tbuckley/cabot-search huggingface dataset:
Canadian cancer site-specific health utility values: Creating the basis for measuring value and costs of therapy.
Authors: Hiten Naik, Doris Howell, Xin Qiu, Catherine Brown, Ashlee Vennettilli, Margaret Irwin, Vivien Pat, Hannah Solomon, Tian Wang, Henrique Hon, Lawson Eng, Mary Mahler, Kyoko Tiessen, Henry Thai, Valerie Ho, Dan Pringle, Wei Xu, Soo Jin Seung, Nicole Mittmann, Geoffrey Liu
Journal: Journal of Clinical Oncology (2014)

7 Background: Health utility values (HUVs) play an integral role when conducting health economic analyses, but a paucity of reference HUVs exists for cancer patients. Using EQ-5D, we generated reference HUVs for multiple malignancies. We further assessed patient willingness to compete the instrument on a regular basis by adding the EQ-5D to an Ontario-wide patient-reported symptom tool mandated by Cancer Care Ontario, the provincial cancer government agency. Methods: 1,831 cancer patients across all non-CNS solid and hematologic cancer sites at the Princess Margaret Cancer Centre completed the EQ-5D instrument; a subset (n=618) were asked about the acceptability of regularly completing the EQ-5D. HUVs were calculated using Canadian valuations. Results: The mean±SD HUV for all patients was 0.81±0.15, but were significantly different across different disease sites (p&lt;0.0001): Testicular cancer, 0.87±0.13; prostate, 0.87±0.15; colorectal, 0.83±0.12; head/neck, 0.82±0.15; lymphoma, 0.82±0.15; breast, 0.81±0.17; esophageal, 0.81±0.16; ovarian, 0.79±0.15; leukemia, 0.78±0.15; lung, 0.78±0.13 and myeloma, 0.77±0.14. Confirming the validity of these HUVs, patients with PRO-ECOG scores of 0, 1, 2 and 3 had HUVs of 0.90±0.14, 0.77±0.11, 0.65±0.14 and 0.59±0.19, respectively (p&lt;0.0001). In patients with solid tumors, those with local disease had HUVs of 0.82±0.15; metastatic disease, 0.80±0.15; p=0.015. 88% of patients reported that the EQ-5D was easy to complete, 92% took less than 5 minutes, 89% were satisfied with its length and 86% were satisfied with the types of questions asked. Importantly, 92% reported that they would complete the EQ-5D, even if it was used solely for research purposes and 73% agreed with the notion of completing it regularly at their clinic visits. Conclusions: We present the first Canadian reference dataset of HUVs for common cancers; stage-and site-specific reference values will be presented at the meeting. Mean HUVs varied by disease site, performance status, and disease severity. Furthermore, a majority of patients surveyed were willing to complete the EQ-5D on a regular basis, suggesting that routine administration is feasible across Ontario.
Chemotherapy-induced neutropenia (neutro) association with survival in metastatic colorectal cancer (MCC): Schedule dependency.
Authors: P. F. Innominato, S. Giacchetti, R. Småland, C. N. J. Focan, C. Garufi, G. A. Bjarnason, S. Iacobelli, S. Tumolo, A. Karaboué, F. Levi
Journal: Journal of Clinical Oncology (2011)

e13024 Background: Circadian clocks control cellular proliferation and drug metabolism over 24 h. However, circadian chronomodulated chemotherapy with 5-fluorouracil, leucovorin and oxaliplatin (chronoFLO4) offered no survival benefit as compared to the non-time stipulated FOLFOX2 in an international randomized trial involving patients (pts) with previously untreated MCC (EORTC05963). We hypothesized that treatment near maximum tolerated dose could disrupt circadian clocks thus impairing the efficacy of chronoFLO4 but not of FOLFOX2. Methods: Pts with available data (N=556) were categorized into three subgroups according to the worst grade of neutropenia experienced during treatment. Distinct multivariate models with time-dependent covariates were constructed for each treatment schedule. Results: Neutropenia incidence (all grades) was 39% on chronoFLO4 and 67% on FOLFOX2 (p<0.0001), and G3-4 was 7% and 25%, respectively (p<0.0001). Neutropenia was more frequent in women than in men (FOLFOX2, p=0.003; chronoFLO4, p=0.04). Median survival was 20.7 months in patients with G3-4 neutropenia as compared to 12.5 months in neutropenia-free patients on FOLFOX2 (p<0.0001). Corresponding figures displayed an opposite trend on chronoFLO4, being 13.7 and 19.4 months respectively (p=0.36). Multivariate analysis confirmed that the occurrence of severe neutropenia independently predicted for a better overall survival on FOLFOX2 (HR=0.56; p=0.015). However, the trend was opposite on chronoFLO4 (HR=1.77; p=0.06) (p for interaction <0.0001). Conclusions: The prediction of a better survival in the neutropenic patients on FOLFOX2 supports the administration of conventional chemotherapy near maximum tolerated dose. The opposite trend shown here for chronoFLO4 supports the novel concept of jointly optimized hematologic tolerability and efficacy through circadian-timed therapy.
Phase III randomized, placebo-controlled trial of carboplatin (C) and paclitaxel (P) with/without veliparib (ABT-888) in HER2- <i>BRCA</i>-associated locally advanced or metastatic breast cancer (BC).
Authors: Shannon Leigh Huggins-Puhalla, Hyo S. Han, Véronique Diéras, Michael Friedlander, George Somlo, Banu Arun, Hans Wildiers, Bella Kaufman, Jean-Pierre M. Ayoub, Melissa Shah, David Burmedi, Qin Qin, Jane Qian, Vincent L. Giranda, Stacie Peacock Shepherd
Journal: Journal of Clinical Oncology (2015)

155 Background: BRCA-mutated tumors are more susceptible to platinum therapy and PARP inhibitors due to underlying defects in homologous recombination repair of DNA damage. In preclinical models the potent oral PARP1/2 inhibitor veliparib was shown to enhance sensitivity to C and to have single-agent activity in BRCA+ cell lines. Phase 1 trials suggest promising antitumor activity and acceptable toxicity of veliparib plus C/P in triple-negative BC (Puhalla et al. Cancer Res 2012;72:PD09-06) and single-agent activity of veliparib in BRCA+ BC (Somlo et al. J Clin Oncol 2014;32:abstr. 1021). This phase III trial assesses efficacy and toxicity of veliparib plus C/P vs C/P alone in patients with HER2− BRCA-associated locally advanced or metastatic BC (NCT02163694). Methods: Phase III randomized, double-blind, placebo-controlled, multicenter trial. Eligible patients (female or male; ≥ 18 years) have HER2−metastatic/locally advanced unresectable BC with (suspected) deleterious BRCA1/2 germline mutations and received 2 or fewer prior lines of DNA-damaging chemotherapy for metastatic BC. In addition, patients must have received ≤ 1 prior line of platinum therapy (any setting) without progression within 12 months of completing treatment. Patients are randomized 2:1 to C/P with veliparib or C/P with placebo, stratified by estrogen and/or progesterone receptor expression, prior platinum therapy, and central nervous system metastases. Veliparib (120 mg p.o. BID) or placebo will be given on Days −2 to 5, C (AUC 6 mg/mL/min i.v.) on Day 1, and P (80 mg/m 2 i.v.) on Days 1, 8, and 15 (21-day cycles). Treatment continues until unacceptable toxicity or progressive disease (PD). Patients in the placebo arm who discontinue due to PD are eligible for crossover to veliparib monotherapy. The primary objective is to assess if the addition of veliparib to C/P increases progression-free survival; additional objectives include evaluation of overall survival, clinical benefit rate, objective response rate, quality of life, and safety. Enrollment began in July 2014 with a planned sample size of 270 patients. Clinical trial information: NCT02163694.
Comparison of the efficacy of gemcitabine with capecitabine and gemcitabine with erlotinib combination chemotherapy in recurrent or advanced pancreatic cancer as first-line treatment: Single-center experience.
Authors: S. Chun, M. Lee, E. Jeon, H. An, T. Hong, Y. You, D. Kim, I. Lee
Journal: Journal of Clinical Oncology (2011)

329 Background: We compared the efficacy and toxicity of gemcitabine with capecitabine (GX), and gemcitabine with erlotinib (GT) chemotherapy for recurrent or advanced pancreatic cancer by retrospective analysis. Methods: Between October 2006 and June 2010, 44 patients with recurrent or advanced pancreatic cancer, diagnosed at Seoul St. Mary's hospital were enrolled. In GT group, gemcitabine 1000mg/m 2 was administered on days 1, 8, 15, 22, 29, 36, 43 followed by a 1-week rest in first treatment cycle (8 weeks), and then D1, 8, 15 followed by a 1-week rest. Erlotinib was taken orally at 150mg daily through the entire cycle. In GX group, gemcitabine 1000mg/m 2 was administered on days 1 and 8. Capecitabine was taken orally at 650mg/m 2 twice daily on day 1-14 of a 21-day cycle. Results: In 44 patients, 26 patients were treated with GT, and 18 patients treated with GX. The median age was 56.58 years in GT and 57.67 years in GX. Median number of cycle was 3.04 in GT and 3.57 in GX, and the dose reduction was significantly more common in GX than GT (50% vs. 19%, p=0.031). No complete response was achieved in either group. In GT, partial response and stable disease were achieved in 6 (23.1%) and 8 (30.8%) patients. In GX, partial response and stable disease were shown in 4 (22.2%) and 7 (38.9%) patients, respectively. No significant differences in two patients groups (p=0.442). GX had more favorable clinical outcome of the time to progression (6.1 months vs. 3.0 months, p=0.002) and the overall survival (11.13 months vs. 6.1 months, p=0.012) than GT. The most common grade 3 or 4 toxicity in GT and GX treatment were hematologic toxicity: anemia (8.3%:0%), neutropenia (34.6%:38.8%), thrombocytopenia (15.4%:11.1%). Grade 3 or 4 hand-foot-syndrome of GX was reported in only one patient. Conclusions: GX showed better time to progression and overall survival outcome than GT, but dose reduction was more common. Although there was no significant difference in response rate, and the less dose intensity, GX regimen may be more effective than GT in advanced pancreatic cancer. Further prospective, randomized trials would be warranted in large scale. No significant financial relationships to disclose.
Avelumab (MSB0010718C), an anti-PD-L1 antibody, as a third-line treatment in patients with advanced gastric or gastroesophageal junction cancer: A phase Ib JAVELIN Solid Tumor trial.
Authors: Do-Youn Oh, Albert C. Lockhart, Deborah Jean Lee Wong, Matthew Hiram Taylor, Marcis Bajars, Anja von Heydebreck, Markus H. Moehler, Howard Safran
Journal: Journal of Clinical Oncology (2016)

TPS188 Background: The programmed death-1 receptor (PD-1) and its ligand (PD-L1) are key therapeutic targets in the reactivation of the immune response against cancer. Avelumab* (MSB0010718C) is a fully human anti-PD-L1 IgG1 antibody being investigated in clinical trials. The phase Ib study (NCT01772004) is an open-label, parallel-group expansion trial in patients (pts) with locally advanced or metastatic (LA/M) solid tumors that includes a heavily pretreated cohort of pts with advanced gastric or gastroesophageal junction adenocarcinoma (GC/GEJ) to evaluate safety and efficacy of avelumab in the 3 rd -line setting. Prior to adding this 3 rd -line cohort, this trial had enrolled a separate cohort with advanced GC/GEJ who had received prior 1 st -line chemotherapy (Chung et al, ECC 2015). Methods: This trial cohort is enrolling pts with histologically confirmed unresectable LA/M GC/GEJ who have been previously treated with 1 st -line combination chemotherapy and 2 nd -line ramucirumab, alone or in combination, and whose disease has progressed during or after ramucirumab treatment. Pts who have received prior treatment with trastuzumab and pts with HER2+ status are allowed. Eligible pts also must have tumor archival material or fresh biopsy, an ECOG performance status of 0 or 1 at the time of trial entry, and disease with ≥ 1 measurable lesion according to RECIST 1.1. Exclusions include prior therapy with immune checkpoint drugs or history of autoimmune disease. Up to 150 eligible pts will receive avelumab at 10 mg/kg as an IV infusion Q2W. Treatment will continue until disease progression, unacceptable toxicity, or any criterion for withdrawal occurs. Primary endpoint is confirmed best overall response (RECIST 1.1) as adjudicated by an IERC. Secondary objectives include assessment of progression-free survival, overall survival, and immune-related efficacy assessments. Association between tumor PD-L1 expression and efficacy will be evaluated. Adverse events will be assessed and graded according to NCI-CTCAE v4.0. Tumor evaluation will be performed every 6 wks until progression. Enrollment in this cohort began in June 2015. *Proposed INN Clinical trial information: NCT01772004.
Mobile application of cognitive behavioral therapy for anxiety and advanced cancer.
Authors: James MacDonald, Nicole Amoyal, Lauren Nisotel, Giselle Katiria Perez, Lara Traeger, Jennifer S. Temel, William F. Pirl, Steven A. Safren, Joseph A. Greer
Journal: Journal of Clinical Oncology (2015)

220 Background: We previously demonstrated the efficacy of a brief, in-person cognitive behavioral therapy (CBT) program for alleviating anxiety in patients with advanced cancer. The aim of the current study was to adapt this program to an interactive, patient-centered mobile tablet application (CBT app) for self-delivery, ideally to enhance dissemination and patient access to the CBT intervention. Methods: Development of the CBT app proceeded in two phases. First, we enrolled five patients with advanced cancer and anxiety (HADS-Anxiety subscale score ≥ 8) to review a preliminary CBT app prototype and to provide qualitative feedback regarding intervention acceptability and utility. Using content analysis of the recorded data, we identified key themes in patient feedback and refined the CBT app content and design accordingly. Finally, a multidisciplinary team of clinical researchers (n=7) specializing in healthcare technology, psychiatry, and psychology conducted an extensive iterative review process to vet and finalize the CBT app intervention. Results: Patients reported that the CBT app content was comprehensible, easily navigated, and helpful in addressing a breadth of concerns relevant to patients with anxiety and advanced cancer. Specifically, patients reported that case examples, tailored feedback, accessible interactive features, and content summaries were important for engagement with the program. The multidisciplinary study team used patient feedback to adapt the CBT app prototype to a tablet design consisting of six modules that teach skills for practicing relaxation, staying present-focused, coping with fears related to cancer, and pacing activities. To enhance patient engagement, features also included homework assignments, symptom distress tracking, and tailored algorithms and branching logic based on patient responses. Conclusions: Patient interviews confirmed acceptability of the CBT app content. Expert clinician feedback also supported the tablet design for self-administration of the intervention to reduce patient burden. We are currently conducting a randomized controlled trial to assess the efficacy of the CBT app for improving anxiety symptoms in patients with advanced cancer. Clinical trial information: NCT02286466.
Prognostic significance of serum HE4 in epithelial ovarian cancer.
Authors: M. Marinaccio, E. Mele, V. Lorusso, A. Larocca, C. Pellegrino, R. Chiappetta, F. Sozzi
Journal: Journal of Clinical Oncology (2011)

5081 Background: Human epididymis protein 4 (HE4), a relatively new marker for ovarian carcinoma, is the product of the WFDC2 (HE4) gene that is overexpressed in patients with ovarian carcinoma. Using an immunoassay, a small study indicated comparable sensitivity for CA 125 and HE4 in postmenopausal women with ovarian cancer. A subsequent and larger study confirmed the sensitivity of HE4. We investigated the possibility of HE4 to predict survival for patients with EOC. Methods: In the present study we measured serum concentration of HE4 in 35 patients with surgically diagnosed EOC since December 2008 until May 2010. All patients received the same standard of care using an integrative model combining surgery, and chemotherapy as appropriate. Of 35 pts. 28 had stage III disease at diagnosis, and 7 stage IV. Blood samples were obtained before surgery, at each IV chemotherapy cycle and every 3 months. The Kaplan-Meier or product-limit method was used to calculate survival.Serum levels of HE4 were determined using assays and kits developed by Fujirebio Diagnostic, Inc. and were performed according to the manufacturer's specifications. Results: At the time of this analysis (December 2010), 7 patients had expired and 18 were censored. The median age at presentation was 54.2 years (range 38.1 - 73.5 years). At baseline (study entry) no patients had low serum HE4 levels (<100 pM). After 3 cycles of planned chemotherapy, 20 pts had lower serum HE4 levels (<100pM) and 15 had high serum HE4 levels (>100pM); at the end of 6 planned cycles 28 pts had lower serum HE4 levels (<100pM) and 7 had yet high serum HE4 levels (>100pM). All pts with a HE4 plasma level > 400pM at the end of the planned treatment died before December 2010. Patients with a reduced HE4 at both baseline and 3 months had the best overall survival. Conclusions: Our data show that HE4 can improve the monitoring of treatment response and disease progression. Reduction in HE4 after 3 or within the 6 planned cycles of chemotherapy is clearly associated with better overall survival in EOC. Patients with a HE4 plasma level >400pM at the end of chemotherapy have a particularly poor prognosis and could be immediately submitted to different chemotherapy regimens or be enrolled in perspective controlled clinical trials.
Tyrosine kinase inhibitors in BCR/ABL positive ALL.
Authors: A. T. Lopez-Enriquez
Journal: Journal of Clinical Oncology (2011)

6536 Background: The treatment of acute lymphocytic leukemia (ALL) represents a success for chemotherapy treatments developed in the early 70’s. The results of similar induction regimes for children and adults gave similar initial high complete remissions but long term survival varied favoring children up to 15 years old with close to 80% long term survivors and a dismal 20-30% for adults. The peculiarity of CNS Leukemic relapse and the need for early specialized treatment was addressed by Omura and Vogler in the 70’s. Although morphologically ALL is either L-1, L-2, L-3, cytogenetics, flow cytometry and molecular studies are sorting out clear subsets. It has been reported that the Philadelphia Chromosome t-9/22 is prevalent in 3% of ALL in children in the ST. Judes series, and 2.3% in the POG group, while it has been reported from 10% to 50% Ph+ in adults with the use of molecular probes. The ABL oncogene from chromosome 9 can be translocated to two distinct regions of the breakpoint cluster region (BCR) locus on chromosome 22, at the 190 for ALL and 220 for CGL. The fusion protein liberates a Tyrosine Kinase that is inhibited by small molecules. Methods: In the last three years since December 2007, we have diagnosed 18 ALL patients referred to our Leukemia Unit at the University Hospital. Eight of eighteen (8/18) or 44% had documented BCR/ABL translocation. Results: All where treated in the modified 19802 ALL protocol/CALGB. We incorporated triple CNS chemotherapy across the protocol, Cytoxan to all patients, for the BCR/ABL +the first patient received and is still in Gleevec the other seven are on Sprycel uninterrupted. The response rate is 100% complete remission with a range of three to thirtysix months. Three patients relapsed in the CNS within the first year but are presently in remission twelve months later. Conclusions: The use of Tyrosine Kinase Inhibitors might change dramatically the prognosis of this subset of patients with ALL. In the adult population more than 50% will probably be BCR/ABL positive. The concomitant use of chemotherapy and tyrosine kinase inhibitors will make a difference in this disease. Chronic Granulocytic Leukemia and Acute Lymphocytic Leukemia ; BCR/ABL positive are clearly two distinct biologic entities with similar molecular targets for the tyrosine kinase inhibitors.
Frequency of physician misconceptions that may drive underuse of radiotherapy (RT) in patients with breast cancer.
Authors: Jessica Zhou, Sarah T. Hawley, Brian Zikmund-Fisher, Nancy K. Janz, Kent A. Griffith, Michael S. Sabel, Jennifer J. Griggs, Steven J. Katz, Reshma Jagsi
Journal: Journal of Clinical Oncology (2012)

237 Background: Registry studies suggest underuse of RT for breast cancer, especially after mastectomy. Because radiation oncology is referral-based, knowledge and attitudes of upstream providers may influence patients’ RT decisions, including whether they even consider it. Methods: We surveyed a random sample of 750 medical oncologists (MO) and 750 surgeons (S) drawn from the AMA Masterfile in 2012; 895 responded. We analyzed responses to scenarios in which RT should be considered from the 766 (403 S, 363 MO) who had seen breast cancer patients in the past year. Results: Mean age was 52; 36% worked in a practice with an academic affiliation. 84% of MO and 64% of S saw more than 10 breast cancer patients in the previous year (p&lt;0.001). 44% participated in multidisciplinary breast clinics. In a 45 yo T1cN0 ER+/PR+/HER2- patient receiving lumpectomy and tamoxifen, half of respondents substantially underestimated the 10-year risk of locoregional recurrence without RT. 19% of MO and 38% of S did not know that guidelines recommend RT in that case, but reassuringly, almost all would refer the patient to radiation oncology (97%). Referral to radiation oncology was less common for node-positive patients after mastectomy; however, in a T1cN1 patient with 2/20 nodes s/p mastectomy (in whom guidelines state that RT should be strongly considered), only 53% of MO and 34% of S recommend RT; 29% of MO and 43% of S would not refer to radiation oncology. If 4/20 nodes were involved (where RT is clearly guideline-recommended), 94% of MO but only 79% of S would recommend RT, and 9% of S would not refer to radiation oncology. The majority (53% of MO, 68% of S) substantially underestimated the risk of LRR in a patient with pN2 disease after mastectomy without RT. Fewer than half knew that the EBCTCG meta-analysis revealed a survival benefit from RT after lumpectomy (45%) or mastectomy (47% of MO, 32% of S, p&lt;0.001). Only 66% of MO and 54% of S recognized the 10-year risk of RT-induced second malignancy to be &lt;1%. Conclusions: Many MO and S who treat breast cancer patients have misconceptions relevant to RT decision-making. Educational interventions targeted towards referring providers may improve the quality of care received by breast cancer patients.