tbuckley/cabot-search huggingface dataset:
A pilot study of the Pathways program to address fear of recurrence and reduce distress among breast cancer survivors.
Authors: Edward Kenji Hadeler, Emily Claire Wong, Matina Elise Mamounas, Carrie D'andrea, Greg Hicks, Laura Esserman, Michelle Melisko
Journal: Journal of Clinical Oncology (2017)

206 Background: Breast cancer patients endorse anxiety and fear of recurrence for years after diagnosis. The Pathways for Survivors is a one-day program intended to address this distress by teaching cognitive behavioral strategies that improve self-efficacy, communication, attitude, and coping. The workshop incorporates an evidence-based program developed by authors/researchers Greg Hicks and Rick Foster, which has been adapted for the breast cancer survivorship population. Methods: Patients who had completed their acute phase of care were invited to attend the workshop. Attendees were asked to complete a series of questionnaires either on paper or electronically at baseline, 1 week and 6 weeks following the program and were consented to have their data used for research. Questionnaires included evaluation of program content and moderator quality, as well as measures to assess the impact of the Pathways intervention including the PROMIS Anxiety and Depression Short Forms, and the Acceptance and Action Questionnaire (AAQ-II). Results: Three sessions were held between 9/2015-9/2016. A total of 27 patients participated (6 in the first, 13 in the second, 8 in the third). Mean age of participants was 49 (range 28-65) years old. Race and ethnicity was: 63% White, 11% Asian, 4% Pacific Islander, 11% other, and 15% Hispanic/Latina (total &gt; 100% due to a patient reporting more than one race/ethnicity). The table below summarizes the change in these scores over time. Evaluations showed that patients were extremely satisfied with the program and moderator, receiving average ratings of 9.6/10 and 10/10, respectively. Conclusions: The Pathways workshop was well received and appears to have at least a short-term impact on breast cancer survivors’ anxiety, depression, and psychological flexibility. [Table: see text]
Retrospective evaluation of RET biomarker status and outcome to vandetanib in four phase III randomized NSCLC trials.
Authors: Adam Platt, Paul Elvin, John Morten, Qunsheng Ji, Emma Donald, Chris Womack, Xinying Su, Li Zheng, Amanda Gladwin, James Robert Vasselli, Jin Soo Lee, Richard H. De Boer, Roy S. Herbst
Journal: Journal of Clinical Oncology (2013)

8045 Background: The prevalence of the tumorigenic KIF5B:RET fusion gene in NSCLC tumors has been estimated at 0.2–6% (Jiu et al 2012; Lipson et al 2012). We retrospectively analyzed tumor samples from 4 Phase III NSCLC trials of vandetanib, a TKI that selectively targets RET, VEGFR and EGFR signaling, to determine the prevalence of RET fusions and other RET biomarkers, and any potential association with outcome to vandetanib (V). Methods: The studies evaluated were ZODIAC (NCT00312377; docetaxel ± V 100mg), ZEAL (NCT00418886; pemetrexed ± V 100mg), ZEPHYR (NCT00404924; V 300mg vs placebo) and ZEST (NCT00364351; V 300mg vs erlotinib). RET biomarkers evaluated included RET fusions (including KIF5B:RET) and RET gene copy number (assessed by a 4-probe FISH assay), as well as RET protein expression (by IHC). Results: Of 4089 patients randomized across the 4 studies, 1291 and 1234 had tumor samples available for FISH and IHC analysis, respectively, with evaluable data obtained for 944 and 1102. RET fusions (in &gt;10% of tumor cells) were detected in 7 of 944 samples (vandetanib, n=3; comparator, n=4), at a prevalence of 0.7% (95% CI, 0.3–1.5%). None of the 3 vandetanib-treated RET fusion-positive patients had an objective RECIST response, although there was radiologic evidence of tumor shrinkage in 2. Overall, 2.8% (n=26) of samples had RET amplification (innumerable RET clusters, or ≥7 copies in &gt;10% tumor cells), 8.1% (n=76) had lower RET gene copy number gain (4–6 copies in ≥40% tumor cells) and 8.3% (n=92) were RET expression positive (signal intensity ++ or +++ in &gt;10% of tumor cells). There was no difference in ORR between vandetanib and comparator for the RET amplification-positive subset (both 8.3% [1/12]), the RET copy number gain subset (9.8% [4/41] vs 9.1% [3/33], respectively) or the RET protein expression-positive subset (15.2% [7/46] and 13.6% [6/44], respectively). Conclusions: The prevalence of RET fusions was estimated at 0.7%. There were too few vandetanib-treated patients with RET fusions to make any firm conclusion regarding association with efficacy. Evidence from the other RET biomarkers tested suggested that these do not infer a differential advantage in patients treated with vandetanib. Clinical trial information: NCT00312377; NCT00418886; NCT00404924.
Real-world treatment patterns and effectiveness among patients with metastatic colorectal cancer (mCRC) treated with ziv-aflibercept (Z) in community oncology practices in the United States (US).
Authors: Jasmina I Ivanova, Kimberly Saverno, Jennifer Sung, Mei Sheng Duh, Chen Zhao, Xiaopeng Cai, Francis Vekeman, Aaron Peevyhouse, Ravinder Dhawan, Charles S. Fuchs
Journal: Journal of Clinical Oncology (2015)

e14554 Background: Real-world treatment patterns and effectiveness often differ from those in clinical trials. This study describes the real-world treatment patterns and effectiveness among mCRC patients (pts) treated with Z in non-academic, community oncology practices in the US. This is the first study to evaluate Z use in routine general practice since its US approval in 8/2012. Methods: De-identified electronic medical records (EMR), 1/2003-7/2014, were analyzed for 218 pts identified from the Vector Oncology Data Warehouse and a large community oncology EMR provider in the US. Pts were required to initiate Z in 2nd-line or later after mCRC diagnosis and have prior oxaliplatin therapy. The distribution of line of therapy of Z initiation and duration of therapy were described. Overall survival (OS) and progression-free survival (PFS) after Z initiation were estimated using Kaplan-Meier analysis. Results: Mean age was 62.8 (±11.2) years (including 28.4% 65-75 y/o, 16.5% > 75 y/o) at Z initiation, and 61.0% were male. Most (91.7%) pts received bevacizumab before Z initiation; and 95.4% initiated Z in combination with FOLFIRI or with another irinotecan-based regimen, among whom 59.6% had prior use of irinotecan. The mean duration of Z treatment was 162.5 (±12.0) days. 24.8% of pts initiated Z in 2nd-line, 31.7% in 3rd-line, 21.6% in 4th-line, and 22.0% in later lines of therapy. For pts initiating Z in 2nd, 3rd, and 4th-line, the median OS was 11.9 (95% CI: 5.1-16.2), 11.1 (6.9-16.7), and 8.1 (5.2-11.4) months, respectively; and the median PFS was 4.4 (2.8-6.5), 4.3 (2.9-6.3), and 3.4 (2.2-5.2) months. Conclusions: Among US pts treated outside of a clinical trial within non-academic community oncology practices, Z was frequently initiated in 3rd or later lines of therapy during the first two years of Z availability. Although Z-treated pts in our cohort were typically more heavily pre-treated and potentially less robust than in the VELOUR clinical trial, the median OS in our cohort for 2nd-line Z pts was approximately one year and comparable to OS in previously published trials of 2nd-line anti-VEGF therapy in mCRC. Funding: Sanofi.
Prevalence of pathogenic mismatch repair mutations in an Irish cohort after clinical and molecular pre-selection.
Authors: Michael P. Farrell, Kian P Hearty, David James Gallagher
Journal: Journal of Clinical Oncology (2017)

574 Background: Lynch syndrome (LS) is a highly penetrant, autosomal dominant multi-system disorder characterised by an inherited predisposition to a range of cancers. LS is caused by germline mutations in one of the mismatch repair (MMR) genes ( MSH2, MLH1, MSH2 and PMS2). Tumours from patients with LS have characteristic features resulting from the underlying molecular involvement of defective MMR, that is, the presence of microsatellite instability (MSI) and the absence of MMR protein expression by immunohistochemistry (IHC) corresponding to the mutated gene. MMR mutations are identified in approximately 60% of microsatellite instability-high (MSI-H) cancer patients fulfilling clinical criteria for LS. We sought to define the prevalence of pathogenic MMR mutations among an Irish cohort following molecular pre-selection with IHC/MSI and BRAF/MLH1 hypermethylation testing Methods: The results of diagnostic MMR genetic screening conducted on individuals following genetic counselling, in the Clinical Cancer Genetics Departments of the Mater Campus between January 2011 to September 2016, were correlated with ages at diagnoses and genetic test result. Results: This clinic-based cohort of affected individuals (n = 35) consisted of 22 females and 13 males. Median age at first cancer diagnosis was 44 years, range 23 to 86, standard deviation 12.3. Deleterious mutations were identified in 16 patients (45.7%), 6 in MLH1, 3 in MSH2, 2 in MSH6 and 5 in PMS2. Thirteen patients had a normal genetics test result (37.1%). Variants of uncertain significance (VUS) were identified in 6 patients (17.1%). With additional molecular testing and co-segregation studies in one family an MLH1 VUS was reclassified as likely pathogenic, facilitating pre-symptomatic testing for family members. This reclassification gives a revised prevalence of pathogenic mutation in this cohort of 48.5% and a VUS detection rate of 14.2%. Conclusions: We report a higher than expected VUS rate following molecular preselection of patients likely to have LS. No mutations were identified in 37% of patients supporting the presence of alternative negative regulators of the MMR pathway.
A phase I study of the safety and pharmacokinetics of DNIB0600A, an anti-NaPi2b antibody-drug-conjugate (ADC), in patients (pts) with non− small cell lung cancer (NSCLC) and platinum-resistant ovarian cancer (OC).
Authors: Michael S. Gordon, David E. Gerber, Jeffrey R. Infante, Jian Xu, David S. Shames, Younjeong Choi, Robert S. Kahn, Kedan Lin, Katie Wood, Daniel J. Maslyar, Howard A. Burris
Journal: Journal of Clinical Oncology (2013)

2507 Background: NaPi2b (SLC34A2) is a multi-transmembrane, sodium-dependent phosphate transporter expressed in non-squamous NSCLC and non-mucinous OC. DNIB0600A is an ADC consisting of a humanized IgG1 anti-NaPi2b monoclonal antibody and anti-mitotic agent, MMAE, that shows anti-proliferative activity in xenograft models. Methods: This study evaluated safety, pharmacokinetics, and pharmacodynamics of DNIB0600A (0.2-2.8 mg/kg) given every 3 weeks (q3w) to pts with NSCLC or OC. A traditional 3+3 design was used for dose escalation followed by expansion by disease at the recommended Phase 2 dose (RP2D). Tumor NaPi2b expression was evaluated in archival tissue. Anti-tumor activity was evaluated per RECIST 1.1. Results: As of 10 Dec 2012, 30 dose escalation pts have enrolled (16 NSCLC; 14 OC), median age 61 (range 45-78), PS 0-1, median number of prior regimens 5 (1-12), received a median of 3 (1-17) doses of DNIB0600A. No DLTs occurred at the maximum assessed dose of 2.8 mg/kg; enrollment in the expansion cohort at 2.4 mg/kg is ongoing. The most common related AEs regardless of Grade were fatigue (43%), decreased appetite (37%), nausea (30%), constipation, dysgeusia, vomiting, and peripheral neuropathy (each 17%), and diarrhea (13%). One pt at 1.8 mg/kg experienced a DLT (Grade 3 dyspnea), however, no additional DLTs occurred through the maximally administered dose of 2.8 mg/kg. Expansion at 2.4 mg/kg was selected based on totality of safety data. No accumulation of total antibody, free MMAE, or conjugated MMAE was observed. Exposure of each analyte was dose proportional. Approximately 70% of NSCLCs and 85% of OC expressed high levels (IHC 2+/3+) of NaPi2b. Of the 18 pts treated at dose levels 1.8-2.8 mg/kg (10 NSCLC; 8 OC) 3 pts had a confirmed partial response (PR) with response durations of 8.8+ (OC), 4.4+ (NSCLC), and 1.4+ (OC) months, censored at data cutoff, and 1 additional pt had an unconfirmed PR (OC). Dose expansion data will be presented. Conclusions: DNIB0600A administered q3w has an encouraging safety profile and evidence of anti-tumor activity in both NSCLC and OC. Further studies are planned. Clinical trial information: NCT01375842.
Demonstration of gender-specific variability in a pharmacokinetic (PK) analysis of the PERSIST-5 trial of adjuvant imatinib (IM) for patients with primary gastrointestinal stromal tumor (GIST) at significant risk of recurrence.
Authors: Joseph Espat, Robert G. Maki, Chandrajit P. Raut, Kevin F Staveley-O'Carroll, Christopher Hunt Keir, Andrea Magley, Ronald P. DeMatteo
Journal: Journal of Clinical Oncology (2013)

10538 Background: ThePERSIST-5 phase II trial is evaluating 5 years of adjuvant IM therapy in patients with resected GIST at significant risk of recurrence. This analysis studied the effect of chronic therapy on steady-state trough levels in patients who received IM for up to 24 months to evaluate potential PK variations. Methods: Eligible patients were adults with KIT+ primary GIST who were considered to be at significant risk for recurrence (primary tumor any site ≥2 cm andmitotic rate ≥5/50 high-power fields, or non-gastric primary GIST ≥5 cm) without metastases. R0 resection of primary GIST was performed ≤12 weeks prior to the first IM dose. Patients are to receive oral IM 400 mg/day for up to 5 years or until progression, relapse, or intolerance. Plasma samples for PK analysis were collected at 1, 4, 12, and 24 months. IM plasma concentrations were measured using a validated liquid chromatography-tandem mass spectrometry assay. Results: In-study assay performance (%CV) was ≤9.6% and bias was -1.3% to 5.2%. IM concentrations ranged from below quantifiable limits to 4798 ng/mL. After daily IM doses for up to 12 months (or 24 months in 3 patients), IM trough levels remained constant over time. The range of IM trough levels (mean ± SD) was 957 ± 750 ng/mL to 1219 ± 822 ng/mL at month 1, and 727 ± 430 ng/mL to 996 ± 405 ng/mL at month 12. Inter-patient variability was 40.7-78.4%. There was no significant difference in IM trough levels between months 1 and 4, 1 and 12, or 4 and 12. Trough levels did not significantly differ by location of GIST. Most notably, mean IM trough concentrations were on average ~33% higher in females vs males. Conclusions: In this study,IM trough levels remained relatively unaltered in patients with high-risk GIST who received adjuvant IM for 1 year. The 33% higher mean trough levels in females warrants further study for clinical decision making. Clinical trial information: NCT00867113. [Table: see text]
Activity and tolerability of SL-401, a targeted therapy directed to the interleukin-3 receptor on cancer stem cells and tumor bulk, as a single agent in patients with advanced hematologic malignancies.
Authors: Arthur E. Frankel, Marina Konopleva, Donna Hogge, David Rizzieri, Christopher Brooks, Thomas Cirrito, Steven Mitchell Kornblau, Gautam Borthakur, Carol Bivins, Guillermo Garcia-Manero, Farhad Ravandi, Tapan M. Kadia, Michael Andreeff, Jorge E. Cortes, Kenneth Hoberman, Michael Szarek, Ivan Bergstein, Hagop M. Kantarjian, Eric K. Rowinsky
Journal: Journal of Clinical Oncology (2013)

7029^ Background: SL-401 is a novel biologic targeted therapy directed to the interleukin-3 receptor (IL-3R). IL-3R is overexpressed on cancer stem cells (CSCs) and tumor bulk relative to normal hematopoietic cells in a wide range of hematologic malignancies including AML and blastic plasmacytoid dendritic cell neoplasm (BPDCN). Since SL-401 targets both leukemia blasts and CSCs, tumor regression and improvement in long-term outcome is expected. The clinical activity and side effect profile of SL-401 were evaluated in a multicenter Phase I/II trial of patients with advanced hematologic cancers. Methods: Eighty-one patients with advanced hematologic cancers, including relapsed or refractory AML (n = 59) and heavily pretreated BPDCN (n = 4), have been enrolled. Patients received a single cycle of SL-401 via 15-minute IV infusion to determine the maximum tolerated dose (MTD) and assess antitumor activity. Results: A single cycle of SL-401 demonstrated single agent activity in relapsed or refractory AML patients, including 2 durable CRs of 8 and 25+ months duration and multiple cases of blast reductions. SL-401, when delivered at therapeutically relevant doses, was associated with &gt; 3-fold greater median overall survival (OS) in AML patients who received 2+ prior lines of treatment relative to historical results. In addition, 3 heavily pre-treated patients with BPDCN, an uncommon malignancy that expresses high levels of IL-3R and is ultrasensitive to SL-401 (IC 50 values in the femtomolar [10 -15 M] range), had CRs, with durations of 5, 3+ and 1+ months. The MTD was 16.6 µg/kg/day; the dose-limiting toxicities of hypoalbuminemia and edema, which are manifestations of capillary leak, occurred at 22.1 µg/kg/day. Other ≥ Grade 3 adverse events included transient transaminase elevations. There was no treatment-related myelosuppression. Conclusions: SL-401 was well tolerated and demonstrated single agent activity in patients with relapsed or refractory AML and BPDCN. Based on these findings, single agent SL-401 given in multiple cycles will be advanced into pivotal studies of AML (3 rd -line) and BPDCN. Clinical trial information: NCT00397579.
Effect of vaccination with autologous tumor-loaded dendritic cells on intratumoral regulatory T cells in metastatic melanoma patients.
Authors: Massimo Guidoboni, Anna Maria Granato, Valentina Ancarani, Elena Pancisi, Massimiliano Petrini, Angela Riccobon, Laura Fiammenghi, Francesco Drago, Laura Ridolfi, Francesco De Rosa, Oriana Nanni, Linda Valmorri, Giovanni Lanza, Luigi Serra, Giorgio Maria Verdecchia, Giuseppe Migliori, Dino Amadori, Ruggero Ridolfi
Journal: Journal of Clinical Oncology (2013)

3040 Background: Vaccination with dendritic cells (DC) is still a valid experimental option for metastatic melanoma (MM). However, only a few patients experience long-lasting objective responses and the majority of clinical responders afterwards relapse and die. Which mechanisms are actually responsible for this “secondary resistance” to whole tumor antigens-loaded DC vaccines is largely unknown. It has been hypothesized that suppressive immune cell subpopulations, regulatory T cells in particular, may progressively accumulate in tumor tissues thus hampering therapy-induced antitumor immune responses along time. To elucidate this issue we evaluated changes induced by immunologically effective DC vaccination in the composition of tumor-associated T cell subpopulations. Methods: 12 patients with MM previously enrolled in a phase I/II DC vaccine trial and for which tumor tissue taken before and after at least 4 induction vaccine doses were available, were included in the study. Intratumoral lymphocytes were evaluated by CD3, CD4, CD8, FoxP3 and GrB immunostainings, and quantified by a computer-assisted method. A nonparametric two-tailed Wilcoxon signed-rank test was utilized for evaluating differences in the distribution of the number of cell positive for each marker on the total cell counts in pre- and post-vaccine biopsies. Results: Our data showed a considerable and statistically significant decrease of intratumoral FoxP3 + regulatory T cells in melanoma tissues after DC vaccination. In addition, the concurrent increase of intratumoral activated cytotoxic T lymphocytes, as shown by CD8 and Granzyme B stainings, indicated that this decrease has likely a functional relevance. Conclusions: Our findings that vaccination with DC loaded with autologous tumor lysate strongly reduces the intratumoral content of regulatory T cells add strength to the rationale for the development of potentially more effective combination schedules where whole tumor antigen-loaded DC vaccine prime and partially activate tumor-specific low-affinity T cells in a first tumor antigen-focusing step, followed by boosting with non-maximal doses of anti-CTLA-4 antibodies.
Combination lapatinib and capecitabine in advanced, incurable squamous cell carcinoma of the head and neck (SCCHN).
Authors: Jared Weiss, David N. Hayes, Kenneth M. Algazy, Arati Suvas Desai, Brenda Horn, Sara Gulino, Dale Flowers, Diane Frazee, Arthur M. Feldman, Arthur P. Staddon, Juneko E. Grilley-Olson, Roger B. Cohen, Corey J. Langer
Journal: Journal of Clinical Oncology (2013)

6094 Background: In an era of increasing use of platinum-based induction chemotherapy and chemoradiotherapy, most metastatic/recurrent SCCHN patients (pts) have received multiple chemotherapeutic agents prior to being diagnosed with incurable disease, at which point PS is often poor, pts are often refractory to multiple agents, and standard therapies (Tx) are unacceptably toxic and inconvenient. Methods: We conducted a phase II study of 44 pts with metastatic/recurrent SCCHN with a primary endpoint of median OS. Pts received capecitabine 1,000 mg/m 2 BID for 14/21 day cycles, with lapatinib at 1,250 mg daily for a total of four cycles. In the absence of disease progression or unacceptable toxicity, pts received maintenance Tx with lapatinib. Prior exposure to any chemotherapy other than capecitabine and lapatinib was allowed, as long as it was as part of therapy delivered with curative intent. Results: 36 of 44 planned patients are assessable at this time. 69% had prior resection, 75% prior radiation and 61% prior chemotherapy, of whom 18 (50%) had received prior platinum. Median age was 62, 11 pts (31%) had PS 0, 22 pts (61%) pts had PS1 and 3 pts (8%) had PS2. Median number of cycles given was 4; 14 pts have gone on to maintenance Tx. The most common grade 3-4 adverse events have included dehydration, diarrhea, and hand-foot syndrome, each occurring in 11% of pts. 2 patients did not have RECIST evaluable disease. Of the remaining 34 patients, 6 pts had PR and 1CR, for an ORR of 21% (24% in assessable pts). As of 1-31-13, 20 pts are alive, 2 are lost to followup, and 14 are deceased. Conclusions: The combination of capecitabine and lapatinib is tolerable and active in metastatic/recurrent head neck cancer, including pretreated patients. OS data, not yet mature, will be required to determine if this regimen is worthy of further testing. Clinical trial information: NCT01044433.
The effect of current smoking on mortality in cancer patients.
Authors: Graham Walter Warren, Anthony Alberg, Kenneth Michael Cummings, Carolyn M. Dresler, Nasser H. Hanna, Jamie S. Ostroff, James Roger Marshall
Journal: Journal of Clinical Oncology (2014)

1580 Background: Smoking is the largest preventable health behavior associated with the development of cancer. An evidence-based estimate is needed to assess the effect of current smoking at diagnosis on mortality for cancer patients. Methods: A MEDLINE literature search was performed to identify studies between 1990-2012 evaluating the effect of current smoking at or following a cancer diagnosis on overall mortality. Only studies collecting tobacco information in close proximity to diagnosis and with at least 200 patients in the analysis were included. Results: A total of 83 studies met criteria reporting on 129,346 patients including 60 studies comparing the effects of current smoking with never smoking and 23 studies reporting the effects of current smoking with former and never smoking combined. Overall 60 studies (72.3%) demonstrated one or more statistically significant negative associations between current smoking and mortality, 6 studies (7.2%) reported near significant negative associations, and 17 studies (20.5%) demonstrated no association. The risks of current smoking were observed across all treatment modalities (surgery, chemotherapy, radiotherapy). Current smoking increased the risk of mortality as compared with never smoking by a median of 52%, as compared with former smoking by a median of 41%, and as compared with former and never smoking combined by 50%. Conclusions: Current smoking increases the risk of overall mortality for cancer patients independent of cancer treatment. The effects of current smoking are distinct from the effects of former or ever smoking.