Median Karnofsky Performance Score Research Articles

Stereotactic Radiosurgery for Patients with Brain Metastases from Hepatopancreaticobiliary Cancers.

The role of stereotactic radiosurgery (SRS) for patients with brain metastases from hepatopancreaticobiliary (HPB) cancers has yet to be established. The authors present a single-institution experience of patients with HPB cancers who underwent SRS when their cancer spread to the brain. We surveyed our Gamma Knife SRS data base of 18,000 patients for the years 1987-2022. In total, 19 metastatic HPB cancer patients (13 male) with 76 brain metastases were identified. The median age at SRS was 61 years (range: 48-83). The primary cancer sites were hepatocellular carcinoma (HCC, 11 patients), cholangiocarcinoma (CCC, 2 patients), and pancreatic carcinoma (PCC, 6 patients). The median Karnofsky Performance Score (KPS) was 80 (range: 50-90). Two patients underwent pre-SRS whole-brain fractionated radiation therapy (WBRT) and eight patients underwent pre-SRS surgical resection. All SRS was delivered in single session. The median margin dose was 18 Gy (range: 15-20). The median cumulative tumor volume was 8.1 cc (range: 1.0-44.2). The median patient overall survival (OS) after SRS was 7 months (range 1-79 months). Four patients had documented local tumor progression after SRS at a median time of 8.5 months (range: 2-15) between SRS and progression. Out of 76 treated tumors, 72 tumors exhibited local control. The local tumor control rate per patient was 78.9%. The local tumor control per tumor was 94.7%. Four patients developed new brain metastases at a median of 6.5 months (range: 2-17) after SRS. No patient experienced adverse radiation effects (AREs). At the last follow-up, 18 patients had died, all from systemic disease progression. Metastatic spread to the brain from HPB cancers occurs late in the course of the primary disease. In this study, all deceased patients ultimately died from primary disease progression. SRS is a non-invasive strategy that maximally preserves quality of life, and our results reported favorable outcomes compared to the existing literature. SRS should be considered as one of the primary management strategies for patients with brain metastatic spread from HPB cancer.

Influence of Surgical Resection on Survival in Glioblastoma with Multiple Localizations—a Multi-Center Retrospective Analysis

INTRODUCTION: The presence of multiple localizations in glioblastoma is rare and associated with poor prognosis. The presence of a visible junction between enhancing lesions on magnetic resonance imaging (MRI) is defined as multifocal (MF), the absence of a dissemination pathway as multicentric (MC). METHODS: Data collection was performed as a multicenter retrospective analysis. From Jan 1, 2008, to Dec 31, 2020 patients presenting with IDH wild-type glioblastoma (CNS WHO grade 4) with multiple localizations were included. Demographic data, tumor size, Karnofsky Performance Score (KPS) before and after surgery were analyzed. EOR was measured by FLAIR and contrast-enhanced MRI. Gross total resection (GTR, residual tumor (RTM) < 5%), subtotal resection (STR, RTM < 30%), partial resection (PR, RTM > 30%), and biopsy (RTM > 75%). RESULTS: This study included 117 patients with a median age of 62 years. 45 (38.5%) patients had MC lesions, 72 (61.5%) MF. Median KPS on admission was similar in both subtypes. Median OS did not differ among MC and MF glioblastomas. In MF glioblastoma, GTR (p = 0.0001) and STR (p = 0.0001) significantly increased the median OS compared to PR and biopsy. Likewise, OS was increased after GTR (p = 0.0272) and STR (p = 0.0272) in MC glioblastoma, as well. Overall, resection significantly increased OS in patients with glioblastoma with multiple localizations compared to biopsy alone. In multivariate logistic regression analysis EOR and chemotherapy were significant and independent predictors of OS in MC and MF glioblastomas. CONCLUSIONS: These data indicate that GTR and STR positively affects OS in patients with MC and MF glioblastoma. These results argue for a more aggressive stance towards surgical treatment of these tumors with particularly poor prognosis, even when GTR is not within reach before resection.

Axicabtagene Ciloleucel in Patients Aged 75 and Older: A Retrospective Cohort Study

Background The treatment of older patients with relapsed/refractory (R/R) aggressive non-Hodgkin B-cell lymphomas (NHL) remains a significant clinical challenge. Chimeric antigen receptor T-cell (CAR-T) therapy represents a potentially curative option, but elderly patients remain underrepresented in relevant clinical trials, and less is known about the safety of CAR-T among patients older than 75 years. Toxicities including cytokine release syndrome (CRS), neurotoxicity (ICANS), arrhythmias, renal failure, and cytopenias may pose higher risk in elderly patients with comorbidities and decreased physiologic reserve compared to younger CAR-T recipients. We sought to characterize outcomes and toxicities of axicabtagene ciloleucel (axi-cel) in a cohort of patients aged ≥ 75 years. Methods This was a retrospective analysis of consecutive patients aged ≥ 75 years with R/R NHL who received axi-cel at New York-Presbyterian/Weill Cornell Medical Center. Data collected included patient characteristics and outcomes including response rates, event-free and overall survival, rates of CRS, ICANS, arrhythmias and severe cytopenias, and length of hospital stay. CRS and ICANS severity were graded following the ASTCT consensus criteria. Cytopenias were graded as per NCI-CTCAE v5.0. Event free survival (EFS) was defined as time to disease progression or death. Results We identified 15 patients with a median age of 78 (range 75-87) years; 6 (40%) were ≥ 80 years of age. 14 patients had a diagnosis of large B-cell lymphoma and 1 had multiply relapsed follicular lymphoma. Ten patients (67%) had received 3 or more prior lines of therapy. Additional baseline characteristics are summarized in Table 1. Among 10 patients (67%) who developed CRS of any grade, only 1 (7%) experienced grade ≥3 CRS; this CRS event was fatal. Five (33%) patients developed ICANS with only 1 patient (7%) developing grade ≥3 ICANS. Two (13%) patients and 10 (67%) patients developed grades 3 and 4 cytopenias within 30 days of infusion, respectively. Four (27%) patients required blood or platelet transfusions within 100 days of infusion. Febrile neutropenia was seen in 8 (53%) patients, and 8 patients had culture or PCR-verified bacterial (33%), viral (40%), or fungal (7%) infections. Only 1 (7%) patient developed a new abnormality on EKG within 30 days of infusion (right ventricular conduction delay). Median length of inpatient stay was 17 days (range 13-35), and 2 (13%) required re-hospitalization within 100 days of infusion. Overall and complete response rates at 100 days post-infusion were 13 (86%) and 11 (73%), respectively. At one year, overall and event-free survival were 72.2% (95% CI: 54.4-99.6%) and 53.3% (95% CI: 33.2%-85.6%), respectively. The median overall survival was 30.8 months with a median follow-up of 21.4 months. One patient experienced treatment-related mortality due to CRS, and 5 (33%) had subsequent disease relapse. Conclusion These results suggest that axi-cel is an effective and well-tolerated treatment for patients age ≥ 75 with R/R NHL. Only 1/15 patients developed grade ≥3 CRS or ICANS which is comparable to reported rates of toxicities in younger patients. Although multiple studies have identified cytopenias and cardiac arrhythmias as major CAR-T toxicities, a minority of our cohort required transfusions, and none developed life-threatening arrhythmias. OS and EFS were also comparable to real-world experience seen in younger patients. This study may be limited by the selection of a relatively fit population of elderly patients; however, the median Karnofsky Performance Score was 80 and ranged as low as 60. Overall, these findings show that axi-cel may be an appropriate strategy for relapsed aggressive NHL in carefully selected patients in their eighth and even ninth decades of life.

Infectious and Non-Infectious Pulmonary Complications in HCT Patients Treated with Post Transplant Cyclophosphamide (PTCy) Based Gvhd Prophylaxis

Introduction: Pulmonary complications are a leading cause of mortality and morbidity amongst pts undergoing hematopoietic stem cell transplantation (HCT). Increasingly, allogeneic HCT recipients are undergoing HCT with PTCy based GVHD prophylaxis. While lower rates of severe GVHD has been reported with PTCy, increased infection and organ toxicity has also been seen compared with standard calcineurin inhibitor (CNI) prophylaxis. The incidence and outcomes of pulmonary complications, both infectious and non-infectious/immune in pts receiving PTCy remain poorly characterized. Therefore, we aimed to assess for these in this study. Methods: We performed a retrospective review of pts between 2012-2022 who underwent 1st allogeneic BMT and received PTCy as part of GVHD prophylaxis. We identified pts requiring hospitalization for pulmonary complications. Infectious cases were categorized as bacterial, fungal, viral, or mixed. Bacterial pneumonia was defined as fever, cough, dyspnea, purulence sputum, and new or progressive radiographic evidence of infiltrate not explained by a non-infectious cause, treated with at least 5 days of antibiotics. Viral and fungal pneumonia were diagnosed based on identified organism. Noninfectious complications included idiopathic pulmonary syndrome (IPS), diffuse alveolar hemorrhage (DAH), cryptogenic organizing pneumonia (COP), and bronchiolitis obliterans syndrome (BOS). IPS was defined as radiographic evidence of alveolar infiltrates, dyspnea, cough, increased work of breathing or oxygen requirements, exclusion of infection or alternate pathology, and treated with high-dose systemic corticosteroids. DAH was defined as radiographic evidence of widespread alveolar injury, increased work of breathing or oxygen requirements, and persistent and progressive bloody return on BAL. COP was defined as pathologic evidence of organizing pneumonia on transbronchial lung biopsy in the absence of pathogens. BOS was defined as FEV1/FVC <0.7 and FEV1 <75% with a ≥10% decline over <2 years. Results: A total of 224 pts were identified. Median age at HCT was 55 years (20-78) (Table 1). 138 (64%) were male. The median comorbidity index (HCT-CI) score was 3 and median Karnofsky Performance Score was 80. 56%(n=125) pts underwent HCT with nonmyoablative conditioning, 78% (n=157) underwent HCT with a haploidentical donor, and 65% (n=145) of grafts were peripheral blood. 4%(n=10) were current smokers at time of HCT, 38% (n=84) were former smokers. 16% (n=35) had an existing diagnosis of asthma or COPD. 72 (32%) pts were hospitalized for pneumonia at any point after HCT. There were 23 bacterial pneumonias (30%), 20 viral (27%), 13 fungal (18%), and 12 were mixed (17%) (Table 2). There were 4 pts (6%)with documented pneumonia of unknown etiology due to rapid progression to death or hospice. 10 pts (4%) developed IPS with a median onset of 153 days (20-354). 2 pts (1%) developed COP with a mean onset of 754 days (388 - 1119). 5 pts (2%) developed BOS with a median onset of 336 days (153-677). 8 pts (4%) developed DAH with a median onset of 48 days (20-152). Among all patients, 57 pts (25%) required mechanical ventilation at any point post-HCT, and 18 pts (8%) were prescribed home oxygen at any point post-HCT. Overall, 80pts (77%) died due to non-relapse causes. 29 deaths (28%) were pulmonary related, (21 (20%) infectious and 8 (8%) noninfectious). Of the noninfectious pulmonary deaths, 3 pts died due to IPS, and 5 died due to DAH. Conclusion: In our cohort of pts receiving PTCy based GVHD prophylaxis, significant infectious pulmonary complications were common and were fatal in 9.4% of pts. Infections were the major driver of pulmonary related mortality, however, we observed noninfectious/immunologic pulmonary complications at a rate within or only slightly below the previously reported ranges among transplanted pts predominantly receiving CNI based prophylaxis.

SURG-11. RISKS AND BENEFITS OF REPEATED RESECTION FOR GLIOBLASTOMA: A SINGLE INSTITUTION REVIEW OF CHARACTERISTICS AND OUTCOMES OF RESECTION OF RECURRENT GLIOBLASTOMA

Abstract Maximal safe resection is standard for newly diagnosed glioblastoma, but for recurrent glioblastoma the value of resection is less clear. We performed a retrospective, single-institution analysis of sequential patients undergoing re-resection for recurrent glioblastoma and analyzed pre-operative risk factors, progression free and overall survival from time of re-resection to death or last follow-up (PFS/OS), and complication rates. Between 2017 and 2022, 38 patients underwent re-resection of glioblastoma (defined by 2016 WHO criteria, 86.8% IDH wild type) and were followed for an average of 157 weeks (range 17-553). The cohort had a mean age of 59.4 years (range 39-87), was 55% male, and included 68.4% MGMT unmethylated tumors. Preoperatively, median Karnofsky Performance Score (KPS) was 80 (range 50-100), and median modified frailty index (mFI-5) was 0 (range 0-4). Re-resection occurred an average of 55.3 weeks after initial resection (SD 59.6, range 5-314), 25.0 weeks after chemotherapy (SD 51.8), and 39.9 weeks after radiation (SD 45.1). Mean OS after re-resection was 67.4 weeks (SD 91.5, range 1-505 weeks), median 59.5 weeks. Average PFS was 24.5 weeks (SD 25.3, range 1-139). The complication rate was 34.2% (n = 15), including 6 patients (15.8%) with a wound infection and 5 (13.1%) with symptomatic hemorrhage. 12 (31.6%) patients had a new neurologic deficit. Postoperative KPS was lower than preoperative KPS (p = .002). Patients with <20 weeks between surgeries, mFI >1, or KPS <80 had higher rates of complications (respectively p = .04, p = .03, p = .03). Patients with mFI >1 or KPS <70 were more likely to die within 30-days of surgery (respectively p = .014; p = .018). Re-resection demonstrated a survival benefit, especially for patients younger than 65 with a mFI of < 2. Though complications were common, post-operative complications were not associated with a shorter overall survival. Consideration for age, frailty, KPS, and timing of surgery may guide selection of patients for re-resection.

RADT-16. A RETROSPECTIVE COMPARISON OF OUTCOMES AFTER WHOLE BRAIN RADIOTHERAPY AND RAPID SIMPLE (RAPPLE) TARGETED THERAPY FOR BRAIN METASTASES IN MATCHED COHORTS OF PATIENTS WITH POOR PROGNOSIS

Abstract BACKGROUND For patients whose poor prognosis does not warrant stereotactic radiosurgery, we use the RAPPLE radiotherapy technique to treat multiple brain metastases. RAPPLE uses single-isocenter, coplanar volumetric modulated arc therapy and a non-stereotactic head-shell with IntegraBite™. Brain metastasis are contoured in a single gross tumour volume and expanded by 3 mm to create a planning target volume, covered by 95-110% of 20 Gy in 5 fractions. Our study compares clinical outcomes after RAPPLE and whole brain radiotherapy (WBRT). METHODS From January 2017 to December 2021, we identified patients receiving a first course of RAPPLE and matched patients receiving a first course of WBRT. Cox regression was used to analyze overall survival and Fine-Gray analysis was used to analyze intracranial progression. For each cohort, we compared patient-reported fatigue before and 2-6 weeks after radiotherapy. RESULTS Each cohort had 137 patients whose median Karnofsky Performance Score was 70. The diagnoses were lung cancer (72%) and other cancers (28%). The median survival was 4.1 months for RAPPLE and 4.2 months for WBRT (log-rank p = 0.8). On multivariable analysis of survival, the radiotherapy technique was not predictive (HR = 0.96, 95%CI: 0.73-1.25, p = 0.7). On multivariable analysis, intracranial progression was more likely after RAPPLE (HR = 1.6, 95%CI: 1.1 – 2.3, p = 0.02). The 18-month risk of intracranial progression was 0.49 for RAPPLE and 0.37 for WBRT (p = 0.04). After RAPPLE, 17% of patients required more focal RT and 4% required salvage WBRT, while after WBRT, 3% required focal RT and 4% required repeat WBRT. After RAPPLE, mean patient-reported fatigue remained stable from baseline to first follow-up (2.18 vs. 2.27, p = 0.9), but after WBRT it worsened (1.95 vs. 2.63, p = 0.002). CONCLUSIONS Ninety-six percent of patients treated with RAPPLE avoided WBRT. Patients reported worse fatigue after WBRT.

RAPid SimPLE (RAPPLE) Targeted Radiation Treatment vs. Whole Brain Radiotherapy: A Retrospective Study of Matched Patients with Brain Metastases and Poor Prognosis

Patients with brain metastases and poor prognosis are often treated with whole brain radiotherapy (WBRT) which can cause a variety of side effects. Our institution devised a new brain-sparing radiotherapy technique to treat multiple brain metastasis for patients whose poor prognosis does not warrant SRS. This study compares the oncologic outcomes of matched patients treated with RAPPLE and WBRT. RAPPLE uses single-isocenter, coplanar volumetric modulated arc therapy and a non-stereotactic head-shell with IntegraBite™. Brain metastasis were contoured in a single gross tumor volume and expanded by 3 mm to create a planning target volume, of which 99.5% was covered with 95-110% of 20 Gy in 5 fractions. Patients treated with a first course of RAPPLE from January 2017 to December 2021 were identified in an institutional database. Using age, cancer diagnosis, and treatment date, we identified a matched cohort of patients receiving a first course of WBRT with 20 Gy in 5 fractions. Overall survival (OS) was calculated using the Kaplan-Meier method, and intracranial progression was calculated using cumulative incidence with a competing risk of death. Log-rank, Cox regression and Fine-Gray analyses were used for comparisons. Paired t-tests were used to compare patient-reported fatigue measured using 5-level Likert scales before and 2-6 weeks after radiotherapy. The RAPPLE and WBRT cohorts each had 137 patients. The matched median age was 69 years. Primary diagnoses were lung cancer (72%) and other cancers (28%). The minimum, median, and maximum numbers of metastases treated with RAPPLE were 1, 3, and 18, respectively. The median Karnofsky Performance Score (KPS) was 70 in both cohorts. The median survival was 4.1 months for RAPPLE and 4.2 months for WBRT, and the 18-month OS was 11% for RAPPLE and 12% for WBRT (log-rank p = 0.8). On multivariable analysis, KPS, diagnosis, extracranial disease, and use of systemic therapy before and after RT were predictive of OS, but use of RAPPLE vs. WBRT was not (HR = 0.97, 95% CI: 0.75-1.25, p = 0.8). The 18-month cumulative incidence of intracranial progression was 0.49 for RAPPLE and 0.37 for WBRT (p = 0.04). After RAPPLE, 17% required more focal RT and 4% required salvage WBRT, while after WBRT, 3% required focal RT and 4% required repeat WBRT. After RAPPLE, mean patient-reported fatigue remained stable from baseline to first follow-up (2.18 vs. 2.27, p = 0.9), but, after WBRT, it worsened from baseline to first follow-up (1.95 vs. 2.63, p = 0.002). As expected, after RAPPLE, more targeted radiotherapy was required for intracranial progression, but there was no difference in OS between the RAPPLE and WBRT cohorts. Patients reported significantly worse fatigue after WBRT. Almost all patients (96%) treated with RAPPLE avoided WBRT.

Clinical Outcomes for Patients with Brain Metastases from Upper Gastrointestinal Cancer Treated with Stereotactic Radiosurgery

Prior studies have reported outcomes for brain metastases from gastrointestinal (GI) primary cancers treated with stereotactic radiosurgery (SRS); however, most include a majority of colorectal cancer. Few studies specifically evaluate SRS treatment response for brain metastases from upper GI cancers. We report our institutional outcomes for patients with upper GI cancers who were treated with SRS for brain metastases. Patients with an upper GI cancer who underwent SRS for brain metastases between 1991 and 2021 were retrospectively reviewed from a single institution IRB-approved database. The primary endpoint was local failure (LF) and secondary endpoint was overall survival (OS). LF was estimated using the Cumulative Incidence Function with death as a competing risk. Survival analysis was performed with the Kaplan-Meier Method. Predictors of cumulative incidence of LF were assessed using competing risk regression. Forty-nine patients with 107 brain metastases were analyzed. Forty-two (86%) patients were male. The median follow-up time was 6.7 months (range: 0.4-61.7 months) and median OS was 7.5 months (range: 0.9-61.7 months). The median Karnofsky Performance Score (KPS) was 80 (range: 40-100). The primary disease site was esophagus in 87 (81%) lesions, pancreas in 10 (9.3%) lesions, stomach in 5 (4.7%) lesions, liver in 2 (1.9%) lesions, gallbladder in 2 (1.9%) lesions, and small intestine in 1 (0.9%) lesion. The median metastasis size was 1.4 cm (range: 0.3-6.7 cm). The median prescription dose and fraction number were 24 Gy (range: 14-30 Gy) and 1 fraction (range: 1-2 fractions), respectively. The cumulative incidence of LF at 6 and 12 months was 5.6% (95% CI: 2.3-11%) and 12% (95% CI: 6.9-20%), respectively. Overall survival at 6 and 12 months was 59% (95% CI: 50-69%) and 35% (95% CI: 27-46%), respectively. On univariate analysis, female gender (HR = 0.19, 95% CI: 0.06-0.61, p = 0.005), Black race (HR = 0.09, 95% CI: 0.03-0.23, p = <0.001), and larger tumors (HR = 1.35, 95% CI: 1.03-1.78, p = 0.03) were significantly associated with local failure. SRS for brain metastases from upper GI cancers is an appropriate treatment option and provides excellent local control. Unlike prior studies that have reported lower local control rates for all GI cancers with brain metastases treated with SRS, our data show that local failure rates in brain metastases from upper GI cancers specifically are more consistent with previously published data from other disease sites. Further studies evaluating SRS treatment response for brain metastases from GI cancers should separate upper GI and lower GI cancers.

LMAP-19 THE ROLE OF STEREOTACTIC RADIOSURGERY IN PATIENTS WITH BRAIN METASTASES FROM COLORECTAL CANCERS

Abstract BACKGROUND AND OBJECTIVES The role of stereotactic radiosurgery (SRS) for patients with brain metastases from colorectal cancers (CRC) has not been established. The authors present a single-institution experience of CRC patients who underwent SRS with metastatic brain spread. METHODS We retrospectively analyzed 112 metastatic CRC patients (64 female, 57.14%) with 450 brain metastases that were treated with Gamma Knife SRS between 2000-2022. The median age at SRS was 63 years (range: 28-86) and the median Karnofsky Performance Score (KPS) was 80 (range: 60-100). The primary sites were colon (86 patients, 76.79%) and rectal (26 patients, 21%). Three patients underwent hypo-fractionated SRS (3 sessions) with a median margin dose of 27 Gy (range: 27- 30). All other patients underwent single-session SRS with a median margin dose of 18 Gy (range: 11-20). RESULTS The median patient survival after SRS was 7 months (range: 1-174). Ninety-eight (87.5%) patients expired at last follow up and 15 patients (15.31%) died related to progressive intracranial disease. KPS &amp;lt; 80 at SRS presentation (p=0.03, HR: 0.63, 95% CI: 0.41-0.96) was associated with inferior overall survival using multivariate analysis. Seventeen patients (15.18%) had documented local tumor progression after SRS, at a median time of 7 months (range: 3-34) between SRS and progression. Twenty-six patients (23.21%) developed new brain metastases at a median of 5 months (range: 2-26) between SRS and new tumor detection. KPS ≥ 80 (p=0.05, HR: 0.96, 95% CI: 0.93-0.99), and &amp;lt; 3 brain metastases at SRS presentation (p&amp;lt;0.01, HR: 3.62, 95% CI: 1.53-8.56) were associated with better distant tumor control on multivariate analysis. The incidence of adverse radiation effects was 5.36%. CONCLUSIONS SRS effectively controls brain metastases from CRC with a low risk of treatment-related toxicity, allowing patients to focus on primary disease management. During follow-up, the development of progressive or additional metastases can be safely treated by repeat SRS.

The transfrontal isthmus approach for insular glioma surgery.

The classic transopercular or transsylvian approach to insular gliomas removes the tumor laterally through the insular cortex. This study describes a new anteroposterior approach through the frontal isthmus for insular glioma surgery. The authors detailed the surgical techniques for resection of insular gliomas through the transfrontal isthmus approach. Fifty-nine insular gliomas with at least Berger-Sanai zone I involvement were removed with the new approach, and extent of resection and postoperative neurological outcomes were assessed. Fifty-nine patients were enrolled in the study, including 35 men and 24 women, with a mean (range) age 44.3 (19-75) years. According to the Berger-Sanai classification system, the most common tumor was a giant glioma (67.8%), followed by involvement of zones I and IV (18.6%). Twenty-two cases were Yaşargil type 3A/B, and 37 cases were Yaşargil type 5A/B. The average angle between the lateral plane of the putamen and sagittal line was 33.53°, and the average width of the isthmus near the anterior insular point was 33.33 mm. The average angle between the lateral plane of the putamen and the sagittal line was positively correlated with the width of the isthmus near the anterior insular point (r = 0.935, p < 0.0001). The median (interquartile range [IQR]) preoperative tumor volume was 67.82 (57.64-92.19) cm3. Of 39 low-grade gliomas, 26 (66.67%) were totally resected; of 20 high-grade gliomas, 19 (95%) were totally resected. The median (IQR) extent of resection of the whole group was 100% (73.7%-100%). Intraoperative diffusion-weighted imaging showed no cases of middle cerebral artery- or lenticulostriate artery-related stroke. Extent of insular tumor resection was positively correlated with the angle of the lateral plane of the putamen and sagittal line (r = -0.329, p = 0.011) and the width of the isthmus near the anterior insular point (r = -0.267, p = 0.041). At 3 months postoperatively, muscle strength grade exceeded 4 in all cases, and all patients exhibited essentially normal speech. The median (IQR) Karnofsky performance score at 3 months after surgery was 90 (80-90). The transfrontal isthmus approach changes the working angle from lateral-medial to anterior-posterior, allowing for maximal safe removal of insular gliomas.

Survival, prognostic factors, hospitalization time and clinical performance status after first cerebral relapse or progression in 54 patients with primary CNS lymphoma not eligible for high dose chemotherapy: a retrospective analysis

BackgroundTreatment of relapsed or refractory primary CNS lymphoma (r/r PCNSL) is difficult, particularly in patients not eligible for high dose chemotherapy with autologous stem cell transplantation (HDC-ASCT). No standard treatment has been defined for these patients yet.MethodsWe retrospectively analyzed survival, prognostic factors, hospitalization time and Karnofsky performance score (KPS) before and after treatment in 54 r/r PCNSL patients with isolated cerebral relapse or progression (n = 23 refractory, n = 31 relapsed) not eligible for HDC-ASCT, who received heterogenous salvage treatments.ResultsTreatments were temozolomide (+ rituximab) (n = 21), high dose methotrexate (HD-MTX)-based therapy (n = 11), whole brain radiotherapy (WBRT)/focal radiotherapy (n = 11), other systemic treatments (n = 2) and best supportive care (BSC, n = 9). Median progression free survival (PFS) and overall survival (OS) were 2.6 months (95% CI 1.0–4.2 months) and 4.8 months (95% CI 3.3–6.3 months), respectively. Eight patients survived for ≥ 3 years (13.1%, n = 3 received temozolomide, n = 3 WBRT, n = 2 HD-MTX-based treatment). Application of any salvage treatment (vs. BSC), younger age at relapse and asymptomatic (vs. symptomatic) relapse were positive prognostic factors. No significant differences in OS were found for the different salvage treatments. Median hospitalization time for treatment was 15/13 days for temozolomide (+ rituximab)/radiotherapy compared to 55 days for HD-MTX-based therapy. Median KPS in assessable patients (n = 41) was 60 (range 30–100) before treatment and 50 (range 20–90) after treatment. In patients with response to treatment (n = 16) KPS improved from 60 (range 40–90) before treatment to 70 (range 50–90) after treatment, while patients with PD (n = 25) deteriorated from 60 (range 30–100) to 40 (range 20–70).ConclusionSurvival for this cohort of r/r PCNSL patients with isolated cerebral relapse or progression was poor. Considering long hospital stays associated with HD-MTX-based chemotherapy and neurotoxicity associated with WBRT, temozolomide might be worth considering with a chance of prolonged survival and avoidance of long hospitalization. Novel therapeutic agents are urgently needed to improve survival in r/r PCNSL patients.

Development of an enhanced recovery protocol after laser ablation surgery protocol: a preliminary analysis.

Enhanced recovery after surgery (ERAS) programs are a model of care that aim to improve patient outcomes, reduce complications, and facilitate recovery while reducing healthcare-associated costs and admission length. While such programs have been developed in other surgical subspecialties, there have yet to be guidelines published specifically for laser interstitial thermal therapy (LITT). Here we describe the first multidisciplinary ERAS preliminary protocol for LITT for the treatment of brain tumors. Between the years 2013 and 2021, 184 adult patients consecutively treated with LITT at our single institution were retrospectively analyzed. During this time, a series of pre, intra, and postoperative adjustments were made to the admission course and surgical/anesthesia workflow with the goal of improving recovery and admission length. The mean age at surgery was 60.7 years with a median preoperative Karnofsky performance score of 90 ± 13. Lesions were most commonly metastases (50%) and high-grade gliomas (37%). The mean length of stay was 2.4 days, with the average patient being discharged 1.2 days after surgery. There was an overall readmission rate of 8.7% with a LITT-specific readmission rate of 2.2%. Three of 184 patients required repeat intervention in the perioperative period, and there was one perioperative mortality. This preliminary study shows the proposed LITT ERAS protocol to be a safe means of discharging patients on postoperative day 1 while preserving outcomes. Although future prospective work is needed to validate this protocol, results show the ERAS approach to be promising for LITT.

Zopiclone versus placebo for short-term treatment of insomnia in patients with advanced cancer—a double-blind, randomized placebo-controlled clinical multicenter phase IV trial

PurposeInsomnia is frequent in patients with advanced cancer, and a variety of pharmacological agents is used to treat this condition. Still, few clinical trials have investigated the effectiveness of pharmacological sleep therapies in this patient group. We aimed to study the short-term effectiveness of zopiclone on sleep quality in patients with advanced cancer who report insomnia.MethodsA randomized, double-blind, placebo-controlled, parallel-group, multicenter, phase IV clinical trial in adult patients with metastatic malignant disease and insomnia. Patients were treated with zopiclone or placebo for six subsequent nights. Primary end point was patient-reported sleep quality during the final study night (NRS 0–10). Secondary end points were patient-reported sleep onset latency (SOL) and total sleep time (TST).ResultsForty-one patients were randomized, with 18 being analyzed in the zopiclone group and 21 in the placebo group. Median age was 66, median Karnofsky performance score was 80, and 56% were male. Mean sleep quality at end of study was 2.9 (CI 2.3 to 3.8) in the zopiclone group and 4.5 (CI 3.6 to 5.4) in the placebo group (p = 0.021). At end of study, SOL was significantly different between the treatment groups: zopiclone 29 min (CI 13 to 51) and placebo 62 min (CI 40 to 87) (p = 0.045). TST was not significantly different across groups: zopiclone 449 min (403 to 496) and placebo 411 min (CI 380 to 440) (p = 0.167).ConclusionZopiclone improved short-term patient-reported sleep quality in this cohort of patients with advanced cancer.Trial registrationClinicalTrials.gov Identifier: NCT02807922.

Safety and Efficacy of Dose-Escalated Radiotherapy with a Simultaneous Integrated Boost for the Treatment of Spinal Metastases

<h3>Purpose/Objective(s)</h3> Dose-escalated radiotherapy (RT) using a spinal simultaneous integrated boost (SSIB) has been recently utilized for treatment of metastatic lesions not amenable to spine stereotactic radiosurgery (SSRS). Prior reports have utilized small sample sizes with short follow-up times. Our goal was to characterize the long-term efficacy and safety of this technique in a large cohort of patients with long term follow-up. <h3>Materials/Methods</h3> We reviewed 58 patients with 63 spinal metastatic sites that were treated with RT using a SSIB between 2012 and 2021. All patients received 30 Gy to the clinical tumor volume (CTV)and 40 Gy to the gross tumor volume, each delivered simultaneously in 10 fractions (GTV). Acute and late toxicities were noted for each patient. Local control (LC) was defined as having no progression on magnetic resonance imaging (MRI) at the SSIB-treated site. Overall survival (OS) was defined as the time from initiation of SSIB to death or last follow up, and was estimated using the Kaplan-Meier method. Multivariable Cox analysis was performed to identify associations with OS and LC. <h3>Results</h3> In our cohort, the median Karnofsky Performance Score (KPS) prior to RT was 80 (interquartile range [IQR], 80-90). Tumor histology was considered to be radioresistant in 81% of patients. Most patients had paraspinal involvement (65%) and epidural extension (82%). The median follow-up was 31 months with a median OS of 18 months (95% confidence interval [CI], 13-27 months). OS at 1, 2, and 3 years were 64%, 45%, and 24%, respectively. Actuarial LC was 98% (CI, 95-100%) and 95% (CI, 89-100%) at 1 and 2 years, respectively. The median GTV and CTV doses were 4123 cGy (range, 3400-4318 cGy) and 3641 cGy (range, 3302-4089 cGy), respectively. The mean cord dose was 2401 cGy (range 59-3168 cGy). The most commonly observed acute toxicities were fatigue (41%), pain (38%), esophagitis (8%), and nausea (8%). However, only one patient (2%) experienced Grade 3 or higher toxicity (pain). At last follow-up, no patients had developed myelopathy and all patients maintained ambulation. Following RT, pain improvement was achieved in 82% with a median pain score of 2 (IQR, 1-4) out of 10 from a pre-RT baseline of 4 (IQR, 3-6). Multivariable Cox analysis revealed that higher KPS score prior to RT (hazard ratio [HR], 0.40, 95%, CI, 0.20-0.84; <i>P</i>=0.016) was associated with longer OS, whereas increased size of PTV (HR 1.003, CI 1.001-1.005; <i>P</i>=0.017) was associated with shorter survival. <h3>Conclusion</h3> Our data show that the use of RT with SSIB provides favorable LC and OS with improved pain relief for selected patients that are not amenable for SSRS. Importantly, there were limited acute toxicities with no observed instances of radiation-induced myelopathy. Multi-institutional validation is warranted.

OS02.7.A The role of epilepsy in elderly patients with Glioblastoma: An Austrian multicenter analysis

Abstract Background Higher age is a significant predictor of poor outcome in glioblastoma multiforme (GBM) patients. Thus, acquisition of a better understanding of additional prognostic factors in these often-frail patients is of utmost importance. Epileptic seizures correlate with improved overall survival (OS) in low-grade gliomas; however, the impact of epilepsy in GBM patients on outcome parameters is poorly defined. Furthermore, persisting epilepsy significantly influences the patients’ quality of life (QoL). This study aims at specifically evaluating the impact of epilepsy in elderly GBM patients. Material and Methods Two Austrian academic neurosurgical centers retrospectively analyzed all elderly (≥65 years) GBM patients with de-novo tumors, who underwent tumor resections between 09/2006 and 07/2021. Epidemiological, histopathological and survival data were gained from patients’ electronic charts and screened for presence of epilepsy preoperatively or during follow-up. Results 391 patients (55% males, 45% females) with a median age at surgery of 73 years (Interquartile Range (IqR) 68.5-77.5) were analyzed. The mean predicted OS was recorded to be 12.4 months (CI95% 10.9-14.0). Median preoperative Modified Rankin Scale (mRS) was 2 (IqR 1-3), and median preoperative Karnofsky performance score was 80 (IqR 60-90). Mean follow-up was 10.4 months (CI95% 9.1-11.6) in our cohort. 95/391 patients (24%) suffered from preoperative epilepsy. 17 (18%) patients still suffered from epilepsy after tumor resection with eight patients who developed new postoperative seizures, and four patients (1.0%) showed a worsening of already preoperatively diagnosed seizures. Major surgery-associated neurological complications included new motor deficits in 29 (7%) and new aphasia in 16 (4%) patients. Logistic regression showed, patients with seizures had significantly lower mRS (OR=0.735 [CI95% 0.563 0.961], p=0.032) and less frequently occipital tumor location (OR=0.347 [CI95% 0.152-0.791], p=0.018). Postoperative epilepsy resulted in significantly prolonged hospitalization after the surgery (OR=2.622[CI95% 1.496-3.979], p=0.009). Survival did not correlate with preoperative epilepsy (p&amp;gt;0.05). However, Cox regression revealed that multifocal tumor location (HR=1.777 [CI95% 1.197-2.639], p=0.025) as well as thalamic involvement (HR=11.121 [CI95% 3.431-36,046], p=0.030) negatively influenced OS. Furthermore, surgery-associated complications shortened OS significantly (HR=1.945 [CI95% 1,296-2,916], p=0.025). Conclusion Even though epilepsy was not found to directly impact survival in elderly GBM patients, we found that surgery led to epilepsy freedom in a significant proportion of our patient cohort, thereby potentially leading to improved QoL. Greatest focus should be set on avoiding any surgery-associated deficits, since these severely influence the OS.

Outcome and prognostic factors of very old patients with primary CNS lymphoma: a retrospective analysis of patients ≥80 years treated with high-dose methotrexate-based chemotherapy

Although >10% of primary CNS lymphoma (PCNSL) patients are ≥80 years, data on this population are limited. We analyzed 19 consecutive octogenarians with PCNSL treated with high-dose methotrexate (HD-MTX)-based chemotherapy at our institution concerning outcome, prognostic factors and living conditions at six-month follow-up for 11 patients alive and in remission. Seven patients received intracerebroventricular (ICV) treatment additional to systemic therapy. Median follow-up was 27.3 months. Median overall survival was 16.3 months. Positive prognosticators of survival were application of ICV treatment (p = 0.033) and female gender (p = 0.015). All 11 patients alive and in remission at 6-month follow-up were living at home with a median Karnofsky performance score of 60 (range 50–90) and a median instrumental activities of daily living score of 3 (range 1–8). HD-MTX-based polychemotherapy including ICV treatment was feasible in this population, patients in remission needed moderate support in everyday live.

Scalp-Sparing Radiation With Concurrent Temozolomide and Tumor Treating Fields (SPARE) for Patients With Newly Diagnosed Glioblastoma.

IntroductionStandard-of-care treatment for patients with newly diagnosed glioblastoma (GBM) after surgery or biopsy includes concurrent chemoradiation followed by maintenance temozolomide (TMZ) with tumor treating fields (TTFields). Preclinical studies suggest TTFields and radiotherapy work synergistically. We report the results of our trial evaluating the safety of TTFields used concurrently with chemoradiation.MethodsThis is a single-arm pilot study (clinicaltrials.gov Identifier: NCT03477110). Adult patients (age ≥ 18 years) with newly diagnosed glioblastoma and a Karnofsky performance score (KPS) of ≥ 60 were eligible. All patients received concurrent scalp-sparing radiation (60 Gy in 30 fractions) with TMZ (75 mg/m2 daily) and TTFields (200 kHz). Maintenance therapy included TMZ and continuation of TTFields. Scalp-sparing radiation treatment was used to reduce radiation dermatitis. Radiation treatment was delivered through the TTFields arrays. The primary endpoint was safety and toxicity of tri-modality treatment within 30 days of completion of chemoradiation treatment.ResultsThere were 30 patients enrolled, including 20 (66.7%) men and 10 (33.3%) women, with a median age of 58 years (range 19 to 77 years). Median KPS was 90 (range 70 to 100). A total of 12 (40%) patients received a gross total resection and 18 (60%) patients had a subtotal resection. A total of 12 (40%) patients had multifocal disease at presentation. There were 20 (66.7%) patients who had unmethylated O(6)-methylguanine-DNA-methyltransferase (MGMT) promotor status and 10 (33.3%) patients who had methylated MGMT promoter status. Median follow-up was 15.2 months (range 1.7 to 23.6 months). Skin adverse events were noted in 83.3% of patients, however, these were limited to Grade 1 or 2 events, which resolved spontaneously or with topical medications. The primary end point was met; no TTFields discontinuation occurred during the evaluation period due to high grade scalp toxicity. A total of 27 (90%) patients had progression, with a median progression-free survival (PFS) of 9.3 months (95% confidence interval (CI): 8.5-11.6 months). The 1-year progression-free survival was 23% (95% CI: 12%-45%). The median overall survival (OS) was 15.8 months (95% CI: 12.5 months-infinity). The 1-year overall survival was 66% (95% CI: 51%-86%).ConclusionsConcurrent TTFields with scalp-sparing chemoradiation is a feasible and well-tolerated treatment option with limited toxicity. A phase 3, randomized clinical trial (EF-32, clinicaltrials.gov Identifier: NCT04471844) investigating the clinical benefit of concurrent TTFields with chemoradiation treatment is currently enrolling.Clinical Trial Registration Clinicaltrials.gov, identifier NCT03477110.

High-Dose Chemotherapy with Autologous Hematopoietic Stem Cell Transplantation in Relapsed or Refractory Primary CNS Lymphoma: A Retrospective Monocentric Analysis of Long-Term Outcome, Prognostic Factors, and Toxicity.

Simple SummaryNo standard treatment is defined for relapsed or refractory (r/r) primary CNS lymphoma (PCNSL). However, high-dose chemotherapy with autologous stem cell transplantation (HCT-ASCT), an efficient first line treatment in younger PCNSL patients, is commonly applied in relapsed or refractory disease, if tolerable. Here, we retrospectively analyzed 59 patients with r/r PCNSL focusing specifically on differences in long-term outcome and toxicity in patients <65 years (n = 33) and ≥65 years (n = 26) of age.High-dose chemotherapy with autologous stem cell transplantation (HCT-ASCT) is reportedly an effective treatment strategy in relapsed or refractory primary CNS lymphoma (r/r PCNSL); however, only selected patients are eligible for this treatment. We retrospectively analyzed outcome, prognostic factors, and toxicity in 59 patients with r/r PCNSL planned to receive HCT-ASCT at our institution between January 2005 and December 2021 (n = 33 < 65 years; n = 26 ≥ 65 years). Median follow-up was 65 months (95% CI 21–109). Median age was 63 years (range 29–76), median Karnofsky performance score (KPS) was 80 (range 30–100). In the entire cohort of 59 patients, median overall survival (OS) was 14 months (95% CI 0–37). In 50/59 (84.7%) patients who completed HCT-ASCT, median progression free survival (PFS) was 12 months (95% CI 3–21) and median OS 30 months (95% CI 0–87). 1-year, 2-year, and 5-year OS rates of 61.2%, 52.3% and 47.1%, respectively, were observed. Six patients (10.2%) died related to treatment (1 during induction treatment, 5 post HCT-ASCT). Age was not prognostic. On univariate analysis, KPS ≥ 80 (p = 0.019) and complete or partial remission before HCT-ASCT (p = 0.026) were positive prognosticators of OS; on multivariate analysis, KPS (p = 0.043) and male gender (p = 0.039) had an impact on OS. The 5-year OS rate in patients with progressive or stable disease after induction treatment was 32.7%. In summary, HCT-ASCT was effective and feasible in this cohort of r/r PCNSL patients. Clinical state, remission status before HCT-ASCT, and gender influenced survival, whereas age did not influence outcome in this study.

The Clinical Frailty Scale as useful tool in patients with brain metastases

PurposeThe Clinical Frailty Scale (CFS) evaluates patients’ level of frailty on a scale from 1 to 9 and is commonly used in geriatric medicine, intensive care and orthopedics. The aim of our study was to reveal whether the CFS allows a reliable prediction of overall survival (OS) in patients after surgical treatment of brain metastases (BM) compared to the Karnofsky Performance Score (KPS).MethodsPatients operated for BM were included. CFS and KPS were retrospectively assessed pre- and postoperatively and at follow-up 3–6 months after resection.Results205 patients with a follow-up of 22.8 months (95% CI 18.4–27.1) were evaluated. CFS showed a median of 3 (“managing well”; IqR 2–4) at all 3 assessment-points. Median KPS was 80 preoperatively (IqR 80–90) and 90 postoperatively (IqR 80–100) as well as at follow-up after 3–6 months. CFS correlated with KPS both preoperatively (r = − 0.92; p < 0.001), postoperatively (r = − 0.85; p < 0.001) and at follow-up (r = − 0.93; p < 0.001).The CFS predicted the expected reduction of OS more reliably than the KPS at all 3 assessments. A one-point increase (worsening) of the preoperative CFS translated into a 30% additional hazard to decease (HR 1.30, 95% CI 1.15–1.46; p < 0.001). A one-point increase in postoperative and at follow-up CFS represents a 39% (HR 1.39, 95% CI 1.25–1.54; p < 0.001) and of 42% risk (HR 1.42, 95% CI 1.27–1.59; p < 0.001).ConclusionThe CFS is a feasible, simple and reliable scoring system in patients undergoing resection of brain metastasis. The CFS 3–6 months after surgery specifies the expected OS more accurately than the KPS.

Recurrent brain metastases: the role of resection of in a comprehensive multidisciplinary treatment setting

BackgroundTreatment decision for recurrent symptomatic brain metastases (BM) is challenging with scarce data regarding surgical resection. We therefore evaluated the efficacy of surgery for pretreated, recurrent BM in a comprehensive multidisciplinary treatment setting.MethodsIn a retrospective single center study, patients were analyzed, who underwent surgical resection of recurrent BM between 2007 and 2019. Intracranial event-free survival (EFS) and overall survival (OS) were evaluated by Kaplan-Maier and Cox regression analysis.ResultsWe included 107 patients with different primary tumor entities and individual previous treatment for BM. Primary tumors comprised non-small cell lung cancer (NSCLC) (37.4%), breast cancer (19.6%), melanoma (13.1%), gastro-intestinal cancer (10.3%) and other, rare entities (19.6%). The number of previous treatments of BM ranged from one to four; the adjuvant treatment modalities comprised: none, focal or whole brain radiotherapy, brachytherapy and radiosurgery. The median pre-operative Karnofsky Performance Score (KPS) was 70% (range 40–100) and improved to 80% (range 0-100) after surgery. The complication rate was 26.2% and two patients died during the perioperative period. Sixty-seven (62.6%) patients received postoperative local radio-oncologic and/or systemic therapy. Median postoperative EFS and OS were 7.1 (95%CI 5.8–8.2) and 11.1 (95%CI 8.4–13.6) months, respectively. The clinical status (postoperative KPS ≥ 70 (HR 0.27 95%CI 0.16–0.46; p < 0.001) remained the only independent factor for survival in multivariate analysis.ConclusionsSurgical resection of recurrent BM may improve the clinical status and thus OS but is associated with a high complication rate; therefore a very careful patient selection is crucial.