Local Control Research Articles

The 5-factor modified frailty index as a prognostic factor for stereotactic radiosurgery in meningioma management

Abstract Purpose Meningiomas are the most frequent primary intracranial malignancy. While surgical resection can confer long term tumor control, stereotactic radiosurgery (SRS) is often used for small, asymptomatic tumors in the adjuvant setting. Frailty has been associated with increased rates of peri-operative morbidity but has yet to be defined in the setting of SRS for meningiomas. We therefore sought to examine the relationship between frailty and clinical/radiographic outcomes of patients with meningiomas who have undergone SRS. Methods A single-center, retrospective cohort study classified patients by their 5-factor modified frailty index (mFI-5) score into pre-frail (0–1) and frail (2–5) at the time of SRS treatment. Evaluations of overall survival (OS), progression free survival (PFS), local control (LC), and distant control (DC) were performed using Kaplan–Meier analysis. Cox proportional hazards regression analysis was used to further define factors associated with OS/PFS. Results 94 patients met inclusion criteria and underwent SRS for meningioma treatment from 2019 to 2023. Analyses compared prefrail (0–1) and frail (2–5) individuals. Kaplan–Meier analysis demonstrated a near significant association between frailty and OS (HR 3.66, 95% CI 0.49–26.8 p = 0.05) with 3-year OS rates of 75.4% in the pre-frail versus 36.6% in the frail group. However, a significant relationship was demonstrated between frailty and PFS (HR: 2.95 95% CI 1.12–7.81, p = 0.02) with 3-year PFS rates of 90.5% in the pre-frail group versus 49.2% in the frail group. Univariable regression analysis demonstrated that frailty, prior surgical excision, and cumulative tumor volume predicted PFS. Conclusion Frailty, as assessed by the mFI-5, did not independently predict OS but did predict PFS in individuals with meningioma undergoing SRS.

Interstitial HDR brachytherapy for anal cancer—results and quality of life

Abstract Purpose While anal cancer is a very rare oncological diagnosis representing less than 2% of lower gastrointestinal tract cancers, the incidence has doubled in the past 20 years. Radical radiochemotherapy with sequential or simultaneous boost is now the standard treatment modality. Interstitial HDR brachytherapy is one of the boost application options. Implementation of new radiotherapy techniques has resulted in improved therapeutic outcomes; however, it is still associated with acute and especially late toxicity. Gastrointestinal disorders and sexual dysfunction are the most frequent factors affecting the long-term quality of cured patients’ lives. Methods A total of 96 patients consecutively treated between 2000 and 2022 with external beam radio-/chemotherapy and an interstitial brachytherapy boost for histologically verified nonmetastatic anal squamous cell carcinoma were evaluated. The median follow-up time was 15.4 years (range 13.4–17.3 years). The primary objective of the study was to assess local control (LC) and quality of life (QoL). The Czech versions of internationally validated EORTC questionnaires were used to evaluate life quality—the basic EORTC QOL-C30 v.3 and the specific QOL-ANL 27 questionnaire. Results Local control was 85.5% at 5 years, 83.4% at 10 years, 83.4% at 15 years, and 83.4% at 20 years, and there was no dependence on clinical stage. The most common forms of acute toxicity were cutaneous and hematological but were gastrointestinal for late toxicities. In the evaluation of quality of life, 80.5% of patients alive at the time participated. In the EORTC quality of life questionnaire C30 v.3, patients rated the functional scale score as 86.2 points (standard deviation [SD] = 12.6) and the symptom score as 15.5 points (SD = 12.5). The global health score achieved 68.4 points (SD = 23.6). The most common symptoms were fatigue with 25.6 points (SD = 20.2) and diarrhea with 19.0 points (SD = 27.8). In the QOL-ANL 27 questionnaire, symptom scales assessing bowel symptoms were scored 27.5 points (SD = 19) in non-stoma patients and 11.9 points (SD = 17.2) in stoma patients. In the single-item symptom scales, the highest scores were rated for frequency of urination with 26.4 points (SD = 30.8), need to be close to a toilet with 22.4 points (SD = 27.3), and self-cleaning more often with 25.3 points (SD = 31.8). In the functional scales assessing sex life and interest, men and women reported scores of 45.2 (SD = 23) and 45.5 points (SD = 19), respectively. Conclusion Boost with interstitial HDR brachytherapy is an established safe method of anal cancer treatment, with excellent results and limited late toxicity. Functioning scales were rated relatively highly in QoL questionnaires, and the overall global health score was comparable to published data. Gastrointestinal difficulties, fatigue, and sexual dysfunction dominated the symptom scales in our cohort.

Lateral facies heterogeneity and carbonate productivity changes during the Lower Jurassic of the Traras Mountains (NW Algeria): local versus regional controls

Lateral facies heterogeneity and carbonate productivity changes during the Lower Jurassic of the Traras Mountains (NW Algeria): local versus regional controls

Cell Adhesion and Local Cytokine Control on Protein‐Functionalized PNIPAM‐co‐AAc Hydrogel Microcarriers

AbstractAchieving adequate cell densities remains a major challenge in establishing economic biotechnological and biomedical processes. A possible remedy is microcarrier‐based cultivation in stirred‐tank bioreactors (STBR), which offers a high surface‐to‐volume ratio, appropriate process control, and scalability. However, despite their potential, commercial microcarriers are currently limited to material systems featuring unnatural mechanical properties and low adaptability. Because matrix stiffness and ligand presentation impact phenotypical attributes, differentiation potential, and genetic stability, biotechnological processes can significantly benefit from microcarrier systems tailorable toward cell‐type specific requirements. This study introduces hydrogel particles co‐polymerized from poly(N‐isopropylacrylamide) (PNIPAM) and acrylic acid (AAc) as a platform technology for cell expansion. The resulting microcarriers exhibit an adjustable extracellular matrix‐like softness, an adaptable gel charge, and functional carboxyl groups, allowing electrostatic and covalent coupling of cell adhesive and cell fate‐modulating proteins. These features enable the attachment and growth of L929 mouse fibroblast cells in static microtiter plates and dynamic STBR cultivations while also providing vital growth factors, such as interleukin‐3, to myeloblast‐like 32D cells over 20 days of cultivation. The study explores the effects of different educt compositions on cell‐particle interactions and reveals that PNIPAM‐co‐AAc microcarriers can provide both covalently coupled and diffusively released cytokine to adjacent cells.

Gain-of-Function and Loss-of-Function Mutations in the RyR2-Expressing Gene Are Responsible for the CPVT1-Related Arrhythmogenic Activities in the Heart

Mutations in the ryanodine receptor (RyR2) gene have been linked to arrhythmia and possibly sudden cardiac death (SCD) during acute emotional stress, physical activities, or catecholamine perfusion. The most prevalent disorder is catecholaminergic polymorphic ventricular tachycardia (CPVT1). Four primary mechanisms have been proposed to describe CPVT1 with a RyR2 mutation: (a) gain-of-function, (b) destabilization of binding proteins, (c) store-overload-induced Ca2+ release (SOICR), and (d) loss of function. The goal of this study was to use computational models to understand these four mechanisms and how they might contribute to arrhythmia. To this end, we have developed a local control stochastic model of a ventricular cardiac myocyte and used it to investigate how the Ca2+ dynamics in the mutant RyR2 are responsible for the development of an arrhythmogenic episode under the condition of β-adrenergic (β-AR) stimulation or pauses afterward. Into the model, we have incorporated 20,000 distinct cardiac dyads consisting of stochastically gated L-type Ca2+ channels (LCCs) and ryanodine receptors (RyR2s) and the intervening dyadic cleft to analyze the alterations in Ca2+ dynamics. Recent experimental findings were incorporated into the model parameters to test these proposed mechanisms and their role in triggering arrhythmias. The model could not find any connection between SOICR and the destabilization of binding proteins as the arrhythmic mechanisms in the mutant myocyte. On the other hand, the model was able to observe loss-of-function and gain-of-function mutations resulting in EADs (Early Afterdepolarizations) and variations in action potential amplitudes and durations as the precursors to generate arrhythmia, respectively. These computational studies demonstrate how GOF and LOF mutations can lead to arrhythmia and cast doubt on the feasibility of SOICR as a mechanism of arrhythmia.

Radiation Therapy for Cutaneous Blastic Plasmacytoid Dendritic Cell Neoplasm: A Case Report and Review of the Literature

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a clinically aggressive hematologic malignancy derived from plasmacytoid dendritic cells. It commonly presents as cutaneous lesions. To date, no standard treatment protocol for BPDCN exists. Traditionally treated similarly to acute leukemia or lymphoma, its prognosis remains poor. Radiation therapy is employed for isolated skin lesions, for patients that are ineligible for chemotherapy due to age or comorbidities and for post-chemotherapy recurrence. However, very limited reports are available on radiotherapy for BPDCN. We present a case involving a 94-year-old BPDCN patient treated with radiation therapy, highlighting an atypical situation of two separate radiotherapy sessions with different dosages for isolated skin lesions. Initially, 45 Gy was administered in 15 fractions (45 Gy/15 Fr), followed by a second session of 30 Gy in 10 fractions (30 Gy/10 Fr) after disease recurrence. This case is unique in detailing radiation therapy for the exceedingly rare BPDCN, particularly dose fractionation. The findings indicate that 45 Gy/15 Fr can provide adequate local control, while even a lower dose of 30 Gy/10 Fr may be effective. This case report contributes to the limited literature by proposing potential therapeutic approaches and dosage guidelines to refine future BPDCN treatment protocols.

Clinical outcomes after extra-articular resection of hip joint tumour using a custom-made osteotomy guide and 3D-printed endoprosthesis with posterior column preserved

AimsFor rare cases when a tumour infiltrates into the hip joint, extra-articular resection is required to obtain a safe margin. Endoprosthetic reconstruction following tumour resection can effectively ensure local control and improve postoperative function. However, maximizing bone preservation without compromising surgical margin remains a challenge for surgeons due to the complexity of the procedure. The purpose of the current study was to report clinical outcomes of patients who underwent extra-articular resection of the hip joint using a custom-made osteotomy guide and 3D-printed endoprosthesis.MethodsWe reviewed 15 patients over a five-year period (January 2017 to December 2022) who had undergone extra-articular resection of the hip joint due to malignant tumour using a custom-made osteotomy guide and 3D-printed endoprosthesis. Each of the 15 patients had a single lesion, with six originating from the acetabulum side and nine from the proximal femur. All patients had their posterior column preserved according to the surgical plan.ResultsPostoperative pathological assessment revealed a negative surgical margin was achieved in all patients. At final follow-up, 13.3% (2/15) died and no recurrence occurred. The overall survival was 81.7% at five years. None of the patients showed any signs of aseptic loosening, and no wound healing issues were observed. In total, 20% (3/15) developed complications, with two cases of early hip dislocation and one case of deep infection. The cumulative incidence of mechanical and non-mechanical failure in this series was 13.7% and 9.3%, respectively, at five years. In this cohort, the mean time to full weightbearing was 5.89 (SD 0.92) weeks and the mean Musculoskeletal Tumor Society score was 24.1 (SD 4.4).ConclusionFor patients with a hip joint tumour who met the inclusion criteria and were deemed suitable for posterior column preservation, a custom-made osteotomy guide combined with 3D-printed endoprosthesis is worth performing when treating patients who require extra-articular resection of the hip joint, as it can achieve adequate margin for local control, maximize bone preservation to maintain pelvic ring integrity, reduce the risk of complications by simplifying the surgical procedure, and allow for more precise reconstruction for better function.Cite this article: Bone Jt Open 2024;5(11):1027–1036.

Efficacy of palliative hemostatic radiotherapy for tumor bleeding and pain relief in locally advanced pelvic gynecological malignancies

Abstract Purpose The appearance of symptomatic tumor-related vaginal bleeding and pain in advanced incurable cancer patients with pelvic gynecological malignancies remains a therapeutic challenge in oncological treatment. The aim of our analysis was to evaluate the efficacy and safety of palliative hemostatic radiotherapy. Methods We retrospectively identified patients who had received palliative hemostatic radiotherapy (RT) at our institution between 2011 and 2023 and evaluated acute toxicity, local control, cessation of bleeding, and pain relief. Results In total, 40 patients with a median planning target volume of 804 cm3 were treated with a median total dose of 39 Gy in 13 fractions, resulting in 6‑month and 1‑year local control rates of 66.9 and 60.8%, respectively. No higher-grade (>grade III) acute RT-induced toxicity appeared. Complete cessation of bleeding was achieved in 80.0% of all patients after a median of 16 days and pain relief was documented in 60.9% at first follow-up. 37.5% of the women required a blood transfusion and 25% an additional tamponade with local hemostatic agents. Successful stopping of bleeding was significantly less frequent in patients receiving anticoagulation concurrently with radiation and in the case of infield re-irradiation. Patients with a higher total RT dose had cessation of bleeding significantly more often, with a cut-off value of at least EQD2 (α/β = 10) = 36 Gy. The applied RT technique and planning target volume had no significant influence on the occurrence of bleeding cessation. Conclusion Palliative hemostatic radiotherapy for locally advanced pelvic gynecological malignancies is safe and effective in achieving high control rates of hemostasis in tumor bleeding and pain relief.

The Evolving Role of Neoadjuvant Radiation Therapy in Pancreatic Adenocarcinoma

Background/Objectives: Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers. Surgical resection is the most reliable chance for cure, but high rates of positive margins and local failure persist. Neoadjuvant therapies (NAT), including chemotherapy and radiation therapy (RT), are being explored to improve surgical outcomes, particularly in borderline resectable (BRPC) and locally advanced pancreatic cancer (LAPC). This review aims to summarize the current landscape and future directions for neoadjuvant RT (NART) in PDAC. Methods: The review includes a detailed analysis of past and ongoing clinical trials investigating various NART approaches in PDAC, with an emphasis on different RT techniques, fractionation schemes, and their integration into multimodal treatment strategies. Results: Early evidence suggests that NART can improve resection margins and local control. However, recent trials, including the Alliance A021501 and LAP-07 trials, have failed to demonstrate significant survival benefits with the addition of RT to NAT. Nevertheless, nuances in trial design and execution continue to keep the question of NART open. Newer approaches, such as stereotactic magnetic resonance-guided adaptive radiation therapy (SMART), show promise in improving local control and survival, but further phase 3 trials are needed. Conclusions: While NART has shown potential in improving local control in PDAC, its impact on overall survival remains unclear. Ongoing trials, particularly those utilizing advanced techniques like SMART, are critical in defining the role of RT in the neoadjuvant setting for PDAC. Collaboration across multidisciplinary teams is essential to optimize treatment strategies and trial outcomes.

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.

RADT-11. FACTORS ASSOCIATED WITH LOCAL FAILURE AFTER STEREOTACTIC RADIATION TO THE SURGICAL BED OF BREAST CANCER PATIENTS WITH A SINGLE BRAIN METASTASIS

Abstract BACKGROUND Metastatic breast cancer is the second most common cancer associated with brain metastases (BCBM). In our study we evaluated variables that influence local control in this breast cancer patients with a single BCBM who underwent surgical resection and stereotactic radiation to resection cavity. METHODS After ethics approval, we conducted a retrospective review of the medical records of BCBM patients treated with stereotactic radiation for BCBM between 2011 to 2022. Only breast cancer patients with a single BCBM who underwent surgical resection and stereotactic radiation to the surgical cavity were included. Clinical and dosimetric variables were analyzed to evaluate their impact on local control. Statistical analysis included descriptive analyses. X2 test was used for categorical variables. Total dose, dose per fraction, biologically effective dose (BED), and planning target volumes were analyzed as both continuous and categorical variables at different thresholds. A binary regression model was applied to study variables shown to impact local control. RESULTS A total of 62 patients included local control was 70.9% at 12 months. HER-2 disease, luminal-B, size of BCBM, time from craniotomy, total dose, inclusion of corridor, and non-cystic lesion were significant for local control. CONCLUSION Our data supports previous publications about the importance of tumor bed delineation, dose and fractionation, and time from craniotomy as factors associated with better local control. Our study shows that the role of BCBM subtype and new systemic therapies in contributing to local and intracranial control should be further explored.

RADT-22. EFFICACY AND SAFETY OF CYBERKNIFE STEREOTACTIC RADIOSURGERY FOR OCCIPITAL CONDYLE METASTASIS

Abstract BACKGROUND Occipital condyle metastasis (OCM) is a rare condition characterized by severe occipital pain and neurological symptoms due to lower cranial nerve deficits, stemming from its anatomical location. Despite the widespread use of stereotactic radiosurgery (SRS) for cranial metastases, its specific impact on OCM remains underexplored. OBJECTIVE This study evaluates the efficacy and safety of CyberKnife SRS in treating OCM, focusing on symptom control and local tumor control. METHOD We retrospectively analyzed cases of OCM treated with SRS at our institute from 2012 to 2023, evaluating patient demographics, presenting symptoms, treatment parameters, and outcomes. Key measures included occipital pain, dysfunctions of cranial nerves IX, X, and XII, and local tumor control. RESULTS Eighteen patients (10 females) with a median age of 64 years (range: 40-79) were treated. Common presentations included occipital pain (44%) and lower cranial nerve deficits (28%). The median target volume was 6.95 cc (range: 0.95-72.7), and the median margin dose was 20 Gy (range: 16-40). The median follow-up period was 7 months (range: 1-44). Notably, only one patient experienced tumor recurrence and subsequently died from primary cancer progression five months after treatment. SRS achieved a 93.8% local tumor control rate over three years, with a median overall survival of 13 months. Among those presenting with symptoms, 87.5% reported pain relief, and 80% observed improvements in cranial nerve function. The only patient without clinical symptom improvement also had tumor recurrence. CONCLUSION CyberKnife SRS is a promising treatment for OCM, offering significant pain relief and improvement in neurological symptoms with excellent local control rates. This non-invasive therapy provides a valuable alternative to surgery, potentially enhancing the quality of life for patients with limited treatment options due to this challenging condition.

RADT-21. EFFICACY AND SAFETY OF DONUT-SHAPED CIRCUMFERENTIAL SPINE CYBERKNIFE STEREOTACTIC BODY RADIOTHERAPY FOR METASTATIC SPINE DISEASE

Abstract BACKGROUND Spinal metastases (SM) with epidural spinal cord compression (ESCC) are challenging to manage due to the risk of radiation-induced injury. Traditional approaches often avoid circumferential stereotactic body radiotherapy (SBRT) because of these risks. The efficacy and safety of donut-shaped circumferential SBRT, which envelops the spinal column while sparing the cord, remains underexplored. OBJECTIVE This study evaluates the safety and efficacy of donut-shaped circumferential spine CyberKnife SBRT in treating spinal metastases, focusing on preventing radiation-induced myelopathy and achieving local tumor control. METHOD We retrospectively analyzed patients treated with donut-shaped circumferential spine SBRT from 2014 to 2023. We evaluated demographics, grade of ESCC (Bilsky), prior treatments, symptoms, treatment parameters, and outcomes. Key measures included SBRT dosimetric data, radiation exposure to the spinal cord or cauda equina, adherence to dose-volume constraints, occurrence of post-SBRT myelopathy, other radiation-induced complications, and local tumor control. RESULTS Forty-eight lesions from 43 patients (median age: 65 years; range: 20-78) were analyzed. Only one patient underwent separation surgery for severe ESCC (Bilsky grade 3). The median clinical target volume (CTV) was 63.77 cc (range: 20.31-270.05), and the median margin dose was 24 Gy (range: 18-30). Over a median follow-up of 8 months (range: 1-91), local tumor control rates were 91.1% at 6 months, 87.1% at 1 year, 82.8% at 3 years, and 62.1% at 5 years. Median overall survival was 17 months. Of 20 lesions exceeding dose constraints, only one patient displayed clinical myelopathy symptoms, correlating with local tumor recurrence. There was no radiographic myelopathy or other radiation-induced complications during follow-up. CONCLUSION Donut-shaped circumferential spine CyberKnife SBRT provides effective and safe treatment for spinal metastases with or without epidural involvement. It achieves substantial local tumor control and has a minimal incidence of radiation-induced myelopathy, offering a viable non-surgical option for managing this complex condition.

SURG-53. LONG TERM FOLLOW-UP OF RESECTION PLUS CESIUM-131 BRACHYTHERAPY FOR PREVIOUSLY IRRADIATED RECURRENT BRAIN METASTASES

Abstract BACKGROUND Recurrent brain metastases (rBM) after previous radiosurgery present a clinical dilemma, as the advantages of reirradiation need to be weighed against the potential of significant radiation toxicity. Salvage resection with Cs-131 brachytherapy offers improved dosimetry due to reduced integral dose to healthy brain compared to repeat radiosurgery. We previously reported initial results of rBM treated with resection and salvage Cs131 brachytherapy; we present an updated analysis of tumor control with extended follow-up. METHODS We analyzed consecutive patients with rBM previously treated with radiosurgery, who underwent salvage resection plus implantation of Cs131 seeds (GammaTile, GT Medical Technologies). The prescribed brachytherapy dose was 60 Gy at 5mm from the cavity. Median follow-up was calculated using reverse Kaplan-Meier. Local recurrence was defined by new nodular contrast enhancement with hyperperfusion within 5mm of the resection cavity. Marginal recurrence was defined as >5mm but not beyond 1cm from the cavity. Local control and overall survival (OS) from brachytherapy were analyzed using Kaplan-Meier. RESULTS Twenty-five patients underwent Cs131 implantation in 30 tumor cavities. The median presurgical rBM maximal diameter was 2.95 cm (range 1.1-6.3). The most common histology was lung adenocarcinoma (n=8, 27%) followed by breast (n=7, 23%) and renal cell (n=3, 10%). Radiographic gross- or near-total resection was achieved in 80% of lesions. The median number of Cs131 seeds implanted was 17, (range 6-30), (median strength 3.5 U/seed). With median follow-up of 37 months (95%CI:29-45), twelve and 24-month OS was 55% and 41%, respectively. Four tumors recurred (3 in-field, one marginal) for a 1- and 2-year local control rate of 87% and 81%, respectively. Data for adverse radiation effects is under analysis and will be presented. CONCLUSIONS With over 3 years of follow-up, intraoperative brachytherapy with collagen-embedded Cs131 implants was associated with durable local control for this challenging clinical scenario. A randomized Phase II trial of Cs131 vs. standard of care for rBM (NCT04690348) is actively accruing.

RADT-50. CLINICAL OUTCOME OF DAILY 5-FRACTIONATED GAMMA KNIFE RADIOSURGERY FOR LARGE BRAIN METASTASES

Abstract INTRODUCTION With the introduction of the Gamma Knife Icon, hypo-fractionated Gamma Knife radiosurgery (GKRS) for large brain metastases (LBMs) is beginning to be performed. This study aimed to assess the clinical outcome and risk of the daily 5-fractionated GKRS for LBMs. METHODS A total of 100 patients who underwent 5-fractionated GKRS for LBMs (> 14cm3) were enrolled. Forty-six were male patients, and the median age was 60 years. Most common primary cancer sites were lung (41 non-small cell cancers), breast (24), and kidney (14). The median tumor volume was 22cm3 (14 – 69cm3) and marginal dose was 35Gy (50% isodose line) in 5 fractions. Median follow-up duration was 18 months (3 – 72 months). RESULTS The last follow-up showed local tumor control in 74 cases. The cumulative 1, 2, and 3-year local tumor control rates were 73, 65, and 60%, respectively. Eighty-six tumors showed best MRI response in a year, and median tumor volume decrease rate was 80% (22 – 100%). Thirty patients experienced dramatically tumor volume decrease (> 95%). Median progression free and overall survival were 7 and 16 months, respectively. Radiation necrosis occurred in 24 patients, of which only 9 had neurological symptoms and treated with steroid and bevacizumab. CONCLUSIONS The daily 5-fractionated GKRS for very LBMs showed favorable local tumor control and acceptable radiation necrosis, but questionable survival benefit. In the future, prospective multi-center study is needed.

EPID-26. STEREOTACTIC RADIOSURGERY FOR CRANIAL NERVE METASTASES: A SINGLE INSTITUTION EXPERIENCE

Abstract Cranial nerve metastases (CNM) can be primary via leptomeningeal metastasis or secondary by spread due to head and neck cancers or due to distant tumor metastasis to the skull base. In addition, they may cause cranial nerve-related symptoms that can impact patient quality of life. We performed a single-center retrospective cohort study of all patients with CNM treated with SRS at our institution between April 2003 and February 2021. Demographic and clinical information were retrieved from the electronic medical record. Median follow-up was 12.9 months. Our study cohort consisted of 9 patients with primary CNM and 8 with secondary CNM – for a total of 17 patients, with a total of 33 lesions (23 primary, 10 secondary). Eleven patients (64.7%) had symptoms caused by cranial nerve metastases. Symptoms were resolved in 5 of 11 patients (45.5%) after SRS. Patients with secondary CNM were more likely to have cranial nerve symptoms and more likely to have resolution of symptoms following SRS. The median time between SRS and symptom improvement was 3 months. Local tumor control was achieved in 30 of 33 lesions (90.9%). Local tumor control at 6 months and at 1 year were 100%. Our study suggests that SRS may be a safe and effective treatment for cranial nerve metastasis providing 90.9% local tumor control at final follow-up, and symptomatic stability or improvement in 90.9% of symptomatic cases. Patients with secondary CNM may stand to benefit more from a symptom management standpoint.

CTNI-75. TRIALS IN PROGRESS: REGISTRY OF SAFETY & EFFICACY IN ADULTS WITH PRIMARY & METASTATIC INTRACRANIAL TUMORS TREATED WITH START (GAMMATILES (CS-131 SOURCE BRACHY-THERAPY)): NCT04427384

Abstract INTRO This is the first observational registry study of R+STaRT, delivered by Cs-131 sources in permanently implanted resorbable collagen tile carriers, for patients with intracranial tumors. METHODS Since October 2020, 37 sites to-date have enrolled 359 patients with primary & metastatic intracranial tumors into the R+STaRT registry to assess the safety & efficacy of the addition of Gamma Tile to medically needed resection. Local control, overall survival, QOL, neurocognition, functional decline, and surgical and radiation associated AE’s are collected at 1, 3, 6, 9,12, 18 and 24 months, then every 6 months through 5 years. RESULTS Demographics include 359 patients, avg. age 57 y.o.. 162 malignant gliomas, 125 metastatic tumors, 38 meningiomas, and 34 rare other tumors. 197 Males (163 White, 23 Black, 5 Asian, and other races) and 157 Females (White 121, 28 Black, 0 Asian, and 8 other races). No unexpected outcomes reported in the hands of experienced providers have occurred, although close clinical-radiographic follow-up, to ensure early detection of possible treatment-effects, is paramount. Steroid-use, and above endpoints, continue to be collected. CONCLUSIONS In this observational registry of Gamma Tiles (Cs-131 source brachy-therapy) added to medically needed resections for patients with primary and metastatic intracranial tumors continues. Data will be used to benchmark clinical outcomes of R+STaRT therapy and allow for comparisons to existing standard-of-care treatments. The outcome measures captured will allow for evaluation of the potential risks and benefits of this treatment approach for patients in a real-world setting.

RADT-28. THE ROLE OF CRANIAL RE-IRRADIATION IN EGFR MUTANT LUNG CANCER PATIENTS WITH BRAIN METASTASES

Abstract INTRODUCTION Re-irradiation with stereotactic radiosurgery (SRS) or whole-brain radiotherapy (WBRT) may be used for treating recurrent brain metastases. Here, we are reporting on the rate of cranial re-irradiation based on our institutional experience in patients with mutated Epidermal Growth Factor Receptor Non-Small Cell Lung Cancer (mEGFR-NSCLC). METHODS This is a retrospective review of patients from three NYP-WCM hospitals with brain metastases treated with radiotherapy and Tyrosine Kinase Inhibitors (TKIs) from December 2012 to May 2023. RESULTS Ninety-eight patients (60.5%) out of 162 with brain metastases from mEGFR-NSCLC were treated with radiation. Twenty-seven patients (27.5%) were treated with WBRT. Among 71 patients treated with SRS, 10 (14.1%) patients underwent surgical resection of the dominant brain lesion followed by fractioned SRS (FSRS) to the surgical bed. Sixty-one (85.9%) patients received SRS for intact brain lesions ranging from single fraction 16-20Gy to FSRT with 24Gy –30Gy in 3-5 fractions based on the size and eloquence of the brain site of the brain metastasis. In the SRS group, fifteen (21.1%) patients required at least one more course of cranial irradiation. The mean duration of local intracranial control between the first and the second course of radiation was 19.6 months [range from 2.0- 56.7 months], while from the start of TKI to the first intracranial failure was 11.3 months [0.8m-45.3 months]. In the WBRT group, two patients (7.4%) were treated with another course of WBRT 20Gy in 5 fractions. These two patients started TKI simultaneously with their first course of WBRT; the mean duration of intracranial local control was 12.8 months [range from 11.6-14.1 months]. Both patients suffered significant cognitive declines. CONCLUSION In the Tyrosine Kinase Inhibitor era, patients with brain metastases from mEGFR-NSCLC have protracted progression-free survival. Multiple courses of cranial re-irradiation may be needed. Stereotactic radiotherapy should be preferred for the best results in preserving cognitive functions.

RTID-05. STUDY PROTOCOL: A MULTICENTER, INTERNATIONAL RANDOMIZED CONFIRMATORY TRIAL: LOW-ENERGY X-RAY INTRAOPERATIVE RADIATION THERAPY (LEX-IORT) VS. ADJUVANT FRACTIONATED STEREOTACTIC RADIOTHERAPY (FSRT) IN THE MANAGEMENT OF BRAIN METASTASES (LEXIMATE)

Abstract BACKGROUND Fractionated stereotactic radiotherapy to the resection cavity boosts local control of resected brain metastases significantly. However, start of systemic tumor-directed treatment may be protracted and in-hospital times prolonged. Lately, lex-ioRT of BM has been described as a safe and effective one stop-shop treatment modality with a 1-year local control rate of up to 98% while potentially improving patient convenience. Study Design: The LEXIMATE-trial is a multicenter, international, randomized open-label confirmatory trial comparing lex-IORT with FSRT of resected BM. In the experimental arm, INTRABEAM (Carl Zeiss Meditec AG) is used to deliver IORT by application of 50-kV photons at a standard dose of 30 Gy prescribed to the applicator surface. Standard linear accelerator or Gamma Knife based FSRT (3-7 fractions) to the surgical bed is used in the control arm. The primary endpoint is the cumulative incidence of local recurrences (as per RANO-BM) considering death without prior local recurrence as competing event. Inclusion criteria include histologically confirmed BM with indication for resection according to EANO-ESMO/ASCO-SNO-ASTRO guidelines, ≤5 other brain lesions compatible with BM and amenable to radiosurgery and history of solid cancer or CT scan suggestive for localized or metastasized solid cancer (except germ cell tumors, lymphoma, small-cell lung cancer). The resection cavity must be <5cm in size, IORT doses to brainstem or optical tract may not exceed 8 Gy. Study design: Randomized, open-label, non-inferiority. Sample size: 70 patients per group to show a non-inferiority of the experimental therapy compared to the control therapy with a power of approximately 80%. DISCUSSION The best radio-oncologic procedure for resected BM remains under debate. The LEXIMATE-trial offers an opportunity to provide more solid prospective data on effectiveness, safety and patient comfort both for established and new RT techniques.

SURG-41. OPTIMIZING PATIENT OUTCOMES IN PETROCLIVAL MENINGIOMA TREATMENT: EVALUATING SURGICAL, RADIOSURGICAL, RADIOTHERAPY AND COMBINED TREATMENT APPROACHES

Abstract Petroclival meningiomas pose a formidable challenge due to their proximity to critical neurovascular structures, necessitating complex surgical interventions with a high risk of complications. Stereotactic radiosurgery (SRS) offers an alternative or complementary treatment option, yet the optimal treatment strategy remains undefined. We aimed to evaluate the local control rates following surgical resection, radiotherapy, and SRS for petroclival meningiomas and to assess the incidence of cranial nerve palsies associated with each treatment modality. This retrospective study reviewed medical records of patients treated for petroclival meningiomas at Stanford University between 1980-April 2024. Pre- and post-treatment radiological data were analyzed to assess local control. Cranial nerve function was evaluated pre- and post-treatment, and at last follow-up. A total of 171 patients (129 females; median age 54.65 years) diagnosed with petroclival meningioma were identified. Treatment modalities included: 31 patients underwent surgical resection alone, 27 received SRS alone, 11 received radiotherapy alone, 36 underwent combined surgical resection and SRS, 28 received combined surgical resection and radiotherapy, 9 were treated with a triad of surgical resection, SRS, and radiotherapy, and 29 were managed with serial imaging alone. The percentage change of tumor volume from diagnosis to follow-up for these groups was -55.6%, 28.9%, 73.0%, -64.9%, -12.0%, 35.3%, and -8.8%, respectively. The incidence of new cranial nerve palsies was highest (68%) in patients who underwent surgical resection. The percentage of worsening pre-existing palsies was greater in patients receiving single-modality non-surgical treatment. Surgery, radiotherapy, and SRS demonstrated promising local control rates for specific patient cohorts with petroclival meningiomas. Patients receiving combination therapies generally fared better than those receiving single-modality treatments, with surgery followed by SRS yielding the best outcome. The incidence of cranial nerve palsies was lower following SRS and radiotherapy compared to surgery. Future research should focus on refining multi-modal treatment strategies to minimize complications and improve patient quality of life.