tbuckley/cabot-search huggingface dataset:
Development of a nomogram to predict overall survival in patients with locally advanced or metastatic gastrointestinal stromal tumor receiving first-line treatment with imatinib.
Authors: D. Goldstein, C. Lee, Y. Hui, B. Shah, D. Yip, G. A. McArthur
Journal: Journal of Clinical Oncology (2010)

10054 Background: Patients with locally advanced or metastatic gastrointestinal stromal tumor constitute a heterogeneous group with variable prognosis. We sought to develop a prognostic nomogram using data from three tertiary referral teaching hospitals. Methods: We identified 108 patients with locally advanced or metastatic disease who had received imatinib as initial treatment. The proportional hazards model was used to develop the multivariable model (nomogram) for overall survival (OS) using pretreatment characteristics. Patients were then grouped into high (score > 80), medium (score 40-80), and low (score<40) risk groups. Nomogram performance was internally validated using the bootstrap resampling technique. Calibration of the nomogram prediction was evaluated by comparing the predicted versus observed probability of OS at 5 years. Results: Metastatic disease (as opposed to locally advanced disease), high mitotic rate, high neutrophil count, and absence of an exon 11 mutation significantly and independently predicted reduced OS. The nomogram provided good prognostic discrimination for these patients (Table). The concordance index between the observed and predicted survival was 0.755. There was good agreement between the observed and predicted PFS probabilities at 5 years. Conclusions: A nomogram that combines multiple baseline characteristics will be a useful prognostic tool in clinical practice and may be valuable for risk stratification of patient with gastrointestinal stromal tumor in future randomized trials. Risk group n Median OS (months) HR 95% CI Low risk (score <40) 11 NR 1.00 Medium risk (score 40 - 80) 28 84 3.89 0.85 17.70 High risk (score > 80) 10 22 12.03 2.41 59.89 NR = not reached Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration GlaxoSmithKline, Novartis, Pfizer Novartis
Patterns of self-reported neurocognitive (NC) deficits in head and neck cancer (HNC) patients during concurrent chemoradiation therapy (CCR).
Authors: S. M. Bond, M. S. Dietrich, B. A. Murphy
Journal: Journal of Clinical Oncology (2010)

e16015 Background: Although changes in NC function are often reported by patients with cancer, few studies have examined this issue in HNC patients receiving CCR. We conducted a prospective observational cohort study to examine NC impairment before, during, and after HNC therapy. Almost half (49%) of patients exhibited impaired baseline neuropsychological function. Here we describe the patterns of self-reported NC function during treatment. Methods: NC deficits were assessed in 59 patients undergoing CCR using the following self-report measures: the Alertness Behavior Subscale (ABS) of the Sickness Impact Profile, the Neurocognitive Subscale of the modified Memorial Symptom Assessment Scale – Short Form (MSAS-SF), and the Confusion Subscale of the Profile of Mood States (POMS). Patients underwent assessments at baseline and weekly during CCR. A group-based, log-likelihood, trajectory modeling approach was used to detect clusters of trajectories (patterns of change) in NC function. Results: The HNC patients were predominantly male (80%), Caucasian (92%), and married (76%), with at least a high school education (86%). Mean age was 55 years (SD 9.2; Range 33-70). Primary sites included: oropharynx (54%), larynx (14%), paranasal sinus/nasal cavity (7%), unknown (7%), nasopharynx (5%), and other (13%). A majority of patients (76%) received induction chemotherapy followed by CCR; the remainder had CCR postoperatively or as primary treatment. Similar patterns of self-reported NC deficits were noted across the three instruments. Three distinct patterns of NC function were identified: (1) patients who perceived higher levels of NC deficits at baseline which persisted through CCR, (2) patients who perceived none to minimal NC deficits at baseline or at any point during therapy, and (3) patients who perceived minimal NC deficits at baseline but reported increasing deficits during therapy. Conclusions: As with other cancers, a proportion of patients present with self-reported NC deficits. In addition, a subset of patients develops perceived NC deficits during CCR. The cause and social/medical implications of NC impairment in these patients are unknown and need to be explored. No significant financial relationships to disclose.
Predictors of guideline treatment nonadherence and the impact on survival in patients with colorectal cancer.
Authors: Robert B. Hines, Alina Barrett, Philip Twumasi-Ankrah, Dominique Broccoli, Kimberly K. Engelman, Joaquina Celebre Baranda, Elizabeth Ablah, Lisette Jacobson, Michelle Redmond, Wei Tu, Tracie Collins
Journal: Journal of Clinical Oncology (2014)

254 Background: We investigated the effect of comorbidity, age, health insurance payer status, and race on the risk of nonadherence with National Comprehensive Cancer Network (NCCN) treatment guidelines for colorectal cancer (CRC) patients. In addition, the prognostic impact of NCCN treatment nonadherence on survival was assessed. Methods: Colon and rectal cancer patients who received primary treatment at Memorial University Medical Center in Savannah, GA from 2003 to 2010 were eligible for this study (final N = 679). Modified Poisson regression was used to obtain risk ratios for the outcome of nonadherence with NCCN treatment guidelines. Hazard ratios (HRs) for the relative risk of CRC-related death were obtained by Cox regression. Results: Guideline-adherent treatment was received by 82.5% of patients. Moderate/severe comorbidity, being uninsured, having rectal cancer, older age, and increasing tumor stage were associated with increased risks of receiving nonadherent treatment. Treatment nonadherence was associated with 4.5 times the risk of CRC-related death (HR, 4.53; 95% CI, 2.56-8.00) in the first year following diagnosis and 2.0 times the risk of death (HR, 1.97; 95% CI, 1.20-3.25) in years 2 to 5. The detrimental effect of nonadherence was demonstrated across all levels of comorbidity and age. Conclusions: Although there are medically justifiable reasons to deviate from NCCN treatment guidelines in CRC patients, patients who received nonadherent treatment had much higher risks of CRC-related death, especially in the first year following diagnosis. This study’s results highlight the importance of cancer health services research to drive quality improvement efforts in cancer care for CRC patients. [Table: see text]
Adjuvant chemoradiation therapy with 5-FU/LV (INT-0116) versus S-1 chemotherapy in completely resected gastric cancer: Practice pattern and feasibility at a single institution.
Authors: Deok Won Hwang, Su Jin Lee, Jeeyun Lee, Se Hoon Park, Joonoh Park, YoungSuk Park, Hoyeong Lim, WonKi Kang
Journal: Journal of Clinical Oncology (2012)

57 Background: Considering the high incidence of gastric cancer worldwide, large-scaled phase III adjuvant trials have been relatively scarcely reported. Until 2010, there have been two large-scaled adjuvant trials in gastric cancer that showed survival benefit from adjuvant chemotherapy +/- radiotherapy: S-1 monotherapy and chemoradiation therapy (CRT) with 5-FU/LV. There has been no direct comparison between S-1 monotherapy and CRT. We analyzed the practice pattern of adjuvant treatment at single institution in Korea in terms of patient’s preference, compliance rate, adverse events between CRT and S-1. Methods: From January 2008 to July 2009, 405 gastric cancer patients who had received adjuvant therapy after curative resection were included for the study. The CRT regimen was INT 0116 protocol. The S-1 monotherapy was to administer 40-60 mg bid, for 28 days, every 6 weeks (8 cycles). Results: Of the total 405 patients, 244 (60.3%) patients had CRT and 161 (39.7%) patients had S-1 monotherapy. The median age was 54 years (range, 24-80) and most of the patients were ECOG PS 0-1. S-1 group was more common than CRT group in Stage II (52.2% for S-1 vs. 47.8% for CCRT) and CRT group was more common in stage III-IV (72.4% for CCRT vs. 27.6% for S-1, p&lt;0.001). The patients’ compliance for the planned treatment was significantly higher in CRT group (95.1% vs. 72.8%, p&lt;0.001). Most common reason for cessation of S-1 therapy was patients’ refusal. For severe adverse events, grade 3-4 neutropenia was substantially more frequent in CRT group (40.2% vs. 8.7%, p&lt;0.001) and GI toxicities of nausea and mucositis were frequent in CRT group when compared with S-1 group (CRT vs S-1; nausea, 5.7% vs &lt;1%; p=0.002; mucositis, 7.4% vs 2.5%; p=0.034). Conclusions: Patients with advanced stage (III–IV) preferred CRT to S-1. The compliance was significantly higher for the CRT group despite of higher incidence of adverse events.
Prevalence of psychosocial distress in a rural community oncology practice and impact of interventions.
Authors: J. S. Smith, D. L. Limesand, M. A. Alikhan
Journal: Journal of Clinical Oncology (2011)

9114 Background: The prevalence of psychosocial distress in cancer patients in rural areas is not well studied. In our rural community practice a partnership has been developed with an off-site local not-for-profit cancer wellness center. The services offered free at this wellness center are individual counseling, support groups, and wellness services such as yoga and massage. In addition, a diagnosis specific psychoeducational program has been established for patients at the clinic location. Methods: All patients at the outpatient oncology clinic were administered the National Comprehensive Cancer Network (NCCN) Distress Thermometer (DT) and Problems List (PL). Those patients who scored a five or more on the DT were contacted by a social worker at the partnering agency and offered psychosocial intervention. Results: Out of 290 patients, 268 patients completed the DT and PL. The mean distress level of the patients who completed the DT was 4.18. Of the total 268 patients who completed the DT, 46% scored a 5 or greater and were therefore contacted for psychosocial intervention. In relation to patient demographics, results are shown in the table. Only 10% of patients accepted interventions at the off-site wellness center. The reasons many gave for nonacceptance include lack of transportation, psychosocial services were too far, belief that psychosocial intervention is not necessary, and not enough time. More than 60% of a disease specific group attended a psychoeducational group led by physicians, nurses, and social workers held at the clinic location and expressed decrease in the distress level. Conclusions: The prevalence of psychosocial distress in this rural population is greater than that reported from urban/academic outpatient clinics. Rural oncology practices pose a unique challenge in regard to patient distress as barriers to utilizing intervention services exist. In our practcice we plan to expand on on-site cancer specific support groups. Patient demographics DT score ≥ 5 (%) Breast cancer 65 Leukemia, lymphoma, multiple myeloma 39 Lung cancer 46 Gynecologic cancers 42 Colorectal cancers 58 Women (overall) 51 Men (overall) 42 Age 20-39 65 Age 40-59 49 Age 60-79 45 Age 80 + 35
Characterization of immune-related adverse events (irAEs) in a phase 3 trial of ipilimumab (Ipi) versus placebo (Pbo) in post-docetaxel mCRPC.
Authors: Tomasz M. Beer, Christopher Logothetis, Winald R. Gerritsen, Eugene D. Kwon, Howard I. Scher, Alberto Bossi, Alfons JM van den Eertwegh, Charles G. Drake, Brent McHenry, David Liu, Karim Fizazi
Journal: Journal of Clinical Oncology (2014)

52 Background: Ipi enhances antitumor immunity by blocking cytotoxic T-lymphocyte antigen-4. We recently reported the results of CA184-043, a phase 3 study of post-docetaxel mCRPC with Ipi vs Pbo, following single-dose radiotherapy (RT). While the study did not meet the primary endpoint of improving overall survival (HR=0.85, p=0.053), Ipi demonstrated antitumor activity in other efficacy endpoints, including progression-free survival. The present analyses further characterize the safety profile of Ipi in this study. Methods: Safety was evaluated for all treated patients (pts; N=393 for Ipi 10 mg/kg, N=396 for Pbo) starting from first study dose and ending 70 days after the last study dose, including maintenance dosing. Results: Any grade (Gr) irAEs occurred in 63.4% and 21.7% of pts in the Ipi and Pbo arms, respectively. Most common Gr 3/4 irAEs were gastrointestinal (GI) (18.1%; mostly diarrhea and colitis). Gr 3/4 liver irAEs (4.6%) were mostly elevations in AST or ALT. Other Gr 3/4 irAEs were uncommon: endocrine (2.0%), skin (1.0%), and neurological (0.3%). Among Ipi-treated pts, there were no meaningful differences in the frequency or severity of GI AEs between those who received baseline pelvic RT and those who did not (n=141 vs 252; any Gr 77.3% vs 69.8%; Gr 3/4 25.5% vs 21.8%, respectively). There were 5 GI perforations in the Ipi arm (3 within 70 days of last dose [2 related, 1 unrelated], 2 after 70 days of last dose, both related), and none in the Pbo arm. Deaths due to study drug toxicity, as per the investigators, occurred in 4 pts (4, Ipi and 0, Pbo). Conclusions: In this study of Ipi in mCRPC, the most frequent severe irAEs were diarrhea and colitis. Most irAEs were manageable using established treatment algorithms. Clinical trial information: NCT00861614. [Table: see text]
Precision oncology: molecular testing and targeted treatment beyond indication.
Authors: Josh John Carlson, Ben Ely, Ryan N. Hansen, Gary H. Lyman
Journal: Journal of Clinical Oncology (2015)

6541 Background: Advances in cancer research indicate that successful treatment may depend more on genomic alterations in the tumor rather than the organ of origin. However, data on the use of off-label molecular testing and targeted treatment is lacking. Our objective was to evaluate off-label testing and targeted treatment in a commercially insured population. Methods: We analyzed data from the MarketScan databases, a large employer-based claims repository, from 2011-2013 on the use of off-label molecular tests and targeted drugs for the top 10 incident cancers. We limited the analysis to the metastatic setting using a previously validated algorithm. We defined off-label use as using the test or agent in a tumor type not included in an FDA-approved medication label. Results: Test use was limited overall, but rose considerably in 2013 with the most use in lung, colon, and breast cancers. There was also limited though non-negligible use of targeted agents with the most common being erlotinib, imatinib, trastuzumab, vemerafinib, and dasatinib. Drug use rates remained relatively constant over the three-year period. Off-label treatment was most common in breast, lung, and colon cancers. Conclusions: There is limited but non-negligible use of off-label molecular testing and targeted treatment in the top 10 incident cancers. Further work will explore predictors of off-label use and patient outcomes. Tests 2011 2012 2013 n % n % n % EGFR 0 0.00% 213 0.37% BRAF 12 0.02% 378 0.66% Bcr-Abl1 0 0.00% 128 0.22% KRAS 6 0.01% 331 0.58% Drugs* Erlotinib 37 0.06% 34 0.05% 25 0.04% Afatinib 0 0.00% 0 0.00% 1 0.00% Dabrafenib 0 0.00% 0 0.00% 5 0.01% Vemurafenib 18 0.03% 20 0.03% 13 0.02% Trastuzumab 17 0.03% 20 0.03% 23 0.04% Lapatinib 6 0.01% 4 0.01% 5 0.01% Imatinib 27 0.04% 23 0.03% 25 0.04% Nilotinib 3 0.00% 1 0.00% 2 0.00% Dasatinib 12 0.02% 18 0.03% 8 0.01% Crizotinib 1 0.00% 6 0.01% 4 0.01% *Trametinib, pertuzumab, trastuzumab emtansine, basutinib had no use reported.
Evaluation of response to enzalutamide (E) consecutively after disease progression on abiraterone/prednisone (AP) and potential predictors of response.
Authors: Hamid Emamekhoo, Paul Elson, Petros Grivas, William Shomali, Natasha Catherine Edwin, Brian I. Rini, Jorge A. Garcia
Journal: Journal of Clinical Oncology (2016)

294 Background: Efficacy data of E immediately after AP failure in castrate resistant prostate cancer (CRPC) is limited. Although clinical cross-resistant has been observed, the optimal sequence of these agents is not defined. Specific patient pt) characteristics on AP could be useful in selecting appropriate pts for subsequent therapy with E. Methods: We retrospectively reviewed records of 40 pts with CRPC treated at the Cleveland Clinic with E immediately after disease progression on AP. We evaluated clinical / pathological features that could predict subsequent response or lack thereof to E. For this exploratory analysis, best % change in PSA (%Ch-PSA) was used as indicator of treatment response. Results: Median age at E initiation was 69 (58-81), median time from diagnosis to AP initiation was 6.1 years (0.9-16.3). Median PSA was 30.9ng/mL (1.5-1680) at the time of AP initiation and 66.9ng/mL (2.52-3130) at E initiation. 30/40 and 35/40 pts had bone metastasis at AP and E initiation, respectively. Prior treatments to AP included Ketoconazole (45%), Docetaxel (35%). Median time to PSA progression on AP was 9.6 m (0.5-49.6) and 2.3 m (1.8-3.1) on subsequent E. 26/39 pts on AP achieved PSA decline &gt;25%; among these 20 had &gt;50% PSA decline. Similarly, 13 and 8 pts receiving subsequent E achieved &gt;25% and &gt;50% PSA decline, respectively. 10/40 pts did not have PSA response with either agent. 4 pts had PSA decline &gt; 50% on both agents. There was no significant correlation between %Ch-PSA on E and %Ch-PSA on AP, pre-E PSA, time to PSA progression on AP, or time from diagnosis to AP. Longer interval between AP and E initiation was associated with better outcome on E (p=.03). Prior treatment to AP did not predict subsequent response to E. Conclusions: Except for the association between longer interval between AP and E initiation with PSA response on subsequent E, other clinicopathological factors did not predict response to consecutive E in this cohort of pts. Identifying clinical and/or molecular factors predictive of response to AP and E in this setting is of critical importance. Ongoing randomized prospective studies will help determine the optimal treatment sequencing in men with CRPC.
Combination of exposure-response and case-control analyses in regulatory decision making.
Authors: J. Yang, Y. Wang, H. Zhao, C. Garnett, J. Gobburu, W. Pierce, G. Schechter, J. Summers, P. Keegan, B. Booth, N. A. Rahman
Journal: Journal of Clinical Oncology (2011)

4087 Background: In 2010, the FDA approved Herceptin (trastuzumab) as treatment for HER2-overexpressing metastatic gastric cancer. The purpose of this analysis was to further evaluate whether the approved dosing regimen for trastuzumab in patients with advanced gastric cancer (AGC) is optimal based on the exposure-response (ER) relationship. Methods: The data was obtained from a randomized, open-label, multicenter, international trial, where patients with AGC received either chemotherapy (FC, n=296) or trastuzumab in combination with chemotherapy (T+FC, n=298). An exploratory Kaplan-Meier analysis was conducted to assess the relationship between trastuzumab exposure and overall survival (OS). To reduce the bias introduced by confounding risk factors, a case-control comparison using propensity score was incorporated in this ER analysis to evaluate whether different trastuzumab exposures resulted in the OS difference in patients receiving T+FC. Results: Survival analysis in patients receiving T+FC suggests that patients in the lowest quartile of exposure, Q1 had substantially shorter OS than those in other quartiles. A stepwise Cox regression model identified five negative prognostic factors for OS: ECOG PS 2; no prior gastrectomy; non-Asian; IHC 0, 1, or 2+ HER2 tumor overexpression; and more than 2 sites of metastatic disease. The result of the case-matched control comparison suggests that adjusting for these factors, patients with higher trastuzumab exposure appeared to benefit from the addition of trastuzumab to chemotherapy over chemotherapy alone. However, patients with the lowest quartile of trastuzumab exposure did not benefit from the addition of trastuzumab treatment. Conclusions: The exploratory subgroup with the lowest Cmin quartile and worse baseline clinical characteristics and no survival benefit from the addition of trastuzumab to chemotherapy and the ER relationship support the FDA recommendation to conduct post marketing clinical trials to investigate a dosing regimen which may yield greater exposure and acceptable safety in this subgroup and, if such a regimen can be identified, to prospectively evaluate whether increasing exposure of trastuzumab results in greater efficacy.
Clinical characterstics and outcomes of patients with BRAF-mutant advanced cancer in a phase I clinic: The University of Texas M. D. Anderson Cancer Center experience.
Authors: H. E. El-Osta, G. S. Falchook, A. M. Tsimberidou, D. S. Hong, A. Naing, K. B. Kim, S. Wen, F. Janku, R. Kurzrock
Journal: Journal of Clinical Oncology (2011)

10535 Background: BRAF mutations are found in diverse malignancies. The current study assesses the clinical characteristics and outcomes of patients with mutant (mut) BRAF advanced malignancies. Methods: Chart review of 80 patients with mutBRAF advanced malignancies and 149 with wild-type (wt) BRAF (matched by tumor type) referred to the Clinical Center for Targeted Therapy. Results: mutBRAF patients had melanoma (N=56); colorectal (N=10); papillary thyroid (N=11); ovarian, (N=2); and esophageal cancer, N=1. Seventy-seven patients had a mutation in codon 600 (62, V600E; 13, V600K; 1, V600R; 1 unreported); two in codon 601; and one, in both codons 600 and 599. NRAS and KRAS mutations were more common in the wtBRAF group (P < 0.005). A trend to longer median survival in melanoma and shorter survival in colorectal cancer was observed in mutBRAF compared to wtBRAF. Patients harboring V600K+ melanoma had more frequent brain and lung metastases (p < 0.05), and a shorter time from diagnosis to metastases and to death (19 vs. 53 months, and 78 vs. 322 months, respectively [p< 0.05]) compared to melanoma patients with other BRAF-type mutations. In multivariate analysis, soft tissue, lung and retroperitoneal metastases were associated with wtBRAF whereas brain metastases were associated with mutBRAF (p < 0.05). Treatment with RAF/MEK targeting agents and any decrease in tumor size after referral correlated with longer survival in mutBRAF patients (p <0.05). Conclusions: BRAF appears to be a druggable mutation that also defines subgroups of patients with phenotypic overlap, albeit with differences that may correlate with histology or site of mutation.