Ifosfamide, Carboplatin, Etoposide Research Articles

N9: Pilot study of novel shortened induction for high-risk neuroblastoma.

10052 Background: N9 induction for high-risk neuroblastoma was designed to limit non-hematological toxicity (especially ototoxicity) and to prevent relapse in the central nervous system (CNS). N9 builds on 2 novel regimens: high-dose cyclophosphamide-topotecan-vincristine (CTV) and ifosfamide-carboplatin-etoposide (ICE), each with good penetration across the blood-brain barrier. Methods: N9 is a pilot study (Clinicaltrials.gov.NCT04947501) to assess feasibility and safety. Secondary/exploratory objectives include response, collection of peripheral blood stem cells (PBSCs; ≥5x106/kg CD34(+) cells sufficient for ≥2 rescues), tumor resection, and assessment of central nervous system relapse. Early stopping rules centered on excessive delay in timing of chemotherapy. Eligibility criteria included age >1-to-<13 years; 1 prior chemotherapy cycle was allowed. CTCAE Version 5.0 and International Neuroblastoma Response Criteria are used.N9 comprises 4 cycles of chemotherapy. Cycles start after absolute neutrophil count is >500/μL, platelets >100,000/μL, and non-hematologic toxicities grade ≤2. Intervals of 21-28 days between start of cycles are foreseen. PBSC collection and surgery follow >3 cycles. Cycles #1 and #4 (CTV): cyclophosphamide 70mg/kg/day, days 1-2, topotecan 2mg/m2/day, days 1-4, and vincristine 0.067mg/kg, day 1. Cycle #2 (ICE): ifosfamide 1500mg/m2/day, days 1-5, carboplatin 400mg/m2/day, days 1-2, and etoposide 100mg/m2/day, days 1-5. Cycle #3: cyclophosphamide (as in CTV) and 72-hr infusions of doxorubicin 75mg/m2 and vincristine 0.067mg/kg. Results: The target number of 15 patients were enrolled: 10/2021-9/2023; age 1.5–9.8 (median 3.3) years; 14 stage M, 1 stage L2; and 10 post-1 cycle of other chemotherapy. They completed N9 without undue toxicity: all cycles started on time, organ functions remained intact, 11/11 patients tested had no ototoxicity, and acute toxicities were typical for myelosuppression (including uncomplicated fever/neutropenia). Responses were complete (n=6), partial (n=5), and stable disease (n=4). The target number of PBSCs was collected in 12 patients (9-75, median 14 x106/kg CD34(+) cells), 4x106/kg in 2 patients, and pending in 1. All patients had gross total resections of the primary tumor. Post-N9, patients did not undergo transplant, but proceeded to immunotherapy (naxitamab) or chemoimmunotherapy (naxitamab+irinotecan-temozolomide). Of 9 with residual disease post-N9, 7 achieved CR (median of 5.6 months from study entry) and 1 achieved metabolic CR (16 months), though 3 subsequently relapsed (no CNS). Conclusions: N9 shows promise for reducing chemotherapy and long-term toxicity. Less chemotherapy without compromising survival is a realistic goal by virtue of the advances with anti-GD2 monoclonal antibodies which, in combination with GM-CSF+low-dose chemotherapy, are highly effective against chemo-resistant disease in bone/bone marrow. Clinical trial information: NCT04947501 .

Response to ifosfamide, carboplatin, etoposide (ICE) vs. dexamethasone, cytarabine cisplatin (DHAP) as salvage chemotherapy in patients with relapsed/refractory lymphoma.

Non-Hodgkin's lymphomas are the eighth-most prevalent malignancy in females and the eleventh in males. No research has been conducted comparing dexamethasone, cytarabine cisplatin (DHAP) vs. ifosfamide, carboplatin, etoposide (ICE) as salvage chemotherapy regimens for relapsed or refractory lymphomas in Pakistan. This study aims to compare the response of ICE vs. DHAP as salvage chemotherapy in patients with relapsed/refractory lymphomas. A prospective follow-up study was conducted at the tertiary care hospital in Karachi, Pakistan, from 2019 to 2020. A total of 58 lymphoma patients after first-line chemotherapy were included in the study. The treatment response was evaluated after two cycles of salvage chemotherapy using WHO assessment criteria, and Cox regression was used to determine the hazard ratios considering the P value ≤0.05 significant. Of 58 patients, 19 (32.8%) patients achieved complete response (CR), and 8 (13.8%) patients achieved partial response (PR), with an overall response rate of overall response rate of 46.6%. In the ICE group, the response was assessed in 19 patients. Overall response was 42.1%, CR was 31.6% and PR was 10.5%. In the DHAP group, response was evaluated in 39 patients, the overall response rate was 48.7%, CR was 33.3% and PR was 15.4%. The hazard ratio for survival in patients with relapsed/refractory lymphomas who received DHAP was 1.40 times (95% CI: 1.27-3.63, P=0.001) compared to patients who received ICE as salvage chemotherapy. DHAP seems to have a marginally better overall response rate than the ICE regimen in patients with refractory or relapsed lymphoma. However, the toxicity profile of patients in both groups was similar.

Acute Kidney Injury in a Patient With a Kidney Transplant and Posttransplant Lymphoproliferative Disorder: A Quiz

A 36-year-old woman with a living donor kidney transplant from her sister 6 years ago presented with a serum creatinine of 1.9 mg/dL, from a baseline of 0.5 mg/dL 1 week prior to presentation. She had received the transplant after reaching kidney failure due to focal segmental glomerulosclerosis and she had been diagnosed with posttransplant lymphoproliferative disorder (PTLD) 2 years ago. Despite completion of therapy with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) and subsequently ICE (ifosfamide, carboplatin, etoposide) 6 months ago, she experienced PTLD progression and new hypermetabolic lesions involving the liver and spleen were seen 1 month ago.

Final results of brentuximab vedotin combined with ifosfamide-carboplatin-etoposide in first refractory/relapsed Hodgkin lymphoma: a lymphoma study association phase I/II study

This phase I/II study assessed the combination of brentuximab vedotin (BV) with ifosfamide-carboplatin-etoposide (ICE) as a second-line therapy in refractory/relapsed (R/R) classical Hodgkin lymphoma (cHL) patients. Phase I study was designed to determine the maximum tolerated dose (MTD) of BV (10 patients) and phase II evaluated the rate of complete metabolic response (CMR) after 2 cycles of BV-ICE (42 patients). There were no dose-limiting toxicities (DLT) during phase I recommending BV 1.8 mg/kg for phase II. Twenty-six patients (61.9%) achieved CMR after 2 cycles of BV-ICE and 37 patients (88%) were transplanted. With a median follow-up of 38 months, the 3-year progression free survival (PFS) and overall survival (OS) rate were 64.3% and 100%, respectively. Hematological toxicities (81%) and infections (21%) were the most frequent adverse event encountered BV-ICE regimen is feasible with manageable toxicities and could be an alternative to other salvage treatments. Trial Registration: ClinicalTrials.gov identifier: NCT02686346

Salvage Autologous Stem Cell Transplantation in Patients with Relapsed or Refractory Primary Central Nervous System Lymphoma

IntroductionPrimary central nervous system lymphoma (PCNSL) is a rare extra-nodal non-Hodgkin lymphoma. This unique disease shows unsatisfactory outcomes comparing to other types of non-Hodgkin lymphoma and limited treatment options are available with relapsed or refractory disease. The purpose of this study is to evaluate outcomes of relapsed or refractory PCNSL patients treated with high-dose chemotherapy followed by autologous stem cell transplantation (ASCT).MethodsThe registry data set of PCNSL, collected from March 1993 to May 2017 at a single institute, Asan Medical Center, was retrospectively reviewed and patients with refractory disease to first-line therapy and who relapsed were sorted. Among selected patients, patients who showed complete response (CR) or partial response (PR) to salvage therapy were enrolled in analyses and divided into two groups with whether high-dose chemotherapy followed-by ASCT was done or not as consolidation therapy. Overall survival (OS) was defined as the time from the day response was evaluated after salvage therapy to any cause of death, and progression free survival (PFS) was defined as the time from the day response was evaluated after salvage therapy to disease progression or any cause of death. Chi square test and Fisher's exact test was done to compare variables in two groups. Survival curves were estimated by Kaplan-Meier methods with log-rank tests and multivariate analysis with Cox-proportional hazards regression analyses was done to evaluate potential confounding effects of known prognostic factors. All statistical analyses were performed using IBM SPSS version 21.0.ResultsTotal 241 patients with diagnosis of PCNSL were identified and 83 patients who had relapsed or refractory to induction chemotherapy were sorted. Among these patients, 39 patients who had CR or PR to salvage chemotherapy were enrolled in analyses. Median follow-up duration was 2.1 years (IQR 0.1-15.49), median OS was 1.5 years (95% CI 0.3-2.7), and median PFS was 1.4 years (95% CI 0.2-2.7). Median age was 63 years (range, 29-77), 69.2% of patients were 60 years or older and 59.0% of patients was male. Thirty patients (76.9%) had high-dose methotrexate based chemotherapy as first-line therapy and 71.8% had overall response (CR or PR). Twenty patients (48.7%) had ICE (ifosfamide, carboplatin, etoposide) + dexamethasone regimen, 22.9% had high-dose methotrexate based regimen. Thirty-one patients (79.5%) showed good performance (ECOG performance status < 2). Among these patients, 16 patients had high-dose chemotherapy followed-by ASCT as consolidation therapy and 23 patients did not. Proportion of patients with good performance status, salvage chemotherapy regimen, response to salvage therapy showed no statistically significant difference between two groups who had salvage ASCT or not. The median age was 55 years old (range 29-64) in salvage ASCT group, and 68 years old (range, 36-77) in non-ASCT. Median OS was 2.5 years [95% CI 0.3-4.6] in salvage ASCT group, and 1.0 years [95% CI 0.4-1.7] in group without salvage ASCT (p = 0.032). Median PFS was 1.5 years in salvage ASCT group, and 0.4 years [95% CI 0.4-0.5] in non-ASCT group (p = 0.027). In multivariate analyses with age, ECOG performance status, CSF protein level, and serum LD level, salvage ASCT revealed its independent prognostic impact for OS with HR of 0.11 [95% CI 0.01-0.96, p = 0.046], and for PFS with HR of 0.13 [95% CI 0.02-0.78, p = 0.025].ConclusionConsolidation therapy with high-dose chemotherapy followed-by ASCT could be a good treatment option in relapsed or refractory PCNSL patients who had response to salvage therapy. Prospective studies are needed to validate our results. DisclosuresNo relevant conflicts of interest to declare.

Combination of brentuximab-vedotin and ifosfamide, carboplatin, etoposide in relapsed/refractory peripheral T-cell lymphoma.

Relapsed/refractory peripheral T-cell lymphomas (PTCL) have a poor prognosis. We aimed at assessing efficacy of ifosfamide, carboplatin, etoposide (ICE) regimen, a known therapeutic option, to which we added brentuximab-vedotin (BV). In this study, we retrospectively analyzed patients with PTCL treated with BV-ICE in our center between July 2014 and March 2018. Fourteen patients received BV-ICE. Median age was 62years (range, 31-73). Main histological subtypes were PTCL-not otherwise specified (29%), angioimmunoblastic T-cell lymphoma (21%), follicular-T helper (21%), or anaplastic large-cell (15%) lymphomas, all were CD30 positive. Overall response was seen in four (29%) patients, and complete response (CR) in two (14%). Most frequent adverse events were infections, and cytopenia. 2-year progression-free and overall survival were 14% and 17.5%, respectively. Patients with relapsed/refractory PTCL treated with BV-ICE can achieve CR, but few had a sustained response. This association should preferably be used as a bridge to stem cell transplant or be followed by maintenance therapy.

NQPC-02 Long-term survival in patients with primary intracranial germ cell tumors treated with surgery, platinum-based chemotherapy, and radiotherapy: a single-institution study

Purpose: In the present study, we performed a retrospective review of patients receiving carboplatin based chemotherapy followed by radiotherapy for newly diagnosed primary intracranial germ cell tumors. In order to identify an optimal germ cell tumor treatment strategy, we evaluated treatment outcomes and toxicity and compliance.Methodology: This study included 110 consecutive patients with newly diagnosed primary intracranial germ cell tumors. The drug doses and administration schedule of carboplatin-etoposide (CARB-VP) were as follows: carboplatin (300 mg/m2 daily for 1 days), and etoposide (100 mg/m2 on days 1 to 3). Ifosfamide-carboplatin-etoposide (ICE) treatment comprised ifosfamide (1500 mg/m2 daily for 3 days), carboplatin (300 mg/m2 daily for 1 days), and etoposide (100 mg/m2 daily for 3 days). Patients with germinomatous germ cell tumors (pure germinoma or germinoma with STGC) basically receive three cycles of CARB-VP and a total dose of 30Gy whole ventricular radiotherapy. We delivered combination therapy consisting of combined ICE chemotherapy and craniospinal irradiation followed by the complete resection of the residual tumor for nongerminomatous malignant germ cell tumors.Results: The median follow-up time was 11.0 years (range, 0.5–37.8 years). The 5-year total survival rates of germinomatous and nongerminomatous germ cell tumors were 97.2% and 66.7%, respectively. The 10-year and 20-year total survival rates of germinomatous germ cell tumors were 95.7% and 90.0%, respectively. Adverse events related to carboplatin based chemotherapy are not detected. Furthermore, no treatment-related deaths were observed.Conclusions: Our treatment with surgery, carboplatin based chemotherapy followed by radiotherapy is effective in treating primary intracranial germ cell tumors, especially in germinomatous group.

Chemotherapy Based Salvage Regimens Are Associated with Poor Outcomes in Refractory Classical Hodgkin Lymphoma

Introduction: The management of classical Hodgkin lymphoma (cHL) with first line therapy continues to evolve resulting in some of the best outcomes in oncology. Around 20-30% of patients with cHL relapse and have to undergo salvage chemotherapy followed by autologous hematopoietic cell transplant (Auto HCT). There are no randomized trials comparing the most common regimens used in second line to date. With the introduction of newer agents in the treatment of cHL, it is essential to identify patients that might benefit from a different approach in first salvage setting. The aim of this study is to assess patterns of relapse and differences in outcomes based on salvage regimens. Methods: We retrospectively identified 193 consecutive patients with cHL treated in our academic medical center. Adult patients treated with ABVD (Adriamycin, Bleomycin, Vinblastine, Decarbazine) for first line were included. The three most common salvage regimens used in our institution included ICE (Ifosfamide, Carboplatin, Etoposide), ESHAP (Etoposide, Steroids, Ara-C, Cisplatin), or IGEV (ifosfamide, Gemcitabine, Vinorelbine). Patients were divided into two groups: those progressing during ABVD or relapsing within 1 year are considered (refractory) versus all other as (late-relapse). Response to salvage therapy and performance of Auto HCT were compared using Chi-square test. Univariate comparison of OS was conducted using Log-rank test. Results: The majority of patients were refractory to front line therapy (69%). As expected, there was predominance of male gender (61%), with median age of 35 yrs (range 13-68 yrs). The distribution of baseline characteristics did not seem to be different between the two groups (Table 1). Refractory patients were more likely to have B symptoms and higher ESR on presentation (Table 1). Of the refractory patients, the majority had initial response to therapy then relapsed within 1 year (65%). On Univariate analysis, late-relapse patients had better overall survival compared to refractory disease (13.5 yrs vs 9 yrs respectively) (p&amp;lt;0.005) (Figure 1). The majority of the patients in both groups received ICE as the primary regimen, followed by ESHAP and IGEV (Table 1). The CR rate was not statistically different among the three salvage regimens (ICE, ESHAP, IGEV as 37%, 29%, 53% respectively) (P=0.248). Late-relapses were more likely to obtain a complete response (CR) to salvage therapy (48% vs 32% respectively) (P=0.025). However, when CR rate stratified by salvage regimen, only refractory patients treated with ICE demonstrated statistically significant worse CR rate compared to late-relapse treated with ICE (32% vs 48% respectively) (P=0.047). The difference was not statistically different for ESHAP and IGEV. While there was a difference in CR rate between relapsed and refractory patients, the difference was not observed in the rate of consolidative Auto HCT between the two groups. On univariate analysis, Auto HCT was associated with improved median overall survival compared to no Auto HCT (11.3 yrs vs 1.6 yrs, respectively) (P&amp;lt;0.001). Conclusions: To our knowledge, this is the largest retrospective comparison study on the outcome of the most common salvage chemotherapy regimens in cHL. Our study highlights the unmet need early introduction for novel non chemotherapy-based interventions in refractory patients. It also shows the consistent CR rate in real world experience in comparison with clinical trials and persistent need for Auto HCT in the salvage setting in the current chemotherapy era. Disclosures Chavez: BeiGene:Speakers Bureau;Bayer:Consultancy;Merck:Research Funding;Morphosys:Consultancy, Speakers Bureau;AstraZeneca:Speakers Bureau;Celgene:Consultancy;Novartis:Consultancy;AbbVie:Consultancy;Genentech:Speakers Bureau;Epizyme:Speakers Bureau;Gilead:Consultancy;Karyopharm:Consultancy;Kite, a Gilead Company:Consultancy, Speakers Bureau;Verastem:Consultancy;Pfizer:Consultancy.Shah:Kite/Gilead, Jazz, Incyte:Research Funding;Moffitt Cancer Center:Current Employment;NCCN: Vice-Chair, Acute Lymphoblastic Leukemia Working Group:Membership on an entity's Board of Directors or advisory committees;Kite/Gilead, Celgene/Juno/BMS, Novartis, Pfizer, Amgen, Spectrum/Acrotech, Precision Biosciences, Beigene, AstraZeneca, Pharmacyclics/Jansen, Adaptive:Honoraria;Kite/Gilead, Precision Biosciences, Novartis, AstraZeneca:Other: TRAVEL, ACCOMMODATIONS, EXPENSES.Sokol:EUSA Pharma:Consultancy, Honoraria, Speakers Bureau;Kyowa/Kirin Inc.:Membership on an entity's Board of Directors or advisory committees;Kymera Therapeutics:Membership on an entity's Board of Directors or advisory committees.Pinilla Ibarz:Takeda:Consultancy, Speakers Bureau;AstraZeneca:Consultancy, Speakers Bureau;Abbvie:Consultancy, Speakers Bureau;Novartis:Consultancy;Sunesis Pharmaceuticals:Consultancy;TG Therapeutics:Consultancy;Sanofi:Consultancy;Pharmacyclics:Consultancy, Speakers Bureau;Janssen:Consultancy, Speakers Bureau.Bello:Celgene:Consultancy, Honoraria, Speakers Bureau;Seattle Genetics:Consultancy, Honoraria, Speakers Bureau.

Lines of Therapy in Patients with Relapsed or Refractory Large B-Cell Lymphoma and Stem Cell Transplant-Intended Treatment

Introduction: Large B-cell lymphoma (LBCL) is the most common subtype of non-Hodgkin lymphoma. Front line therapy is curative in about 60% of patients; however, about 30% of patients relapse and about 10% are refractory. For patients failing the front line, stem cell transplant (SCT) is currently the only curative option in second line of therapy (LOT2). This study examined real-world treatment patterns with curative intent in patients with relapsed or refractory LBCL to understand the unmet medical need in the United States. Methods: This retrospective study used IBM MarketScan® Commercial and Medicare Supplemental Databases. Patients with ≥2 LBCL diagnoses on different days in 1/1/2012 - 3/31/2019 were identified (index date = date of the earliest LBCL diagnosis). Patients who were ≥18 years of age on the index date, had ≥1 claim for any LBCL treatment on or following the index date, ≥6 months of data prior to (baseline) and ≥12 months of data after (follow up period) the index date, and had no baseline LBCL diagnosis were included. Treatment patterns, including lines of therapy (LOT), treatment regimen, duration of LOT and time from the end of a previous LOT to the subsequent LOT, were examined. All patients were required to receive first LOT (LOT1) of R-CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone +/- rituximab), EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin hydrochloride +/- rituximab), or regimens with anthracycline. Of those, patients were further required to receive LOT2 with SCT-intended intensive therapy or platinum-based chemotherapy as recommended by the National Comprehensive Cancer Network (NCCN). Patients were intended for SCT if they received an SCT-intended LOT2 regimen or received SCT regardless of LOT2 regimen. SCT was identified from the LOT2 start date to the end of the study period. All analyses were stratified by whether a patient was intended for SCT and by receipt of SCT. Results: A total of 3,443 patients with LBCL received an eligible front-line therapy (mean age 59.2 years, male 56.9%, length of follow up 2.5 years, National Cancer Institute (NCI) adapted Deyo-Charlson comorbidity index 0.83). Top comorbidities were other malignancy (63.3%), diabetes (23.3%), psychiatric disturbance (13.9%), and chronic pulmonary obstructive disease (13.2%). Among the LBCL patients, 564 (16.4%) received LOT2 with 197 (34.9%) patients SCT-intended and 367 (65.1%) not SCT-intended (Figure 1). SCT-intended patients were significantly younger than SCT-non-intended patients (55.9 vs. 60.9 years, p&amp;lt;0.001), and patients who received SCT were younger than those who did not receive SCT (53.6 vs. 59.7 years, p&amp;lt;0.001). Among the 197 patients intended for SCT, only 55.3% (n=109/197) received NCCN recommended LOT2 for intensive therapy: ICE (ifosfamide, carboplatin, etoposide) +/- rituximab (32.5%) and GemOx (gemcitabine, oxaliplatin) +/- rituximab (19.3%) were the most common regimens. SCT-intended patients initiated LOT2 nearly one year (345 days) after and third line of therapy (LOT3) 501 days after their LBCL index diagnosis (Figure 2). Duration of LOT decreased as patients moved on to later LOTs (LOT1=121 [standard deviation (SD)=69], LOT2=89 [SD=145] and LOT3=46 [SD=23] days). Likewise, the time between 2 consecutive LOTs decreased (194 [SD=258] days between end of LOT1 and start of LOT2, 124 [SD=182] days between end of LOT2 and start of LOT3). Steroids were often prescribed during LOT1 (82.2%) and LOT2 (74.6%) as concomitant therapy. Among the 109 patients receiving SCT-intended regimens, only 34 (31.2%) went on to receive SCT. An additional 88 patients received SCT without being observed to receive an SCT-intended regimen. They might have received therapy in the inpatient setting, which could not be captured in claims data. Among the 82 patients with LOT3, 60.1% received SCT and 9.8% received Chimeric antigen receptor (CAR) T cell therapy. Conclusion: The findings provide insight into real-world treatment patterns in patients with LBCL who received SCT-intended therapy. A small proportion of LBCL patients received NCCN recommended SCT-preparative regimens in LOT2 and only 31% of them received SCT. This highlights the magnitude of unmet need for relapsed or refractory LBCL patients. Future studies should examine the impact of new therapies on the management of LBCL. Disclosures Thornton Snider: Kite, A Gilead Company: Current Employment; Gilead Sciences: Current equity holder in publicly-traded company, Research Funding; Precision Medicine Group: Ended employment in the past 24 months, Research Funding. Cheng:Kite, A Gilead Company: Current Employment, Current equity holder in publicly-traded company. Song:IBM Watson Health: Research Funding. McMorrow:IBM Watson Health: Current Employment. Diakun:IBM Watson Health: Current Employment, Research Funding.

Current Selection Patterns, Toxicities and Outcomes of Pre-Transplant Salvage Treatment Regimens in Patients with Relapsed/Refractory Hodgkin Lymphoma: Results of a Multicenter Retrospective Analysis

Current Selection Patterns, Toxicities and Outcomes of Pre-Transplant Salvage Treatment Regimens in Patients with Relapsed/Refractory Hodgkin Lymphoma: Results of a Multicenter Retrospective Analysis

Treatment Outcomes of Early-Stage Natural-Killer/T-Cell Lymphomas Treated with Chemoradiotherapy: Data from 3 Tertiary Cancer Centres in Singapore

Background: Extranodal natural killer/T cell lymphoma (ENKL) is an aggressive Epstein-Barr virus (EBV) associated lymphoma with a strong geographical predilection for Asia and South America. While treatment outcomes of advanced stage (AS) disease (i.e., stage III and IV) are uniformly poor, early stage (ES) disease treated with concomitant or sequential chemotherapy (ChT) and radiotherapy (RT) can yield good long-term outcomes. Currently there is no standard therapy for ES ENKL. We describe our experience treating patients with ES ENKL in 3 tertiary cancer centres in Singapore. Method: We performed a retrospective analysis using data from Singapore Lymphoma Study Group database which captures patients from 3 largest tertiary cancer centres in Singapore: National Cancer Centre Singapore (NCCS), Singapore General Hospital (SGH) and National University Cancer Institute, Singapore (NCIS). We included patients with stage I or II ENKL that were treated with ChT and RT from 1996 to March 2019. Patients who did not receive treatment or received radiotherapy alone were excluded. We recorded data on patient demographics, chemotherapy regimen, radiotherapy dosage, sequencing of treatment, response and survival outcomes. End of treatment overall response rates (ORR) included those who achieved complete response (CR) and a partial response (PR). Progression free survival (PFS) was defined as date of diagnosis to date of progression, relapse or death. Overall survival (OS) was defined as date of diagnosis to date of death from all causes. Survival distributions were estimated by the Kaplan-Meier method. Assuming cox proportional hazards models, univariate analysis for OS was performed and Wald tests were used to evaluate the statistical significance. All the statistical analysis was performed using R. Results: There were 56 patients who fulfilled the inclusion criteria. Forty (71%) were male, 47 (84%) were Chinese and the median age of this cohort was 50 (range 18-80). Thirty-one (55%) patients had stage I disease and all had nasal involvement. All patients had ECOG performance status of 0 or 1 and most had low or low-intermediate international prognostic index (IPI) score. Ten patients (18%) had B-symptoms and LDH was elevated in 22 (39%). Pre-treatment positron emission tomography-computed tomography (PET/CT) was performed in 36 (64%) patients. Pre-treatment EBV titres were tested in only 23 patients and they were detected in 17 (74%) of patients. Twenty-five patients (45%) had sandwich (ChT, RT then ChT), 25 (45%) had ChT followed by RT, while 6 had RT followed by ChT. None had concurrent ChT/RT. The most commonly used ChT regimen was ICE (ifosfamide, carboplatin, etoposide) in 19 patients and SMILE (steroids, methotrexate, ifosfamide, L-asparaginase, etoposide) was used in 9 patients. Most patients (75%) did not receive L-asparaginase containing regimens. The median RT dose was 50Gy. The ORR for this cohort was 87.5% and 7 patients (12.5%) progressed at the end of treatment. Our median duration of follow up is 3.5 years (range: 0.25 - 21.6 years). The 5-year OS for stage I and II disease were 78.5% (95% CI, 64.2%-96.0%) and 65.6% (95% CI 47.5% to 90.5%) respectively. The 5-year PFS for stage I and II disease was 78.5% (95% CI 64.2%-96.0%) and 58.8% (95% CI 40.9% to 84.5%) respectively. On univariate analysis, only the sequence of therapy i.e., the sandwich ChT-RT-ChT approach when compared to sequential treatment with ChT followed by RT, was associated with better OS with a hazard ratio (HR) of 0.18 (95% CI 0.04 to 0.84 , p = 0.03). When L-asparaginase containing regimens were compared against those without, no statistical significant difference was observed in OS in ES ENKL, with HR of 3.38 (95%CI 0.44-26.15, p=0.243) Conclusion: Survival outcomes for ES ENKL especially that of stage I ENKL, are good with chemoradiotherapy. This contrasts against the treatment outcomes of AS ENKL. It is likely that many patients in this study were under-staged since PET scans were only performed in 64% of patients. Within the limits of this retrospective analysis and the small numbers, the ICE chemotherapy regimen appears to be an effective treatment when "sandwich"-sequenced with radiotherapy. Disclosures Lim: National Cancer Centre Singapore: Employment.

Treatment Practices and Outcomes in Older Adults with Relapsed/Refractory Diffuse Large B-Cell Lymphoma Treated in the Veterans Health Administration

Background: Diffuse large B-cell lymphoma (DLBCL) is the most common aggressive Non-Hodgkin lymphoma, with approximately one third of patients not responding (or relapsing) after receiving first-line (1L) therapy, typically a multi-agent chemoimmunotherapy regimen containing rituximab and doxorubicin. These patients may be treated with a second-line (2L) chemotherapy (CT) or chemoimmunotherapy (CIT) regimen, with the intention to proceed to a high-dose therapy followed by an autologous stem cell transplant (SCT). Unfortunately, a significant proportion of older patients are unable to tolerate such treatment. There is little data on treatment practices and outcomes in older DLBCL patients receiving 2L CT or CIT after failure of 1L therapy. Using electronic healthcare record data from the largest integrated health system in the United States, the Veterans Health Administration (VHA), we examined real-world outcomes of DLBCL patients ≥ 65 years of age receiving 2L CT or CIT following 1L therapy with rituximab and doxorubicin containing regimens.Methods: DLBCL patients diagnosed from 2001-2015 and treated at the VHA were identified by linking information from the VA Clinical Registry System (VACRS) in the VHA Corporate Data Warehouse (CDW) to administrative, laboratory and pharmacy data, and clinical notes in the CDW. Patients were included in the analysis if they: had no evidence of a prior malignancy, were diagnosed with DLBCL, received 1L therapy containing rituximab and doxorubicin for ≥ 21 days, then subsequently received a 2L CT or CIT, and were ≥ 65 years of age at time of 2L treatment. Patient age, gender, race/ethnicity; stage at diagnosis, lactate dehydrogenase (LDH), and Charlson Comorbidity Index (CCI) were extracted from VACRS and/or CDW. Patients were censored at end of study observation period (Dec 31, 2016) or if a second cancer diagnosis occurred following their DLBCL diagnosis. Patients were divided into 2 groups: Group 1 included patients receiving a 2L regimen that, per the National Comprehensive Cancer Network (NCCN) guidelines, is typically used with intention to proceed to high-dose therapy; Group 2 included patients receiving a regimen that, per NCCN, is used in non-candidates for high-dose therapy. Receipt of SCT was identified using ICD codes and/or clinical notes.Results: 230 DLBCL patients met our inclusion criteria. Of these, 223 (97%) were male and 171 (74%) were of non-Hispanic, white ethnicity. Baseline characteristics (at time of 1L) were as follows: 156 (68%) had stage III-IV disease, 154 (67%) had LDH > ULN, and median CCI was 4 (IQR:2-5). The majority of patients (217, 94%) received RCHOP as 1L, with the remaining receiving RCHOP + etoposide (13, 6%). Two thirds of patients, (151, 66%) started 2L within 1 year of starting 1L with a median of 10.6 months between start of 1L and start of 2L. Patients were almost equally divided between the two groups, with Group 1 (109, 47%) and Group 2 (121, 53%). Of the 109 Group 1 patients, 68 (62%) received ifosfamide, carboplatin, etoposide (ICE) +/- rituximab (R), and 22 (20%) received etoposide, methylprednisolone, cytarabine, cisplatin (ESHAP) +/- R. Of the 109 Group 1 patients, 14 (13%) proceeded to SCT within VHA (SCT outside VHA was not extracted for this study).The remaining 121 Group 2 patients received 2L therapy with the following: bendamustine (B) +/- R (28, 23%), gemcitabine, oxaliplatin (Gem-Ox) +/- R (21, 17%), cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) +/- R (17, 14%), cyclophosphamide, etoposide, vincristine, prednisone (CEOP) +/- R (14, 12%), cyclophosphamide, etoposide, prednisone, procarbazine (CEPP) +/- R (12, 10%); CHOP + etoposide +/- R (6%), lenalidomide +/- R (6%). Fewer than 10 of these patients proceeded to SCT. The median OS of all patients was 8 months.Conclusions: This is the first study that details treatment practices and outcomes in a nationwide cohort of older adult patients (≥ 65 years old) with relapsed/refractory DLBCL. Approximately half of these older patients did not receive or were not candidates for regimens typically used with intent for high-dose therapy and autologous transplant. OS for the entire cohort was less than a year. Despite significant advances in available treatments for DLBCL, there remains an unmet need in treatment of relapsed/refractory DLBCL, especially in older patients who have difficulty tolerating high-dose regimens. [Display omitted] DisclosuresHalwani:Takeda: Research Funding; Seattle Genetics: Research Funding; Pharmacyclics: Research Funding; Miragen: Research Funding; Kyowa Hakko Kirin: Research Funding; Immune Design: Research Funding; Genentech, Inc.: Research Funding; Bristol-Myers Squibb: Research Funding; Amgen: Research Funding; Abbvie: Research Funding. Schulz:Genentech: Employment, Equity Ownership; Roche: Equity Ownership. Li:Roche: Equity Ownership; Genentech: Employment. Masaquel:Genentech: Employment, Equity Ownership; Roche: Equity Ownership. Halloran:Genentech, Inc.: Employment, Equity Ownership; Janssen Pharmaceuticals, Inc: Employment, Equity Ownership. Delong-Sieg:Roche: Equity Ownership; Genentech, Inc.: Employment. Sauer:Genentech: Research Funding; Abbvie: Research Funding; Pharmacyclics: Research Funding; COHRDATA: Research Funding; Amgen: Research Funding.

Hematopoietic Stem Cell Transplant Utilization in Relapsed/Refractory Hodgkin Lymphoma: A Population Level Analysis of Statewide Claims Data

Introduction: In the era of novel therapies, the first and subsequent lines of therapies are rapidly evolving in the treatment of patients with Hodgkin lymphoma (HL) in order to optimize disease control and reduce long term health risks. Hematopoietic stem cell transplant (HSCT) is often used following treatment failure. While utilization of HSCT can be ascertained from transplant-specific registries, the treatment path for patients with relapsed/refractory HL leading up to HSCT is largely unknown. We developed an algorithm to define a cohort of commercially insured patients with HL from 2009-2013 in the Massachusetts All Payer Claims Database (MA APCD) who received HSCT. Further, we describe treatment characteristics of this cohort.Methods: The Patient Protection and Affordable Care Act of 2010 established requirements for states to assess healthcare outcomes which resulted in at least 16 states establishing All Payer Claims Databases. The MA APCD provides detailed medical claims data, physician provider data, and pharmacy data for all commercially insured patients in the state, regardless of site of care. Moreover, each patient is assigned a unique identifier, which allows us to follow patients even if they change insurer (“insurance churning”). To our knowledge, no studies exist using APCD for HL from any state.We identified a cohort with HL who underwent HSCT during the study period from among 7,613 cases with ICD-9 diagnostic codes for HL and of those, 695 had ICD-9 codes for both HL and HSCT. To identify incident HSCT cases during our study period, we developed and iteratively refined an algorithm using ICD-9 diagnostic and procedure codes, dates of service, and length of stay which narrowed the cohort to 178 patients. After review of the medical and pharmacy claims databases by an oncologist (AW), 113 patients were identified as part of the final cohort who underwent autologous and/or allogeneic HSCT. Reasons for exclusion include not HL (34), not HSCT (8), and prevalent (i.e. “history of”) HSCT only (23). We then summarized initial treatment, salvage treatment, and HSCT where data were available.Results: Among this commercially insured cohort of 113 patients who received HSCT, the median age was 39.0 years and 51.3% were female. Initial therapy data were identified for 65 of the 113 patients (58%); 58 (89.2%) received doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD). Of the 60 people for whom salvage therapy data could be discerned, 32 (53.3%) received ifosfamide, carboplatin, etoposide (ICE), 11 (18.3%) received gemcitabine, vinorelbine, liposomal doxorubicin (GVD), 11 (18.3%) received other chemotherapy, and 6 (10%) received brentuximab vedotin. Notably, 92 (81.4%) of all transplants were autologous, 10 (8.9%) were allogeneic transplant, and 9 (8.0%) were autologous followed by allogeneic transplant. Of the 64 patients with initial therapy data, median time to HSCT after completion of initial treatment was 238.5 days (25th-75th percentile, 151.5-428.0). Additionally, 25 HSCT were performed during the year 2009 and 20 of these had unknown initial chemotherapy regimens. Our dataset was limited to the years 2009-2013 and this missing chemotherapy information is most likely due to initial treatment prior to 2009.Conclusion: We successfully developed and refined an algorithm to help identify HSCT among patients with HL within a large statewide claims database. We characterized a cohort of patients with relapsed/refractory HL, including patterns of initial and salvage treatments in a sizeable subset of patients. Median time to HSCT demonstrates that the majority of patients undergo transplant for relapsed/refractory disease within a year of completing initial treatment. Future directions include determining reasons for incomplete information on initial and salvage therapy, such as insurance product or type, different sites of care within community and academic practices, and potential referral patterns into the state for HSCT care. As less than 5% of cancer patients are enrolled onto clinical trials, partnerships between clinical experts and data science are a powerful way to use large claims databases to study more representative patient populations. DisclosuresRodday:Seattle Genetics: Research Funding. Kumar:Seattle Genetics: Research Funding. Parsons:Seattle Genetics: Research Funding.

Randomized, Placebo-Controlled, Phase III Trial of Fosaprepitant, Ondansetron, Dexamethasone (FOND) Versus FOND Plus Olanzapine (FOND-O) for the Prevention of Chemotherapy-Induced Nausea and Vomiting in Patients with Hematologic Malignancies Receiving Highly Emetogenic Chemotherapy and Hematopoietic Cell Transplantation Regimens: The FOND-O Trial

Evidence supports olanzapine for prophylaxis of chemotherapy-induced nausea/vomiting (CINV) for highly emetogenic chemotherapy; however, most studies focus on solid malignancies and single-day regimens. A randomized, double-blinded, placebo-controlled trial was conducted to compare the addition of olanzapine to triplet therapy (fosaprepitant, ondansetron, dexamethasone [FOND-O]) versus triplet therapy alone (FOND) in preventing CINV in hematology patients receiving single-day and multiple-day highly emetogenic chemotherapy and hematopoietic cell transplant (HCT) regimens (NCT02635984).The primary objective of this study was to compare complete response (CR; no emesis and minimal nausea, <25 mm on a 100-mm visual analog scale) during the overall assessment period (chemotherapy days plus 5 days after). Secondary objectives were the number of emesis, number of rescue medications, percent achieving minimal nausea, and percent achieving complete protection (CP; no emesis, rescue antiemetic, or significant nausea), all of which are reported as acute (chemotherapy days), delayed (5 days after chemotherapy), and overall phases. Olanzapine 10 mg or matching placebo were given on each chemotherapy day and 3 days after. Adults with hematologic malignancy receiving HCT regimens of melphalan, BEAM (carmustine, etoposide, cytarabine, melphalan), busulfan (Bu)/cyclophosphamide (Cy), Bu/fludarabine (Flu), Bu/melphalan, FluCy, FluCy-total body irradiation (TBI), etoposide-TBI, and ICE (ifosfamide, carboplatin, etoposide) or 7+3 chemotherapy regimens were included. An estimated 98 patients were required using alpha = .05 and 80% power.No significant differences existed in baseline characteristics between FOND-O (n = 51) and FOND (n = 50) arms. Mean duration of olanzapine was 7.7 days (range, 4 to 11). Discontinuation for possible adverse events occurred in 3 placebo and 0 olanzapine patients. CR was significantly higher for FOND-O in overall (55% versus 26%, P = .003) and delayed (60.8% versus 30%, P = .001) but not acute (P = .13) phases. Significantly more patients receiving FOND-O achieved no more than minimal nausea in overall (P = .001) and delayed phases (P = .0002), as well as fewer overall mean emesis counts (P = .005). CP rates were not different in any assessment phase (P ≥ .05 each). Within the HCT subgroup (n = 64), the CR, CP, and no significant nausea rates were significantly better for FONDO-O in overall and delayed phases (all P < .05). Analysis within the HCT subgroup revealed significant improvement in outcomes in delayed and overall phases with FOND-O in the autologous but not allogeneic cohort.Addition of olanzapine to an NK-1–based triplet antiemetic regimen significantly improved clinically relevant outcomes in the HCT population.

Brentuximab for Refactory Hodgkin’s Lymphoma: A Case Report

Hodgkin's lymphoma (HL) continues to be an intriguing, and fascinating lymphoma [1]. HL is expected to cure the majority of patients. Brentuximab vedotin is a CD30 antibody. We survey efficacy of brentuximab in patient with HL who was resistant to treatment. A 43 year old male referred with cough and right supraclavicular lymphadenopathy. His disease was HL, nodular sclerosis type (stage IIB and grade II) with megakaryocytosis in bone marrow aspiration (BMB). He was treated with 6 cycles of induction chemotherapy including adriamycin, bleomycin, vinblastine and dacarbazine (ABVD) and achieved a complete remission by imaging assessment. Then he received ifosfamide, carboplatin, etoposide (ICE) plus brentuximab vedotin (1.8 mg/kg every 3 weeks) regimen for 6 courses. At the end of this time he been eligible for autologous bone marrow transplantation (BMT). Bone marrow was done and after 13 days with good engraftment the patient discharge hospital. Therapists should be try with a specific target when they need a new and potent treatment like BMT for an active disease. Brentuximab vendotin is a new drug in policy of recurrence that it used for a few of cases in Iran.

An extremely rare neoplasm, histiocytic sarcoma: A report of two cases with an aggressive clinical course

Abstract Histiocytic sarcoma (HS) is an extremely rare malignant neoplasm accounting for less than 1% of all hemato-lymphoid neoplasms. Sixty percent of all cases are metastatic at presentation and the prognosis is poor. Two cases of HS with an aggressive clinical course are presented. The first case was a 58-year-old man admitted to our hospital with back pain and paresthesia of the lower extremities. Magnetic resonance imaging (MRI) of the thoracic spine revealed a mass measuring 48 × 15 mm between the T2‒T5 paravertebral area, entering the spinal channel via the neural foramen and compressing the spinal cord. The mass was completely resected and pathological and immunohistochemical staining confirmed the diagnosis of HS. After three cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) and two cycles of carboplatin/paclitaxel, the patient died due to disease progression after 9 months. The second case is a 48-year-old man who presented with fever and weight loss, and complained of back pain for 2 months. Thoracic vertebral MRI revealed a lesion destructing the T6, T7 and T9 vertebral corpus and a mass measuring 2.5 × 2 cm near the T6‒T7 transverse process. Total-body fluorodeoxyglucose positron emission tomography (FDG-PET) imaging revealed bilateral inguinal hypermetabolic lymph nodes measuring 10 × 14 mm and osteolytic destructive bone lesions on the vertebral colon and pelvic bones. Pathological and immunohistochemical staining of bone marrow aspirate confirmed the diagnosis of HS. After three cycles of ifosfamide, carboplatin, etoposide (ICE) chemotherapy, the patient died due to disease progression after 3 months. Conclusions HS is an extremely rare malignant neoplasm of the monocytic/macrophage lineage, with no standardized chemotherapy regimen for multisystemic disease. Metastatic patients have a more aggressive clinical course than those with unifocal disease.

Risk Factors Predicting Outcomes for Primary Refractory Hodgkin Lymphoma Patients Treated with Salvage Chemotherapy and Autologous Stem Cell Transplantation

Introduction:Limited information exists on the best treatment strategy for Primary Refractory (ref) Hodgkin Lymphoma (HL). For the past 20 years, we have treated patients (pts) on sequential ifosfamide, carboplatin, etoposide (ICE)-based clinical trials with the intent to undergo high dose therapy (HDT) and autologous stem cell transplantation (ASCT). As previously reported (Moskowitz, Blood 2010) and confirmed by other centers, a negative PET scan prior to ASCT predicts for marked improvement in outcome in pts with relapsed HL. We aimed to identify risk factors that predict PET response to salvage chemotherapy in ref HL and evaluate outcomes following HDT and ASCT in this patient population.Methods:From 10/1/94 to 7/10/15, 192 ref HL pts were treated on sequential trials at MSKCC. Demographic and clinical factors were collected. Event free survival (EFS) and overall survival (OS) were calculated from the date of histologic confirmation of ref disease, estimated by Kaplan-Meier method, and compared by the log rank test. Events included relapse or death. Cox regression was used for the multivariate regression model. Patients were selected to receive a radiation-based conditioning regimen if all sites of nodal disease could be encompassed into a radiation field.Results:Patient characteristics included a median age of 31 (range 14-79) with 54% female. B symptoms, extranodal disease, stage IV disease, and disease bulk > 5cm were present in 31%, 48%, 44%, 40%, respectively.In the intent-to-treat (ITT) population, 41% had a positive post-salvage PET scan. As analyzed by ITT, median EFS was 8.9 years with a median OS of 10.4 years. On multivariate analysis, the presence of B symptoms and bulk >5cm at documentation of ref disease predicted for a reduced chance of achieving a negative PET after salvage therapy, with an odds ratio (OR) of 2.03 for B symptoms and 2.13 for bulk >5cm.For the 169 (88%) transplanted patients, 68% had a negative pre-ASCT PET. Radiation based conditioning was used for 70% of the pts. Median EFS was 12.8 yrs and median OS was not reached with a median follow-up of 3.6 yrs (range, 0.55 to 18.04 yrs) for the surviving patients (Figure 1). On multivariate analysis, both stage (IV vs I-III) and persistent PET abnormality pre- ASCT correlated with a shorter EFS. A risk stratification model was created and pts could be divided into 4 groups. 1) stage I-III disease and a negative PET pre-ASCT, the median EFS was not reached; 2) stage I-III disease and a positive PET pre-ASCT scan-the OR of an event was 4.04 (95% CI 1.93 to 8.45) with the median EFS not reached, 3) Stage IV disease and a negative PET pre-ASCT, the OR was 3.78 (95% CI 1.64 - 8.74) with a median EFS of 8.9 yrs, 4) Stage IV disease and a positive PET pre-ASCT, the OR was 8.22 (95% CI 3.99 to 16.94) with a median EFS of 0.9 yrs (Figure 2).Conclusions:B symptoms and bulk >5cm predicted for residual PET avidity after salvage therapy in ref HL. Persistent PET abnormality pre-ASCT and stage were risk factors for earlier relapse and death and can be used to prognosticate survival. Further studies are needed to determine optimal therapy for patients with multiple risk factors. [Display omitted] [Display omitted] DisclosuresMoskowitz:GSK: Research Funding; Merck: Consultancy, Research Funding; Seattle Genetics: Consultancy, Research Funding.

Successful treatment of primary intracranial sarcoma with the ICE chemotherapy regimen and focal radiation in children.

OBJECT Primary CNS sarcomas are very rare pediatric tumors with no defined standard of care. METHODS This study was a retrospective review of children diagnosed with a primary CNS sarcoma and treated at 2 Canadian tertiary care centers between 1995 and 2012. This report focuses on patients with cerebral hemispheric tumor location due to their specific clinical presentation. RESULTS Fourteen patients with nonmetastatic primary CNS sarcoma were identified; in 9 patients, tumors were located in the cerebral hemisphere and 7 of these patients presented with intratumoral hemorrhage. One infant who died of progressive disease postoperatively before receiving any adjuvant therapy was not included in this study. The final cohort therefore included 8 patients (4 males). Median patient age at diagnosis was 11.8 years (range 5.8-17 years). All tumors were located in the right hemisphere. Duration of symptoms prior to diagnosis was very short with a median of 2 days (range 3-7 days), except for 1 patient. Three (37.5%) patients had an underlying diagnosis of neurofibromatosis Type 1 (NF1). Gross-total resection was achieved in 5 patients. The dose of focal radiation therapy (RT) ranged between 54 Gy and 60 Gy. Concomitant etoposide was administered during RT. ICE (ifosfamide, carboplatin, etoposide) chemotherapy was administered prior to and after RT for a total of 6-8 cycles. Seven of the 8 patients were alive at a median time of 4.9 years (range 1.9-17.9 years) after treatment. CONCLUSIONS In this retrospective series, patients with primary CNS sarcomas located in the cerebral hemisphere most commonly presented with symptomatic acute intratumoral hemorrhage. Patients with NF1 were overrepresented. The combination of adjuvant ICE chemotherapy and focal RT provided encouraging outcomes.

Bevacizumab/high-dose chemotherapy with autologous stem-cell transplant for poor-risk relapsed or refractory germ-cell tumors

BackgroundHigh-dose chemotherapy (HDC) using sequential cycles of carboplatin/etoposide is curative for relapsed germ-cell tumors (GCT). However, outcomes of high-risk patients in advanced relapse remain poor. We previously developed a new HDC regimen combining infusional gemcitabine with docetaxel/melphalan/carboplatin (GemDMC), with preliminary high activity in refractory GCT. Given the high vascular endothelial growth factor expression in metastatic GCT and the synergy between bevacizumab and chemotherapy, we studied concurrent bevacizumab and sequential HDC using GemDMC and ifosfamide/carboplatin/etoposide (ICE) in patients with poor-risk relapsed or refractory disease. Patients and methodsEligibility criteria included intermediate/high-risk relapse (Beyer Model), serum creatinine ≤1.8 mg/dl and adequate pulmonary/cardiac/hepatic function. Patients received sequential HDC cycles with bevacizumab preceding GemDMC (cycle 1) and ICE (cycle 2). The trial was powered to distinguish a target 50% 2-year relapse-free survival (RFS) from an expected 25% 2-year RFS in this population. ResultsWe enrolled 43 male patients, median age 30 (20–49) years, with absolute refractory (N = 20), refractory (N = 17) or cisplatin-sensitive (N = 6) disease, after a median 3 (1–5) prior relapses. Disease status right before HDC was unresponsive (N = 24, progressive disease 22, stable disease 2), partial response with positive markers (PRm+) (N = 8), PRm- (N = 7) or complete response (N = 4). Main toxicities were mucositis and renal. Four patients (three with baseline marginal renal function) died from HDC-related complications. Tumor markers normalized in 85% patients. Resection of residual lesions (N = 13) showed necrosis (N = 4), mature teratoma (N = 2), necrosis/teratoma (N = 3) and viable tumor (N = 4). At median follow-up of 46 (9–84) months, the RFS and overall survival rates are 55.8% and 58.1%, respectively. ConclusionsSequential bevacizumab/GemDMC–bevacizumab/ICE shows encouraging outcomes in heavily pretreated and refractory GCT, exceeding the results expected in this difficult to treat population. ClinicalTrials.govNCT00936936.

Neoadjuvant chemotherapy reduces blood loss during the resection of pediatric choroid plexus carcinomas.

OBJECT Choroid plexus carcinomas (CPCs) are rare brain tumors originating from the ventricular choroid plexus. They account for 2%-4% of all pediatric brain tumors and are most frequently seen in very young children. This pediatric proclivity, in combination with a marked vascularity, renders an aggressive resection a difficult and often dangerous endeavor. Blood losses of several total blood volumes in small children are not uncommon, sometimes forcing the neurosurgeon to abort the procedure, often leaving residual tumor. Great extent of tumor resection is an accepted beneficial factor for overall survival. Therefore, a second resection usually follows the administration of adjuvant chemotherapy. Second-look surgery appears to be associated with markedly decreased blood loss. Histological examination of specimens obtained at a second intervention shows decreased vascularity and fibrotic changes in tumor tissue. At the Hospital for Sick Children in Toronto, this empirical finding led to the strategy of neoadjuvant chemotherapy to minimize blood loss and maximize cytoreduction. The authors undertook this study to assess the potentially beneficial effect of neoadjuvant chemotherapy on blood loss during surgery for CPCs. METHODS In this retrospective cohort review, the demographic, clinical, and treatment parameters of 22 consecutive patients diagnosed with CPC are presented. All underwent surgical treatment at the Hospital for Sick Children from 1982 to 2013. Special attention was given to the impact of neoadjuvant chemotherapy on extent of resection and intraoperative blood loss. Extent of resection was calculated based on perioperative neuroimaging, and amount of blood loss was estimated based on transfusion parameters and perioperative changes in hematocrit. RESULTS Ten patients did not receive neoadjuvant chemotherapy, and 12 were treated with 2-5 cycles of ICE (ifosfamide, carboplatin, etoposide) chemotherapy in a neoadjuvant fashion. The 22 patients included in the study underwent a total of 37 tumor resection surgeries. In all of the cases in which neoadjuvant chemotherapy was used, at least a near-total resection (> 95% of tumor volume) was achieved. Patients who underwent gross-total resection had prolonged overall survival. Of the 37 resections, 18 were performed after chemotherapy. Mean blood loss in the neoadjuvant chemotherapy group was 22% of total estimated blood volume as opposed to 96% in patients without preoperative chemotherapy. CONCLUSIONS In children with CPC, the administration of neoadjuvant chemotherapy decreases intraoperative blood loss and increases extent of resection with a significant positive effect on overall survival.