Results of Stereotactic Body Radiotherapy With CyberKnife-M6 for Primary and Metastatic Lung Cancer.

Background: The aim of the study was to evaluate the efficacy of stereotactic body radiotherapy (SBRT) using the CyberKnife-M6 (CK-M6) with lung optimized treatment (LOT) module in patients with primary lung cancer and lung metastases. Methods: Forty-two lesions from 35 patients were treated between 2019 and 2022. Four-dimensional computed tomography images were obtained when the patients were in a free breathing modality. Tracking modality was selected prospectively according to the visibility of the target. The median prescribed dose was 48 Gy in four fractions (fx) (28 - 55 Gy/1- 7 fx). The median age was 68 years (47 - 82 years), and 43% of cases were adenocarcinoma. The median lesion size was 15 mm (6 - 36 mm). Results: Complete, partial and stable responses were obtained as 26%, 62%, and 9.5% at a median of 2 months (1 - 6 months), and 35.5%, 47.5% and 5% at the 12th month evaluation, respectively. Grade 3 and higher toxicity was not observed in any case. The mean and 2-year overall survival (OS) was 31.5 months and 54%, and the local recurrence-free survival (LRFS) was 29.6 months and 51%, respectively. In univariate analysis, target lesion type, complete response (CR), and higher esophagus maximum dose were favorable factors for OS and LRFS (P < 0.05). The CR at 12th month evaluation remained significant in multivariate analysis in terms of OS (hazard ratio = 8.602, 95% confidence interval: 1.05 - 70.01; P = 0.044). Conclusions: A mean LRFS of 29.6 months and OS of 31.5 months were obtained in patients with primary and metastatic lung cancer. With a median treatment time of 25 min, motion-managed strategy with CK-M6-LOT-based SBRT is an effective, safe, and comfortable treatment method for lung cancer.

Remineralization of lytic spinal metastases after radiation therapy - A retrospective cohort study comparing conventional external beam radiation therapy with stereotactic ablative body radiation.

Introduction: Osteolytic spinal metastases (SM) have a higher risk of fracture. In this study we aim to confirm the remineralization of lytic SM after radiation therapy. Secondary the influence of SBRT compared to cEBRT and tumor type will be analyzed. Methods: A retrospective cohort study was performed. Results: 87 patients, 100 SM were included. 29 received SBRT, 71 cEBRT. Most common primary tumors were breast (35 %), lung (26 %) and renal (11 %). Both cEBRT and SBRT resulted in a significant increase of bone mineral density (BMD) (83.76 HU ± 5.72 â†’ 241.41 HU ± 22.58 (p < 0.001) and 82.45 ± 9.13 â†’ 179.38 ± 47.83p = 0.026). There was a significant increase in absolute difference of BMD between the SM and reference vertebrae (p < 0.001). There was no significant difference between SBRT and cEBRT. There was no increase of BMD in renal lytic SM after radiation therapy (pre-treatment: 85.96 HU ± 19.07; 3 m 92.00 HU ± 21.86 (p = 0.882); 6 m 92.06 HU ± 23.94 (p = 0.902); 9 m 70.44 HU ± 7.45 (p = 0.213); 12 m 98.08 HU ± 11.24 (p = 0.740)). In all other primary tumors, a significant increase of BMD after radiation therapy was demonstrated (p < 0,05). Conclusion: We conclude that the BMD of lytic SM increases significantly after radiation therapy. Lytic SM of primary renal tumors are the exception; there is no significant remineralization of renal lytic SM after radiation therapy. There is no benefit of SBRT over cEBRT in this remineralization. These findings should be taken into account when deciding on surgery in the potentially unstable group defined by the spinal instability neoplastic score.

Repeated HyperArc radiosurgery for recurrent intracranial metastases and dosimetric analysis of recurrence pattern to account for diffuse dose effect on microscopical disease.

Aims: Evaluate effectiveness and safety of multiple HyperArc courses and patterns of progression in patients affected by BMs with intracranial progression. Methods: 56 patients were treated for 702 BMs with 197 (range 2-8) HyperArc courses in case of exclusive intracranial progression. Primary end-point was the overall survival (OS), secondary end-points were intracranial progression-free survival (iPFS), toxicity, local control (LC), neurological death (ND), and whole-brain RT (WBRT)-free survival. Site of progression was evaluated against isodoses levels (0, 1, 2, 3, 5, 7, 8, 10, 13, 15, 20, and 24 Gy.). Results: The 1-year OS was 70 %, and the median was 20.8 months (17-36). At the univariate analysis (UVA) biological equivalent dose (BED) > 51.3 Gy and non-melanoma histology significantly correlated with OS. The median time to iPFS was 4.9 months, and the 1-year iPFS was 15 %. Globally, 538 new BMs occurred after the first HA cycle in patients with extracranial disease controlled. 96.4 % of them occurred within the isodoses range 0-7 Gy as follows: 26.6 % (0 Gy), 16.5 % (1 Gy), 16.5 % (2 Gy), 20.1 % (3 Gy), 13.1 % (5 Gy), 3.4 % (7 Gy) (p = 0.00). Radionecrosis occurred in 2 metastases (0.28 %). No clinical toxicity of grade 3 or higher occurred during follow-up. One- and 2-year LC was 90 % and 79 %, respectively. At the UVA BED > 70 Gy and non-melanoma histology were significant predictors of higher LC. The 2-year WBRT-free survival was 70 %. After a median follow-up of 17.4 months, 12 patients deceased by ND. Conclusion: Intracranical relapses can be safely and effectively treated with repeated HyperArc, with the aim to postpone or avoid WBRT. Diffuse dose by volumetric RT might reduce microscopic disease also at relatively low levels, potentially acting as a virtual CTV. Neurological death is not the most common cause of death in this population, which highlights the impact of extracranial disease on overall survival.

Radiotherapy for subependymal giant cell astrocytoma: time to challenge a historical ban? A case report and review of the literature.

BACKGROUND: Subependymal giant cell astrocytoma is a benign brain tumor that occurs in patients with tuberous sclerosis complex. Surgical removal is the traditional treatment, and expert opinion is strongly against the use of radiotherapy. Recently, success has been reported with the mTor inhibitor everolimus in reducing tumor volume, but regrowth has been observed after dose reduction or cessation. CASE REPORT: We present the case of a 40-year-old Asian female patient treated successfully for growing bilateral subependymal giant cell astrocytoma with fractionated stereotactic radiotherapy before everolimus became available. After a follow-up of 8 years, everolimus was administered for renal angiomyolipoma and the patient was followed up until 13 years after radiotherapy. Successive magnetic resonance imaging demonstrated an 80% volume reduction after radiotherapy that increased to 90% with everolimus. A review of the literature was done leveraging Medline via PubMed, and we assembled a database of 1298 article references and 780 full-text articles in search of evidence for contraindicating radiotherapy in subependymal giant cell astrocytoma. Varying results of single-fraction radiosurgery were described in a total of 13 cases. Only in two published cases was the radiation dose of fractionated radiotherapy mentioned. One single publication mentions an induced secondary brain tumor 8 years after whole-brain radiotherapy. CONCLUSION: There is no evidence of contraindication and exclusion of fractionated radiotherapy in treating subependymal giant cell astrocytoma. Our experience demonstrates that subependymal giant cell astrocytoma, as other benign intracranial tumors, responds slowly but progressively to radiotherapy and suggests that fractionated stereotactic radiotherapy holds promise to consolidate responses obtained with mTor inhibitors avoiding regrowth after cessation.

Stereotactic Radiosurgery with Volumetric Modulated Arc Radiotherapy: Final Results of a Multi-arm Phase I Trial (DESTROY-2).

AIMS: To present the final results of a phase I trial on stereotactic radiosurgery (SRS) delivered using volumetric modulated arc therapy (VMAT) in patients with primary or metastatic tumors in different extracranial sites. MATERIALS AND METHODS: The DESTROY-2 trial, planned as a prospective dose escalation study in oligometastatic (one to five lesions) cancer patients relied on the delivery of a single high dose of radiation utilizing high-precision technology. The primary study endpoint was the definition of the maximum tolerated dose (MTD) of SRS-VMAT. The secondary objectives of the study were the evaluation of safety, efficacy, and long-term outcomes. All patients consecutively observed at our radiotherapy unit matching the inclusion criteria were enrolled. Each enrolled subject was included in a different phase I study arm, depending on the tumor site and the disease stage (lung, liver, bone, other), and sequentially assigned to a particular dose level. RESULTS: Two hundred twenty seven lesions in 164 consecutive patients (male/female: 97/67, median age: 68 years; range: 29-92) were treated. The main primary tumors were: prostate cancer (60 patients), colorectal cancer (47 patients), and breast cancer (39 patients). The maximum planned dose level was achieved in all study arms, and the MTD was not exceeded. 34 Gy, 32 Gy, 24 Gy, and 24 Gy were established as the single-fraction doses for treating lung, liver, bone, and other extracranial lesions, respectively. The prescribed BED 2Gyα/ß:10 to the planning target volume ranged from 26.4 Gy to 149.6 Gy. Twenty-seven patients (16.5%) experienced grade 1-2 and only one grade 3 acute toxicity, which was a pulmonary one. In terms of late toxicity, we registered only 5 toxicity>G2: a G3 gastro-intestinal one, three G3 bone toxicity, and a G3 laryngeal toxicity. The overall response was available for 199 lesions: 107 complete response (53.8%), 50 partial response (25.1%), and 31 stable disease (15.6%), leading to an overall response rate of 94.5%. Progression was registered only in 11 cases (5.5%). The overall response rate in each arm ranged from 88.6% to 96.4%. The overall two-year local control, distant metastasis free survival, disease free survival, and overall survival were 81.7%, 33.0%, 25.4%, and 78.7% respectively. CONCLUSION: In conclusion, the planned doses of 34 Gy, 32 Gy, 24 Gy, and 24 Gy were successfully administered as single-fractions for the treatment of lung, liver, bone, and other extracranial lesions, respectively, in a prospective SRS dose-escalation trial. No dose-limiting toxicities were registered, and minimal acute and late toxicity were reported. New indications for SRS are currently being studied in oligoprogressive patients receiving targeted drugs or in combination with immunotherapy. The DESTROY-2 trial represents, in our opinion, a credible starting point for future modern radiosurgery trials.

Choroidal Metastasis From Papillary Renal Cell Carcinomas: A Case Report and a Review of the Literature.

Choroidal metastasis originating from renal cell carcinomas (RCCs) is rare. To the best of our knowledge, 31 cases of choroidal metastasis from RCC have been reported in the English literature as of January 31, 2024. Nevertheless, physicians need to be vigilant in recognizing this condition, as its progression impacts the quality of life (QOL) of affected patients. In Case 1, a 60-year-old male with a medical history of papillary RCC experienced a deterioration in visual acuity (VA) and was diagnosed with solitary choroidal metastasis. Subsequently, multiple metastases were identified, prompting the initiation of a combination therapy regimen consisting of pembrolizumab plus axitinib. Despite treatment, progression of choroidal metastasis and a further decline in VA were observed. The patient underwent stereotactic radiotherapy and experienced complete resolution of the choroidal metastasis, accompanied by a slight improvement in VA. In Case 2, a 76-year-old man presented with a renal tumor accompanied by lung metastases. He underwent nephrectomy, and the histological diagnosis was papillary RCC. We initiated combination therapy consisting of nivolumab plus cabozantinib. The patient experienced a decrease in VA during treatment. We identified extensive fine metastases scattered throughout the bilateral choroid. We administered axitinib, but the patient experienced bilateral blindness. Given the absence of established therapy for choroidal metastasis, it is crucial to maintain flexibility in treatment selection. Local or systemic approaches should be used as deemed appropriate for each individual case.

Dose-Related Visual Outcomes in the Treatment of Choroidal Melanoma with Stereotactic Radiotherapy.

Introduction: Stereotactic radiotherapy (SRT) in the treatment of choroidal melanoma (CM) may be indicated if the tumour is located close to the optic nerve or is unsuitable for a radiotherapeutic plaque. It is thought that the rate of visual decline and ocular sequelae with SRT is influenced by dose and location of radiation in relation to important visual structures. This study therefore aimed to look at these prognoses with respect to localisation and dose of radiation when treatment of CM with SRT occurs. Methods: A retrospective data analysis was conducted on all patients at Dunedin Hospital (DH) from August 2001 to May 2017 who were followed up for 4 years. SRT consisted of 50 Gy divided into five fractions over 5 days to tumours, with 2-mm treatment margins. The primary outcome measure was retention of functional vision - better than hand movements (HMs) within the treated eye. Secondary outcome measures included time to non-functional vision (HM or less) in relation to location, dose and tumour thickness, the presence of radiation retinopathy, local and metastatic tumour progression, enucleation, and disease-specific mortality. Results: Seventy-five patients were identified in this study. Follow-up was incomplete in 10 patients, and 4 patients became deceased within the 4-year study period. Twenty-nine patients (48%) retained visual acuity (VA) better than HMs in the treated eye at 4 years, and thirty-two (52%) of patients did not. Calculated dose to the optic nerve and macula and proximity of the tumour to the optic nerve and macula were not statistically determinative of vision outcomes, although presenting VA was. Fifty-six per cent of patients developed radiation retinopathy involving the macula. The local progression, metastatic progression and enucleation rates were 4.6%, 6%, and 12.3%, representing 3, 4, and 8 patients, respectively. Conclusion: This study demonstrates that approximately half of patients treated with SRT can expect to maintain functional vision better than HM at 4 years. The rate of visual decline and final vision outcome are independent of location of the tumour in relation to the optic nerve and macula. While it affirms that SRT achieves high rates of local tumour control and eye retention, preservation of functional VA remains an unpredictable endpoint for individual cases and highlights the therapeutic challenge of this treatment modality.

Assessing tumor volumetric reduction with consideration for setup errors based on mathematical tumor model and microdosimetric kinetic model in single-isocenter VMAT for brain metastases.

The volumetric reduction rate (VRR) was evaluated with consideration for six degrees-of-freedom (6DoF) patient setup errors based on a mathematical tumor model in single-isocenter volumetric modulated arc therapy (SI-VMAT) for brain metastases. Simulated gross tumor volumes (GTV) of 1.0 cm and dose distribution were created (27 Gy/3 fractions). The distance between the GTV center and isocenter (d) was set at 0-10 cm. The GTV was translated within 0-1.0 mm (Trans) and rotated within 0-1.0° (Rot) in the three axis directions using affine transformation. The tumor growth volume was calculated using a multicomponent mathematical model (MCTM), and lethal effects of irradiation and repair from damage during irradiation were calculated by a microdosimetric kinetic model (MKM) for non-small cell lung cancer (NSCLC) A549 and NCI-H460 (H460) cells. The VRRs were calculated 5 days after the end of irradiation using the physical dose to the GTV for varying d and 6DoF setup errors. The tolerance value of VRR, the GTV volume reduction rate, was set at 5%, based on the pre-irradiation GTV volume. With the exception of the only one A549 condition where (Trans, Rot) = (1.0 mm, 1.0°) was repeated for 3 fractions, all conditions met all the tolerance VRR values for A549 and H460 cells with varying d from 0 to 10 cm. Evaluation based on the mathematical tumor model suggested that if the 6DoF setup errors at each irradiation could be kept within 1.0 mm and 1.0°, there would be little effect on tumor volume regardless of the distance from the isocenter in SI-VMAT.

What is the optimal isodose line for stereotactic radiotherapy for single brain metastases using HyperArc?

PURPOSE: The study aimed to investigate the optimal isodose line (IDL) in linear accelerator-based stereotactic radiotherapy for single brain metastasis, using HyperArc. We compared the dosimetric parameters for target and normal brain tissue among six plans with different IDLs. METHODS: This study included 30 patients with single brain metastasis. We retrospectively generated six plans for each tumor with different IDLs (80%, 70%, 60%, 50%, 40%, and 33%) using HyperArc. All treatment plans were normalized to the prescription dose of 35 Gy in five fractions which was covered by 95% of the planning target volume (PTV), defined by adding a 1.0 mm margin to the gross tumor volume (GTV). The dosimetric parameters were compared among the six plans. RESULTS: For GTV > 0.1 cm3, the ratio of brain-GTV volumes receiving 25 Gy to PTV (V25Gy/PTV) was significantly lower at IDL 40%-70% than at IDL 80% and 33% (p < 0.01, retrospectively). For GTV < 0.1 cm3, V25Gy/PTV decreased continuously as IDL decreased. The values of D99% and D80% for GTV increased with decreasing IDL. An IDL of 50% or less was required to achieve D99% of greater than 43 Gy and D80% of greater than 50 Gy. The mean values of D99% and D80% for IDL 50% were 44.3 and 51.9 Gy. CONCLUSION: The optimal IDL is 40%-50% for GTV > 0.1 cm3. These lower IDLs could increase D99% and D80% of GTV while lowering V25Gy of normal brain tissue, which may help reduce the risk of radiation necrosis and improve local control.

Stereotactic body radiation therapy for primary renal cell carcinoma: A review on behalf of the CC-AFU.

INTRODUCTION: The incidence of localized renal cell carcinoma (RCC) is on the rise among individuals aged 70 and older. While the gold standard for treatment remains surgical resection, some elderly and frail patients with comorbidities are not eligible for this procedure. In selected cases, percutaneous thermal ablation, such as cryotherapy, microwave and radiofrequency, offers less invasive options. General anesthesia is sometimes necessary for such treatments, but most of the procedures can be conducted using mild or deep conscious sedation. This approach is preferably recommended for small cT1a tumors situated at a distance from the renal hilum and/or ureter. Active surveillance remains an alternative in the case of small low grade RCC although it may induce anxiety in certain patients. Recent research has highlighted the potentials of stereotactic ablative body radiotherapy (SABR) as a noninvasive, well-tolerated, and effective treatment for small renal tumors. This narrative review aims to explore recent advances in SABR for localized RCC, including appropriate patient selection, treatment modalities and administration, as well as efficacy and tolerance assessment. MATERIAL AND METHODS: We conducted a literature review using the terms [kidney cancer], [renal cell carcinoma], [stereotactic radiotherapy], [SBRT], and [SABR] in the Medline, PubMed, and Embase databases, focusing on prospective and relevant retrospective studies published in English. RESULTS: Studies report local control rates ranging from 70% to 100% with SABR, highlighting its efficacy in treating RCC. The decline in glomerular filtration rate (GFR) is approximately -5 to -17mL/min over the years following SABR. Common toxicities are rare, primarily CTCAE grade 1, include fatigue, nausea, chest or back pain, diarrhea, or gastritis. CONCLUSION: Stereotactic ablative body radiotherapy (SABR) may be considered as a viable option for patients with localized RCC who are not suitable candidates for surgery with a high local control rate and a favorable safety profile. This approach should be discussed in a multidisciplinary meeting and results from ongoing clinical trials are awaited.

The Safety and Efficacy of the Combination of Sacituzumab Govitecan and Palliative Radiotherapy-A Retrospective Multi-Center Cohort Study.

Sacituzumab govitecan (SG) is a new treatment option for patients with metastatic triple-negative and hormone receptor-positive, HER2-negative breast cancer. This antibody-drug conjugate is currently approved as monotherapy. Palliative radiotherapy is frequently used to treat symptomatic metastases locally. Concurrent use of SG and irradiation was excluded in clinical trials of SG, and there are currently limited published data. We report here a systematic review, as well as a retrospective multi-center study of 17 patients with triple-negative breast cancer who received concurrent SG and radiotherapy. In these patients, concurrent use was found to be efficient, safe and well tolerated. There were no apparent differences in moderate or severe acute toxicity according to the timing of SG administration.

Long-Term Results of Stereotactic Radiotherapy in Patients with at Least 10 Brain Metastases at Diagnosis.

PURPOSE: to evaluate an SRT approach in patients with at least 10 lesions at the time of BM initial diagnosis. METHODS: This is a monocentric prospective cohort of patients treated by SRT, followed by a brain MRI every two months. Subsequent SRT could be delivered in cases of new BMs during follow-up. The main endpoints were local control rate (LCR), overall survival (OS), and strategy success rate (SSR). Acute and late toxicity were evaluated. RESULTS: Seventy patients were included from October 2014 to January 2019, and the most frequent primary diagnosis was non-small-cell lung cancer (N = 36, 51.4%). A total of 1174 BMs were treated at first treatment, corresponding to a median number of 14 BMs per patient. Most of the patients (N = 51, 72.6%) received a single fraction of 20-24 Gy. At 1 year, OS was 62.3%, with a median OS of 19.2 months, and SSR was 77.8%. A cumulative number of 1537 BM were treated over time, corresponding to a median cumulative number of 16 BM per patient. At 1-year, the LCR was 97.3%, with a cumulative incidence of radio-necrosis of 2.1% per lesion. Three patients (4.3%) presented Grade 2 toxicity, and there was no Grade ≥ 3 toxicity. The number of treated BMs and the treatment volume did not influence OS or SSR (p > 0.05). CONCLUSIONS: SRT was highly efficient in controlling the BM, with minimal side effects. In this setting, an SRT treatment should be proposed even in patients with ≥10 BMs at diagnosis.

Pelvic lymph node motion during cone-beam computed tomography guided stereotactic radiotherapy.

Background and purpose: Stereotactic body radiotherapy (SBRT) is increasingly applied for pelvic lymph node recurrence. Thus far, knowledge on pelvic lymph node motion during CBCT-guided SBRT is lacking and the applied margins vary between institutions. This study evaluated pelvic lymph node motion during CBCT-guided SBRT and assessed the currently applied PTV margins of 3 and 5 mm. Material and methods: In total, 45 pelvic lymph node metastases were included. One observer delineated 45 GTVs on planning CT, 224 GTVs on pre-fraction and 216 on post-fraction CBCT. The GTV centroid coordinates were derived from all images for inter- and intrafraction motion analysis. Additionally, we assessed the influence of treatment time and lesion location on lesion motion. The expected coverage of a 3-mm and 5-mm PTV margin was assessed using the inclusiveness index for GTVs on pre- and post-fraction CBCT. Results: Lymph node interfraction motion was limited to 5 mm in 96-97 % of fractions for all translational directions and intrafraction lesion motion was limited to 3 mm in 97-100 % of fractions. Para-rectal lesions (11 %) were associated with significantly larger inter- and intrafraction motion compared to other pelvic locations and treatment duration showed no correlation with lesion motion. The mean (sd) lesion inclusiveness index was 99 % (5 %) for the 5-mm PTV margin and 96 % (9 %) for the 3-mm margin. Conclusion: Pelvic lymph node motion during CBCT-guided stereotactic radiotherapy was within the widely applied PTV margin of 5 mm, providing an opportunity to reduce this margin for pelvic lymph node SBRT.

Prospective phase II trial on ablative stereotactic body radiation therapy (SBRT) for medically inoperable thoracic nodes metastases.

BACKGROUND: Oligometastases in mediastinal nodes are increasingly prevalent, posing challenges for treatment with stereotactic body radiotherapy (SBRT) due to proximity to organs at risk (OARs). We report the results of a single prospective observational phase II trial on ablative SBRT for medically inoperable thoracic nodes metastases (NCT02970955). MATERIAL AND METHODS: Since 2017, patients with < 3 nodal metastases were evaluated by the tumor board and included if deemed inoperable. SBRT was delivered using risk adaptive approach based on number, site and size of metastatic nodes (50 Gy/5fractions, 60 Gy/8fractions, 70 Gy/10 fractions). Planning target volume (PTV) partial underdosage was allowed. The primary end point was local control (LC) at 12 months. Secondary end points were: acute and late toxicities, overall survival (OS), progression free survival (PFS), and time to next systemic therapy (TTNS). RESULTS: Between 03/2017-11/2021, 32 patients (41 nodal metastases) were included. NSCLC (13pts), breast (5pts) and colorectal cancer (4pts) were the most represented primary tumour. In 66 % cases, partial PTV undercoverage was necessary. LC at 1 and 2 years was 93.5 % and 82.3 %, respectively. Treatment was well-tolerated with no acute or late toxicity ≥ G3. Median OS was 59.7 months. OS at 1 and 2 years was 96.9 % and 83.8 % respectively. Median PFS was 12.2 months. PFS at 1 and 2 years was 53.1 % and 31.3 %, respectively. CONCLUSION: This trial supported the feasibility and safety of ablative SBRT for thoracic nodes metastases thanks to risk adaptive approach allowing to delay of new systemic therapies. Larger studies are needed to confirm these observations.

Stereotactic radiotherapy vs whole brain radiation therapy in EGFR mutated NSCLC: Results & reflections from the prematurely closed phase III HYBRID trial.

BACKGROUND: All known randomized trials of stereotactic radiotherapy (SRT) versus whole brain radiotherapy (WBRT) for brain metastases (BMs) comprise mixed histologies. The phase III HYBRID trial (NCT02882984) attempted to evaluate the non-inferiority of SRT vs. WBRT specifically for EGFR-mutated non-small cell lung cancer (EGFRm NSCLC) BMs. METHODS: Inclusion criteria were ≤ 5 BMs (any size) from treatment-naïve EGFRm NSCLC. All patients started a first-generation tyrosine kinase inhibitor on the first day of WBRT (37.5 Gy/15 fractions) or SRT (25-40 Gy/5 fractions per tumor volume). The primary endpoint was 18-month intracranial progression-free survival (iPFS; intention-to-treat). RESULTS: The trial commenced in June 2015 and was closed in April 2021 after screening 208 patients but enrolling 85 (n = 41 WBRT, n = 44 SRT; median follow-up 31 and 36 months, respectively). Respectively, 9.5 % vs. 10.2 % of patients experienced intracranial progression at 18 months, and the median iPFS was 21.4 vs. 22.3 months (p > 0.05 for all). The SRT arm experienced higher overall survival and cognitive preservation (p < 0.05 for all). The most notable reason for low enrollment was patients not wishing to risk neurocognitive decline from WBRT. CONCLUSIONS: Although this phase III trial was underpowered, there was no evidence that SRT yielded outcome detriments compared to WBRT for EGFRm NSCLC BMs. Lessons from prematurely closed trials are valuable, as they often provide important experiential perspectives for investigators designing/executing future trials. In the current era, randomized trials involving WBRT without cognitive sparing measures may be at high risk of underaccrual; trial investigators are encouraged to carefully consider our experience when attempting to design such trials. However, trials of molecular-/biologically-stratified patients are highly recommended as the notion of "individualized medicine/oncology" continues to expand.

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.

Fractionated stereotactic radiotherapy of intracranial postoperative cavities after resection of brain metastases - Clinical outcome and prognostic factors.

Background and Purpose: After surgical resection of brain metastases (BM), radiotherapy (RT) is indicated. Postoperative stereotactic radiosurgery (SRS) reduces the risk of local progression and neurocognitive decline compared to whole brain radiotherapy (WBRT). Aside from the optimal dose and fractionation, little is known about the combination of systemic therapy and postoperative fractionated stereotactic radiotherapy (fSRT), especially regarding tumour control and toxicity. Methods: In this study, 105 patients receiving postoperative fSRT with 35 Gy in 7 fractions performed with Cyberknife were retrospectively reviewed. Overall survival (OS), local control (LC) and total intracranial brain control (TIBC) were analysed via Kaplan-Meier method. Cox proportional hazards models were used to identify prognostic factors. Results: Median follow-up was 20.8 months. One-year TIBC was 61.6% and one-year LC was 98.6%. Median OS was 28.7 (95%-CI: 16.9-40.5) months. In total, local progression (median time not reached) occurred in 2.0% and in 20.4% radiation-induced contrast enhancements (RICE) of the cavity (after median of 14.3 months) were diagnosed. Absence of extracranial metastases was identified as an independent prognostic factor for superior OS (p = <0.001) in multivariate analyses, while a higher Karnofsky performance score (KPS) was predictive for longer OS in univariate analysis (p = 0.041). Leptomeningeal disease (LMD) developed in 13% of patients. Conclusion: FSRT after surgical resection of BM is an effective and safe treatment approach with excellent local control and acceptable toxicity. Further prospective randomized trials are needed to establish standardized therapeutic guidelines.

Long-term outcomes of neuroendoscopic cyst partial resection combined with stereotactic radiotherapy for craniopharyngioma.

PURPOSE: The aim of this study was to evaluate the treatment outcomes of neuroendoscopic cyst partial resection (ECPR) combined with stereotactic radiotherapy (SRT) for cystic craniopharyngiomas. METHODS: In this retrospective study, 22 craniopharyngioma patients undergoing ECPR combined with SRT were included. This combination therapy was indicated for suprasellar cystic craniopharyngiomas in patients whose pituitary function was preserved but would be difficult to preserve in direct surgery. The outcomes of combination therapy, including tumor control and postoperative visual and pituitary functions, were investigated. RESULTS: ECPR was safely performed, and cyst shrinkage was accomplished in all cases. After ECPR, visual function improved in 12 of 13 patients (92%) with visual field disturbance and did not deteriorate in any patients. Pituitary function was preserved in 14 patients (64%) and deteriorated in eight patients (36%) after ECPR. As a complication of ECPR, meningitis occurred because of a wound infection in one patient. In 18 of 22 patients (82%), the tumor was controlled without further treatment 19 - 87 months (median, 33 months) after SRT. Hypopituitarism was an adverse event after SRT in two of the 18 patients who achieved tumor control. Four patients (18%) had enlarged cysts after SRT. Postoperative pituitary function was significantly more likely to deteriorate in cases of extensive detachment from the ventricular wall, and retreatment was significantly more common in cases with hypothalamic extension. CONCLUSION: Although limited to some cases, ECPR combined with SRT is a less invasive and useful therapeutic option for suprasellar cystic craniopharyngiomas. However, its long-term prognosis requires further evaluation.

The Impact of Multileaf Collimator Size on Single Isocenter Dynamic Conformal Arcs-Based Radiosurgery for Brain Metastases.

PURPOSE: To compare the plan quality of stereotactic radiosurgery (SRS) between 2.5-mm and 5-mm multileaf collimator (MLC) and investigate the factors' influence on the differences by MLC size. METHODS: Seventy-six treatment plans including 145 targets calculated with a single isocenter multiple noncoplanar dynamic conformal arc (DCA) technique using automatic multiple brain metastases (MBM) treatment planning system. Conformity index (CI), gradient index (GI), lesion underdosage volume factor (LUF), healthy tissue overdose volume factor (HTOF), geometric conformity index (g), and mean dose to normal organs were compared between 2.5-mm and 5-mm MLC. Then the factors that influenced the differences of these parameters were investigated. The impact of target size was also investigated for CI and GI values of individual targets (n=145), and differences between 2.5-mm and 5-mm MLC were analyzed. RESULTS: All parameters except for LUF were significantly better in plans with 2.5 mm MLC. Target size was a significant factor for difference in HTOF, and distance between targets was a significant factor for difference in brain dose and GI. Among 145 metastases, the average inverse CI was 1.35 and 1.47 with 2.5-mm and 5-mm MLC, respectively (p<0.001). The average GI was 3.21 and 3.53, respectively (p<0.001). For individual targets, target size was a significant factor in CI and GI both with 2.5-mm and 5-mm MLC (p-value: <0.001, each). CI and GI were significantly better with 2.5-mm than 5-mm MLC. CI was almost >0.67 except for ≤5mm targets with 5-mm MLC. Also, GI was almost smaller than 3.0 for >10 mm targets both with 2.5-mm and 5-mm MLC. CONCLUSIONS: MBM with 5-mm MLC was almost fine. However, it may be better to use a conservative margin for larger metastases. It may also be better to avoid SRS with 5-mm MLC for patients with ≤5 mm target size.

Dosimetric comparison of proton therapy and CyberKnife in stereotactic body radiation therapy for liver cancers.

Stereotactic body radiation therapy (SBRT) has been increasingly used for the ablation of liver tumours. CyberKnife and proton beam therapy (PBT) are two advanced treatment technologies suitable to deliver SBRT with high dose conformity and steep dose gradients. However, there is very limited data comparing the dosimetric characteristics of CyberKnife to PBT for liver SBRT. PBT and CyberKnife plans were retrospectively generated using 4DCT datasets of ten patients who were previously treated for hepatocellular carcinoma (HCC, N = 5) and liver metastasis (N = 5). Dose volume histogram data was assessed and compared against selected criteria; given a dose prescription of 54 Gy in 3 fractions for liver metastases and 45 Gy in 3 fractions for HCC, with previously published consensus-based normal tissue dose constraints. Comparison of evaluation parameters showed a statistically significant difference for target volume coverage and liver, lungs and spinal cord (p < 0.05) dose, while chest wall and skin did not indicate a significant difference between the two modalities. A number of optimal normal tissue constraints was violated by both the CyberKnife and proton plans for the same patients due to proximity of tumour to chest wall. PBT resulted in greater organ sparing, the extent of which was mainly dependent on tumour location. Tumours located on the liver periphery experienced the largest increase in organ sparing. Organ sparing for CyberKnife was comparable with PBT for small target volumes.