Fractionated Stereotactic Radiotherapy Research Articles

Stereotactic radiosurgery and radiotherapy for brainstem metastases: An international multicenter analysis.

Brainstem metastases (BSM) present a significant neuro-oncological challenge, resulting in profound neurological deficits and poor survival outcomes. Stereotactic radiosurgery (SRS) and fractionated stereotactic radiotherapy (FSRT) offer promising therapeutic avenues for BSM despite their precarious location. This international multicenter study investigates the efficacy and safety of SRS and FSRT in 136 patients with 144 BSM treated at nine institutions from 2005 to 2022. The median radiographic and clinical follow-up periods were 6.8 and 9.4 months, respectively. Predominantly, patients with BSM were managed with SRS (69.4%). The median prescription dose and isodose line for SRS were 18 Gy and 65%, respectively, while for FSRT, the median prescription dose was 21 Gy with a median isodose line of 70%. The 12-, 24-, and 36-month local control (LC) rates were 82.9%, 71.4%, and 61.2%, respectively. Corresponding overall survival rates at these time points were 61.1%, 34.7%, and 19.3%. In the multivariable Cox regression analysis for LC, only the minimum biologically effective dose was significantly associated with LC, favoring higher doses for improved control (in Gy, hazard ratio [HR]: 0.86, p < .01). Regarding overall survival, good performance status (Karnofsky performance status, ≥90%; HR: 0.43, p < .01) and prior whole brain radiotherapy (HR: 2.52, p < .01) emerged as associated factors. In 14 BSM (9.7%), treatment-related adverse events were noted, with a total of five (3.4%) radiation necrosis. SRS and FSRT for BSM exhibit efficacy and safety, making them suitable treatment options for affected patients.

Extended Long-Term Outcome After Conservative Decompressive Microsurgery and Routine Adjuvant Fractionated Stereotactic Radiotherapy for Symptomatic Cavernous Sinus Meningiomas

BACKGROUND AND OBJECTIVES: Cavernous sinus meningiomas (CSM) pose one of the most difficult to treat subgroup of skull base meningiomas. The purpose of this study was to evaluate the efficacy of an interdisciplinary treatment approach for symptomatic CSM which incorporated conservative function preserving microsurgery and routine adjuvant fractionated stereotactic radiotherapy (FSRT). METHODS: A homogenous group of patients with symptomatic primary CSM with extracavernous extension was treated between 2005 and 2012. All patients were available for a minimum follow-up of 5 years. Clinical follow-up included detailed examination of oculomotor deficits, visual status, and endocrinologic function. Radiologic follow-up was conducted by tumor volumetry. RESULTS: Overall, 23 patients were included in this study (78.3% women; median age 58 years). Diplopia was the most common presenting symptom, followed by headache and visual disturbances. Surgical morbidity was low (3/23; 13%). FSRT was applied after a median of 2 months after surgery. At a median clinical follow-up of 113 months, 70.45% of the presenting symptoms had improved, 25% remained unchanged, and in 2 cases (4.54%), worsening occurred. Overall tumor regression was evident in 19/21 World Health Organization 1 and in 1/2 of World Health Organization 2 CSM, respectively, at a median radiological follow-up of 103 months. CONCLUSION: Our findings demonstrate the efficacy of an interdisciplinary treatment approach for symptomatic primary CSM with extracavernous extension with decompression of neurovascular elements followed by FSRT. Precise preoperative planning and intraoperative decision making in combination with routine postoperative radiotherapy can achieve excellent tumor control, improve neurologic function, and minimize long-term morbidity.

1226 Early Versus Delayed Fractionated Stereotactic Radiotherapy for Nonfunctioning Pituitary Adenoma

INTRODUCTION: Stereotactic radiosurgery (SRS) can be used to treat residual or recurrent pituitary adenomas with good control rates. Fractionated stereotactic radiotherapy (FSRT) is a viable alternative with similar outcomes. It is currently unknown whether FSRT should be performed early for residual tumor or delayed until progression occurs. METHODS: A retrospective review of patients who underwent FSRT for a NFPA between January 2004 to December 2022 at a single institution was performed. We compared the endocrinologic, ophthalmologic, and radiographic outcomes in FSRT delivered as ADJ and PRG treatment. RESULTS: 75 patients were analyzed, with a median follow-up of 53 months. FSRT was administered to 35 and 40 patients as ADJ and PRG, with a median time to treatment of 5.5 and 40 months, respectively. The tumor control rate was 94.3% for ADJ and 95.0% for PRG. Treatment resulted in four (11.4%) versus seven (17.5%) new endocrinopathies and two (5.7%) versus one (2.5%) new visual deficits for ADJ versus PRG. A survival analysis of time-to-new endocrinopathy showed no difference between the two cohorts. Median time from surgery to new endocrinopathy was 15.5 months for ADJ and 102.0 months for PRG (p = 0.02). The rate of new endocrinopathy at five years was 22.2% in for ADJ and 18.8% for PRG (p = 0.80). CONCLUSIONS: FSRT is effective in treating NFPA for residual and progressive tumors, with excellent tumor control rates comparable to SRS and a low risk of developing new endocrinopathies and visual deficits. The delayed treatment in the PRG cohort resulted in a greater duration until the development of a new endocrinopathy, suggesting that observation followed by FSRT on tumor progression may delay the onset of hypopituitarism while maintaining similar effectiveness in tumor control.

The Recent Management of Vestibular Schwannoma Radiotherapy: A Narrative Review of the Literature.

Radiotherapy (RT) plays an important role in the therapeutic management of vestibular schwannoma (VS). Fractionated stereotactic radiotherapy (FSRT) or radiosurgery (SRS) are the two modalities available. The purpose of this article is to review the results of VS RT studies carried out over the last ten years. A literature search was performed with PubMed and Medline by using the words vestibular schwannoma, acoustic neuroma, radiotherapy, and radiosurgery. In small (<3 cm) VS, SRS offers a local control rate of >90%, which seems similar to microsurgery, with a favorable tolerance profile. Hypofractionated FSRT (three to five fractions) is a relatively recent modality and has shown similar outcomes to normofractionated FSRT. Hearing preservation may highly differ between studies, but it is around 65% at 5 years. SRS and FRST are non-invasive treatment options for VS. SRS is often preferred for small lesions less than 3 cm, and FSRT for larger lesions. However, no randomized study has compared these modalities.

Salvage Microsurgery Following Failed Primary Radiosurgery in Sporadic Vestibular Schwannoma

Management of sporadic vestibular schwannoma with radiosurgery is becoming increasingly common globally; however, limited data currently characterize patient outcomes in the setting of microsurgical salvage for radiosurgical failure. To describe the clinical outcomes of salvage microsurgery following failed primary stereotactic radiosurgery (SRS) or fractionated stereotactic radiotherapy (FSRT) among patients with sporadic vestibular schwannoma. This was a cohort study of adults (≥18 years old) with sporadic vestibular schwannoma who underwent salvage microsurgery following failed primary SRS/FSRT in 7 vestibular schwannoma treatment centers across the US and Norway. Data collection was performed between July 2022 and January 2023, with data analysis performed between January and July 2023. Salvage microsurgical tumor resection. Composite outcome of undergoing less than gross total resection (GTR) or experiencing long-term facial paresis. Among 126 patients, the median (IQR) age at time of salvage microsurgery was 62 (53-70) years, 69 (55%) were female, and 113 of 117 (97%) had tumors that extended into the cerebellopontine angle at time of salvage. Of 125 patients, 96 (76%) underwent primary gamma knife SRS, while 24 (19%) underwent linear accelerator-based SRS; the remaining patients underwent FSRT using other modalities. Postoperative cerebrospinal fluid leak was seen in 15 of 126 patients (12%), hydrocephalus in 8 (6%), symptomatic stroke in 7 (6%), and meningitis in 2 (2%). Each 1-mm increase in cerebellopontine angle tumor size was associated with a 13% increased likelihood of foregoing GTR (64 of 102 patients [63%]) or long-term postoperative House-Brackmann grade higher than I (48 of 102 patients [47%]) (odds ratio, 1.13; 95% CI, 1.04-1.23). Following salvage microsurgery, tumor growth-free survival rates at 1, 3, and 5 years were 97% (95% CI, 94%-100%), 93% (95% CI, 87%-99%), and 91% (95% CI, 84%-98%), respectively. In this cohort study, more than half of patients who received salvage microsurgery following primary SRS/FSRT underwent less than GTR or experienced some degree of facial paresis long term. These data suggest that the cumulative risk of developing facial paresis following primary SRS/FSRT by the end of the patient's journey with treatment approximates 2.5% to 7.5% when using published primary SRS/FSRT long-term tumor control rates.

Evaluating contouring accuracy and dosimetry impact of current MRI-guided adaptive radiation therapy for brain metastases: a retrospective study

BackgroundMagnetic resonance imaging (MRI) guided adaptive radiotherapy (MRgART) has gained increasing attention, showing clinical advantages over conventional radiotherapy. However, there are concerns regarding online target delineation and modification accuracy. In our study, we aimed to investigate the accuracy of brain metastases (BMs) contouring and its impact on dosimetry in 1.5 T MRI-guided online adaptive fractionated stereotactic radiotherapy (FSRT).MethodsEighteen patients with 64 BMs were retrospectively evaluated. Pre-treatment 3.0 T MRI scans (gadolinium contrast-enhanced T1w, T1c) and initial 1.5 T MR-Linac scans (non-enhanced online-T1, T2, and FLAIR) were used for gross target volume (GTV) contouring. Five radiation oncologists independently contoured GTVs on pre-treatment T1c and initial online-T1, T2, and FLAIR images. We assessed intra-observer and inter-observer variations and analysed the dosimetry impact through treatment planning based on GTVs generated by online MRI, simulating the current online adaptive radiotherapy practice.ResultsThe average Dice Similarity Coefficient (DSC) for inter-observer comparison were 0.79, 0.54, 0.59, and 0.64 for pre-treatment T1c, online-T1, T2, and FLAIR, respectively. Inter-observer variations were significantly smaller for the 3.0 T pre-treatment T1c than for the contrast-free online 1.5 T MR scans (P < 0.001). Compared to the T1c contours, the average DSC index of intra-observer contouring was 0.52‒0.55 for online MRIs. For BMs larger than 3 cm3, visible on all image sets, the average DSC indices were 0.69, 0.71 and 0.64 for online-T1, T2, and FLAIR, respectively, compared to the pre-treatment T1c contour. For BMs < 3 cm3, the average visibility rates were 22.3%, 41.3%, and 51.8% for online-T1, T2, and FLAIR, respectively. Simulated adaptive planning showed an average prescription dose coverage of 63.4‒66.9% when evaluated by ground truth planning target volumes (PTVs) generated on pre-treatment T1c, reducing it from over 99% coverage by PTVs generated on online MRIs.ConclusionsThe accuracy of online target contouring was unsatisfactory for the current MRI-guided online adaptive FSRT. Small lesions had poor visibility on 1.5 T non-contrast-enhanced MR-Linac images. Contour inaccuracies caused a one-third drop in prescription dose coverage for the target volume. Future studies should explore the feasibility of contrast agent administration during daily treatment in MRI-guided online adaptive FSRT procedures.

The Radiosurgery Society Case-Based Discussion of the Management of Head and Neck or Skull Base Paragangliomas with Stereotactic Radiosurgery and Radiotherapy

Stereotactic radiosurgery (SRS) and fractionated stereotactic radiotherapy (FSRT) have been used for the treatment of head and neck or skull base paraganglioma for a considerable time, demonstrating promising local control rates and a favorable safety profile compared with surgical approaches. Nevertheless, the choice of treatment must be carefully tailored to each patient's preferences, tumor location, and size, as well as anticipated treatment-related morbidity. This case-based review serves as a practical and concise guide for the use of SRS and FSRT in the management of head and neck or skull base paragangliomas, providing information on the diagnosis, treatment, follow-up considerations, and potential pitfalls.

CyberKnife-based stereotactic radiosurgery or fractionated stereotactic radiotherapy in older patients with brain metastases from non-small cell lung cancer.

We analyzed clinical results of CyberKnife (CK)-based stereotactic radiosurgery (SRS) or fractionated stereotactic radiotherapy (FSRT) in older patients (age ≥65 years) affected by brain metastases (BM) from non-small cell lung cancer (NSCLC). Forty-three older patients with 92 BM were treated with CK-based SRS/FSRT at our institution between 2009 and 2019. The end-point was overall survival (OS). Univariate and multivariate analyses were performed to identify the prognostic factors influencing OS. The in-field local control (IFLC) within the SRS/FSRT field was also assessed. During a median follow-up period of 18 months, the median OS was 32 months. NSCLC-specific graded prognostic assessment (GPA) (p = 0.027) was an independent significant factor affecting OS in the multivariate analysis. The median IFLC period was 31 months, and the total BM volume (p = 0.025) appeared to be a significant feature of IFLC. No adverse events >grade 2 were reported after SRS/FSRT. CK-based SRS/FSRT is a safe and efficient option for older patients with BM arising from NSCLC, showing good OS without severe side effects. GPA, which was consisted in age, performance status, extra-cerebral metastasis, and number of BM, seemed to be predictive factors for OS.

QLTI-03. FRACTIONATED PREOPERATIVE VS POSTOPERATIVE STEREOTACTIC RADIOTHERAPY FOR PATIENTS WITH MELANOMA BRAIN METASTASES: A COST UTILITY ANALYSIS

Abstract INTRODUCTION Stereotactic radiosurgery (SRS) followed by surgical resection is an emerging treatment paradigm for brain metastases. Preoperative SRS may improve outcomes such as rates of radiation necrosis (RN) and leptomeningeal disease (LMD) compared to postoperative SRS. However, the impact of this paradigm shift on metrics such as cost of care and hospital length of stay is unclear. In this study, we sought to categorize these metrics for melanoma metastases, specifically. METHODS A retrospective analysis identified patients who underwent surgical resection and fractionated stereotactic radiation therapy (FSRT) for melanoma brain metastases. Demographics, medical history, systemic and local treatment modalities, imaging, and postoperative course were collected. Perioperative cost of care was analyzed beginning two weeks preoperatively and concluded at four-weeks postoperatively. Continuous variables were analyzed via non-parametric two-sided t-tests and ANOVAs. Categorical variables were analyzed via Chi-squared tests. RESULTS Forty-two patients underwent 43 craniotomies for melanoma metastases. The mean age at surgery was 59.6 years-old and the male predominance was 65.1%. Total cost of perioperative care was more expensive among those treated with neoadjuvant (n = 11) FSRT compared to those who underwent postoperative (n = 32) FSRT ($262,072 vs $174,646; p = 0.0254). Mean length of stay for craniotomies was similar between groups (p = 0.1674), although trending down among the neoadjuvant FSRT group (4.5 days) among the neoadjuvant FSRT group versus the postoperative FSRT group (7.0 days). CONCLUSIONS In this study, neoadjuvant FSRT had an increased cost of care in the perioperative period, and similar lengths of hospital stay for craniotomy. Preoperative FSRT for melanoma metastases may result in shorter LOS, however, comes with an increased cost of care. Further investigation of itemization of healthcare costs to identify areas of improvement for neoadjuvant therapy is warranted.

Fractionated Stereotactic Radiotherapy vs. Stereotactic Radiosurgery for Vestibular Schwannoma: Local Control, Hearing Preservation, and Toxicities

The use of radiation therapy (RT) in vestibular schwannoma (VS) is well-established, but limited studies detail outcomes in patients treated with fractionated stereotactic radiotherapy (FSRT) versus stereotactic radiosurgery (SRS). In this study, we provide an outcome-based comparison of FSRT versus SRS in patients with VS with emphases on local control, hearing preservation, and toxicities. We hypothesize that FSRT and SRS will have similar rates of local control with FSRT having improved rates of hearing preservation. Patients treated at a single tertiary referral center between 2013 and 2018 for VS using FSRT (46.8 Gy in 26 fractions) or SRS (12 Gy in 1 fraction) were identified. Records from radiation oncology, neurosurgery, and otolaryngology were included. Endpoints included local control, defined as absence of tumor progression or need for salvage treatment, hearing preservation, quantified by Gardner-Robinson (GR) scoring and defined as maintaining GR1-2 hearing, and toxicities as per Common Terminology Criteria for Adverse Events (CTCAE), version 5. A total of 77 patients with VS were identified, of which 50 had FSRT and 27 had SRS. In the FSRT group, the median patient age was 58 years (range 23-81) and 50% were female, whereas the median patient age was 68 years (range 24-90) and 41% females were in the SRS group. 81% (n = 35) patients in the FSRT group and 24% (n = 6) in the SRS group had serviceable hearing prior to RT. Median follow-up was 51.2 months (range 4.3-103.2) in the FSRT group and 21.0 months (range 2.7-98.6) in the SRS group. The 2-year, 3-year, and 5-year local control rates in the FSRT and SRS groups were 100% and 100%, 97% and 76%, 94% and 76%, respectively. Of those with local progression, 33% (n = 1) in the FSRT group was salvaged with stereotactic body radiation therapy (SBRT) and 100% (n = 2) in the SRS group was salvaged with FSRT. For patients with serviceable hearing prior to RT, hearing preservations rates were 46% and 17% with a median time to hearing loss of 8.2 months (range 4.0-59.5) and 7.7 months (range 2.0-11.9) in the FSRT and SRS groups, respectively. Progression-free survival analyses showed superior hearing preservation in those treated with FSRT compared to SRS (p-value = 0.0064), especially those receiving FSRT who initially presented with GR1 vs GR2 hearing (p-value = 0.0095). There were 60 reported toxicities with 12% (n = 7) Grade 2+ in the FSRT group, whereas the SRS group had 5 toxicities with 40% (n = 2) Grade 2+. Both FSRT and SRS provide favorable local control for VS, with most progressions salvageable. Hearing preservation rate is higher in the FSRT group. This favors the use of FSRT in those with serviceable hearing, with patients with baseline GR1 hearing demonstrating additional benefit. Further prospective randomized studies are needed to better identify treatment outcomes and prognostic factors.

Radiation Necrosis following SRS or FSRT with Higher BED for Brain Metastases >20 mm

In the RTOG 90-05 study, the maximum tolerated dose of single-fraction radiosurgery (SRS) for lesions 21-30 mm was 18 Gy (BED 45 Gy12). However, patients of the RTOG study were previously irradiated with median 60 Gy (brain tumors) or 30 Gy (brain metastasis). Thus, the max. tolerated BED for lesions not irradiated before may be >45 Gy12. This study investigated safety and efficacy of SRS or fractionated stereotactic radiotherapy (FSRT) with BED >49 Gy12 for radiotherapy-naive brain metastases >20 mm. Data of 169 patients who received SRS or FSRT alone with BED >49 Gy12 for 1-4 brain metastases (2011-2022) were retrospectively analyzed. Thirty-two patients had lesions >20 mm (21-30 mm, n = 27; 21-40 mm, n = 4; >40 mm, n = 1). SRS was performed with 20 Gy (n = 9; 53.3 Gy12) or 19 Gy (n = 2; 49.1 Gy12), prescribed to the 60-80% isodose line (PTV = GTV). FSRT was Linac-based delivering 3 x 10 Gy (n = 3; 55 Gy12), 3 x 11 Gy (n = 4; 63.3 Gy12), 7 x 6 Gy (n = 1; 63 Gy12), 9 x 5 Gy (n = 1; 63.8 Gy12), 10 x 4 Gy (n = 11; 53.3 Gy12), or 12 x 4 Gy (n = 1; 64 Gy12), prescribed to the 80% isodose line (PTV = GTV+1-2 mm). SRS and FSRT were compared for grade ≥2 radiation necrosis (RN), local control (LC) and survival (OS). Fractionation [SRS (n = 89) vs FSRT (n = 48)] and lesion size (≤20 vs >20 mm) were studied in terms of RN rates. Kaplan-Meier method and log-rank test were used for univariate analyses and the Cox proportional hazards model for multivariate analyses. In patients with lesions >20 mm, SRS and FSRT were compared (Fisher's exact/Chi square test) for age, gender, KPS, year of SRS/FSRT, primary tumor, number/site of lesions, systemic treatment, and extracranial metastases. In patients with lesions >20 mm, significantly more patients receiving SRS had a KPS >80 than patients treated with FSRT (91% vs 29%, p = 0.002); otherwise, distributions of patient characteristics were balanced. In patients with lesions >20 mm, SRS was associated with significantly higher RN rates at 1 year (50% vs 9%) and 2 years (50% vs 9%) on univariate analysis (p = 0.012), which remained on multivariate analysis (HR: 0.10; 95% CI: 0.01-0.94, p = 0.044). No significant differences were found for LC (p = 0.21) at 1 year (75% vs 70%) and 2 years (75% vs 53%), and OS (p = 0.09) at 1 year (36% vs 59%) and 2 years (27% vs 46%). In patients with lesions ≤20 mm, 1- and 2-year RN rates following SRS were both 4%, compared to 0% and 15% respectively after FSRT (p = 0.60). In the SRS group, RN rates were significantly higher with lesions >20 mm (vs ≤20 mm) on univariate (p<0.001) and multivariate (HR: 3.82, 95% CI: 1.70-8.58, p = 0.001) analyses. In the FSRT group, max. diameter had no significant impact on RN rates (p = 0.93). Given the limitations of this study, FSRT with BED >49 Gy12 appears associated with a low risk of RN when used for brain metastases >20 mm. SRS with 1x19-20 Gy may not be optimal for metastases >20 mm but appears safe for lesions ≤20 mm. Prospective trials are warranted.

Fractionated Stereotactic Radiotherapy in the Management of Dural Recurrence of Olfactory Neuroblastoma

Treatment protocols for dural recurrence among esthesioneuroblastoma patients have not been standardized. We assess the outcomes of fractionated stereotactic radiotherapy (FSR) for patients with olfactory neuroblastoma (ONB) dura-based recurrences. We identified ONB patients with dura-based recurrences treated with FSR after prior radiotherapy who were enrolled between 2013 and 2022 in our prospective head and neck reirradiation and skull base registries. In-field tumor control (within 2 cm of prescribed radiotherapy volume) and out-of-field tumor control (non-contiguous or contralateral dura, nodal, or distant metastases) were analyzed. Thirteen patients with 28 dural lesions were included in this analysis. All patients were initially treated with surgery to their primary paranasal sinus disease; 69% with a craniofacial approach followed by adjuvant radiotherapy to a median dose of 63 Gy (range 60-72.4 Gy) prescribed to the resected tumor bed. Patients re-presented with dural recurrence at median 58.3 months (range 35.0 - 163.0 months) from completion of their initial treatment. Two patients underwent dural resections. On presentation of recurrence, 4 patients had 1 lesion treated, with a median of 2 lesions treated (range 1-4 lesions). All dural based tumors were treated with FSR to a median dose of 27 Gy in 3 fractions delivered QOD. 68Ga-DOTATATE PET/CT was utilized for FSR treatment planning in 31% of cases. The median follow up from FSR was 23.3 months (range: 13.1 - 51.6 months). The 1-year overall survival and progression free survival was 75% and 38%, respectively. The 1- and 2-year in-field control rate was 85% and 75%, respectively. Among treated lesions, 25 of 28 (89%) responded or remained stable following FSR. Two patients (3 lesions) had evidence of in-field radiographic progression at 17 and 9 months, respectively. Five patients (38%) experienced progression in the contralateral or non-contiguous dura, and 5 patients (38%) developed distant metastases. The overall out-of-field progression rate was 58% at 1 year. There was no grade 3 or higher toxicity observed. Three patients (23%) developed asymptomatic changes on MRI consistent with brain necrosis, all of which occurred in a previously irradiated region. In the largest single institution study of FSR reirradiation for ONB dural recurrence to date, high local control rates with minimal toxicity are attainable. However, subsequent out-of-field dural recurrences and/or distant metastases remain problematic.

Long-Term Outcomes of Non-Vestibular Cranial Nerve Schwannomas Treated with Fractionated Stereotactic Radiotherapy and Stereotactic Radiosurgery

Non-vestibular cranial nerve schwannomas (NVCNS) are rare tumors that account for approximately 10% of cranial nerve schwannomas. They are commonly treated with radiation therapy (XRT) due to their location often precluding safe resection. We examined the long-term outcomes of NVCNS treated with XRT as primary management and for post-operative salvage. We conducted a retrospective review of patients with NVCNS treated with fractionated stereotactic radiation therapy (FSRT) or Gamma Knife Stereotactic Radiosurgery (GK-SRS) from 1996 to 2018 at our institution. We examined patient demographics, cranial nerve (CN) involvement, CN function pre-/post-XRT, treatment volume (TV), toxicity, surgery pre-XRT, and local control. Kaplan-Meier analysis was performed for evaluation of local control. We identified 66 patients (38 female, 28 male) with NVCNS, a portion of whom had tumors involving more than one cranial nerve. Forty-six (69.7%) were treated with FSRT (median dose 50.4 Gy in 1.8 Gy/fraction; range 45-54 Gy), and 20 (30.3%) with GK-SRS (median dose 12 Gy; range 12-15 Gy). Median follow-up time was 92.5 months (5-306). Median Karnofsky Performance Status was 90 (70-100). Median age at start of XRT was 45 years old (15-92). Prior to XRT, 34.8% (23) of patients had surgical resection, with median time from surgery to XRT of 4.25 months (0.5-130 months). Median treatment volume was 4.72 cc (0.26-29). The cranial nerve most commonly involved was CN V (48.4%), followed by CN X (15.2%), CN VII (13.6%), CN VI (6.1%), CN XII (6.1%), CN III (6.1%), and CN IX (3%). Twenty-nine (43.9%) patients experienced grade 1 acute toxicity during treatment. Six (9%) patients experienced grade 1 chronic toxicity. No grade 2 or higher acute or chronic toxicity was observed. No significant difference in rates of acute or chronic toxicity was observed between patients treated with GK-SRS vs. FSRT. Post-XRT, 37 patients (56.1%) had improvement in CN function/symptom, 24 patients (36.3%) had stable function/symptoms, and 5 patients (7.6%) had worsening function/symptoms. Local control at one and five years was 100%. In-field recurrence was observed in one patient (1.5%), at 9 years post-XRT. For salvage this patient was treated with a second course of FSRT to the recurrent tumor. Our large institutional series with long term follow up showed excellent local control of NVCNS treated with FSRT or GK-SRS both for primary management and post-operative salvage. Treatment is well tolerated, with high rates of preservation or improvement of CN function, and minimal acute and chronic toxicity.

Stereotactic Radiotherapy or Whole Brain Radiotherapy Combined with Pyrotinib and Capecitabine in HER2-Positive Advanced Breast Cancer Patients with Brain Metastases (BROPTIMA): A Prospective, Phase Ib/II Single-Arm Clinical Study

Approximately half of patients with advanced HER2-positive breast cancer (BC) will develop brain metastases (BM) over time. Local therapy including stereotactic radiotherapy (SRT) and whole brain radiotherapy (WBRT) is the main initial treatment in malignant tumor patients with BM. However, more than 50% patients after radiotherapy in one year suffered intracranial recurrence. Pyrotinib, a small molecule, irreversible, pan-ErbB receptor tyrosine kinase inhibitor (TKI), has a high potency for controlling BM and reducing the occurrence of brain metastases in advanced HER2-positive BC patients. We hypothesized that SRT or WBRT combined with pyrotinib and capecitabine could decrease intracranial progression in HER2 positive BC with newly diagnosed BM. In this prospective single-arm phase Ib/II trial (NCT04582968), eligible patients were assigned to either fractionated stereotactic radiotherapy (FSRT) or whole-brain radiation therapy (WBRT), combined with pyrotinib and capecitabine. The primary endpoint was one-year CNS progression-free survival (PFS) rate. Secondary endpoints included intracranial objective response rate (IC-ORR) according to RANO-BM criteria, progression-free survival (PFS), overall survival (OS) and evaluation of safety and neurocognitive function. From January 2020 to August 2022, 40 patients were enrolled. Twenty-nine patients were treated with FSRT in 8 Gy per fraction with 3 to 5 fractions and 11 were treated with WBRT in 3 Gy per fraction with 10 fractions, and then received chemotherapy in a time frame starting from 0 to 7 days after radiotherapy. At a median follow-up of 17.3 months, 1-year CNS-PFS rate was 74.9% (95% CI 61.9-90.7%) and median CNS-PFS was 18 months (95% CI, 15.5 to NA months). One-year PFS rate was 66.9% (53.1-84.2%) and median PFS time was 17.6 months (95% CI 12.8-34.1 months). The best intracranial response rate (IC-ORR: complete response and partial response) was 92.5% (37/40). The most common grade 3 or worse toxicity was diarrhea (7.5%) and asymptomatic radiation necrosis was detected in 4 of 67(6.0%) lesions treated with FSRT. No differences of neurocognitive function evaluated by MMSE (Mini-Mental State Exam) were observed between different groups at any time point. Radiotherapy combined with pyrotinib and capecitabine resulted in a promising efficacy that crossed the pre-specified boundary in patients with HER2-positive advanced breast cancer with brain metastases. This is the first prospective study showing the efficacy and safety of CNS radiotherapy concurrent with pyrotinib and capecitabine in patients with BM from HER2-positive breast cancer. Further investigation in a randomized controlled study is warranted.

Risk Factors Associated with Development of Peritumoral Edema Following Stereotactic Radiosurgery and Radiotherapy for Intracranial Meningioma

Peritumoral edema (PTE) is a potential adverse effect following radiotherapy for intracranial meningioma. The purpose of this study is to identify which baseline factors may increase risk for PTE. A retrospective chart review was conducted of 431 patients who underwent primary radiotherapy to 480 radiographically-defined intracranial meningiomas between January 2008 and December 2021 within an integrated health care system. Patients with prior surgical management were excluded. Patients were treated with frameless LINAC-based image-guided single fraction stereotactic radiosurgery (SRS) (32.9%), 5 fraction SRS (FSRS) (30.8%), or fractionated stereotactic radiotherapy (FSRT) (36.3%). Pre- and post-radiotherapy MRI studies were reviewed to evaluate for PTE following treatment. An event was defined as new or worsening PTE compared to pre-radiotherapy imaging or development of new symptoms post-radiotherapy. Univariate and stepwise logistics regression analyses were performed to compare the risk of PTE between groups. Median follow-up was 85.8 months (IQR: 49.4-125.4). Median patient age was 66 years (IQR: 56-73). Patients treated with SRS (median age: 61 years) were younger than those treated with FSRS/FSRT (median age: 68 years) (p<0.001). Lesions treated with SRS (median volume: 1.33cc) were smaller than those treated with FSRS/FSRT (median volume: 6.36cc) (p<0.001). For all-comers, 68 (14.2%) lesions developed any PTE, and 27 (5.6%) developed symptomatic PTE (SPTE). Of these, 4 patients developed symptoms post-treatment without radiographic evidence of new or worsening PTE. Incidence of PTE/SPTE by site was as follows: base of skull (BOS): 10.3%/6.1%, convexity: 22.7%/7.6%, falcine: 17.6%/4.1%, parasagittal: 27.8%/8.3%, posterior fossa/tentorium 7.0%/0.0%. Incidence of PTE/SPTE by technique was as follows: SRS: 6.3%/3.8%, FSRS: 20.9%/7.4%, FSRT: 15.5%/5.7%. On univariate analysis, age >65 (OR = 2.17 (95% CI: 1.26-3.77) p = 0.006), tumor volume (OR = 1.05 (1.02-1.08), p = 0.003), pre-treatment PTE (OR = 6.82 (95% CI: 3.59-12.94) p<0.001), and convexity/falcine/parasagittal (CFPS) location (OR = 2.52 (95% CI: 1.49-4.23) p<0.001) were associated with increased incidence of PTE. On multivariate analysis, age >65 (OR = 1.91 (95% CI: 1.05-3.45) p<0.03), tumor volume (OR = 1.04 (95% CI: 1.00-1.08) p = 0.03), pre-treatment PTE (OR = 4.64 (95% CI: 2.33-9.24) p<0.001), and CFPS location (OR = 2.53 (95% CI: 1.41-4.52) p = 0.002) were associated with increased incidence of PTE. Two patients with PTE underwent resection for local failure which revealed atypical meningioma. Age >65, larger tumor volume, presence of pre-treatment PTE, and CFPS location were associated with increased incidence of PTE following radiotherapy. Patients with these risk factors should be counseled regarding post-treatment effects. Infrequently, PTE following treatment may be an indicator of higher-grade meningioma.

Borderline Resectable Pancreatic Cancer: Impact on Neoadjuvant Response Post Integration of MRI Guided Adaptive Radiation Therapy

The optimal neoadjuvant therapy regimen for patients with borderline resectable pancreas cancer (BRPC) remains to be defined, with a recent ALLIANCE study reporting that chemotherapy alone prior to resection is an acceptable standard of care. However, pathologic differences in response between patients receiving chemotherapy alone and chemotherapy with radiation with stereotactic technique is not clear. In this study, we sought to compare differences in pathologic outcomes between patients undergoing surgery in 2018 compared with 2021 at our comprehensive cancer center, after the new data of chemotherapy alone had been reported and after our center integrated stereotactic MRI guided online adaptive radiotherapy (SMART). Newly diagnosed BRPC patients were included on this IRB approved study if they were treated on our institutional clinical pathway with initial chemotherapy (FOLFIRINOX or Gemcitabine based) followed by 5 fraction stereotactic body radiation therapy (SBRT) with the intention of primary tumor resection. After surgical resection, tumor response was classified by the Tumor Regression Grading (TRG) System of the College of American Pathology on a scale from 0 (complete response) to 3 (poor response). In 2018 when patients were treated on a conventional Linac, the median SBRT dose was 40.5 Gy compared with 46.1 Gy in 2021 after SMART integration. In 2018, 54 BRPC patients were treated and 52% were explored. Of those, 72% were resected with a 95% (19/20) rate of R0 resection. In 2021, 66 BRPC patients were treated and 45% were explored. Of those, 74% were resected with a 100% (22/22) rate of R0 resection. In 2018, pathological results showed that 55% (11/20) had lymphovascular invasion (LVI) and 90% (18/20) had perineural invasion (PNI) with a median tumor size of 2.5 cm. The average lymph node ratio in 2018 was 0.06 in 2018 and 0.05 in 2021. In 2021, pathological results showed that 36% (8/22) had LVI and 64% (14/22) had PNI with a median tumor size of 2.2 cm. In 2018, 43% of surgeries required portal vein (PV) resection compared with 27% in 2021. In 2018, of those patients who underwent surgery, 65% (13/20) received both chemotherapy and SBRT compared to 10% (2/20) with chemotherapy alone. In 2021, 73% (16/22) received chemotherapy and SBRT prior to surgery compared with 27% (6/22) who received chemotherapy only. Patients who received chemotherapy only (n = 8) had an average TRG of 2.1 compared to the patients receiving combination therapy (29) with an average TRG of 1.8. This data suggests that higher ablative dose delivery with SMART following systemic therapy may be associated with improved pathologic outcomes, with less LVI, PNI, portal vein resection and improved TRG scores. Further prospective study is needed to confirm improved pathologic outcomes with SMART and to optimize patient selection regarding which patients benefit the most from the combination of chemotherapy and SBRT.

Cardiac and Great Vessel Toxicity with Single Fraction Stereotactic Body Radiotherapy in Early-Stage Lung Cancer

The relationship between thoracic radiotherapy and cardiovascular (CV) morbidity is an area of interest. When considering stereotactic body radiotherapy (SBRT) in the management of early-stage lung cancer, reports suggest CV dose may correlate with survival. To study this association for single fraction SBRT (SF-SBRT), we performed a retrospective review of patients treated at our institution assessing for associations between this dose schedule and CV toxicity. For the interval 2010-2022, we surveyed our IRB-approved prospective registry for SF-SBRT patients with tumors within 1 cm of the heart or any of the great vessels (GVs). Distance of the tumor to these structures was stratified as: directly contacting, within 0.5 cm, from 0.5-1 cm, or > 1 cm. Medical records were reviewed post-SBRT for CV events including: myocardial infarction (MI), heart failure (HF), structural heart damage (valvular or wall abnormalities), vascular damage (aneurysm, dilation, other abnormalities), hemoptysis, and arrhythmia which were correlated with lesion location and history. Four hundred four patients treated with SF-SBRT to 34 Gy in 1 fraction were identified. 35 patients (8.7%) had 36 lesions within 1 cm of the heart or GVs. 68.6% of patients were female and 74.3% were Caucasian. The median age was 72.5 years (range: 60-91), median Charlson comorbidity score was 6, median KPS was 80, and median ASCVD score was 21.0%. 33 patients had a smoking history with a median of 50 pack years. 12 patients (34.3%) had an arrhythmia prior to SBRT, 5 (14.2%) had prior HF, and 9 (25.7%) had prior MI or CV disease. All cases were non-small cell lung cancer or radiographic malignancy with 1 case of small cell lung cancer. Median tumor size was 1.6 cm. 91.4% of patients had stage I disease. Median follow-up was 2.26 years (0.37-4.0). Seven lesions (19.4%) were abutting the heart or GVs, 14 (38.9%) were within 0.5 cm, and 15 (41.7%) were from 0.5-1 cm. 54 events were observed with a median of 1 event per patient (0-5). The most common events were arrhythmia (15), vascular damage (9), structural damage (12), heart failure (9), and MI (6). The most commonly associated vascular structure was the aortic arch, while the most commonly involved substructures of the heart were the right atrium and left ventricle. 12 events occurred in the direct contact group, 17 in the < 0.5 cm group, and 25 in the 0.5-1 cm group. Patients with heart associated lesions accounted for 8 events, while those with vessel associated tumors accounted for 46. While cardiac events are relatively common in the medically inoperable SBRT population, they did not appear to be more common with tumors directly contacting major cardiovascular structures than for those with some separation. Most events could be attributed to medical causes other than SBRT. Further study is needed to clarify the potential role of radiation in events without direct explanation.

Early Versus Delayed Fractionated Stereotactic Radiotherapy for Nonfunctioning Pituitary Adenoma

Fractionated stereotactic radiotherapy (FSRT) is a common modality used to treat pituitary adenomas with good control rates. It is not known whether FSRT should be performed early or delayed until progression occurs. We compared FSRT in treating nonfunctional pituitary adenomas (NFPA) as an adjuvant (ADJ) or on-progression (PRG) therapy. A retrospective review of patients who underwent FSRT for an NFPA between January 2004 and December 2022 at a single institution was performed. We compared endocrinologic, ophthalmologic, and radiographic outcomes in FSRT delivered as ADJ and PRG treatment. Seventy-five patients were analyzed, with a median follow-up of 53 months. FSRT was administered to 35 and 40 patients as ADJ and PRG, with a median time to treatment of 5.5 and 40 months, respectively. The tumorcontrol rate was 94.3% for ADJ and 95.0% for PRG. Treatment resulted in 4 (11.4%) versus 7 (17.5%) new endocrinopathies and 2 (5.7%) versus 1 (2.5%) new visual deficits for ADJ versus PRG. A survival analysis of time to new endocrinopathy showed no difference between the 2 cohorts. The median time from surgery to new endocrinopathy was significantly different between ADJ and PRG, at 15.5 and 102.0 months, respectively. FSRT is effective in treating NFPA for residual and progressive tumors, with excellent tumor control rates and a low risk of developing new endocrinopathies and visual deficits. Delaying treatment delayed the development of new endocrinopathies, suggesting that observation with FSRT on tumor progression may delay the onset of hypopituitarism and maintain similar effectiveness in tumor control.

P20.09.A FRACTIONATED STEREOTACTIC RADIOTHERAPY (FSRT) AS A TREATMENT FOR TRIGEMINAL SCHWANNOMAS

Abstract BACKGROUND Trigeminal schwannomas (TS) represent 1-8% of all intracranial schwannomas and 0.1-0.5% of all intracranial tumors Treatment strategies are mainly based on limited published data and case reports. The most common treatment is surgical resection. However, it can rarely be completed. Fractionated stereotactic radiotherapy (FSRT) has the potential to be a valuable and safe alternative to control growing or symptomatic TS. The aim of this review is to analyze clinical RESULTS , toxicity and tumor control rates obtained with this technique when treating this pathology in our short series of cases. MATERIAL AND METHODS Medical records of 18 patients treated from January 2007 to December 2018 were reviewed. 15 of them presented symptoms at the moment of diagnosis (83.3%) and the remaining 3 were radiological findings. Surgery was previously performed in 2 cases. Regarding radiotherapy scheme, all patients received 1.8-2Gy daily fractions to a median of 50,0 Gy. The median follow-up time was 62.7 months. RESULTS The outcome after radiotherapy was favourable in 16 of 18 patients (88.8%), clinical improvement was achieved in 52.94% while stability of symptoms was reached in 35.29%. Tumor growth was controlled in 82.35% of cases, even with tumor decrease observed in 5.88%. Acute toxicity was detected in 23.53% and it consisted in increased pain, sensitive alterations and diplopia. All well tolerated with adjusted corticoids and pain medication scheme. Clinical worsening and radiographic progression was shown in 2 out 17 patients and surgery was needed as salvage treatment in both cases (11.76%). However, one of them presented these outcomes in a period in which pseudoprogression could not be excluded (less than 2 years after treatment). CONCLUSION FSRT such as primary or adjuvant treatment accomplishes good clinical results and tumoral control, being an alternative for those patients with comorbidities not suitable for a surgical treatment or who preferred a non-invasive treatment. Regarding toxicity, FSRT is mainly a well tolerated treatment among patients. Prospective multicenter studies should be run in order to accomplish statistically significant results. Also, it is the second case series that reports the flare effect.

Impact of magnetic resonance imaging-related geometric distortion of dose distribution in fractionated stereotactic radiotherapy in patients with brain metastases.

The geometric distortion related to magnetic resonance (MR) imaging in adiagnostic radiology (MRDR) and radiotherapy (MRRT) setup is evaluated, and the dosimetric impact of MR distortion on fractionated stereotactic radiotherapy (FSRT) in patients with brain metastases is simulated. An anthropomorphic skull phantom was scanned using a1.5‑T MR scanner, and the magnitude of MR distortion was calculated with (MRDR-DC and MRRT-DC) and without (MRDR-nDC and MRRT-nDC) distortion-correction algorithms. Automated noncoplanar volumetric modulated arc therapy (HyperArc, HA; Varian Medical Systems, Palo Alto, CA, USA) plans were generated for 53patients with 186 brain metastases. The MR distortion at each gross tumor volume (GTV) was calculated using the distance between the center of the GTV and the MR image isocenter (MIC) and the quadratic regression curve derived from the phantom study (MRRT-DC and MRRT-nDC). Subsequently, the radiation isocenter of the HA plans was shifted according to the MR distortion at each GTV (HADC and HAnDC). The median MR distortions were approximately 0.1 mm when the distance from the MIC was < 30 mm, whereas the median distortion varied widely when the distance was > 60 mm (0.23, 0.47, 0.37, and 0.57 mm in MRDR-DC, MRDR-nDC, MRRT-DC, and MRRT-nDC, respectively). The dose to the 98% of the GTV volume (D98%) decreased as the distance from the MIC increased. In the HADC plans, the relative dose difference of D98% was less than 5% when the GTV was located within 70 mm from the MIC, whereas the underdose of GTV exceeded 5% when it was 48 mm (-26.5% at maximum) away from the MIC in the HAnDC plans. Use of adistortion-correction algorithm in the studied MR diagnoses is essential, and the dosimetric impact of MR distortion is not negligible, particularly for tumors located far away from the MIC.