Quantitative Cerebrospinal Fluid Circulating Tumor Cells are a Potential Biomarker of Response for Proton Craniospinal Irradiation for Leptomeningeal Metastasis

Background Leptomeningeal metastasis (LM) involves CSF seeding of tumor cells. Proton craniospinal irradiation (pCSI) is potentially effective for solid tumor LM. We evaluated whether circulating tumor cells (CTCs) in the CSF (CTCCSF), blood (CTCblood), and neuroimaging correlates with outcomes after pCSI for LM. Methods We describe a single-institution consecutive case series of 58 patients treated with pCSI for LM. Pre-pCSI CTCs, the change in CTC post-pCSI (ΔCTC), and MRIs were examined. Central nervous system progression free survival (CNS-PFS) and overall survival (OS) from pCSI were determined using Kaplan Meier analysis, Cox proportional-hazards regression, time-dependent ROC analysis, and joint modeling of time-varying effects and survival outcomes. Results The median CNS-PFS and OS were 6 months (IQR:4-9) and 8 months (IQR:5-13), respectively. Pre-pCSI CTCCSF<53/3mL was associated with improved CNS-PFS (12.0 vs 6.0 months, p<0.01). Parenchymal brain metastases (n=34, 59%) on pre-pCSI MRI showed worse OS (7.0 vs 13 months, p=0.01). Through joint modeling, CTCCSF was significantly prognostic of CNS-PFS (p<0.01) and OS (p<0.01). A ΔCTC-CSF≥37 cells/3mL, the median ΔCTC-CSF at nadir, showed improved CNS-PFS (8.0 vs 5.0 months, p=0.02) and further stratified patients into favorable and unfavorable subgroups (CNS-PFS 8.0 vs 4.0 months, p<0.01). No associations with CTCblood were found. Conclusion We found the best survival observed in patients with low pre-pCSI CTCCSF and intermediate outcomes for patients with high pre-pCSI CTCCSF but large ΔCTC-CSF. These results favor additional studies incorporating pCSI and CTCCSF measurement earlier in the LM treatment paradigm.

MPC-6 Clinical significance of whole chromosomal aberration signatures in non-metastatic medulloblastomas treated with 18Gy of craniospinal irradiation

Background: One of the most significant challenges is a reduction in the dose of craniospinal irradiation (CSI) in patients with medulloblastoma to minimize neurological sequelae. However, a North American clinical trial failed to show the prognostic non-inferiority of lower-dose irradiation compared to that associated with standard-dose radiation therapy for non-metastatic medulloblastomas. A European retrospective study revealed that whole chromosomal aberration signatures (WCASs) are a potential prognostic factor in Group 3/4 medulloblastoma without metastasis, but whether the molecular signature has the same clinical impact in patients treated with lower-dose CSI remains unknown. Methods: We conducted DNA methylation analysis using an Illumina Infinium Human Methylation EPIC BeadChip array to investigate molecular prognostic markers in 23 medulloblastoma patients who were registered in the Japan Pediatric Molecular Neuro-Oncology Group and treated with lower-dose CSI relative to standard treatment. A WCAS was defined as the presence of at least two of three chromosomal changes as follows: chromosome (chr) 7 gain, chr 8 loss, and chr 11 gain.Results: All patients presented with no residue or a residual tumor smaller than 1.5 cm2 after surgery without metastasis. The median age at onset was 6.9 years, and the median follow-up period was 80.6 months. CSI was delivered at a median dose of 18.0 Gy. Regarding molecular subgrouping, there were 5 WNT, 2 SHH, 1 Group 3, and 15 Group 4 medulloblastomas. Seven patients with Group 3/4 medulloblastomas showed WCASs and had significantly better prognosis than those without the alteration (5-year progression-free survival 100% vs. 63%, p = 0.046). Two late relapses occurred at 89 and 115 months after diagnosis, respectively, and one of these patients presented with a WCAS.Conclusion: WCAS may be a molecular prognostic marker not only in patients with medulloblastoma treated with standard-dose CSI but also in those treated with lower-dose irradiation.

Non-functional pituitary carcinoma

We present as case to review and present the clinical features, diagnosis and treatment of non-functional pituitary carcinoma (NFPC). We operated on a case of NFPC. After surgery, gamma knife therapy, temozolomide chemotherapy and whole craniospinal irradiation, the patient still had poor tumor control and died 7 months after operation. FPC is very rare. It needs to be diagnosed with a combination of clinical suspicion, imaging and dynamic monitoring. It is necessary to find more effective methods to control the progress of tumor while routine treatment fails.

RADT-34. OLFACTORY PERCEPTION DURING PROTON RADIATION AND DIFFERENCES IN FREQUENCY OF OLFACTORY PERCEPTIONS BASED ON PROTON CRANIOSPINAL IRRADIATION TECHNIQUE FOR PEDIATRIC BRAIN TUMOR PATIENTS

BACKGROUND Unusual olfactory perception has been reported during brain radiation treatments but is infrequent and does not typically interfere with the ability to deliver treatment or cause notable distress. METHODS We performed a retrospective review of 127 pediatric patients treated with proton radiation therapy (PRT) for primary brain tumors in a single institution between 2016-2021. Patients received PRT to the brain as part of craniospinal irradiation (CSI) followed by a boost to the brain. Proton CSI was delivered with 3D-CRT protons (n=53) or pencil beam scanning technique (PBS) (n=74). Within the PBS group, treatment delivery to the CSI utilized a single PA field (n=24) or two posterior oblique fields (n=50). We collected data on abnormal olfactory sensations, nausea/vomiting, and the use of medical intervention for those symptoms. RESULTS Our cohort included 80 males and 47 females. The median age of patients was 10 years old (range, 3 – 21). Seventy-one patients received concurrent chemotherapy. Prior to PRT, 31 patients were nauseous. During the radiation course, 104 patients developed worsening nausea while 63 patients reported episodes of emesis. Four patients vomited while receiving radiation. Seventeen patients reported olfactory perceptions during CSI. We found a higher rate of olfactory perception in patients treated with PBS (n=16, 22%) than 3D-CRT (n=1, 2%) (p=0.001) and, within the PBS group, patients treated with a single PA field (n=11, 46%) than two oblique fields (n=5, 10%) (p=0.002). Seventy-eight patients required intervention including addition of anti-emetic or anti-anxiety medication. Two patients required sedation due to the malodorous smell during CSI. We did not find any significant difference in nausea/vomiting based on treatment technique. CONCLUSIONS PBS and PBS technique influence olfactory perceptions but not the occurrence of the rate of nausea/vomiting. Further studies should be performed to validate these findings and determine techniques to minimize unpleasant olfactory perceptions.

RADT-26. PROTON VERSUS PHOTON CRANIOSPINAL IRRADIATION FOR ADULT MEDULLOBLASTOMA: A DOSIMETRIC AND TOXICITY ANALYSIS

Medulloblastoma is a posterior fossa tumor rarely diagnosed in adults. Treatment includes craniospinal irradiation (CSI). Proton CSI is increasingly utilized to decrease radiation dose to normal tissues, despite the lack of randomized data demonstrating decreased toxicity compared to photon CSI. This single institution retrospective study of 39 adult medulloblastoma patients includes nineteen patients treated with photon CSI prior to 2015, and twenty treated with proton CSI thereafter. Median age was 28 years (range 18-66). Molecular subtype was most commonly sonic hedgehog (68%). The most common fractionation schedule was 36 Gy CSI in 20 fractions (85% of photon and 58% of proton patients) with a boost to 54-55.8 Gy (92%). Proton CSI delivered significantly lower mean doses to the cochleae (median 32 Gy vs. 44 Gy), lacrimal glands (8 vs. 36 Gy), lens (2 vs. 28 Gy), parotid glands (3 vs. 26 Gy), pharyngeal constrictors (6 vs. 15 Gy), esophagus (2 vs. 29 Gy), heart (0 vs. 14 Gy), lungs (1 vs. 7 Gy), liver (0.1 vs. 7 Gy), and skin (38 vs. 51 Gy) (all p< 0.001). Patients receiving proton CSI had significantly lower rates of acute dysphagia of any grade (5% vs. 35%, p= 0.044) and decreased median weight loss during radiation (+1.0 vs. -2.8 kg, p= 0.011). Acute hospitalization was associated with increased weight loss (p= 0.009). Median follow-up was 2.9 and 12.9 years for proton and photon patients, respectively, limiting late toxicity and outcome comparisons. At last follow-up five photon patients had died (two of progressive disease, three without recurrence ages 41-63) and 21% had experienced major cardiovascular events. At 10 years, 89% were alive and 82% were recurrence free. In conclusion, this study demonstrates dosimetric improvements with proton CSI, potentially leading to decreased acute toxicity including dysphagia and weight loss during treatment.