bluuebunny/crossref_metadata_2025_split huggingface dataset:
Weekly nab-paclitaxel in combination with carboplatin as first-line therapy in patients (pts) with advanced non-small cell lung cancer (NSCLC): Analysis of patient-reported neuropathy and taxane-associated symptoms.
Authors: Hirsh Vera , Okamoto Isamu , Hon Jeremy K. , Dakhil Shaker R. , Page Ray D. , Orsini James , Zhang Hui , Renschler Markus Frederic , Socinski Mark A. 
Published: March 2020

TPS7618 Background: Neuropathy and its associated symptoms are dose-limiting toxicities of taxane-based regimens. Measuring disease symptoms has utility for maintaining a balance between the benefits and costs of treatment. In a phase III trial nab-paclitaxel (nab-P, 130 nm albumin-bound paclitaxel particles) + carboplatin (C) vs solvent-based paclitaxel (sb-P) + C significantly improved the primary endpoint of overall response rate (ORR) (25% vs 33%, P = 0.005), with a 1-month improvement in median overall survival (OS; P = NS), and an improved tolerability profile in pts with advanced NSCLC. Here we report on patient-assessed neuropathy and taxane-associated symptoms, important factors in a palliative patient setting. Methods: Pts with untreated stage IIIB/IV NSCLC were randomized 1:1 to C AUC 6 day 1 and either nab-P 100 mg/m2 on days 1, 8, 15 (n = 521) or sb-P 200 mg/m2 day 1 (n = 531) q 21 days. Treatment was continued until disease progression. Safety was assessed per the Common Terminology Criteria for Adverse Events (CTCAE) v3.0. The mean change from baseline to day 1 of each cycle for the neuropathy, pain, and hearing subscales of Functional Assessment of Cancer Therapy (FACT)‑Taxane v 4.0 were assessed. Results: 1031 (98%) pts completed FACT-Taxane at baseline, and 987 (94%) during follow-up or at completion of treatment. Baseline scores for neuropathy and pain were well balanced. Significant treatment effects favoring nab-P/C were noted for patient-reported neuropathy (P < 0.001), neuropathic pain hands/feet (P < 0.001), and hearing loss (P = 0.002). Physician-assessed rates of neuropathy were significantly lower in the nab-P/C arm vs the sb-P/C arm: 47% vs 63%, P < 0.001, all grades; 3% vs 12%, P < 0.001, grade 3/4, respectively. More pts treated with nab-P/C vs sb-P/C had no neuropathy (53% vs 47%, P < 0.001). Conclusions: nab-P/C was associated with statistically and clinically significant reductions in patient-reported neuropathy, neuropathic pain in the hands and feet, and hearing loss compared with sb-P/C. Patient-reported outcomes for neuropathy were consistent with physician assessment.
A phase II randomized study of bortezomib/dexamethasone (Bort/Dex) with or without elotuzumab (Elo) in patients (pts) with relapsed/refractory multiple myeloma (RR MM) (CA204-009).
Authors: Jakubowiak Andrzej J. , White Darrell , Moreau Philippe , Facon Thierry , Vij Ravi , Kroog Glenn Scott , Kopit Justin , Singhal Anil , Palumbo Antonio Pierangelo 
Published: March 2020

TPS8114 Background: MM is rarely curable and pts typically relapse or become refractory to current treatments. Elo is a humanized monoclonal IgG1 antibody targeting the cell surface glycoprotein CS1, which is highly expressed on >95% of MM cells with little to no expression on normal tissues. The mechanism of action of Elo is primarily natural killer (NK) cell-mediated antibody-dependent cellular cytotoxicity (ADCC) against myeloma cells. Elo + Bort significantly enhanced antimyeloma activity in a mouse xenograft model vs either agent alone. The addition of Bort enhanced the ADCC activity of Elo in preclinical studies. In a phase I study of Elo + Bort in pts with RR MM, objective response rate (ORR) was 48%, median progression-free survival (PFS) was 9.5 months, and activity was observed in 2/3 patients (67%) refractory to Bort (Jakubowiak et al. J Clin Oncol, in press). This study will assess if the addition of Elo to Bort/Dex improves PFS and, if so, whether magnitude of the improvement is linked to FcγRIIIa polymorphism. Methods: Pts (N=150) with RR MM after 1 or 2 prior therapies will be randomized in a 1:1 ratio to receive Bort 1.3 mg/m2 IV or SQ (Cycles 1-8: days 1, 4, 8, and 11; Cycles ≥9: days 1, 8, and 15) and Dex with or without Elo. Elo dose and schedule is 10 mg/kg IV (Cycles 1-2: days 1, 8, and 15 [21-day cycles]; Cycles 3-8: days 1 and 11 [21-day cycles]; Cycles ≥9: days 1 and 15 [28-day cycles]). In the arm without Elo, Dex 20 mg PO is scheduled for Cycles 1-8: days 1, 2, 4, 5, 8, 9, 11, and 12; and Cycles ≥9: days 1, 2, 8, 9, 15, 16. In the arm with Elo, Dex 20 mg PO is scheduled for Cycles 1-2: days 2, 4, 5, 9, and 11; Cycles 3-8: days 2, 4, 5, 8, 9, 12; Cycles ≥9: days 2, 8, 9, and 16) on weeks without Elo, and on weeks with Elo, Dex 8 mg PO and 8 mg IV is scheduled on the same day as Elo. Treatment will continue until disease progression, unacceptable toxicity, or withdrawal of consent. Patients refractory or intolerant to Bort will be excluded. Efficacy will be assessed on day 1 of each cycle by IMWG criteria. The primary endpoint is PFS. Secondary endpoints include ORR and PFS/ORR in pts with ≥1 FcγRIIIa V allele. As of February 1, 2012, 1 pt was enrolled. NCT01478048.
A single-arm, open-label, multicenter phase I/II study of the combination of panobinostat (pan) and carfilzomib (cfz) in patients (pts) with relapsed/refractory multiple myeloma (RR MM).
Authors: Berdeja Jesus G. , Mace Joseph , Lamar Ruth E. , Gian Victor , Murphy Patrick Brian , Patel Manish R. , Hart Lowell L. 
Published: March 2020

TPS8115 Background: Despite novel therapies, MM remains an incurable disease. Changes in histone modification are commonly found in human cancers including MM. Preclinical studies demonstrate synergistic anti-MM activity with histone deacetylase inhibitors (HDACi) and proteasome inhibitors (PI) through the dual inhibition of the proteasome and aggresome pathways. Pan is an oral pan-HDACi which has shown synergy with bortezomib in clinical studies. Cfz is a 2nd generation PI which has shown marked anti-MM activity with an improved safety profile. In this trial we evaluate the safety and efficacy of the combination of pan and cfz in pts with RR MM. Methods: This multi-center US study plans to enroll up to 52 adults with RR MM. The phase I study will determine the MTD of the combination of cfz and pan and follow a standard dose escalation design. Pan will be administered orally three times weekly during weeks 1 and 3 of each 28-day cycle (Days 1, 3, 5, 15, 17, 19) at a starting dose of 20 mg. Cfz will be administered intravenously on Days 1, 2, 8, 9, 15, and 16 of each 28-day cycle. Cfz starting dose will be 20mg on days 1,2 of cycle 1 with escalation to the corresponding dose level beginning at 27 mg , if well tolerated. Dose modifications will not be permitted during cycle 1 unless a pt experiences a DLT. A maximum of four dose levels will be evaluated. Approximately 24 pts will be enrolled during the phase I portion to establish the MTD. In the phase II portion of this study, pts with RR MM will receive treatment with the optimal dose of pan and cfz established during phase I. Pts will be assessed for response to treatment after each cycle (4 weeks). Pts with objective response or stable disease will continue treatment until disease progression or unacceptable toxicity occurs. The primary endpoint is to establish the optimal doses of cfz and pan that can be administered to pts with RR MM (phase I) and to evaluate the overall response rate (phase II). Secondary endpoints include time-to-progression, progression-free survival, overall survival and safety. Approximately 25 pts are planned for the phase II portion. Current status: As of 1/27/12 3 patients have been enrolled.
A phase I/II trial of BKM120 combined with vemurafenib (PLX4032) in BRAFV600E/k mutant advanced melanoma.
Authors: Kantor Andrea , Daud Adil , Munster Pamela N. , Ea Roth , Algazi Alain Patrick 
Published: March 2020

TPS8602 Background: Vemurafenib induces transient objective responses in half of BRAFV600E mutant melanoma patients and a median PFS of 5.3 months (NEJM. 2011;364:2507-2516). BRAF mutations are not sufficient to cause melanoma, but the combination of BRAFV600E mutation and PTEN loss is sufficient to recapitulate the malignant melanoma phenotype in vivo (Nat. Genet. 2009;41:544-552). PTEN loss and PI3K activation are common in BRAF mutant metastatic melanoma, and PI3K activation has been implicated as a cause acquired resistance to BRAF inhibitors (Cancer Cell. 2010;18:683-695). This phase I/II study is the first trial to test the safety and efficacy of combining a potent BRAF inhibitor, vemurafenib, with a potent PI3K inhibitor, BKM120, in patients with metastatic BRAF mutant melanoma. Methods: Design: Phase I patients receive a single dose of oral BKM120 (d -7) then vemurafenib twice daily with BKM120 daily (starting on c1d1). PK analysis is performed for BKM120 alone and for both drugs in combination. Doses of both drugs will be escalated in 3+3 scheme. Phase II patients receive continuous dosing of vemurafenib twice daily and BKM120 daily. Serial biopsies for PD and mRNA expression analyses are required for patients with visible or palpable tumors. Reimaging will be performed every 8 weeks.Eligibility: This study is enrolling BRAFV600E/K mutant metastatic melanoma patients with no prior exposure to BRAF inhibitors or PI3K inhibitors, ECOG PS ≥ 2 and adequate organ function. Endpoints: The primary endpoint for phase 1 is the recommended phase 2 dose of the combination. The primary endpoint for phase II is the 6 month PFS rate. Secondary endpoints include median PFS and OS. Baseline PTEN expression and changes is pS6 protein levels will be examined as predictors of efficacy, and changes in gene expression profiles will be assessed. Summary: This is the first trial examining the safety and efficacy of combined BRAF/PI3K inhibition in BRAF mutant melanoma patients.
Assessing clinical appropriateness on a population basis within a regional cancer network.
Authors: Casali Paolo Giovanni , Licitra Lisa F. , Bufalino Rosaria , Pizzo Fabrizio , Tricomi Marco , Bertulli Rossella , Torresani Michele , Beretta Giordano D. , Labianca Roberto , Siena Salvatore , Bersani Maurizio , Pierotti Marco 
Published: March 2020

TPS9155 Background: The Lombardia Cancer Network (ROL: “Rete Oncologica Lombarda”) connects all cancer resources of the Lombardia region, with 9,000,000-plus citizens, to improve quality of cancer care and patient data sharing. Assessment of appropriateness of cancer care on a population basis is an aim. Implementation of electronic records is partial and heterogeneous. However, clinical discharge reports for both inpatients and oupatients are released as “pdf” files onto a secure regional health care information system, accessible by physicians. Methods: ROL includes 58 oncology premises. Clinical practice guidelines are annually updated within this oncology community. For each solid cancer, guidelines enlist all main clinical presentations (“disease phases”), along with their “treatment options” (either “standard”, “individualized”, or “investigational”). ROL upgraded the existing non-structured electronic clinical discharge report into a field-based resource, with both free-text (17) and codified (25) fields. Two codified fields enlist, respectively, disease phases as per guidelines, and the corresponding treatment options. If they match, the strategic medical decision is considered tentatively “appropriate”. Even the report of a single encounter within a disease phase is enough to make this work. Results: Currently, the instrument is being incorporated stepwisely within the information systems of all oncology facilities, though a central web-based tool is also available. More than 36,000 reports were released in 2011. Appropriateness assessment proved feasible on a pilot set of patients. A research project is underway to detect causes of mistakes and mismatches, by automatically analyzing free-text fields. A training effort is ongoing to improve clinicians’ learning curve on semantics. Conclusions: To assess clinical appropriateness on a population basis in a large region, we exploited two key bottlenecks: 1) the electronic discharge report, within patient information flows, to cope with a variety of local information systems; 2) the disease phase, within the cancer-specific clinical decision-making process, to cope with a likely lack of reports from a substantial proportion of encounters.
A phase II study of dasatinib therapy in children and adolescents with newly diagnosed chronic phase chronic myelogenous leukemia (CML-CP) or Philadelphia chromosome-positive (Ph+) leukemias resistant or intolerant to imatinib.
Authors: Zwaan Michel , Stork Linda C. , Bertrand Yves , Gore Lia , Hijiya Nobuko , De Souza Carmino , de Martino Lee Maria Lucia , Bradley-Garelik M. Brigid , Kearns Pamela 
Published: March 2020

TPS9594 Background: Dasatinib is a BCR-ABL inhibitor approved for treatment in adult patients (pts) with newly diagnosed Ph+ CML-CP; CML resistant/intolerant to prior therapy, including imatinib; and Ph+ acute lymphoblastic leukemia (ALL). There are no established dasatinib treatment regimens for children/adolescents with relapsed/refractory leukemia, but pediatric trials are underway. A phase I dose-escalation study of dasatinib in pediatric pts with refractory solid tumors (n=28) and imatinib-refractory, Ph+ leukemia (n=11) reported a maximum tolerated dose of 85 mg/m2 twice daily in solid-tumor pts and at least a partial cytogenetic response (CyR) in all evaluable CML pts (n=9) (Aplenc, J Clin Oncol 2011). Preliminary results from a phase I dose-escalation study in pediatric pts with subtypes of relapsed/refractory leukemia (NCT00306202) indicate that dasatinib was well tolerated up to 120 mg/m2 (Zwaan, Blood 2010 [abstr 2265]). Further study of dasatinib in pediatric pts is warranted. Methods: To evaluate the safety and efficacy of dasatinib monotherapy in children/adolescents with newly diagnosed CML-CP or Ph+ leukemias resistant/intolerant to imatinib, a phase II nonrandomized, global study of dasatinib in pts birth to <18 y is ongoing (NCT00777036): Cohort 1 (C1), Ph+ CML-CP pts resistant/intolerant to imatinib; Cohort 2 (C2), Ph+ ALL, accelerated or blast phase CML pts resistant/intolerant to or relapsed after imatinib therapy; or Cohort 3 (C3), newly diagnosed, treatment-naïve Ph+ CML-CP pts. Treatments are once daily with dasatinib 60 mg/m2 (C1/C3) or 80 mg/m2 (C2) for ≥24 months. Primary endpoints are major CyR (C1), complete hematologic response (C2), and complete CyR (C3). Secondary endpoints include safety, tolerability, best response, time to/duration of response, survival, and molecular response rates. BCR-ABL mutations are evaluated. First patient first visit was March 2009; estimated trial completion is September 2016. As of January 2012, 63 pts (n=27 aged <12 y; n=36 aged ≥12 y) have been treated in C1/C2 (n=41) and C3 (n=22). Enrollment is ongoing at 79 sites.
Elevated risk of second malignant neoplasms in pediatric germ cell tumor patients.
Authors: Rodrigues Maria Clarissa de Faria Soares , Rodriguez-Galindo Carlos , Ribeiro Karina Braga , Frazier A. Lindsay 
Published: March 2020

10010 Background: The probability of cure is very high for children with germ cell tumors (GCT), but late effects from cisplatinum can be quite significant. In addition to the immediate effects of oto-, neuro and nephrotoxicity, data from men treated for testicular cancer shows that the rate of second malignant neoplasm (SMN) is doubled and that a man treated before age 20 has a 50% chance of SMN by age 75. This study was designed to assess the risk of SMN among individuals treated for malignant GCT during childhood. Methods: We included all patients 0-19 years old with a primary diagnosis of malignant GCT registered in the Surveillance, Epidemiology and End Results (SEER) in the period 1973-2008. We analyzed tumors occurring at least 12 months after the first primary. Standardized incidence ratios (SIR) and 95% confidence intervals (CI) were calculated using SEER Stat, version 8.0.1. Results: The cohort comprised 1997 patients (798 women and 1,199 men); 86.3% had primary gonadal tumors (91% in men and 79.5% in women). The median age at diagnosis of the primary malignancy was 17 years (17 for males ; 15 for females), and for second malignancies was 27 (27 for males; 30 for females). Fifty eight SMNs were observed (21 in females; 37 in males). Among women, higher risk was observed to developing breast cancer (n=5; SIR=1.29; 95% CI= 0.42-3.02), thyroid cancer (n=5; SIR= 3.40; 95% CI= 1.1-7.93) and brain cancer (n=3; SIR= 9.19; 95% CI=1.89-26.85). Twenty-seven out of 37 second primary tumors observed in men were contralateral testicular tumors, conferring a 16.2 fold higher risk of developing this neoplasm (95% CI= 10.67-23.58). When the analysis excluded testis as a second site, a higher risk was noted for the development of pancreatic cancer (SIR=19.06; 95% CI=2.31-68.83) and leukemia (SIR=3.55; 95% CI=0.43-12.81). Conclusions: Rates of SMN are elevated in both men and women treated as children for pediatric germ cell tumors. Men need to be made aware of risk in contralateral testicle. The rates of SMN may continue to rise with longer follow up. The attribution of treatment type to risk of SMNs is not possible due to the lack of this information in SEER database.
Impact of socioeconomic status on extent of disease at diagnosis and cancer and ocular outcomes in retinoblastoma: A population-based analysis.
Authors: Truong Bao , Green Adam L. , Friedrich-Medina Paola , Kamihara Junne , Frazier A. Lindsay , Ribeiro Karina Braga , Rodriguez-Galindo Carlos 
Published: March 2020

10011 Background: The strong correlation between early diagnosis and improved outcomes has been consistently reported for retinoblastoma; extent of disease and eye preservation are associated with delayed diagnosis. In this study, we aimed to analyze the impact of socioeconomic status (SES) and ethnicity on extent on disease and cancer and ocular outcomes. Methods: All retinoblastoma cases (0-9 years) recorded in 18 SEER registries between 2000-2009 were included. The county-based disparity variables analyzed included poverty level, education attainment, language isolation, crowding, and percentage of immigrants. The cut-off values were defined as the median values for the cohort of patients. We also analyzed the impact of gender, race, and ethnicity. We tested for the association between SES and ethnicity with the percentage of extraocular disease and enucleation. Relative survival was calculated using Ederer II method; estimates were compared using Z-score. Results: We identified 753 cases. Percentage of extraocular cases was consistently higher in US counties with low SES indicators: higher vs. lower poverty status (29.3% vs. 22.1%, p=0.028); lower vs. higher education attainment (30.6% vs. 22.7%, p=0.003); higher vs. lower crowding (33.2% vs. 18.1%, p<0.001); higher vs. lower language isolation (32.2% vs. 19.3%, p<0.001); higher vs. lower percentage of immigrants (30.1% vs. 21.4%, p=0.008). Hispanic patients had significantly higher percentage of extraocular disease (35.2% vs. 20.9%, p<0.001). Poor ocular outcomes, reflected by high percentage of enucleation, were associated with counties with low education attainment (p=0.025), and with Hispanic origin (p=0.019). Decreased survival was associated with language isolation (p=0.016), but not with Hispanic origin or other SES indicators. Conclusions: Our study highlights significant disparities in the care and outcome of children with retinoblastoma. A low SES negatively impacts extent of disease, presumably by limiting access to primary care and delaying diagnosis. Hispanic patients have more advanced disease and higher enucleation rates, although survival is not significantly different.
Metastatic neuroblastoma confined to distant lymph nodes (stage 4N) to predict outcome in patients with stage 4 disease: A study from the International Neuroblastoma (NB) Risk Group (INRG) Database.
Authors: Morgenstern Daniel Alexander , London Wendy B. , Stephens Derek , Volchenboum Samuel Louis , Hero Barabara , Di Cataldo Andrea , Nakagawara Akira , Shimada Hiroyuki , Ambros Peter F , Matthay Katherine K. , Cohn Susan Lerner , Pearson Andrew DJ , Irwin Meredith 
Published: March 2020

10015 Background: Patients with metastatic NB typically have a poor prognosis; however case series have suggested that those with 4N disease may have improved outcomes. Methods: Retrospective analysis of data from INRG database for patients diagnosed 1990–2002. 4N patients (INSS stage 4 disease confined to distant lymph nodes) were compared to the balance of stage 4 patients (‘non-4N’), excluding those with missing metastatic site data. 5-yr estimates of overall (OS) and event-free survival (EFS) were calculated ± standard error (Kaplan-Meier method). Patient characteristics were compared by Mann-Whitney or Fisher’s exact/Chi-square tests. Results: 2,250 INSS stage 4 patients with complete data were identified, of whom 146 (6%) had 4N disease. For 4N patients, EFS and OS (5-yr: 77% ± 4%, 85% ± 3%), were significantly better than EFS and OS (5-yr: 35% ± 1%, 42% ± 1%) for non-4N stage 4 patients (p<0.0001). 4N patients were more likely to be younger (median age at diagnosis 1.2 yr vs 2.5 yr for non-4N; p<0.0001) and have tumors with favourable International Neuroblastoma Pathologic Classification (INPC) (63% vs 26%, p<0.0001), differentiating grade (21% vs 8%, p=0.006), lower MKI (p=0.0011) and non-MYCN amplified tumors (89% vs 69%, p<0.0001). Within subgroups defined by age at diagnosis and MYCN status, 4N pattern of disease remained significantly associated with improved outcomes. For patients aged ≥547 days at diagnosis and MYCN non-amplified, 5-yr EFS for 4N patients (n=42) was 63% ± 8% vs 27% ± 2% for non-4N (n=785); OS 74% ± 7% vs 38% ± 2% (both p<0.0001). Within this subgroup, favourable INPC and differentiating grade remained more frequent in the 4N vs non-4N patients (45% vs 10%, p<0.0001; 45% vs 8%, p=0.0017, respectively). Conclusions: 4N represents a subgroup of metastatic patients with better outcome than other INSS stage 4 patients. These findings indicate that the biology and response to treatment of 4N tumors differs from other stage 4 tumors, and different therapies should be considered for this cohort. Future exploration of biological factors determining pattern of metastatic spread and response to therapy is warranted.