tbuckley/cabot-search huggingface dataset:
Long term impact of hyperleukocytosis in newly diagnosed acute myeloid leukemia patients undergoing allogeneic stem cell transplantation: An analysis from the acute leukemia working party of the EBMT
Authors: Jonathan Canaani, Myriam Labopin, Gerard Socié, Anne Nihtinen, Anne Huynh, Jan Cornelissen, Eric Deconinck, Tobias Gedde‐Dahl, Edouard Forcade, Patrice Chevallier, Jean H. Bourhis, Didier Blaise, Mohamad Mohty, Arnon Nagler
Journal: American Journal of Hematology (2017)

Up to 20% of acute myeloid leukemia (AML) patients present initially with hyperleukocytosis, placing them at increased risk for early mortality during induction. Yet, it is unknown whether hyperleukocytosis still retains prognostic value for AML patients undergoing hematopoietic stem cell transplantation (HSCT). Furthermore, it is unknown whether hyperleukocytosis holds prognostic significance when modern molecular markers such as FLT3-ITD and NPM1 are accounted for. To determine whether hyperleukocytosis is an independent prognostic factor influencing outcome in transplanted AML patients we performed a retrospective analysis using the registry of the acute leukemia working party of the European Society of Blood and Marrow Transplantation. A cohort of 357 patients with hyperleukocytosis (159 patients with white blood count [WBC] 50 K-100 K, 198 patients with WBC ≥ 100 K) was compared to 918 patients without hyperleukocytosis. Patients with hyperleukocytosis were younger, had an increased rate of favorable risk cytogenetics, and more likely to be FLT3 and NPM1 mutated. In multivariate analysis, hyperleukocytosis was independently associated with increased relapse incidence (hazard ratio [HR] of 1.55, 95% confidence interval [CI], 1.14-2.12; P = .004), decreased leukemia-free survival (HR of 1.38, 95% CI, 1.07-1.78; P = .013), and inferior overall survival (HR of 1.4, 95% CI, 1.07-1.84; P = .013). Hyperleukocytosis retains a significant prognostic role for AML patients undergoing HSCT.
Tumor mutation status of Hodgkin lymphoma survivors with secondary lung adenocarcinoma.
Authors: David Alan Bond, Gregory Alan Otterson, Neil Dunavin
Journal: Journal of Clinical Oncology (2013)

9600 Background: In a multi-institutional, retrospective study of 1976 patients treated for Hodgkin's lymphoma (HL) from 1969-2007, 55 patients developed second primary lung cancers a median of 19.5 years after treatment. Of these 55 cases, 32 were identified as lung adenocarcinoma (ACA). The development of targeted therapies in recent years has made the detection of specific genomic alterations important for disease prognosis and treatment in lung ACA. The prevalence of certain genomic alterations (EGFR, ALK, and KRAS) is highly correlated with smoking history. We hypothesize that the prevalence of genomic alterations also may differ in patients with a significant exposure to radiation. Methods: This observational retrospective case series includes 6 patients treated with mediastinal radiation for HL who subsequently developed lung ACA. All patients were treated at Ohio State University Wexner Medical Center. Patients were identified by searching billing diagnosis codes in the electronic medical record and by query of the physicians in the department of thoracic oncology at our institution. IRB approval was obtained. Results: The average age at diagnosis of HL was 25 years (range 18-46) and the average age at diagnosis of lung cancer was 58 (range 52-73). All patients were treated with radiation therapy; two patients were treated additionally with chemotherapy. None of the patients received HDT-ASCT. The average time from diagnosis of HL to diagnosis of lung cancer was 33 years. Of our six cases, 2 were positive for EGFR mutations and the other four were triple negative (-EGFR, -ALK, -KRAS). Three were never smokers, one had a 1.5 pack year history, and two had 10 pack year histories. Lung cancer stages at diagnosis were 1B (n=2), 2B (n=1), 3A (n=2), 4 (n=1). Conclusions: To our knowledge, this is the first report of mutational status of second primary lung ACA following radiation therapy for Hodgkin disease. Although the number of patients is small, the higher prevalence of the EGFR mutation in this sample suggests that ACA related to radiation therapy may have a similar mutational profile to that of never smokers. Further investigation is needed to define the disease characteristics of lung ACA in HL survivors.
High-dose (HD) irinotecan in patients with recurrent unresectable high-grade gliomas on glucoronidation-enhancing anticonvulsants (GEACs): A phase I/II study
Authors: R. V. Larocca, A. Cervera, J. B. Hargis, S. D. Glisson, G. H. Goldsmith, M. A. M. Laureano, B. Foreman
Journal: Journal of Clinical Oncology (2004)

1578 Background: Irinotecan is an antineoplastic agent with antitumor activity in patients with glioma. The primary objective of this study is to evaluate the objective response rate and time to progression for HD irinotecan in patients with recurrent high-grade gliomas who are concomitantly receiving GEACs. The secondary objective is to determine the optimal dosing of irinotecan on a q2wk schedule and evaluate dose-related toxicities in that setting. Methods:Patients with radiographic evidence of progressive high-grade astrocytic neoplasms receiving GEACs were enrolled in this prospective, nonrandomized trial: all had received prior chemotherapy (1–2 systemic chemotherapeutic regimens [n = 10] and Gliadel wafers [n = 3]). An initial cohort of 15 patients will be treated with irinotecan at a dose of 750 mg/m2 q3wk. Results: Eleven patients were enrolled from October 2001–October 2003: 64% were men and mean age was 45.6 years (range 32–70). Median ECOG performance status at baseline was 2 (range 0–2); 82% had glioblastoma multiforme and 18% anaplastic astrocytoma. To date, no patient achieved a partial or complete response by WHO criteria. Median time to progression of the entire cohort was 5 months. Seven patients had stable disease lasting ≥5 months. Two patients had stable disease lasting 10 months (glioblastoma multiforme) and 11 months (anaplastic astrocytoma), respectively. Four patients had disease progression within 3 months. Median survival of the entire cohort is 7 months. To date, no grade 4 toxicities have been observed (Table). Conclusions: HD irinotecan appears to be safe when combined with GEACs in this poor-prognosis patient group and has modest activity at the current dosing schedule. Once 15 patients have been enrolled, a q2wk schedule of irinotecan will be initiated in the phase I component of the study. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Pfizer Pfizer Pfizer Pharmacia Pfizer Pfizer
Everolimus in combination with paclitaxel and carboplatin in patients with advanced melanoma: A phase II trial of the Sarah Cannon Research Institute (SCRI).
Authors: Ralph J. Hauke, Jeffrey R. Infante, Kent C. Shih, Mark S. Rubin, Edward Arrowsmith, Robert C. Whorf, John D. Hainsworth
Journal: Journal of Clinical Oncology (2012)

8556 Background: The PI3k/AKT pathway is activated in most metastatic melanomas; mTOR is a critical component of this pathway. Everolimus, an mTOR inhibitor, has demonstrated single-agent activity in patients with advanced melanoma. We evaluated the efficacy and toxicity of everolimus in combination with paclitaxel/carboplatin in patients with advanced melanoma. Methods: Eligible patients had stage IV or unresectable stage III melanoma, unselected for braf status, previously untreated with chemotherapy or targeted agents. Previous immunotherapy was allowed. Additional eligibility criteria: ECOG PS 0 or 1; measurable disease; no active brain metastases; adequate bone marrow, kidney, and liver function; informed consent. All patients received paclitaxel 175mg/m 2 , 1-3 hour IV infusion, and carboplatin AUC 6.0 IV on day 1 of each 21-day cycle. Everolimus 5mg PO was given daily. Patients were evaluated for response every 6 weeks; treatment continued until progression or undue toxicity. Median progression-free survival (PFS) for paclitaxel/carboplatin treatment is 4 months; we looked for a median PFS of 6 months with this novel combination. Results: Seventy patients were treated between 2/2010 and 2/2011; median age 63, 90% had stage IV melanoma. 91% of patients received at least 2 cycles of therapy; median cycles received: 4 (range: 1-25+). Twelve patients (17%) had partial responses; an additional 42 patients (60%) had stable disease at first reevaluation. After a median 13 months of followup, the median PFS for the entire group was 4 months (95% CI: 2.8 – 5.0 months); 96% had progressed during the first 12 months. Median survival was 10 months (95% CI: 7.3 – 10.9 months). Toxicity was as previously described with these agents; neutropenia was the most common grade 3/4 toxicity (27%). Only 3 patients stopped treatment due to toxicity. Conclusions: The addition of everolimus to paclitaxel/carboplatin was feasible and well-tolerated; however, efficacy results were similar to those reported with paclitaxel/carboplatin alone. Further development of this combination regimen for treatment of metastatic melanoma is not recommended.
Quality of life assessment as a prognostic tool in breast cancer
Authors: R. Neelam, D. Gupta, D. Brikshavana, R. D. Levin, J. Granick, J. Grutsch, T. Wodek, C. G. Lis
Journal: Journal of Clinical Oncology (2004)

6122 Background: While the use of quality of life (QoL) assessments has been increasing in the clinical oncology community, few studies have examined the prognostic significance of QoL in breast cancer. To examine this issue, we investigated the association between baseline QoL and survival in breast cancer. Methods: A case series of 105 patients with stages I-IV breast cancer treated at Cancer Treatment Centers of America® at Midwestern Regional Medical Center between March 2001 and October 2003 were included in this study. QoL was evaluated using the EORTC QLQ-C30 (EORTC) and the Ferrans and Powers Quality of Life Index (QLI). Patients were dichotomized into two groups based on the median scores for all QoL domains. Kaplan Meier method was used to evaluate survival. Log-Rank test was used to study the equality of survival distributions across strata. Results: Patients with QLI health function scores above the median (17.65) had an overall median survival of 22.8 months, compared to those with scores below the median, 15.74 months (p = 0.004). Similarly, patients with global health EORTC scores above the median (58.33) had an overall median survival of 23.21 months compared to 11.57 months for those with scores below the median (p=0.002). Both associations retained statistical significance even after controlling for tumor stage (QLI health function, p = 0.003 and EORTC global health, p = 0.001). Conclusion: This study suggests that baseline QoL can provide useful prognostic information in breast cancer. Further studies should focus on more extensive evaluation of the prognostic significance of QoL in the cancer treatment setting. No significant financial relationships to disclose.
Prognostic value of DLL3 expression and clinicopathologic features in small cell bladder cancer (SCBC).
Authors: Vadim S. Koshkin, Paul Elson, Cristina Magi-Galluzzi, Jesse McKenney, Karen Streator Smith, Bonnie Shadrach, Hamid Emamekhoo, Kumiko Isse, Laura Saunders, Edward Kavalerchik, Scott Dylla, Sheila Bheddah, Noah Theiss, Sky Watson, Andrew J. Stephenson, Amr Farouk Fergany, Brian I. Rini, Jorge A. Garcia, Petros Grivas
Journal: Journal of Clinical Oncology (2017)

382 Background: SCBC is rare with limited data on treatment and outcomes. DLL3, a Notch pathway protein, is expressed in small cell lung cancer (SCLC) and neuroendocrine tumors. Phase I/II trials of the anti-DLL3 antibody-drug conjugate, rovalpituzumab tesirine, are ongoing in SCLC and other solid tumors. DLL3 expression in SCBC and its prognostic implications are unknown. Methods: A retrospective review of clinicopathologic features of 63 patients (pts) with biopsy-confirmed SCBC at Cleveland Clinic (1993-2016) was conducted. Percentage (%) of small cell component (SC%) was defined by independent pathology review in all pts. The % of tumor cells expressing DLL3 (DLL3%) was assessed in 53 pts. Multivariable analyses (MVA) were used to identify predictors of overall survival (OS), progression-free survival (PFS) and time to progression (TTP) (p ≤ .05). Results: Median age was 71 (39-90), 83% were men, 77% current/former smokers, 41 (65%) had cystectomy and 22 (35%) only TURBT. Estimated median OS, PFS and TTP were 22.8, 13.7 and 21.1 months from diagnosis. Median SC% was 100% (5-100%) and 79% of tumors were ≥ 50% SC. DLL3 expression of any level was noted in 68% (36/53) of tumors; 58% of tumors had DLL3 expression in &gt; 10% of cells. SC% correlated with DLL3% (r = 0.33, p = .01). In MVA, increased DLL3% was associated with shorter OS and PFS, while increased SC% was associated with shorter PFS and TTP. Higher pT at cystectomy was associated with shorter OS (Table). Conclusions: Higher DLL3 expression and SC% are associated with worse outcomes in SCBC. Most SCBC tumors express DLL3, a therapeutic target tested in clinical trials. Genomic, epigenetic, transcriptomic and PDL1 evaluation in SCBC are also being pursued to define molecular context. DLL3 expression and other prognostic factors. [Table: see text]
Phase I trial of daily PI3Kα inhibitor BYL719 plus letrozole (L) or exemestane (E) for patients (pts) with hormone receptor-positive (HR+) metastatic breast cancer (MBC).
Authors: Payal Deepak Shah, Shanu Modi, Farrah Mikhail Datko, Mary Ellen Moynahan, Stephen Zamora, Gabriella D'Andrea, Diana Lake, Shari Beth Goldfarb, Sujata Patil, Sharat Singh, Emma J. Langley, Phillip Sangwook Kim, Anne M. Covey, Betty Ann Caravella, Michael F. Berger, Mario E. Lacouture, Clifford A. Hudis, Jose Baselga, Sarat Chandarlapaty, Maura N. Dickler
Journal: Journal of Clinical Oncology (2014)

2605 Background: Hyperactivation of phosphatidylinositol 3-kinase (PI3K) signaling is implicated in endocrine therapy resistance. Addition of an α-selective PI3K inhibitor to hormonal therapy may be tolerable and beneficial in hormone resistant HR+ MBC. Methods: This 3+3 dose-escalation trial studied daily oral PI3K inhibitor (BYL719) added to standard dose aromatase inhibitor L (Arm A) or E (Arm B). Pts with HR+ MBC, any/no PIK3CA mutation, and on L/E were eligible. A cycle (C) was 28 days. Endpoints were dose-limiting toxicity (DLT), tolerability (CTCAE 4.0), and efficacy (RECIST v1.1). Paired tumor biopsies were performed for genomic and proteomic correlatives. Results: 14 pts (median (M) age: 55 (30-69) yrs), 7 per arm, received a M of 2 (<1-7) cycles. All were evaluable for toxicity. PIK3CA status was mutant/wild-type/unknown in 8/5/1 pts. M number of prior MBC therapies was 2 (1-12) in Arm A and 6 (2-14) in Arm B. BYL719 was given at 2 dose levels (DL0, 300mg; DL-1, 250mg). Both arms had similar toxicities. DLTs were maculopapular rash (N=2), hyperglycemia (N=2), and abdominal pain (N=1). Toxicity required dose de-escalation (4pts) and study discontinuation (2 pts). Treatment-related events included: G2 mucositis (21%), hyperglycemia (14%), dyspepsia (14%), fatigue (14%); G3 maculopapular rash (50%; 6/7 cases occurred on days 10-14 of C1; skin biopsies showed non-specific inflammation), hyperglycemia (7%) and abdominal pain (7%). There were no G≥4 treatment-related events. Of 9 pts evaluated for efficacy, 8 week best response was SD in 5 pts (included 1 pt with -29%, 1 with -19%) and PR in 1 pt with heavily pre-treated (including prior L) PIK3CA-mutated MBC to liver (C5+ on Arm A after initial DLT). Conclusions: Continuously dosed BYL719 with L or E shows promising antitumor activity in this hormone-refractory population. Early onset maculopapular rash results in frequent dose de-escalations. We are now exploring the addition of supportive dermatologic measures and non-continuous BYL719 dosing schedules. Examination of pharmacodynamic markers of PI3K inhibition and tumor genotype is ongoing. Further safety and efficacy data will be presented. Clinical trial information: NCT01870505.
A pilot trial of hu14.18-IL2 in patients with completely resectable recurrent stage III or stage IV melanoma.
Authors: Mark R. Albertini, Erik Ranheim, Jacquelyn A Hank, Cindy Zuleger, Thomas McFarland, Jennifer Collins, Erin Clements, Sharon M. Weber, Tracey Weigel, Heather B. Neuman, Gregory K Hartig, David Mahvi, MaryBeth Henry, Jacek Gan, Richard Yang, KyungMann Kim, Stephen Gillies, Paul M. Sondel
Journal: Journal of Clinical Oncology (2014)

9044 Background: Phase I testing of the hu14.18-IL2 immunocytokine (IC), a mAb reactive with GD2 disialoganglioside, linked to IL2, in patients (pts) with melanoma showed immune activation, reversible toxicities, and a maximal tolerated dose of 7.5 mg/m2/day. Preclinical data in IC-treated tumor bearing mice with low tumor burden documents striking antitumor effects. Thus, we studied IC in melanoma pts in remission but at high risk for recurrence. Methods: Pts with completely resectable recurrent stage III or stage IV melanoma were scheduled to receive 3 cycles of IC at 6 mg/m2/d IV over 4 hours on days 1, 2 and 3 of each 28-day cycle. Pts were randomized to surgical resection of all sites of disease either following (Group A) or prior to (Group B) IC cycle 1. Primary objectives were to evaluate histological evidence of IC anti-tumor activity, time to recurrence, and overall survival (OS). Results: Twenty melanoma pts (11 recurrent stage III, 8 stage IV, one unknown primary) were randomized to Group A (11 pts) or B (9 pts). Two Group B pts did not receive IC due to persistent disease following surgery. Seven of 18 IC-treated pts remain free of recurrence, with median recurrence-free survival of 5.8 months (95% confidence interval: 2.3 months, not yet reached). Eleven of 18 IC-treated pts are still alive (median follow-up of surviving pts: 34.6 months (range: 19.8-47.5 months)). Toxicities were similar to those previously reported for IC. Immunohistologic evaluations of resected tumors showed variable inflammation and tumor necrosis between pts and no clear differences between Groups A and B. Predominant inflammatory cells were CD3+ T cells and CD163/CD68+ macrophages. Twelve pts had evaluable tumor samples for GD2 analysis and 6/12 showed expression of GD2 on melanoma cells (high (2 pts); low/moderate (4 pts); and undetectable (6 pts)). There was no correlation between GD2 expression (positive vs negative) and time to recurrence (logrank p-value=0.572). Conclusions: Prolonged tumor-free survival was seen in melanoma pts at high risk for recurrence who were treated with IC. GD2 expression was detected in 50% of pts. The immunological activation by IC with manageable toxicities suggests potential for combination treatments. Clinical trial information: nct00590824.
Meta-analysis of hematologic toxicities in patients with solid tumors treated with everolimus.
Authors: Tomohiro Funakoshi, Asma Latif, Matt D. Galsky
Journal: Journal of Clinical Oncology (2013)

e15580 Background: Everolimus is an orally administered targeted agent that inhibits mammalian target of rapamycin (mTOR) signaling involved in tumor growth and proliferation. Hematologic toxicities associated with everolimus have been reported with a substantial variation in the incidences among clinical studies without a systematic attempt to synthesize these data. We performed a systemic review and meta-analysis of published clinical trials to evaluate the overall risk of everolimus-related hematologic toxicities. Methods: We searched Medline and the American Society of Clinical Oncology online database of meeting abstracts up to December 2012 for relevant clinical trials. Eligible studies included phase II and III trials in patients with solid tumors treated with everolimus that reported adequate safety data profile reporting neutropenia, thrombocytopenia or anemia based on the CTCAE of the NCI. The relative risk (RR), summary incidence and 95% confidence intervals (CI) were calculated. Results: For the incidence analysis, we included a total of 1,090 patients from 14 studies (three phase III and 11phase II trials) considering only arms with everolimus as a single agent. The incidence of everolimus -associated all-grade and high-grade (Grade 3-4) hematologic toxicities were, respectively: neutropenia: 21.7% and 3.7%; thrombocytopenia: 36.0% and 4.7% and anemia: 61.2% and 4.4%. For the RR calculation, seven randomized trials with everolimus in only one of the arms in addition to similar therapy in both arms were available (five phase III and two phase II trials, representing 2,462 patients). Everolimus -treated patients had a significantly increased risk of all-grade neutropenia (RR = 2.24; 95% CI, 1.51–3.32), all-grade (RR = 9.19; 95% CI, 4.51–18.70) and high-grade (RR = 7.46; 95% CI, 2.58–21.61) thrombocytopenia and all-grade (RR = 1.58; 95% CI, 1.25–1.99) and high-grade (RR = 3.92; 95% CI, 1.46–10.52) anemia. RR of high-grade neutropenia was 1.40 (95% CI: 0.70-2.78; p=0.34). Conclusions: Everolimus is associated with a significant increase in the risk of developing all-grade and high-grade thrombocytopenia and anemia and all-grade neutropenia compared with control.
Ambulatory Hemodynamic Monitoring Reduces Heart Failure Hospitalizations in “Real-World” Clinical Practice
Authors: Akshay S. Desai, Arvind Bhimaraj, Rupinder Bharmi, Rita Jermyn, Kunjan Bhatt, David Shavelle, Margaret M. Redfield, Robert Hull, Jamie Pelzel, Kevin Davis, Nirav Dalal, Philip B. Adamson, J. Thomas Heywood
Journal: Journal of the American College of Cardiology (2017)