biobanks alongside large radiotherapy randomised controlled trials with dose variance (to demonstrate an interaction between radiosensitivity signature and dose); (3) a validation of clinical-grade cost-effective assays that are deliverable within current healthcare infrastructure; and (4) an integration with biomarkers of other determinants of radiation response.