bluuebunny/crossref_metadata_2025_split huggingface dataset:
Endocrine outcome for children with embryonal brain tumors treated with craniospinal irradiation on the SJMB96 trial
Authors: Gajjar A. , Merchant T. , Sklar C. , Wallace D. , Xiong Z. , Shelso J. , Broniscer A. , Fouladi M. , Kun L. , Laughton S. 
Published: March 2020

9571 Background: To investigate the relationship between endocrine deficits with the radiation (RT) dose to the hypothalamic- pituitary axis (HPA) in medulloblastoma/PNET patients treated with risk-adapted craniospinal irradiation (CSI) followed by chemotherapy. Methods: 88 patients who survived at least 2 years from diagnosis were included in this analysis. CSI doses were 23.4 Gy or 36–39.6 Gy depending on clinical risk; the primary tumor site received 55.8 Gy. All pts had regular endocrine follow-up and screening to test for growth hormone (GH), thyroid hormone (TH) and adrenocorticotrophin hormone (ACTH) deficiency. Patients that had abnormal results on the screening tests underwent further evaluation by stimulation testing of the HPA. Only patients diagnosed with central hypothyroidism were included in the analysis for TH deficiency. Results: Of the 88 pts included in the study cohort, 77 pts had abnormal screening tests and underwent provocative testing. The median radiation dose to the hypothalamus was 42 Gy (26–57 Gy) and pituitary was 44 Gy (26–58 Gy). Patients receiving higher RT doses to the pituitary had a significantly higher incidence of growth hormone deficiency with 4-year estimates of 100 ±3% for those receiving = 44Gy and 82±7% for those receiving < 44 Gy (p=0.024). Four-year estimates of thyroid hormone deficiency for patients receiving = 44 Gy to the pituitary were 67±21% and 18±14% for those receiving < 44 Gy (p<0.010). There was no correlation between the dose to the pituitary with the incidence of ACTH deficiency. The estimated change in height z-score for patients receiving < 44 Gy to the pituitary was - 0.53 units per year (-0.44 to -0.63) compared with -0.70 units per year (-0.62 to -0.78) for those receiving = 44 Gy. Conclusions: Data from this prospective study demonstrate that RT to the HPA is the key determinant for developing endocrinopathies in patients with medulloblastoma/PNET. No significant financial relationships to disclose.
BCIRG 007: First overall survival analysis of randomized phase III trial of trastuzumab plus docetaxel with or without carboplatin as first line therapy in HER2 amplified metastatic breast cancer (MBC)
Authors: Pegram M. , Forbes J. , Pienkowski T. , Valero V. , Eiermann W. , Von Minckwitz G. , Martin M. , Crown J. , Taupin H. , Slamon D. 
Published: March 2020

LBA1008 Background: Based on preclinical synergism between docetaxel (T), carboplatin (C) and trastuzumab (H), BCIRG conducted a phase III trial in HER2-positive MBC to evaluate efficacy and safety of H in combination with T or TC. Methods: 263 patients (pts) with HER2 FISH+ MBC were randomized to TH (H with T 100mg/m2) or TCH (H with T 75mg/m2 and C AUC=6). Chemotherapy was given every 3 weeks (q3w) for 8 cycles with weekly H at 2mg/kg (loading dose of 4 mg/kg) followed by H q3w at 6 mg/kg until progression. Pts were stratified by centre and prior (neo) adjuvant taxane chemotherapy. Primary endpoint was Time To disease Progression (TTP). Secondary endpoints include overall survival, response rate, duration of response (DR), clinical benefit (CB) and safety. Results: 131 pts were treated in each arm Pt characteristics were well balanced in both groups. A first efficacy analysis was conducted at 204 events. There was no significant difference between TH and TCH in median TTP (11.1 vs 10.4 mos, p=0.57), ORR (73% in both arms), DR (10.7 vs 9.4 mos) and CB (67% in both arms). At 39 months of median follow-up, median overall survival was 36.40 and 36.57 months in TH and TCH arms respectively. More patients on TCH received the max number of chemotherapy cycles, and numerically fewer patients on TCH discontinued treatment as a result of non hematological toxicity. The most common gr 3/4 toxicities were: Neutropenic infection that was 16.8% vs 9.2% respectively for TH and TCH, thrombocytopenia (2% vs 15%), asthenia (5% vs 12%), anemia (5% vs 11%), and diarrhea (2% vs 10%). Two pts died (1.5%) due to sepsis in TCH. Absolute LVEF decline > 15 % were seen in 5.5 % vs 6.7 % of pts. One pt (0.8%) had a symptomatic CHF in TH arm. Conclusion: Both TH (T 100) and TCH (T 75) were highly effective treatment regimens in women having HER2-positive MBC, demonstrating high response rates, median TTP > 10 months, and median overall survival > 36 months in both TH and TCH. Cardiac toxicity was no significant problem with either treatment. [Table: see text]
Preemptive versus deferred lamivudine in preventing chemotherapy (CT) interruptions in hepatitis B (HBV) carriers with non-hematological malignancy—preliminary report of a randomized phase III study
Authors: Ngan R. K. , Yiu H. Y. , Cheng H. C. , Kwan C. K. , Lam T. W. , Tsang D. , Kwok P. , Cheng W. W. , Au K. H. , Wong K. H. , Yip T. C. 
Published: March 2020

LBA19684 Background: About 10% cancer patients (pts) are HBV carriers in endemic areas, who have a risk of HBV reactivation with CT preventable by Lamivudine (Lam). Methods: Pts seropositive for HBV surface antigen (HBsAg+) planned to receive ≥ 4 cycles of CT for non-hematological malignancy were randomized to receiving either preemptive Lam during and for 8 weeks after CT (arm I), or observation only and deferred Lam at biochemical hepatitis reactivation (arm II). All pts had normal liver enzymes & clotting profiles, age 18–75 & KPS >50 before entry. Serial clotting profile, liver enzyme and HBV DNA levels were monitored during CT and for 15 weeks post-CT. The endpoints include % of CT interruptions due to HBV reactivation (primary), HBV reactivation %, CT drug dose intensity levels & HBV reactivation-free survival (all secondary). 110 pts are estimated to give a power of 90% to detect the projected difference in the primary endpoint at 2-sided alpha error of 0.05. Results: Pt accrual was completed in 1/07. As at 3/07, 92 (81%) of the 114 pts randomized have completed the study or died, and were included for analysis. Breast & lung cancer constituted 71% of the cancers. There was no statistical difference in pt, cancer, CT, or viral characteristics between the 2 arms. Results are summarized in table . All 4 pts with CT interruptions and 11/14 pts with HBV reactivation had breast cancer. No difference in CT drug dose intensity levels was observed. Steroid used in the anti-emetic regimen was a significant factor in predicting viral reactivation in arm II pts in multivariate analysis. Conclusions: Although the incidence of CT interruptions was low in unselected pts without preemptive Lam, it was much higher in breast cancer pts despite deferred Lam, who also had significant rates of biochemical hepatitis & viral reactivation. Preemptive Lam should be given to breast cancer pts, & considered in other cancer pts receiving CT who are HBsAg+. [Table: see text] No significant financial relationships to disclose.
Final results of the EORTC Intergroup randomized phase III study 40983 [EPOC] evaluating the benefit of peri-operative FOLFOX4 chemotherapy for patients with potentially resectable colorectal cancer liver metastases
Authors: Nordlinger B. , Sorbye H. , Collette L. , Glimelius B. , Poston G. J. , Schlag P. M. , Rougier P. , Bechstein W. , Walpole E. , Gruenberger T. 
Published: March 2020

LBA5 Background: The 5-year survival after resection of colorectal cancer liver metastases is 30% but recurrence is common. This study evaluates the benefit of combining peri-operative chemotherapy and surgery for patients with initially resectable liver only metastases from colorectal cancer (LM). Methods: Between September 2000 and July 2004, 364 pts with up to 4 LM were randomized between peri-operative FOLFOX4 (oxaliplatin 85mg/m2 and LV5FU2), 6 cycles before and 6 cycles after surgery, (CT), and surgery alone (S). The primary endpoint was progression free survival (PFS) with the goal to increase median PFS by 40% (HR=0.71). Safety was a secondary endpoint (already reported at ASCO 2005). PFS results are reported at the 2-sided 0.0434 significance level (adjusting for one interim analysis). Results: Baseline characteristics were similar in both arms. Eleven of 182 pts were ineligible in each arm, mostly for more advanced disease. In the CT arm, a median of 6 pre-op cycles were delivered and 151 patients were resected. 115 pts (63%) received post-op CT, with a median number of 6 cycles and a relative dose intensity of 79% to 86%. In the S arm, 152 pts were resected. Due to the nature of the trial, evaluation of resectability (relevant for eligibility) was based on pre-op imaging, but 31/182 pts (CT arm) and 30/182 pt (S arm) could not undergo resection. There were 2 (S arm) and 1 (CT arm) deaths after surgery. At a median follow-up of 3.9 years, 254 PFS events were reported (240 in eligible pts) and the results are as shown in the table . Conclusions: Peri-operative FOLFOX4 chemotherapy improved PFS over surgery alone in patients whose metastases were actually resected. The benefit was slightly diluted when also pts considered resectable on imaging but eventually not resected were taken into account. FOLFOX4 given peri-operatively is safe and does not prevent the pts from undergoing surgery. [Table: see text] [Table: see text]
Adjuvant low-dose interleukin-2 (IL2) plus interferone-alpha (IFN) in operable renal cell cancer (RCC). A phase III, randomized, multicenter, independent trial of the Italian Oncology Group for Clinical Research (GOIRC)
Authors: Passalacqua R. , Buzio C. , Buti S. , Labianca R. , Porta C. , Boni C. , Rondini E. , Camisa R. , Sabbatini R. , Artioli F. , Caminiti C. 
Published: March 2020

LBA5028 Background: For pts with non-metastatic RCC, no standard adjuvant treatment exists. Immunotherapy (IT) using IFN and/or IL2 is effective in metastatic disease setting. Low and chronically repeated doses of IL2 plus IFN induce a persistent stimulation of the immune system with no relevant toxicity. Methods: From July1994 to March 2006, surgically treated RCC pts were randomized to the following arms: A) low-dose IT; B) control arm. IT consisted of a 4-week cycle of s.c. IL2 (5 days/wk, 1 million UI/sqm bid d 1,2 and 1 million UI/sqm × 1 d 3,4,5) + IFN (1,8 million UI/sqm d 3,5 of each week). Cycles were repeated every 4 months for the first 2 years and every 6 months for the remaining 3 years. Each patient received 12 cycles in 5 years. Inclusion criteria were as follows: histological diagnosis of RCC, age <75 yrs, radical or partial nephrectomy within the past 3 months, pT1 (diameter of T > 2,5 cm), T2, T3 a-b-c; pN0-pN3, M0; good cardiac and renal function and no autoimmune disease. Based on a planned sample size of 320 pts, the trial was designed to have a 80% power to detect a 15% improvement in 5-year survival. Results: A total of 310 pts were randomized: 157 on arm A, 153 on arm B. Pts characteristics were well balanced between the two arms. At a median follow-up of 52 months, 77 pts relapsed: 35 in arm A and 42 in arm B. In the first 5 years of observation, disease free survival (DFS) curves were similar in the two arms, but diverged thereafter. DFS at 5 and 10 years was 0.73 and 0.73 in arm A vs 0.73 and 0.60 in arm B with an estimated Hazard Ratio (HR) of 0.84 (95% CI: 0.54–1.33 p=0.47). Efficacy of IT was more evident in patients with good PS (HR 0.78; 0.47–1.30 p=0.35); age<60 yrs (HR 0.61; 0.31–1.19 p=0.15), and low tumor grade (HR 0.70; 0.38–1.27 p=0.24). As for overall survival, 59 deaths were observed with no differences between the two arms. Toxicity was mild and limited to WHO grade 1 or 2 in the majority of cases. Conclusions: Low-dose adjuvant IL2+IFN is feasible in RCC and seems to reduce the risk of recurrence after 5 years from diagnosis. Follow-up update is still ongoing. No significant financial relationships to disclose.
Phase III study of immediate versus delayed docetaxel after induction therapy with gemcitabine plus carboplatin in advanced non-small cell lung cancer: Updated report with survival
Authors: Fidias P. , Dakhil S. , Lyss A. , Loesch D. , Waterhouse D. , Cunneen J. , Chen R. , Treat J. , Obasaju C. , Schiller J. 
Published: March 2020

LBA7516 Background: Gemcitabine (G) plus carboplatin (C) therapy is active in patients with advanced non-small-cell lung cancer (NSCLC). For nonprogressing patients, optimal timing of second-line therapy with a non-cross-resistant agent is unclear. This Phase III, randomized trial assessed the efficacy and safety of docetaxel (D) administered either immediately after GC induction therapy or upon disease progression (PD). Methods: Patients having either Stage IIIB with pleural effusion or Stage IV NSCLC were enrolled. Prior chemotherapy for NSCLC was not permitted. For GC induction, G 1000 mg/m2 was administered on Days 1, 8 followed by C AUC 5 on Day 1. After four 21-day cycles, nonprogressors were randomized to either the immediate D group (D 75 mg/m2 administered on Day 1 every 21 days, for a maximum of 6 cycles) or the delayed D group (patients given best supportive care after randomization and the same D regimen after first evidence of PD) treatment arms. Primary endpoint was overall survival (OS). Additional analyses included response rates, toxicity and progression-free survival (PFS). Results: Results are summarized in the table below. OS was not statistically different (p=0.071) between the two D arms. However, 31 patients (20.1%) in the delayed D arm and 38 patients (24.8%) in the immediate D arm were censored for OS analysis. PFS analysis (from randomization to first evidence of PD or death) showed a statistically significant (p=<0.0001) improvement in the immediate D arm. D given to NSCLS patients immediately after GC induction did not increase toxicity. Conclusions: Comparison of PFS for each D arm suggests a possible clinical benefit for immediate D therapy. However, even though OS trended in favor of immediate D therapy, the OS result did not reach statistical significance. The implications of these results will be discussed. [Table: see text] [Table: see text]
A randomized phase III trial of active symptom control (ASC) with or without chemotherapy in the treatment of patients with malignant pleural mesothelioma: First results of the Medical Research Council (MRC) / British Thoracic Society (BTS) MS01 trial
Authors: Muers M. , Fisher P. , Snee M. , Lowry E. , O'Brien M. , Peake M. , Rudd R. , Nankivell M. , Pugh C. , Stephens R. J. 
Published: March 2020

LBA7525 Background: Although chemotherapy is widely used in the treatment of mesothelioma it has never been compared in a randomized trial with ASC alone. Two chemotherapy regimens that had shown good symptom palliation in phase II studies were chosen for investigation. Methods: Patients with malignant pleural mesothelioma were randomized to ASC alone (regular follow-up in a specialist clinic, and treatment could include steroids, analgesics, bronchodilators, palliative radiotherapy, etc), ASC+MVP (4 × 3-weekly cycles of mitomycin 6g/m2, vinblastine 6mg/m2, and cisplatin 50mg/m2), or ASC+N (12 weekly injections of vinorelbine 30mg/m2). 420 patients were required to detect a 3-month improvement in median survival with ASC+CT (both chemotherapy arms combined). Quality of Life (QL) was assessed using the EORTC QLQ-C30. Results: 409 patients were accrued (136 ASC, 137 ASC+MVP, 136 ASC+N). Median age: 65 years, male: 91%, Performance status 0: 23%, Epithelial histology: 73%, Stage III: 33%, Stage IV: 48%. In the ASC+MVP group 61% received all 4 cycles, and in the ASC+N group 49% received at least 10 weekly cycles. Good symptom palliation (defined as prevention, control or improvement) was achieved in all 3 groups, and no between-group differences were observed in 4 pre-defined QL subscales (physical functioning, dyspnoea, pain and global QL). A small (not conventionally significant) survival benefit was seen for ASC+CT (349 deaths, HR 0.89, 95%CI 0.72, 1.12, p=0.32). Median survival: ASC: 7.6 months, ASC+CT: 8.5 months. Exploratory analyses suggested a survival advantage for vinorelbine compared to ASC alone (HR 0.81, 95%CI 0.63, 1.05, p=0.11), with a median survival of 9.4 months, but no evidence of a benefit with MVP (HR 0.98, 95%CI 0.76, 1.28), p=0.91). Conclusions: This is the 2nd largest ever randomized trial in mesothelioma and the first to compare ASC with or without chemotherapy. Although the addition of chemotherapy to ASC did not result in a conventionally significant survival benefit, there was an indication that vinorelbine should be investigated further, and that MVP probably has no role in this disease. [Table: see text]
Female fertility preservation (FP) at pediatric cancer centers: A report from the Children’s Oncology Group (COG).
Authors: Levine Jennifer , Quinn Gwendolyn P. , Klotsky James , Kelvin Joanne Frankel , Cherven Brooke , Bryson Elyse , Ahmed-Winston Sameeya , Frederick Natasha , Brackett Julienne , Meacham Lillian , Freyer David Robert , Dvorak Christopher , Chow Eric Jessen 
Published: March 2020

11567 Background: Preserved fertility after cancer is a priority for female survivors and their families. Embryo/oocyte cryopreservation are standard of care (SOC) for post-pubertal females. Experimental ovarian tissue cryopreservation (OTC) is the only current option for pre-pubertal girls. We surveyed COG sites about their FP infrastructure and practices. Methods: A REDcap survey was emailed to one individual previously identified as knowledgeable about FP or the Principal Investigator at each COG site. Site specific factors associated with outcomes were determined using logistic regression. All study procedures were IRB-approved. Results: Responses were received from 144 of 220 sites (65%). Discussions about fertility at diagnosis were reported as routinely held with all females “at risk” of infertility, all post pubertal females, and all females at 113 (78%), 94 (65%), and 65 (45%) of sites respectively. Embryo/oocyte cryopreservation was offered at 95 (70%) institutions and independently associated with large (>120 new patients/year) sites (OR 6.0 95%CI 1.6-22.8) and presence of a FP navigator/team (OR 4.7 95%CI 1.7-13.5). OTC was offered at 64 (48%) sites: 34 (25%) by referral to another institution, 18 (13%) under an IRB protocol, and 12 (9%) as a clinical service. OTC accessibility was associated with large sites (OR 3.2 95% CI 1.1-8.9) and a FP navigator/team (OR 3.2 95%CI 1.4-7.0). A total of 102/133 (77%) sites use gonadotropin releasing hormone analogues (GnRHa) for any indication; 90 (68%) for menstrual suppression, 75 (56%) with the goal of ovarian suppression for fertility preservation, and 27 (20%) for contraception. Conclusions: Variation in FP services exists across COG. Discussion of infertility risk is not universal. The availability of OTC at treating institutions is limited. The presence of an FP navigator/team is a modifiable factor associated with greater likelihood of accessing SOC and experimental options. Despite conflicting evidence and lack of endorsement from professional societies, GnRHa’s are commonly used for FP. These survey results suggest FP services remain inadequate but highlight opportunities for improvement and areas of needed research.
Impact of geriatric vulnerability on outcomes of older patients in allogeneic hematopoietic cell transplantation.
Authors: Lin Richard Jirui , Elko Theresa A , Devlin Sean M. , Flynn Jessica , Jakubowski Ann Alice , Shahrokni Armin , Dahi Parastoo , Perales Miguel-Angel , Sanchez-Escamilla Miriam , Tamari Roni , Shaffer Brian Carl , Sauter Craig Steven , Papadopoulos Esperanza Bouza , Castro-Malaspina Hugo , Gyurkocza Boglarka , Barker Juliet Naomi , Maloy Molly A , Korc-Grodzicki Beatriz , Giralt Sergio 
Published: March 2020

7017 Background: Older patients are at increased risk for complications and death following allogeneic hematopoietic cell transplantation (allo-HCT). Traditional transplant-specific prognostic indices such as hematopoietic cell transplant comorbidity index (HCT-CI) may not capture all underlying geriatric vulnerabilities, and in-depth evaluation by a geriatrician prior to transplant may not always be available. We hypothesize that routine pre-transplant assessments by interdisciplinary clinical providers may help uncover additional geriatric deficits. Methods: Using an institutional database of 457 adults age 60 years and older (range 60-78.7) who underwent first allo-HCT for hematological malignancies from 2010 to 2017, we retrospectively examined the prevalence and the prognostic impact of pre-transplant geriatric deficits identified by interdisciplinary clinical providers including geriatric domains of functional activity, cognition, medication, nutrition, mobility, and routine laboratory tests. Results: With a median follow-up of 37 months for survivors, the 3-year probability of overall survival (OS) was 50% (95% CI 45-55). The 2-year cumulative incidence of non-relapse mortality (NRM) was 25% (95% CI 22-28). Among pre-transplant geriatric variables, we found that impairment in instrumental activities of daily living (IADL) was associated with increased NRM and inferior PFS and OS. In multivariate analyses, mismatched donor, age-adjusted HCT-CI > 4 (aaHCTCI), and IADL impairment were associated with NRM, while high/very high disease risk index (DRI), IADL impairment, and positive CMV status were associated with OS. The combination of IADL impairment with either aaHCTCI or DRI readily stratifies NRM and OS, respectively. Conclusions: Our findings establish a simple assessment tool to risk stratify older patients prior to allo-HCT using IADL and aaHCTCI and DRI. These results may provide an entry point for prospective, interventional trials to reduce NRM and toxicities for older allo-HCT patients.
Response to brentuximab vedotin by CD30 expression: Results from five trials in PTCL, CTCL, and B-cell lymphomas.
Authors: Jagadeesh Deepa , Horwitz Steven M. , Bartlett Nancy L. , Advani Ranjana H. , Jacobsen Eric D. , Duvic Madeleine , Gautam Ashish , Rao Shangbang , Onsum Matthew , Fanale Michelle , Kim Youn H. 
Published: March 2020

7543 Background: Brentuximab vedotin (BV), an antibody-drug conjugate targeting CD30, has been evaluated in multiple trials in patients (pts) with peripheral T-cell lymphoma (PTCL), cutaneous T-cell lymphoma (CTCL), or B-cell lymphoma. We examined the ability of CD30 expression level to predict response to BV across these patient populations. Methods: Data were integrated from 275 pts with PTCL, CTCL, and B-cell lymphoma treated with BV from 5 prospective clinical trials. Study SGN35-012 evaluated BV plus rituximab or BV monotherapy in pts with relapsed/refractory non-Hodgkin lymphoma. The ALCANZA study compared BV to physician’s choice of methotrexate or bexarotene in pts with mycosis fungoides (MF) or primary cutaneous anaplastic large cell lymphoma (pcALCL). Three investigator-sponsored trials evaluated BV monotherapy in pts with relapsed PTCL, MF, and pcALCL (35-IST-030, 35-IST-001, 35-IST-002). Exploratory analyses were conducted to examine the relationship between CD30 expression and objective response rate (ORR) for pts with CD30 expression ≥10%, <10%, or undetectable (0%) by IHC (malignant cells or lymphoid infiltrate; local review). Results: 143 pts had tumors with CD30 <10%, including 58/143 with undetectable CD30. Activity with BV was observed at all levels of CD30 expression, including CD30=0 (Table). Analysis of the interaction between CD30 and duration of response is ongoing and will be presented in the final poster. ORR by CD30 expression, n/N (%). Clinical trial information: NCT01421667, NCT02588651, NCT01578499, NCT01352520, NCT01396070. Conclusions: CD30 expression levels ≥10%, <10%, or undetectable did not predict response to BV in a range of CD30-expressing lymphomas: Clinical responses occurred in pts with CD30 low and CD30 undetectable lymphomas. Limitations of IHC, the dynamic nature and heterogeneity of cell-surface CD30 expression, and multiple mechanisms of action of BV may all contribute to this observation.[Table: see text]