tbuckley/cabot-search huggingface dataset:
Medical oncology patient readmissions: Are they preventable?
Authors: Andrew S. Epstein, Christopher Crosbie, Steven Martin, Barbara Egan, Tabitha Goring, Douglas Koo, Chhavi Kumar, Cori Salvit, Marinela Capanu, Leonard Saltz
Journal: Journal of Clinical Oncology (2014)

6589 Background: As part of the Affordable Care Act, Centers for Medicare and Medicaid Services has initiated programs for certain non-cancer index admissions aimed to improve patient care and reduce costs, via preventing readmissions (defined as an admission within 30 days of a discharge). Readmissions for cancer patients have not been extensively evaluated, and might or might not be reasonably preventable. We therefore examined readmissions of patients on an inpatient service of a comprehensive cancer center. Methods: An institutional electronic database was queried to identify patients with a readmission and for demographics and other data related to the readmissions of patients to the Gastrointestinal (GI) Oncology service of Memorial Sloan Kettering Cancer Center (MSKCC). Of these, 50 patients were randomly selected for manual review to assess reasons for index admission and readmission, nature of index admission discharge plan, and whether readmission was preventable (defined pre-study as likely preventable by either prolongation of the index admission or a foreseeable, and accomplishable change in an agreed upon index admission discharge plan). Results: Between September 1, 2008 and March 1, 2013, 3,995 patients with GI cancers had an index admission to the MSKCC GI Oncology Service, of whom 876 (22%) had at least one readmission. Index admission discharge plans for these 876 index admissions were as follows: home without supportive services (64%), home with supportive services (32%), rehab facility (2%), home hospice (1%), or long term care facility (1%). From the 50 manually-reviewed cases, the most common diagnosis categories for either index admission or readmission were infection, pain, or GI issues. For each readmission, the diagnosis was different from the index admission diagnosis in 64% of the cases. Disagreement between the care team and patient/family about index admission discharge plan was documented in 10% of cases. One case (2%) was preventable. Conclusions: Readmissions in this population are common and reflect high disease burden. Our data suggest that readmissions in the population studied do not overall represent lapses in care or discharge management during the index admission and are not reasonably preventable.
Encouraging patients to see GP doesn’t increase early dementia diagnoses
Authors: Susan Mayor
Journal: BMJ (2017)

Sending patients information about seeking advice for potential memory problems increased GP consultations but did not change GP referrals to memory services or lead to earlier diagnosis of dementia, a randomised trial in general practice has shown.

Many people with dementia are diagnosed late in the illness, reducing their capacity to plan for the future or receive symptomatic treatment. Researchers investigated whether sending older people a personal letter from their GP with …
Human epidermal growth receptor-2 overexpressing early operable primary breast cancers in older (≥70 years) women: Biology and clinical outcome in comparison with younger (&lt;70 years) patients.
Authors: Binafsha Manzoor Syed, Andrew R. Green, Dal Morgan, Ian O. Ellis, Kwok-Leung Cheung
Journal: Journal of Clinical Oncology (2013)

e11608 Background: There is dearth of literature reporting the prevalence and biological characteristics as well as the long-term clinical outcome of HER2 positive tumors in older women. This study aimed to analyse their biological characteristics and compare them with their younger counterparts from a single centre with long-term clinical follow-up. Methods: Over 37 years (1973-2010), 1,758 older (≥70 years) women with early operable (&lt;5cm) primary breast cancer were managed in a dedicated clinic and have complete clinical information available. Of these 813 patients underwent primary surgery and 575 had good quality tumour samples available for tissue microarray (TMA) analysis using immunohistochemistry. Comparison was made with data from a well-characterised younger (&lt;70years) series (N=1,711) treated between1986 - 1998 (before adjuvant trastuzumab became standard) in our institution. Thirty-nine (7.6%) and 140 (8.2%) patients from the older and younger series respectively (p=0.56) had HER2-positive tumours. Results: See Table. Conclusions: The HER2 positive tumours in older women showed relatively less aggressive phenotype and did not show any inferior long-term clinical outcome despite not having received chemotherapy as compared to the younger patients. The precise role of different adjuvant systemic therapies in this population needs to be delineated. [Table: see text]
Tolerability of the Intergroup 0099 regimen in locally advanced nasopharyngeal cancer with a focus on patients' nutritional status
Authors: M. Bahl, L. L. Siu, G. R. Pond, J. Kim, I. F. Tannock, A. Bayley, B. Cummings, J. Waldron, J. Ringash, B. O'Sullivan
Journal: Journal of Clinical Oncology (2004)

5572 Background: By showing a survival benefit over radiation alone, the INT 0099 trial of concurrent chemoradiotherapy for locally advanced nasopharyngeal cancer (NPC) set a new standard of practice. This retrospective review documents our institutional experience with this regimen in terms of treatment tolerability, compliance, and weight changes. We also evaluated the impact of feeding tubes on weight recovery. Methods: All NPC patients treated between 01/1998 and 12/2002 with the INT 0099 regimen at our institution were identified. Information on treatment compliance, toxicity, weight change and feeding tube use was recorded. Patients were grouped by therapy completion status and by feeding tube status (prophylactic, therapeutic or none received). Results: Of 78 consecutive patients, 75 were evaluable. Compliance with radiotherapy was excellent with all but 2 patients completing full dose on schedule. Only 43% of patients received all three cycles of concurrent Cisplatin and 33% received the intended dose intensity without modification. Sixty-one percent of patients received all three cycles of adjuvant chemotherapy. Patients who successfully completed therapy had a higher average baseline weight and were more likely to have had a feeding tube inserted prophylactically. The 35 patients who did not receive a feeding tube had the least drop in weight and recovered to 92.1% of baseline at one year. Amongst the 2 groups with feeding tubes, those with prophylactic insertion (n=23) had a more gradual drop in weight, and recovered to a greater degree at one year (93.6%), versus those with a feeding tube inserted therapeutically during treatment (n=17) who recovered to 87.2% of baseline weight at one year. Feeding tubes were well tolerated in most patients. Conclusions: The INT 0099 regimen was generally delivered with modifications to the chemotherapy component, as in the original trial. The prophylactic insertion of a feeding tube may facilitate therapy completion and weight recovery in some patients. No significant financial relationships to disclose.
Targeting EGFR and ERBB3 in lung cancer patients: Clinical outcomes in a phase I trial of MM-121 in combination with erlotinib.
Authors: Lecia V. Sequist, Manuel R. Modiano, Olivier Rixe, David Michael Jackman, Karen Andreas, Joseph Pearlberg, Victor M. Moyo, Wael A. Harb
Journal: Journal of Clinical Oncology (2012)

7556 Background: Erlotinib is effective in NSCLCs with wild-type EGFR and shows enhanced benefit in EGFR mutation-positive cancers. However, resistance invariably develops, often involving persistent ErbB3 signaling and activation of the PI3K/AKT survival pathway. We present the full results of the Phase 1 study evaluating the safety and tolerability of erlotinib plus MM-121 a fully human IgG2 monoclonal antibody (mAb) to ErbB3. Methods: Eligible patients had advanced stage NSCLC, and ECOG 0-2. Seven cohorts were enrolled, evaluating varying levels of the MM-121 and erlotinib, as well as alternate MM-121 infusion schedules. Tumor response was assessed every 8 weeks. Dose levels were determined by safety and pharmacokinetic (PK) data, and immunogenicity, efficacy endpoints and exploratory biomarker evaluations were performed. Results: From February 2010 – July 2011 32pts entered the study (median age 63y; 45% male; 18% ECOG 0, 82% ECOG 1. 56% had adenocarcinoma and 30% pts received 3 or more lines of prior therapies (range 0-7) with 91% having had prior platinum. 65% had wild-type EGFR status and were never treated or never responded to EGFR-TKIs (EGFRwt) and 28% had acquired resistance to erlotinib treatment (EGFRresist). The most common toxicities (any grade) observed were diarrhea (82%), rash (64%), and fatigue (64%). DLTs observed in different cohorts were diarrhea, mucositis, rash and failure to thrive. Clinical activity was observed including 1 PR (an EGFR TKI naïve EGFR mutant) and 14 SD. Average duration of disease stabilization was 21.6 wks (range 7.1 -89.3 wks). Median PFS is 8.1 weeks and the 16 week PFS rate was 41% in the overall population. For EGFRwt and EGFRresist pts the median PFS were 7.7 weeks and 15.1 weeks, and the 16 week PFS rates were 32% and 44%, respectively. 7/20 EGFRwt pts and 5/9 EGFRresist pts achieved SD. Conclusions: This study suggests that the combination of erlotinib and MM-121 has an acceptable safety profile in heavily pre-treated NSCLC patients with and without EGFR mutations. Early signals of patient benefit were seen and a large randomized phase II study is ongoing.
First interim exploratory analysis of immune response in patients with advanced non-small cell lung cancer receiving viagenpumatucel-l (HS-110) in combination with low-dose cyclophosphamide in an ongoing phase II trial.
Authors: Roger B. Cohen, Daniel Morgensztern, William Vincent Walsh, Lyudmila Bazhenova, Anton M. Melnyk, J. Thaddeus Beck, John J. Nemunaitis, Taylor Houghton Schreiber, Melissa Leigh Price
Journal: Journal of Clinical Oncology (2015)

3077 Background: Viagenpumatucel-L (HS-110), consists of an allogeneic NSCLC cell line, selected for high expression of a series of tumor antigens shared by NSCLC patients, which has been stably transfected with gp96-Ig. Cell-secreted gp96-Ig then delivers these cell-derived antigens directly to a patient's own antigen presenting cells, and shuttles those antigens to MHC-I via the cross-presentation pathway, leading to the preferential trafficking to MHC-I and exclusive activation of CD8+ cytotoxic T cells with limited or no activation of CD4+ helper T cells. Viagenpumatucel-L is currently being evaluated in a randomized phase II trial in combination with low-dose cyclophosphamide versus physician's choice chemotherapy. Methods: In support of the first planned exploratory analysis in this trial, the peripheral blood immune response was evaluated for the initial cohort of patients randomized to the treatment arm and treated for at least 9 weeks of therapy. Peripheral blood mononuclear cells were evaluated by flow cytometry for detection of circulating leukocyte subsets, regulatory T cells, myeloid derived suppressor cells, activated T cells and expression of immune checkpoint molecules on T cells. Cytokine and chemokine arrays from patient serum samples were also evaluated. Results: The combination of viagenpumatucel-L and low-dose cyclophosphamide was well tolerated in this first cohort of patients. Increased PD-1, Tim-3 and Ki67 was observed on CD8+ T cells isolated from peripheral blood over the treatment period, which may indicate CD8+ T cell activation and proliferation in response to HS-110. Conclusions: If these trends are observed in the full cohort of patients, the data may provide mechanistic evidence of HS-110 and support combination therapy with anti-PD-1/L1 antibodies. Clinical trial information: NCT02117024.
Total pathologic complete response (tpCR) and event-free survival (EFS) with subcutaneous (SC) or intravenous (IV) trastuzumab in HER2-positive early breast cancer (EBC).
Authors: Christian Jackisch, Roberto Hegg, Daniil Stroyakovskiy, Jin Seok Ahn, Bohuslav Melichar, Shin-Cheh Chen, Aulde Crepelle-Flechais, Dominik Heinzmann, Mona Shing, Xavier B. Pivot
Journal: Journal of Clinical Oncology (2015)

585 Background: HannaH (NCT00950300) compared SC and IV trastuzumab (Herceptin SC [H SC] and IV [H IV]) as neoadjuvant–adjuvant therapy for HER2-positive EBC; the co-primary endpoints, pCR and serum trough concentration, were non-inferior between H SC and H IV. Prior studies have indicated that pCR is reasonably likely to predict for long-term efficacy outcomes in patients (pts) with EBC, and tpCR (absence of invasive neoplastic cells in ipsilateral lymph nodes and the breast) is considered more likely to be predictive than pCR. Methods: HannaH is a phase III, open-label, multicenter, randomized trial. Pts received 4 cycles of neoadjuvant docetaxel followed by 4 cycles of 5-fluorouracil/epirubicin/cyclophosphamide administered concurrently with 3-weekly H SC (600 mg fixed dose) or H IV (8 mg/kg loading, 6 mg/kg maintenance doses). Post-surgery, pts received 10 cycles of adjuvant H SC or H IV to complete 1 year of therapy. In an exploratory analysis, we used Cox regression to assess the correlation between the secondary endpoints tpCR and EFS (time from randomization to local, regional, or distant recurrence, contralateral breast cancer, or death). EFS rates per subgroup were estimated using the Kaplan–Meier (K–M) method. Results: In all, 297 pts were randomized to the H SC arm and 299 to the H IV arm; intent-to-treat (ITT) populations were 294 and 297 pts, respectively. At 40 months’ median follow-up, Cox regression indicated that pts in the ITT population who achieved tpCR had a reduced risk of an EFS event compared with those who did not: H SC arm hazard ratio (HR) = 0.38 (95% CI, 0.22–0.65); H IV arm HR = 0.32 (95% CI, 0.18–0.60). Results were similar between arms: treatment-tpCR interaction P = 0.67. Three-year EFS rates according to tpCR are shown in the Table. Results were consistent for pCR and the efficacy per protocol population. Conclusions: In each of HannaH’s two treatment arms, H SC or H IV, tpCR correlated with improved long-term efficacy outcomes (EFS) in pts who received neoadjuvant–adjuvant therapy for HER2-positive EBC. Clinical trial information: NCT00950300. H SC n = 294 H IV n = 297 tpCR n = 108 No tpCR n = 186 tpCR n = 94 No tpCR n = 203 K–M 3-year EFS rate, % 88 69 87 67 95% CI 82–94 62–76 80–94 61–74
Posttransplant maintenance therapy in multiple myeloma: the changing landscape
Authors: S Sengsayadeth, F Malard, B N Savani, L Garderet, M Mohty
Journal: Blood Cancer Journal (2017)

Abstract Transplant-eligible patients with multiple myeloma (MM) now have extended survival after diagnosis owing to effective modern treatment strategies that include new agents in induction therapy, autologous stem cell transplant (ASCT), consolidation therapy and posttransplant maintenance therapy. Standard of care for newly diagnosed, fit patients includes ASCT and, often nowadays, posttransplant maintenance. Several large studies have shown the efficacy of maintenance with thalidomide, lenalidomide and bortezomib in the treatment scheme of MM with regards to prolonging progression-free survival and, to a lesser degree, overall survival. Herein we discuss the data currently available to support the use of maintenance therapy in patients after ASCT as well as the newer available agents that may be a part of its changing landscape in the years to come.
<i>EGFR</i> status and daily dose: Effect on tumor growth inhibition in cancer patients treated with dacomitinib (PF-00299804).
Authors: Ana Ruiz-Garcia, Pasi A. Janne, Keunchil Park, Nobuyuki Yamamoto, Nagdeep Giri, Carlo Bello, Joseph P. O'Connell
Journal: Journal of Clinical Oncology (2012)

e18093 Background: Dacomitinib (D) is a highly selective, irreversible small molecule pan-human epidermal growth factor (EGFR/HER) inhibitor. The effect of mean D daily dose (exposure) on tumor growth dynamics was analyzed using a longitudinal exposure-response tumor growth inhibition model. Methods: Estimated parameters included tumor shrinkage rate (K D ), which changes over time as resistance to therapy develops according to an exponential decay function where λ = slope of the dynamic shrinkage rate change; and tumor growth rate constant (K L ). eDose, the effect of mean D daily dose changes on tumor shrinkage rate, was tested in the base model to establish the best relationship between tumor shrinkage and drug exposure. Model parameters were estimated using a population (pop) approach. Pop pharmacodynamic analyses included data from 4 clinical trials (3 phase I and 1 phase II) of D (15–45 mg QD) in patients (pts) with advanced solid tumors. Multiple tumor size (SLD) measurements were collected from each pt. Data analysis used nonlinear mixed effects modeling (NONMEM, v 7.1.2). After visual inspection of relationships between covariates (weight, age, creatinine clearance, bilirubin, ALT, baseline ECOG PS, race, sex, EGFR status) and individual parameter estimates of K D ; subpopulation analysis was carried out in pts with confirmed EGFR status (mutation [mu] or wild type [WT]) to quantify the potential effect of EGFR status on K D . Results: SLD values over time were collected from 200 pts (47% male). For a typical pt, K L = 0.63 year -1 ; K D = 1.6 year -1 ; developed therapy resistance over time (λ) = 13.7 year -1 ; and eDose = 0.45. Drug-specific parameters affecting tumor shrinkage (K D , λ, eDose) and the disease-specific K L were well estimated with low relative standard errors. Visual inspection of relationships between covariates and individual parameter estimates showed a higher shrinkage rate (K D ) for pts with EGFR mu vs those with WT EGFR. Conclusions: D mean daily dose affected tumor growth dynamics. Tumor shrinkage rate at an averaged daily dose below 45 mg QD was lower vs 45 mg QD. EGFR status was a significant covariate affecting tumor shrinkage rate (83% less shrinkage in pts with EGFR WT vs. pts with EGFR mut).
Whole blood mRNA expression for prognosis of metastatic clear cell renal carcinoma (mCCRCC).
Authors: Karthik Giridhar, David W. Hillman, Carlos Sosa, Candace Lee Dalpiaz, Brian Addis Costello, Fernando Quevedo, Henry C. Pitot, Roxana Stefania Dronca, Donna Ertz, John C. Cheville, Krishna Donkena, Manish Kohli
Journal: Journal of Clinical Oncology (2017)

500 Background: The Memorial Sloan Kettering Cancer Center (MSKCC) prognostic score is based on clinical parameters and has several limitations. We analyzed whole blood mRNA expression in mCCRCC patients (pts) and compared it to MSKCC for predicting overall survival (OS). Methods: A prospective collection of whole blood in PAXgene RNA tubes from mCCRCC pts was performed between 2011 and 2015 with uniform processing. A discovery set (DS) of 19 randomly selected pt samples was used to generate whole transcriptome RNA sequencing and signatures describing differential gene expression patterns associated with OS. We calculated the fragment per kilobase of transcript per million (FPKM) of each transcript and gene to identify correlations between the differentially expressed genes and MSKCC score. Candidate genes were selected based on statistical significance (p&lt;0.05) and associations with OS. In an independent validation set (VS) of 47 pts with mCCRCC, we used the nCounter Analysis System (NanoString Technologies, Seattle, WA, USA) to quantify gene transcript expression selected from the DS. Cox regression and Kaplan-Meier analysis were used for association of candidate mRNAs in the VS with OS (time of metastatic recurrence to death or last follow-up). We compared our gene signature to the MSKCC prognostic score for poor versus good survival. Results: In the DS, at a median follow-up of 4.13 years (yrs) (range: 1.3-4.5), 11 patients had died. We identified eighteen genes in the DS with statistically significant differential gene expression patterns and ability to discriminate patient OS. In the VS at a median follow-up of 4.9 yrs (range: 0.1-11.3), twenty-five patients had died. We confirmed two of the eighteen selected genes that had strong prognostic significance: BAG1 [hazard ratio (HR) 0.31, p=0.007] and NOP56 [HR 0.28, p=0.004]. Comparing OS between good and poor outcome groups for these 2 scores, our two-gene panel had higher prognostic ability (HR 20.07, p &lt;0.0001) than the MSKCC prognostic score (HR 3.19, p 0.04). Conclusions: Prognostic value of using whole blood mRNA gene profiling in mCCRCC is feasible and should be prospectively confirmed in larger studies.
Safety interim data from a three-arm phase II study evaluating safety and pharmacokinetics of the oral transforming growth factor-beta (TGF-ß) receptor I kinase inhibitor LY2157299 monohydrate in patients with glioblastoma at first progression.
Authors: Antoine F Carpentier, Alba Ariela Brandes, Santosh Kesari, Juan Manuel Sepúlveda, Helen Wheeler, Oliver L. Chinot, Lawrence Cher, Joachim Peter Steinbach, Pol M. Specenier, Ann Cleverly, Irene Tomlin, Durisala Desaiah, Michael M. F. Lahn, Wolfgang Wick
Journal: Journal of Clinical Oncology (2013)

2061 Background: Based on preclinical data suggesting an additive antitumor effect of a TGF-ß inhibitor and lomustine, a phase II study was initiated to evaluate the activity of this combination in patients with glioblastoma after first progression. We here report are the safety and PK interim data. Methods: Lomustine was given every 6 weeks as approved, starting on day 7 of cycle 1. LY2157299 (300 mg/day) was administered as intermittent dosing (each cycle = 14 days on followed by 14 days off). Patients received lomustine with either LY2157299 or placebo thereby blinding for LY2157299, while patients receiving LY2157299 alone were unblinded (randomization 2:1:1). Toxicity was assessed using CTCAE, version 4.0. Results: After 31 patients had completed at least 1 cycle (28 days, 3 weeks of lomustine), 50 patients had received at least 1 dose of study drug (LY2157299 or lomustine). Aggregate safety data of the 31 patients are provided: 1 patient died on treatment due to multi-organ failure, not considered related to study treatment. At least 3 patients had the following TEAEs with severity, of grade 3 or 4, and drug relatedness (DR, specific drug not indicated): vomiting (n = 5, 4 DR), fatigue (n = 5, 3 DR,1gr 3), dysphasia (n = 4,1 gr 3), other nervous system disorder (n = 4, 3 gr 3), constipation (n = 3), nausea (n = 3, 3 DR), confusion (n = 3, 1 gr 3). Other grade 3/4 TEAEs observed were: abdominal pain, allergic reaction (DR), fall, syncope, pain, lymphocytes, ANC and thrombocytopenia (all DR) and alanine aminotransferase – in 1patient each. No difference in the LY2157299 concentrations between LY2157299 monotherapy and combination arms was observed. Conclusions: The combination of lomustine with LY2157299 or placebo is consistent with the known profile of lomustine with no unexpected clusters of adverse events and similar to a previous phase I study (Azaro et al. abstract 2042, J Clin Oncol. 30, 2012). The phase II study continues after the first interim assessment on safety. Clinical trial information: NCT01582269.