Median Karnofsky Performance Status Research Articles

BMET-32OUTCOMES OF GAMMA KNIFE RADIOSURGERY IN BRAIN METASTASES FROM NEUROENDOCRINE TUMORS

BACKGROUND: Neuroendocrine tumors (NETs) can originate in any organ but most commonly arise from the lungs. Despite cranial irradiation, small cell lung cancer (SCLC) often metastasizes to the brain. Stereotactic radiosurgery (SRS) is an established treatment for brain metastases yet little is known about the utility of SRS in the treatment of NETs especially noting their unique natural history. METHODS: Thirty-three patients with brain metastases from NETs who underwent Gamma Knife radiosurgery (GKRS) were retrospectively reviewed. Median age and Karnofsky performance status were 61 years (range, 30-76 years) and 80 (range, 60-90), respectively. Primary site was lung (87.9%), cervix (6.1%), esophagus (3%) and prostate (3%). Ten patients (30.3%) received upfront GKRS, 7 of whom had NETs other than SCLC. Kaplan-Meier survival and Cox regression analyses were performed to determine prognostic factors for survival. RESULTS: Of 130 evaluable lesions, 116 (89.2%) showed complete or partial response 4 to 6 weeks after GKRS. With median follow-up of 5.3 months, local and distant brain recurrence occurred in 1 patient (3.3%) and 20 patients (66.7%), respectively. The 6 and 12-month local (LRFS) and distant brain recurrence-free survival (DBRFS) were 100%/84% and 40.1%/29.3%, respectively. Median overall survival (OS) after GKRS was 6.9 months. Upfront GKRS and more than 1 GKRS course were prognostic for better OS and the number of brain metastases was prognostic for DBRFS on multivariate analyses. Toxicity developed in 13 lesions (10%) in 9 patients; hemorrhage (n = 2 lesions), necrosis (n = 8 lesions) and edema requiring steroids (n = 10 lesions). No cases of grade 3 or higher necrosis occurred. Patients treated with whole brain radiation prior to GKRS did not have higher toxicity rates than patients treated with upfront GKRS. CONCLUSIONS: GKRS is an effective treatment option for patients with brain metastases from NETs with excellent local control despite slightly higher toxicity rates than expected.

Carboplatin and Etoposide in Heavily Pretreated Patients with Progressive High-Grade Glioma

Background: Treatment of recurrent anaplastic glioma and glioblastoma remains a particular challenge in neurooncology. The lack of controlled trials results in poor evidence for all therapeutic options. Upon recurrence, many patients are treated with bevacizumab or one of the frequently used nitrosoureas such as lomustine. However, patients who still present in overall good condition after failure of multiple lines of therapy may ask for additional therapy. Methods: Here, we report our experience with the use of carboplatin in combination with etoposide as fourth- or fifth-line therapy in patients with progressive high-grade glioma. Results: The median Karnofsky performance status at the beginning of treatment was 80%. The median progression-free survival (PFS) was 2.5 months. PFS at 6 months was 0%. Administration of carboplatin and etoposide was associated with grade 3 or 4 hematotoxicity in 8 of 12 patients. Conclusion: Carboplatin in combination with etoposide has an unfavorable risk-benefit profile in heavily pretreated glioma patients.

Upfront treatment with temozolomide and bevacizumab (TEMOBEVA) in patients with bulky, multifocal glioblastoma and/or with severe neurological impairmen.

e13037 Background: Optimal treatment of patients with bulky or multifocal glioblastoma, or with severe neurological impairment is not well established. We evaluated here the impact of upfront Temozolomide (TMZ) and bevacizumab (BEV) in such patients. Methods: This retrospective study included 43 patients from 3 French centres between December 2010 and December 2014. Patients were considered not eligible for surgery or initial chemoradiation either due to tumor volume precluding an upfront chemoradiotherapy with TMZ, or due to multifocality or severe neurological impairment. Initial combination of TMZ (150 to 200 mg/m2/d, 5d every 28d) plus BEV (10mg/kg every 14d) was delivered. Responding patients received radiotherapy (60 Gy in 30 fractions) plus concomitant TMZ (75mg/m2/d), with or without BEV (10mg/kg every 14d). Results: Forty-three patients were analyzed (median age 60 years, median Karnofsky Performance Status (KPS) 70). Thirty-two patients (74%) were classified in the RTOG RPA group V-VI. Median nu...

Stereotactic radiosurgery in combination with up-front high-dose methotrexate as a first-line treatment for newly diagnosed primary central nervous system lymphoma.

The efficacy of stereotactic radiosurgery (SRS) instead of whole brain radiotherapy (WBRT) following high-dose methotrexate (HD-MTX) for primary central nervous system lymphoma (PCNSL) is unclear. To clarify whether SRS in combination with up-front HD-MTX supplements the effect of HD-MTX in remaining or refractory lesions after initial HD-MTX treatment. The authors conducted a retrospective review for newly diagnosed PCNSL patients who underwent SRS after HD-MTX as a first-line treatment. The local control (LC), the progression-free survival (PFS), the recurrence patterns, the salvage treatments, the overall survival (OS), the Karnofsky Performance Status (KPS), the activities of daily living (ADL) were analyzed as well as radiosurgical parameters. Twenty patients underwent SRS for 51 lesions with the median volume of 0.45 cm(3). The median age at SRS was 67 (range 37-82). The median KPS at SRS was 90. The LC rate at 2 years was 86.0 %, the median PFS after SRS was 17 months, necessitating additional SRS and chemotherapy. The median OS was 52 months. No significant side effects related to SRS were observed. During follow-up period, the good ADL preservation was achieved for 13 months from SRS. Patients with KPS ≥ 90 at SRS demonstrated longer ADL preservation (32 months from SRS). SRS following up-front HD-MTX without WBRT provided excellent LC, acceptable OS and the long ADL preservation period. These benefits may be more emphasized especially in patients with good KPS, but should be validated in a large patient population.

Patient-Reported Outcomes for Determining Prognostic Groups in Veterans With Advanced Cancer

ContextPhysicians overestimate survival in patients with advanced cancer. Patient-reported outcomes could provide another way to estimate survival. We previously reported four prognostic groups based on Karnofsky Performance Status, Functional Assessment of Cancer Therapy physical well-being subscale, and Memorial Symptom Assessment Scale-Short Form physical symptom distress subscale scores. ObjectivesTo determine the validity of these four prognostic groups. MethodsWe performed prospective surveys. Data from a total of 880 Veterans Affairs Medical Center patients, 417 in the First Cohort and 463 in the Validation Cohort, were analyzed. Both inpatients and outpatients were prospectively recruited in Institutional Review Board-approved studies from August 1999 to September 2009. Survival was measured from the date of entry until death or December 1, 2009. Patients completed self-assessments with the Functional Assessment of Cancer Therapy and Memorial Symptom Assessment Scale-Short Form. Analysis of variance was used to test differences between groups in continuous variables; a generalized Wilcoxon test was used for differences between groups for survival. ResultsThe average age in the Validation Cohort was 66.5 years and 98% were men. The majority of patients had metastatic cancer (90%), with lung (28%) and prostate (26%) cancers being predominant. The median Karnofsky Performance Status was 70. Median survival was 33, 46.5, 124, and 209.5 days for the four prognostic groups (P < 0.0001, all pair-wise comparisons P < 0.02). ConclusionThe four prognostic groups remained distinct in the prospective cohort. Small differences in patient-reported physical well-being can halve survival estimates. Patient-reported outcomes can correct for physician overestimate of prognosis. This study provides a way to use patient-reported outcomes for prognosis in patients with advanced cancer, with important implications for assessment.

Is stereotactic radiosurgery a rational treatment option for brain metastases from small cell lung cancer? A retrospective analysis of 70 consecutive patients.

BackgroundBecause of the high likelihood of multiple brain metastases (BM) from small cell lung cancer (SCLC), the role of focal treatment using stereotactic radiosurgery (SRS) has yet to be determined. We aimed to evaluate the efficacy and limitations of upfront and salvage SRS for patients with BM from SCLC.MethodsThis was a retrospective and observational study analyzing 70 consecutive patients with BM from SCLC who received SRS. The median age was 68 years, and the median Karnofsky performance status (KPS) was 90. Forty-six (66%) and 24 (34%) patients underwent SRS as the upfront and salvage treatment after prophylactic or therapeutic whole brain radiotherapy (WBRT), respectively. Overall survival (OS), neurological death-free survival, remote and local tumor recurrence rates were analyzed.ResultsNone of our patients were lost to follow-up and the median follow-up was 7.8 months. One-and 2-year OS rates were 43% and 15%, respectively. The median OS time was 7.8 months. One-and 2-year neurological death-free survival rates were 94% and 84%, respectively. In total, 219/292 tumors (75%) in 60 patients (86 %) with sufficient radiological follow-up data were evaluated. Six-and 12-month rates of remote BM relapse were 25% and 47%, respectively. Six-and 12-month rates of local control failure were 4% and 23%, respectively. Repeat SRS, salvage WBRT and microsurgery were subsequently required in 30, 8 and one patient, respectively. Symptomatic radiation injury, treated conservatively, developed in 3 patients.ConclusionsThe present study suggested SRS to be a potentially effective and minimally invasive treatment option for BM from SCLC either alone or after failed WBRT. Although repeat salvage treatment was needed in nearly half of patients to achieve control of distant BM, such continuation of radiotherapeutic management might contribute to reducing the rate of neurological death.

R-MPV followed by high-dose chemotherapy with TBC and autologous stem-cell transplant for newly diagnosed primary CNS lymphoma

AbstractHigh-dose methotrexate-based chemotherapy is the mainstay of treatment of primary central nervous system lymphoma (PCNSL), but relapses remain frequent. High-dose chemotherapy (HDC) with autologous stem-cell transplant (ASCT) may provide an alternative to address chemoresistance and overcome the blood-brain barrier. In this single-center phase-2 study, newly diagnosed PCNSL patients received 5 to 7 cycles of chemotherapy with rituximab, methotrexate (3.5 g/m2), procarbazine, and vincristine (R-MPV). Those with a complete or partial response proceeded with consolidation HDC with thiotepa, cyclophosphamide, and busulfan, followed by ASCT and no radiotherapy. Primary end point was 1-year progression-free survival (PFS), N = 32. Median age was 57, and median Karnofsky performance status 80. Following R-MPV, objective response rate was 97%, and 26 (81%) patients proceeded with HDC-ASCT. Among all patients, median PFS and overall survival (OS) were not reached (median follow-up: 45 months). Two-year PFS was 79% (95% confidence interval [CI], 58-90), with no events observed beyond 2 years. Two-year OS was 81% (95% CI, 63-91). In transplanted patients, 2-year PFS and OS were 81%. There were 3 treatment-related deaths. Prospective neuropsychological evaluations suggested relatively stable cognitive functions posttransplant. In conclusion, this treatment was associated with excellent disease control and survival, an acceptable toxicity profile, and no evidence of neurotoxicity thus far. This trial was registered at www.clinicaltrials.gov as NCT00596154.

Outcomes Following Re-irradiation for Symptomatic Brain Metastasis

We retrospectively analyzed outcomes of patients who underwent reirradiation for brain metastasis. We analyzed the records of 23 patients with brain metastasis who were initially treated with palliative brain radiotherapy (RT) and were retreated with a second course of brain RT between June 2008 and December 2012. WBRT, 3DCRT, and SRS were used for brain metastasis. The median dose of the first course of WBRT was 30 Gy (range, 23.4-30 Gy). The dose of the first course of 3DCRT for the lesion was 30 Gy in 3 Gy per fraction. The median dose of the first course of SRS was 16 Gy in one fraction (range, 12-24 Gy). The median dose of the second course of WBRT was 27.5 Gy (range, 12-30 Gy). The median dose of the second course of 3DCRT for the lesion was 30 Gy (range, 25-30 Gy). The dose of the second course of SRS was 16 Gy in one fraction. The second course of WBRT was administered on the basis of radiographically proven disease progression with clinical symptoms. With a median follow-up of 25 months, the overall symptom resolution rate was 47.8%. The rate of palliative efficacy was 82.6% including patients with stable disease. The median survival time after initiation of reirradiation was 3.2 months. The median Karnofsky performance status (KPS) value prior to reirradiation was 30, and the median KPS value following reirradiation was 60. Reirradiation of brain metastasis is feasible and effective in select patients with performance status of KPS ≥ 60 (Eastern Cooperative Oncology Group (ECOG) 0-2) prior to reirradiation.

Stereotactic Radiosurgery for Renal Cancer Brain Metastasis: Prognostic Factors and the Role of Whole-Brain Radiation and Surgical Resection.

Background. Renal cell carcinoma is a frequent source of brain metastasis. We present our consecutive series of patients treated with Stereotactic Radiosurgery (SRS) and analyse prognostic factors and the interplay of WBRT and surgical resection. Methods. This is a retrospective study of 66 patients with 207 lesions treated with the Cyberknife radiosurgery system in our institution. The patients were followed up with imaging and clinical examination 1 month and 2-3 months thereafter for the brain metastasis. Patient, treatment, and outcomes characteristics were analysed. Results. 51 male (77.3%) and 15 female (22.7%) patients, with a mean age of 58.9 years (range of 31–85 years) and a median Karnofsky Performance Status (KPS) of 90 (range of 60–100), were included in the study. The overall survival was 13.9 months, 21.9 months, and 5.9 months for the patients treated with SRS only, additional surgery, and WBRT, respectively. The actuarial 1-year Local Control rates were 84%, 94%, and 88% for SRS only, for surgery and SRS, and for WBRT and additional SRS, respectively. Conclusions. Stereotactic radiosurgery is a safe and effective treatment option in patients with brain metastases from RCC. In case of a limited number of brain metastases, surgery and SRS might be appropriate.

High Dose-Chemotherapy Followed By Autologous Peripheral Blood Stem Cell Transplantation for Patients with Refractory or Recurrent Primary Central Nervous System Lymphoma –Results of a Multicenter Study By the Germany Collaborative PCNSL Study Group

Introduction: Primary central nervous system lymphoma (PCNSL) relapses in up to 60% after conventional chemotherapy. The prognosis of refractory or recurrent PCNSL is very poor with a median survival of up to 5 months. Whole brain radiotherapy may improve survival up to 10 months, but is associated with significant neurotoxicity. High-dose chemotherapy (HDT) and autologous stem-cell transplantation (ASCT) have demonstrated high efficacy in the treatment of newly-diagnosed primary CNS lymphoma (PCNSL) in younger patients (pts.). To evaluate the efficacy of this approach, we initiated a prospective multicenter phase II study with HDT and ASCT for relapsed PCNSL. This trial is registered at ClinicalTrials.gov (NCT 00647049)Patients and Methods: Thirty eight pts. <65 years were treated within the phase II trial, chemotherapy (CHT) consisted of 2 cycles of Rituximab (3,75mg/m²), AraC (2x 3 g/m2) plus thiotepa (TT, 40 mg/m2) followed by rG-CSF and stem-cell-mobilization after the 1st cycle. Conditioning regimen included BCNU (400 mg/m2) and TT (4x5 mg/kgBW) followed by ASCT. Patients not in complete remission after HDT and ASCT underwent WBRT.Results: From 2007 to 2012, 38 pts (18 female, 20 male) with relapsed (n=31) or refractory (n=7) PCNSL from 10 German centers were enrolled and evaluable for analysis (median age 58 years, range 37-66 years). All pts had aggressive B-cell lymphomas (DLBCL). Median Karnofsky performance status at diagnosis was 90% (range 60-100). Patients were intensively pretreated, all pts underwent HD-MTX within the first-line-treatment, 15 of 38 pts were treated within the Bonn protocol. Thirty-one of 38 pts (81,6%) received HDT and ASCT according to protocol. Three pts died before PBSCT, 4 further pts were treated off study due to PD (n=2), refusal of HDT (n=1) and insufficient stem cell harvest (n=1). Regarding the primary endpoint in the intent-to-treat population, 22 pts (57,9%) achieved complete (CR) and and 5 (13,2%) partial remission (PR) after HDT and ASCT, respectively. In patients treated per protocol, the CR and PR-rate rate was 71% and 16,1% respecticely. The overall respinse rate in the per protocol population was 86,1%. Six pts in PR after HDT and ASCT received consolidating WBRT. After a median 39-month follow-up (range 0-48 mo), 1 and 2 years OS was 63% and 57%, respectively. Median survival of the intent-to-treat population was 29 months. Further results will be presented.Conclusion: Sequential systemic application of high-dose cytostatic agents followed by HDT+ASCT is highly effective as salvage therapy for pts. with relapsed or refractory PCNSL. DisclosuresIllerhaus:Riemser: Honoraria. Wolf:Bayer: Honoraria; Geo Pharma: Honoraria. Stilgenbauer:Pharmacyclics, Janssen: Honoraria, Research Funding.

Hypofractionated stereotactic radiosurgery with concurrent bevacizumab for recurrent malignant gliomas: the University of Alabama at Birmingham experience.

Nearly all patients with malignant glioma will have disease recurrence. Our purpose was to define the treatment toxicity and efficacy of concurrent bevazicumab (BVZ) with hypofractionated stereotactic radiosurgery (SRS) of relatively larger targets for patients with recurrent MG. A retrospective review of 21 patients with recurrent malignant glioma (18 glioblastoma, 3 WHO grade III glioma), treated at initial diagnosis with surgery and standard chemoradiation, was performed. All patients had concurrent BVZ with hypofractionatedSRS, 30 Gy in 5 fractions, with or without concurrent chemotherapy (temozolomide or CCNU). Median patient age was 54 years, median Karnofsky Performance Status was 80, and median target size was 4.3 cm (range, 3.4-7.5 cm). Eleven patients (52%) had previously failed BVZ. One patient had grade 3 toxicities (seizures, dysphasia), which resolved with inpatient admission and intravenous steroids/antiepileptics. Treatment-related toxicities were grade 3 (n = 1), grade 2 (n = 9), and grade 0-1 (n = 11). Kaplan-Meier median progression-free survival and overall survival estimates (calculated from start of SRS) for GBM patients (n = 18) were 11.0 and 12.5 months, respectively. Concurrent chemotherapy did not appear to show any statistically significant efficacy benefit or have any propensity for toxicity. BVZ concurrent with hypofractionated SRS was well tolerated by this cohort of patients with relatively larger targets. Ongoing randomized trials with more moderate radiotherapy dosing may help establish the efficacy of this regimen, though intricacies of this approach, including patient selection, radiation target volume delineation/size, and optimal radiation dose, will need further evaluation.

Volumetric modulated arc therapy for lung stereotactic radiation therapy can achieve high local control rates.

PurposeThe aim of this study was to report the outcome of primary or metastatic lung cancer patients undergoing volumetric modulated arc therapy for stereotactic body radiation therapy (VMAT-SBRT).Methods and materialsFrom October 2010 to December 2013, consecutive 67 lung cancer patients received single-arc VMAT-SBRT using an Elekta-synergy system. All patients were treated with an abdominal compressor. The gross tumor volumes were contoured on 10 respiratory phases computed tomography (CT) datasets from 4-dimensional (4D) CT and merged into internal target volumes (ITVs). The planning target volume (PTV) margin was isotropically taken as 5 mm. Treatment was performed with a D95 prescription of 50 Gy (43 cases) or 55 Gy (12 cases) in 4 fractions for peripheral tumor or 56 Gy in 7 fractions (12 cases) for central tumor.ResultsAmong the 67 patients, the median age was 73 years (range, 59–95 years). Of the patients, male was 72% and female 28%. The median Karnofsky performance status was 90-100% in 39 cases (58%) and 80-90% in 20 cases (30%). The median follow-up was 267 days (range, 40–1162 days). Tissue diagnosis was performed in 41 patients (61%). There were T1 primary lung tumor in 42 patients (T1a in 28 patients, T1b in 14 patients), T2 in 6 patients, three T3 in 3 patients, and metastatic lung tumor in 16 patients. The median mean lung dose was 6.87 Gy (range, 2.5-15 Gy). Six patients (9%) developed radiation pneumonitis required by steroid administration. Actuarial local control rate were 100% and 100% at 1 year, 92% and 75% at 2 years, and 92% and 75% at 3 years in primary and metastatic lung cancer, respectively (p = 0.59). Overall survival rate was 83% and 84% at 1 year, 76% and 53% at 2 years, and 46% and 20% at 3 years in primary and metastatic lung cancer, respectively (p = 0.12).ConclusionsUse of VMAT-based delivery of SBRT in primary in metastatic lung tumors demonstrates high local control rates and low risk of normal tissue complications.

Patient-reported outcomes for determining prognostic groups in veterans with stage IV solid tumors starting systemic therapy.

48 Background: A Recursive Partitioning Analysis (RPA) prognostic algorithm based on quality of life and symptoms predicted 4 groups with distinct median survivals in patients with metastatic solid tumors receiving chemotherapy (ASCO 2013, Abst 9567). We update our findings. Methods: The RPA algorithm is based upon Karnofsky performance status (KPS), Functional Assessment of Cancer Therapy (FACT) physical well-being (PWB) subscale, and Memorial Symptom Assessment Scale Short Form (MSAS-SF) physical symptom distress (PHYS) subscale. Starting in 2007, a convenience sample of Veterans who were prescribed systemic treatment for their cancer was enrolled in an IRB approved protocol, and completed quality of life (FACT- G) and symptom (MSAS SF) questionnaires at the first cycle of treatment. We analyzed records of patients with stage IV metastatic solid tumors enrolled through June 2013, and determined survival as of June 15, 2014. Analyses were performed with STATA 11.0. Results: There were 97 patients(pts). The median age was 64 yrs, range 27-88. Males comprised 95 (98%) pts. First line chemotherapy was given to 78 (80%) pts. The most common primary sites were lung cancer 33 (35%), prostate 17 (17%) and colon 11 (11%) pts. Median KPS was 90% range 40-100%, PWB median 23 (range 6-28), and MSAS SF median PHYS 0.76 (range 0-3.2). Overall median survival was 285 days (range 6-2,358) and 80 pts (82%) had died. There was 1 pt in group 1, 58 in group 2, 12 in group 3, and 23 in group 4. The patient in group 1 had uterine sarcoma. Median survival (days) by RPA group was 155 for group 1, 177 for group 2, 292 for group 3, and 674 for group 4 (p=.011). Conclusions: These preliminary findings suggest that this algorithm is capable of dividing patients with metastatic solid tumor who are starting systemic therapy into prognostic groups. Further development is indicated.

Defining the Optimal Planning Target Volume in Image-Guided Stereotactic Radiosurgery of Brain Metastases: Results of a Randomized Trial

To identify an optimal margin about the gross target volume (GTV) for stereotactic radiosurgery (SRS) of brain metastases, minimizing toxicity and local recurrence. Adult patients with 1 to 3 brain metastases less than 4 cm in greatest dimension, no previous brain radiation therapy, and Karnofsky performance status (KPS) above 70 were eligible for this institutional review board-approved trial. Individual lesions were randomized to 1- or 3- mm uniform expansion of the GTV defined on contrast-enhanced magnetic resonance imaging (MRI). The resulting planning target volume (PTV) was treated to 24, 18, or 15 Gy marginal dose for maximum PTV diameters less than 2, 2 to 2.9, and 3 to 3.9 cm, respectively, using a linear accelerator-based image-guided system. The primary endpoint was local recurrence (LR). Secondary endpoints included neurocognition Mini-Mental State Examination, Trail Making Test Parts A and B, quality of life (Functional Assessment of Cancer Therapy-Brain), radionecrosis (RN), need for salvage radiation therapy, distant failure (DF) in the brain, and overall survival (OS). Between February 2010 and November 2012, 49 patients with 80 brain metastases were treated. The median age was 61 years, the median KPS was 90, and the predominant histologies were non-small cell lung cancer (25 patients) and melanoma (8). Fifty-five, 19, and 6 lesions were treated to 24, 18, and 15 Gy, respectively. The PTV/GTV ratio, volume receiving 12 Gy or more, and minimum dose to PTV were significantly higher in the 3-mm group (all P<.01), and GTV was similar (P=.76). At a median follow-up time of 32.2 months, 11 patients were alive, with median OS 10.6 months. LR was observed in only 3 lesions (2 in the 1 mm group, P=.51), with 6.7% LR 12 months after SRS. Biopsy-proven RN alone was observed in 6 lesions (5 in the 3-mm group, P=.10). The 12-month DF rate was 45.7%. Three months after SRS, no significant change in neurocognition or quality of life was observed. SRS was well tolerated, with low rates of LR and RN in both cohorts. However, given the higher potential risk of RN with a 3-mm margin, a 1-mm GTV expansion is more appropriate.

415O - Alternating Electric Fields Therapy for Recurrent Glioblastoma - Novottf-100A System: Updated Outcomes and Toxicity Based on the Analysis of Patient Registry Data

ABSTRACT Aim: To present updated outcomes and toxicity data from patients with recurrent glioblastoma treated with the commercially available NovoTTF-100A System using patient registry database. Methods: The NovoTTF-100A device has been available by prescription at 126 oncology centers in the United States since November 2011. We retrospectively analyzed the outcomes and toxicity data from patients who were prescribed the device from November 2011 to November 2013 as treatment for recurrent glioblastoma. Overall survival (OS) was calculated based on social security death registry data. It was defined as the time from the treatment start until the date of death or last known date patient was alive. We analyzed performance status, compliance records, treatment history and adverse effects for all subjects. Results: There were 148 female and 309 male patients (n = 457) who were treated with NovoTTF-100A System. The median age was 55 years (range 18 to 86). Median Karnofsky Performance Status (KPS) was 80 (range 10-100) and 33% of patients were at their first recurrence when therapy was initiated. Over half of the patients (n = 252) received bevacizumab prior to NovoTTF- 100A therapy. The median OS was 9.6 (95% [CI] 8.0 to 13.7) months and the median treatment duration was 4.1 (95% [CI] 3.5 to 4.8) months. The average patient compliance with the use of the device was 70%. OS was positively correlated with higher compliance (= > 75%) and KPS (70-100), and negatively correlated with recurrence number and prior use of bevacizumab. Debulking surgery prior to the introduction of NovoTTF-100A therapy did not influence OS. The most common device-related adverse events included skin reactions (24.3%), neurological disorders (10.4%), heat sensation (8.9%), electric sensation (7.7%) and headache (5.7%). Conclusions: Treatment with NovoTTF-100A System, as prescribed in the neuro-oncology clinical practice to patients with recurrent glioblastoma offers favorable outcomes when compared to historical data. Patient compliance with the prescribed use of the system is high and positively correlates with improved survival. Bevacizumab naive patients benefit more while patients with poor KPS and multiple prior recurrences benefit less from this treatment. NovoTTF-100A System is well tolerated and has no new unexpected toxicities since its introduction to clinical practice. Disclosure: M.M. Mrugala: On Advisory Board of Novocure. PI on the clinical trial sponsored by Novocure; H.H. Engelhard: I have participated in Novocure's Advisory Boards; N. Butowski: I participated in Novocure's Advisory Board; D.D. Tran: I have received honorarium from Novocure for advisory board and speaker bureau; Y. Kew: I have participated in Novocure's Advisory Boards; R. Cavaliere: I have been a consultant for Novocure; J. Villano: Member of a speakers bureau and served on an advisory board for Novocure. D. Bota: Novocure Advisory Board; S. Kesari: I have received funding for advisory board meetings and clinical trials sponsored by Novocure; J. Rudnick: I have been a consultant for Novocure; A. Sumrall: I have been a Faculty Speaker and participated in an Advisory Board for Novocure; J.J. Zhu: Novocure Advisory Board; E.T. Wong: I received research funding from Novocure.

P11.05 * LENALIDOMIDE IN THE TREATMENT OF RELAPSED PRIMARY CENTRAL NERVOUS SYSTEM LYMPHOMA (PCNSL)

BACKGROUND: Lenalidomide is an immunomodulator agent that exhibits efficacy in multiple myeloma and haematological malignancies including refractory/relapsed diffuse large B-cell (DLBC) systemic lymphoma. METHODS: Retrospective review of PCNSL patients treated with lenalidomide at the Pitie-Salpetriere hospital. Inclusion criteria were: 1) immunocompetent status 2) pathologically proven diagnosis of DLBC-PCNSL, 3) recurrent or refractory disease after at least two prior chemotherapy treatments, including intravenous high-dose methotrexate and cytarabine based regimens, 4) lenalidomide administered orally, at a dose of 25 mg/day on days 1-21 of a 28-days cycle. MRI scans were performed monthly. Response was evaluated according to the IPCG criteria. RESULTS: Between June 2011 and March 2013, 6 patients (4 women and 2 men) met the inclusion criteria. Lenalidomide was given as 3rd line in four patients, as 4th line in one and 5th line in one. Median age was 73.5 years (range 64-78) and median Karnofsky Performance Status was 60 (range 40-70). Two patients achieved complete response (CR). Patient 1 received a total of 9 monthly cycles of lenalidomide without any steroids and is still in remission after a follow-up of 18 months from the start of the treatment. Patient 2 achieved a CR and was off-steroids at the time of CR, but relapsed during the 3rd cycle and died after 14 weeks. Patient 3 achieved a partial response after one cycle but died suddenly during the 2nd cycle. Patients 4, 5 and 6 progressed and died 2, 5 and 6 months respectively after the start of lenalidomide. One of them who suffered from an oculo-cerebral relapse demonstrated a partial ocular response while progressing in the brain. Apart from the sudden death of unknown cause, the treatment was well tolerated. None of the patients experienced any grade III or IV toxicity. CONCLUSIONS: These results suggest that lenalidomide exhibits activity in heavily pre-treated PCNSL and is well tolerated in elderly patients. Lenalidomide efficacy on PCNSL needs to be evaluated prospectively, alone or in association with other cytotoxic agents. A phase II trial combining rituximab and lenalidomide for recurrent PCNSL is on-going in France ({type:clinical-trial,attrs:{text:NCT01956695,term_id:NCT01956695}}NCT01956695).

P17.64 * ANGIOGENIC AND PROCOAGULANT FACTORS IN PLASMA OF BRAIN TUMOUR PATIENTS TREATED WITH BEVACIZUMAB

BACKGROUND: Glioblastoma (GBM) is one of the most vascularized human tumors and GBM cells produce proangiogenic factors, including vascular endothelial growth factor (VEGF). Bevacizumab (BV), a monoclonal antibody against VEGF, has shown antitumor activity, but so far no biomarkers have been identified to predict outcome. The purpose of the present study was to investigate the possible predictive value of circulating VEGF, von Willebrand factor (vWF) and procoagulant factors in patients with recurrent GBM. METHODS: We conducted a prospective analysis of recurrent malignant gliomas (MG) patients treated with BV alone or in combination with chemotherapy performing serial evaluations of plasma VEGF levels, vWF antigen and procoagulant factors such as thrombin-antithrombin complex (TAT), prothrombin fragment F1 + 2 (F1 + 2), Factor VIII and D-Dimer. Baseline, and post-treatment samples were collected at each administration of BV. RESULTS: Forty-nine recurrent MGs (glioblastoma = 26, astrocytoma = 17, oligodendroglioma = 6) who received BV at 10 mg/kg intravenously every 3 weeks, of whom 26 in association with chemotherapy were included in the study. Median age was 45 years (22-73), median Karnofsky performance status was 80 (60-100). Out of the 48 evaluable, 17 partial responses (35%), 7 stable disease (15%) and 24 disease progressions (50%) were observed. At baseline all patients presented with laboratory signs of coagulation activation (i.e. high TAT and FVIII levels). Circulating plasma levels of VEGF and vWF antigen significantly increased in all patients post-treatment of BV (p = 0.0001 and 0.009 respectively). No responder patients showed significantly higher vWF antigen levels than responders (p = 0.01) after second administration of BV. CONCLUSIONS: These preliminary data suggest that low vWF antigen levels might help predict response in recurrent MG patients treated with BV. This marker should help clinicians to decide the right therapy, advise them of the generation of mechanisms of drug resistance during antiangiogenic treatment.

Nutritional Factors Predict Survival in Patients Receiving Concurrent Chemoradiation Therapy for Locally Advanced Esophagus Cancer

There is a lack of consensus regarding optimal nutritional support for locally-advanced esophagus cancer patients undergoing chemoradiation (CRT). This study identifies key variables and nutritional interventions which may predict survival outcomes in this high-risk population. Clinical and treatment related features were identified for 73 patients with locally advanced esophagus cancer treated with curative intent with combined radiation and chemotherapy between 7/2010 and 7/2013. T-tests and chi-square analyses compared patient and treatment characteristics related to nutritional interventions, overall nutritional status, survival characteristics, and presence of a feeding tube. Survival was estimated using Kaplan-Meier and Cox regression analyses. Of 73 patients identified, 61 patients had sufficient follow-up and were included in the analysis. At a median follow-up of 15 months, 46% were alive and 54% had recurrent disease. The median age was 63 years (range 38-91) and median Karnofsky Performance Status was 90% (range 60-100%). Histology of primary tumor was 74% adenocarcinoma, 23% squamous cell carcinoma, and 3% other. Median weight loss pre-RT was 7% and post-RT was 4.7%. 43% of patients had pretreatment feeding tubes which were used for an average of 2.1 weeks (SD = 2.8). For patients with pre-CRT feedings tubes, median survival was significantly lower than for those not requiring feeding tubes (12 vs 21 months, p = 0.017). 75% of patients had nutritional consultation, with a median of 2 nutrition notes during RT (range 0-11). Patients with four or more nutritional notes had significantly lower median survival (16 vs 31 months, p = 0.016). Patients with feedings tubes were statistically more likely to have a greater number of nutritional notes (p = 0.019). While pre-CRT albumin <3.4 was predictive of lower survival (p = 0.018), post-CRT albumin and pre- and post- CRT serum total protein did not significantly impact survival. Percent weight loss before RT was associated with lower survival (p = 0.011) while percent weight loss during CRT was not. Survival was significantly higher with pre-CRT regular or soft diet versus diet restriction of liquid or NPO (p = 0.001). Poor survival is predicted by factors suggesting inadequate nutritional status prior to RT, including weight loss, albumin level, and liquid or NPO diet. Even with feeding tube placement and frequent nutritional support, survival remains low, suggesting the need for even more aggressive supportive strategies in this patient population.

P13.19 * HYPOFRACTIONATED RADIOTHERAPY IN PATIENTS WITH HIGH GRADE GLIOMAS AND POOR PROGNOSTIC FACTORS: A RETROSPECTIVE STUDY

PURPOSE: The standard treatment for patients with high-grade gliomas (HGG) and limited life expectancy is not well defined. Patients with an age over 65 years, poor Karnofsky performance status (KPS) and surgical biopsy/partial resection could not benefit from the combination of radiotherapy (60 Gy in 30 fractions) and chemotherapy with temozolomide (TMZ). In these patients hypofractionated radiotherapy (HypoRT) or TMZ alone have been suggested adequate treatments without significant differences in term of overall survival (OS) and progression free survival (PFS) compared to the standard approach. Furthermore, new clinical trials are investigating the role of a combination of HypoRT and TMZ. The aim of this retrospective study is to evaluate the outcome of HypoRT, with or without TMZ, in a cohort of HGG with poor prognostic factors. MATERIALS AND METHODS: Between January 2006 and December 2013, 69 patients with a diagnosis of HGG and poor prognostic factors (age ≥65 and/or KPS ≤60) were treated at our Institution. All patients were discussed in the Brain Tumor Board and treated with a dose of 42 Gy in 14 fractions with a conformal radiation treatment technique. TMZ was added either in elderly patients with no comorbidities or in poor KPS patients with younger age. Concomitant TMZ was given at a dose of 75 mg/m2 /d while adjuvant TMZ at a dose of 150-200 mg/m2 for 5 days every 28 days until tumor progression or unacceptable toxicity. During follow up a contrast-enhanced MRI was performed 4 weeks after the HypoRT, and thereafter every 3 months. The primary endpoint was overall survival (OS) measured from HypoRT start, according to the Kaplan-Meier method. RESULTS: Median age was 65 years (range, 34-80 years) and median KPS was 60 (range, 50-90). Fifty-four patients (78.3%) received a surgical resection (51 partial and 3 complete resections) and 15 patients (21.7%) underwent a biopsy. Fifty-eight patients had an histological diagnosis of glioblastoma, 7 of grade III glioma and 4 of high grade gliomas (not other specified). Five patients (7%) received concomitant, 5 (7%) concomitant and adjuvant and 13 (19%) adjuvant only TMZ. Median follow-up was 7.7 months (range, 1-34 months). The median survival time (MST) was 7 months; 6-month and 12-month OS rates were 54.4% and 29.5%, respectively. Univariate analysis was used to test the effects of prognostic factors on survival and none of these showed a statistical significance. After multivariate analysis there was a trend toward a better outcome with the addition of adjuvant TMZ (MST 9 vs. 6 months, Log Rank p = 0.06). CONCLUSIONS: Median survival of this cohort of HGG with poor prognostic factors is comparable to the data published in the literature. Adjuvant chemotherapy could improve OS, but prospectives studies with larger sample size and longer follow-up are needed.

Upfront stereotactic radiosurgery in patients with brain metastases from small cell lung cancer: retrospective analysis of 41 patients.

BackgroundAlthough the efficacy of prophylactic or therapeutic whole brain radiotherapy (WBRT) for brain metastases (BM) from small cell lung cancer (SCLC) is well established, the role of stereotactic radiosurgery (SRS) has yet to be determined. In the present retrospective analysis, we investigated whether upfront SRS might be an effective treatment option for patients with BM from SCLC.MethodsWe analyzed 41 consecutive patients with a limited number of BM (≤ 10) from SCLC who received SRS as the initial treatment. No prophylactic and therapeutic WBRT was given prior to SRS. The median patient age was 69 years and the median Karnofsky performance status (KPS) score was 90. Repeat SRS was given for new distant lesions detected on follow-up neuroradiological imaging, as necessary. Overall survival, neurological death, and local and distant BM recurrence rates were analyzed. The survival results were tested with three prognostic scoring systems validated for SCLC: Diagnosis-specific graded prognostic assessment (DS-GPA), Radiation therapy oncology group -recursive partitioning analysis and Rades’s survival score.ResultsOne- and 2-year overall survival rates were 44% and 17%, respectively. The median survival time was 8.1 months. Survival results replicated the DS-GPA (P = 0.022) and Rades’s survival score (P = 0.034). On multivariate analysis, patients with high KPS (hazard ratio (HR): 0.308, P = 0.009) and post-SRS chemotherapy (HR: 0.324, P = 0.016) had better overall survival. In total, 95/121 tumors (79%) in 34 patients (83%) with sufficient radiological follow-up data were evaluated. Six- and 12-month rates of local control failure were 0% and 14%, respectively. Six- and 12-month distant BM rates were 22% and 44%, respectively. Repeat SRS, salvage WBRT and microsurgery were subsequently required in 18, 7 and one patient, respectively. Symptomatic radiation injury developed in two patients and both were treated conservatively.ConclusionsOur survival analyses with the validated prognostic grading systems suggested upfront SRS for limited BM from SCLC to be a potential treatment option, with patient survival being slightly more than eight months after SRS. Although SRS provided durable local tumor control, repeat treatment was needed in nearly half of patients to achieve control of distant BM.