Oncological Outcomes After Hippocampus-Sparing Whole-Brain Radiotherapy in Cancer Patients With Newly Diagnosed Brain Oligometastases: A Single-Arm Prospective Observational Cohort Study in Taiwan

BackgroundPromisingly, the technique of hippocampus sparing during WBRT (HS-WBRT) might preserve NCFs. In this research, we examined oncological outcomes, with emphasis on neurologic/non-neurologic causes of death, CNS progression, and leptomeningeal disease (LMD) recurrence in cancer patients who underwent HS-WBRT.MethodsOne hundred and fourteen cancer patients with newly diagnosed brain oligometastases underwent HS-WBRT were consecutively enrolled. The cumulative incidence of cancer-specific deaths (neurologic or non-neurologic), LMD recurrence, and the composite endpoint of CNS progression (CNS-CE) as the first event were computed with a competing-risks approach to characterize the oncological outcomes after HS-WBRT.ResultsPatients with intact brain metastases had a significantly increased likelihood of dying from non-neurologic causes of death associated with early manifestation of progressive systemic disease (hazard ratio for non-neurologic death, 1.78; 95% CI, 1.08–2.95; p = 0.025; competing-risks Fine–Gray regression), which reciprocally rendered them unlikely to encounter LMD recurrence or any pattern of CNS progression (HR for CNS-CE as the first event, 0.13; 95% CI, 0.02–0.97; p = 0.047; competing-risks Fine–Gray regression). By contrast, patients with resection cavities post-craniotomy had reciprocally increased likelihood of CNS progression which might be associated with neurologic death eventually.ConclusionsPatterns of oncological endpoints including neurologic/non-neurologic death and cumulative incidence of CNS progression manifesting as LMD recurrence are clearly clarified and contrasted between patients with intact BMs and those with resection cavities, indicating they are clinically distinct subgroups.Trial RegistrationClinicalTrials.gov, Identifier: NCT02504788, NCT03223675.

Managing Central Nervous System Spread of Lung Cancer: The State of the Art

Brain metastases (BrM) are common in both non–small-cell lung cancer and small-cell lung cancer. Substantial progress in BrM management has occurred in the past decade related to advances in both radiation and medical oncology. Recent and ongoing radiation trials have focused on increasing the candidacy for focal therapy of BrM with stereotactic radiosurgery; reducing the toxicity and improving patient selection for whole brain radiotherapy; and, in small-cell lung cancer, evaluating brain magnetic resonance imaging surveillance without prophylactic cranial irradiation, hippocampal avoidance in prophylactic cranial irradiation and whole brain radiotherapy, and the role of upfront stereotactic radiosurgery for BrM. In medical oncology, the development of multiple tyrosine kinase inhibitors with encouraging CNS activity and emerging data on the CNS activity of immune checkpoint inhibitors in some patients have opened the door to novel systemic and multidisciplinary treatment strategies for the management of BrM. Future research will focus on more robust characterizations of the CNS activity of targeted therapy and immunotherapies, as well as optimal integration and patient selection for multidisciplinary strategies involving CNS-active drugs, radiation therapy, and CNS surveillance.

Isolated Leptomeningeal Progression in a Patient with NTRK Fusion+ Uterine Sarcoma: A Case Report

While neurotrophic tropomyosin receptor kinase (NTRK) fusions represent rare oncogenic drivers (&#x3c;1% of solid cancers), the recent approval of NTRK inhibitors (larotrectinib and entrectinib) led to dramatic responses in patients with NTRK fusion+ tumors. Both drugs have phase I data, demonstrating efficacy in the central nervous system (CNS), including both primary brain tumors and brain metastases. We present a 29-year-old woman who was diagnosed with <i>NTRK3-SPECC1L</i> fusion+ undifferentiated uterine sarcoma and underwent resection, chemotherapy, and radiotherapy. Two years later, lung metastases were discovered. She was started on larotrectinib with complete response. She remained stable on larotrectinib until she presented with altered mental status and seizures. MRI demonstrated leptomeningeal enhancement, but because leptomeningeal progression from sarcoma is exceedingly rare and her symptoms improved dramatically with antiepileptics, these findings were initially attributed to seizures. After 2 unrevealing lumbar punctures and stable systemic imaging, a brain biopsy demonstrated metastatic sarcoma, still showing NTRK positivity. She underwent whole brain radiotherapy and was switched to entrectinib, but had clinical progression 1 month later and transitioned to hospice. This case demonstrates the efficacy of NTRK inhibitors in rare and aggressive cancer but highlights that these patients can develop isolated CNS progression even in the setting of CNS-penetrant drugs. CNS progression can occur if there is incomplete CNS drug penetration, discordance in molecular profiles between CNS and systemic disease, or acquired NTRK inhibitor resistance. In this case, CNS disease maintained the NTRK fusion status, but either inadequate CNS penetration or development of a resistance gene may explain the isolated CNS progression.

NQPC-5 Does high-dose methotrexate-based chemotherapy for relapsed primary CNS lymphoma increase a risk of leukoencephalopathy with prior whole brain radiotherapy?

Backgrounds: Standard care for primary central nervous system lymphoma (PCNSL) comprises high-dose (HD) methotrexate (MTX) -based chemotherapy with or without consolidation whole brain radiotherapy (WBRT). HD-MTX administration following WBRT has been suggested to increase a risk of leukoencephalopathy. However, given that there are no other agents with efficacy similar to or better than MTX, patients with relapsed PCNSL may often be treated with regimens containing HD-MTX if the initial MTX treatment achieved a long-term complete remission. Here, we retrospectively analyzed prevalence and an extent of white mater damages in association with prior WBRT in patients with relapsed PCNSL treated with HD-MTX based therapy. Patients & methods: Among 79 patients with relapsed/refractory PCNSL in a total of 162 patients with newly-diagnosed PCNSL treated in our institution from April, 2000 to February, 2021, 35 patients were identified with evaluable KPS, MMSE, and Fazekas scale data at both baseline and follow-up periods. Of the 35 patients, 22 were treated with chemotherapy at a relapse (10 with prior WBRT, while 12 without WBRT), and were included in this preliminary study. Results: In the WBRT group (male/female: 5/5), median age was 65 years (range, 45–73), initial median KPS was 70 (40–90), and median WBRT dose was 27 Gy (23.4–40). Median progression-free survival (mPFS) was 11.8 months, and median overall survival (mOS) was not reached. In the non-WBRT group (M/F 8/4), median age 75 (62–84), initial mKPS 80 (50–90), mPFS 16.2 m, and mOS not reached. Initial KPS and MMSE score tended to be worse in WBRT group, presumably due to enrichment of patients with poorer performance status and more comorbidities. A decline in the Fazekas score was not associated with MMSE deterioration.Conclusions: The preliminary analysis was not informative enough, and further extensive imaging analysis will be exploited.

Stereotactic radiosurgery for brain metastases from pelvic gynecological malignancies: oncologic outcomes, validation of prognostic scores, and dosimetric evaluation

IntroductionStereotactic radiosurgery is a well-established treatment option in the management of brain metastases. Multiple prognostic scores for prediction of survival following radiotherapy exist, but are not disease-specific or validated for radiosurgery in women with primary pelvic gynecologic malignancies metastatic to the brain. The aim of the present study is to evaluate the feasibility, safety, outcomes, and impact of established prognostic scores.MethodsWe retrospectively identified 52 patients treated with radiotherapy for brain metastases between 2008 and 2021. Stereotactic radiosurgery was utilized in 31 patients for an overall number of 75 lesions; the remaining 21 patients received whole-brain radiotherapy. Kaplan-Meier survival analysis and the log-rank test were used to calculate and compare survival curves and univariate and multivariate Cox regression to assess the influence of cofactors on recurrence, local control, and prognosis.ResultsWith a median follow-up of 10.7 months, overall survival rates post radiosurgery were 65.3%, 51.3%, and 27.7% for 1, 2, and 5 years, respectively, which were significantly higher than post whole-brain radiotherapy (p=0.049). Five local failures (6.7%) were detected, resulting in 1 and 2 year local cerebral control rates of 97.4% and 94.0%, respectively. Univariate factors for prediction of superior overall survival were high performance status (p=0.030) and application of three prognostic scores, especially the Recursive Partitioning Analysis score (p=0.028). Uni- and multivariate analysis revealed that extracranial progression prior to radiosurgery was significant for inferior overall survival (p<0.0001). Radionecrosis was diagnosed in five women (16%); long-term neurotoxicity was significantly worse after whole-brain radiotherapy compared with radiosurgery (p=0.023).ConclusionStereotactic radiosurgery for brain metastases from pelvic gynecologic malignancies appears to be safe and well tolerated, achieving promising local cerebral control. Prognostic scores were shown to be transferable and radiosurgery should be recommended as primary intracranial treatment, especially in women with no prior extracranial progression and Recursive Partitioning Analysis class I.

Effect of brain radiotherapy strategies on prognosis of patients with EGFR-mutant lung adenocarcinoma with brain metastasis

Purpose Epidermal growth factor receptor (EGFR)-mutant lung cancers have a high risk of developing brain metastases (BM). Whole brain radiotherapy (WBRT), local radiotherapy, and WBRT + Boost are frequently used for treatment of BM. This retrospective study aimed to evaluate the difference in efficacy of these radiotherapy modes in patients with EGFR-mutant lung adenocarcinoma with BMs. Further, we determined the optimal radiotherapy regimen for patients based on Lung-molGPA. Methods and materials We retrospectively enrolled 232 patients with EGFR-mutant lung adenocarcinoma with BMs. Patients were divided into three groups based on the different modes of brain radiotherapy: WBRT group, local radiotherapy group, and WBRT + Boost group. Graded prognostic assessment for lung cancer using molecular markers (Lung molGPA), overall survival (OS), and intracranial progression-free survival (iPFS) were calculated. Kaplan–Meier was used to compare iPFS and OS in different groups. Results The median OS for the WBRT (n = 84), local radiotherapy (n = 65), and WBRT + Boost (n = 83) cohorts was 32.8, 59.1, and 41.7 months, respectively (P = 0.0002). After stratification according to the Lung-molGPA score, the median OS for the WBRT (n = 56), local radiotherapy (n = 19), and WBRT + Boost (n = 28) cohorts was 32.5, 30.9, and 30.8 months, respectively, in subgroup with score 1–2 (P = 0.5097). In subgroup with score 2.5–4, the median OS for the WBRT (n = 26), local radiotherapy (n = 45), and WBRT + Boost (n = 54) cohorts was 32, 68.4, and 51 months, respectively (P = 0.0041). Conclusion The present study showed that in patients with EGFR-mutant lung adenocarcinoma with BM, local radiotherapy and WBRT + Boost perform similarly well both in the subgroups with low and high scores of Lung-molGPA. Considering the side effect caused by whole brain radiotherapy, we recommended local radiotherapy as optimal brain radiation mode for those subtype lung cancer patients.

Reirradiation of Whole Brain for Recurrent Brain Metastases: A Case Report of Lung Cancer With 12-Year Survival

Whole brain radiotherapy (WBRT) for brain metastases (BMs) was considered to be dose limited. Reirradiation of WBRT for recurrent BM has always been challenged. Here, we report a patient with multiple BMs of non-small-cell lung cancer (NSCLC), who received two courses of WBRT at the interval of 5 years with the cumulative administration dose for whole brain as 70 Gy and a boost for the local site as 30 Gy. Furthermore, after experiencing relapse in the brain, he underwent extra gamma knife (GK) radiotherapy for local brain metastasis for the third time after 5 years. The overall survival was 12 years since he was initially diagnosed with NSCLC with multiple brain metastases. Meanwhile, each time of radiotherapy brought a good tumor response to brain metastasis. Outstandingly, during the whole survival, he had a good quality of life (QoL) with Karnofsky Performance Score (KPS) above 80. Even after the last GK was executed, he had just a mild neurocognitive defect. In conclusion, with the cautious evaluation of a patient, we suggest that reirradiation of WBRT could be a choice, and the cumulative radiation dose of the brain may be individually modified.

RADT-24. SYNTHETIC TREATMENT OF CENTRAL NERVOUS SYSTEM EWING/PRIMITIVE NEUROECTODERMAL TUMOR (EWING/PNET): A CASE REPORT

Ewing/PNET is a rare tumor of the central nervous system. After the standard treatment, there’re still 86.7% of patients had recurrence and no standard treatment after recurrence. Here we report a case of Ewing/PNET with a good survival after synthetic treatment to provide evidence for future clinical strategies. A 23-year-old male underwent resection of the left frontal tumor on April 28, 2017, the pathological diagnosis was Ewing/PNET. He received whole brain radiotherapy 36Gy in 18 fractions, and tumor bed boost to 56Gy in 28 fractions, with 3 courses of Nedaplatin adjuvant chemotherapy. The tumor recured 23 months after the surgery. The patient underwent the second resection, followed by 4 courses of ADM+VCR+CTX/IE chemotherapy. However, 27 months after the first surgery, the tumor evaluation progressive resection of recurrent tumors in the anterior cranial base-ethmoid sinus. During the chemotherapy, MRI showed that tumor still increased. There was a mass in the root of the forehead and nose. After the third recurrence, the patient received re-radiotherapy (50Gy in 25 fractions) 29 months later after the first RT. The tumor was significantly reduced after radiotherapy. Physical examination showed that the sense of smell continued to weaken, the visual acuity was the same as before. 8 courses of VIT (Irinotecan, vincristine, temozolomide) were followed by second RT, tumor was assessed every 2 courses. 44 months after the first surgery, he suffered a third recurrence in spina cord. And then he received rescue RT (20Gy in 10 fractions) in the recurrent tumor. The tumor was reduced after local radiotherapy. He was undergoing follow-up till May 2021, And the OS is 49 months. In conclusion, the incidence of this disease is low, especially in adults. However, the prognosis is poor. Early detection, early operation, combined with radiotherapy and chemotherapy are promising to improve the efficacy of Ewing/PNET.