tbuckley/cabot-search huggingface dataset:
Use of gemcitabine-platinum (Gem-P) in patients with advanced gall bladder (GB) cancer: A more aggressive disease compared to the West—Tata Memorial Centre (TMC) experience.
Authors: Bhawna Sirohi, Vipul Sheth, Ashish Singh, Alok Gupta, Mahesh Goel, Mukta Ramadvar, Shailesh V. Shrikhande
Journal: Journal of Clinical Oncology (2014)

349 Background: GB cancer is a common cancer in northern India. Gem-P is currently the standard of care for pts with advanced biliary tract cancers based on the ABC02 study which had 61 pts with GB cancer with a clinical benefit rate (CR+PR+SD) of 85%. Indian patients have a higher risk disease and present at a more advanced stage than in the West and data on treatment is lacking. Methods: This is retrospective analysis of the prospectively maintained database of 131 pts with advanced GB cancer treated at TMC between Jan 2012-May 2013. Aim of the study is to assess the clinical benefit rate in this group of pts with the Gem-P. Pts received cisplatin 25 mg/m2 and gemcitabine 1000 mg/m2 on D1 and D8 of a 21day cycle, for gem-oxaliplatin, pts received gemcitabine 1000mg/m2 on D1 and oxaliplatin 100mg/m2 on D2 every 14 days. Response was assessed after 3-4 cycles. Results: Of the 131 patients, 110 pts were treated with Gem-P (95 oxaliplatin, 15 cisplatin; 1 received cetuximab-Gem-P) and 21 (16%) pts received best supportive care alone in view of poor performance status and deranged organ function. Median age was 53 years (range, 27-76), 82F/49 M; median CA19.9 206 (&lt;2-2251660); median CEA 6.9 (0.8-3541); site of metastases was liver in 66 (50%), nodal in 74(56%), peritoneal in 29(22%) and bilateral ovarian in 5(3.8%) patients. Of the 110 pts treated with GEM-P, PS was 0-1 in 91% of patients; median number of cycles received was 4 (1-12); grade 3 &amp;4 toxicities were- thrombocytpenia-12 (11%), neutropenia -2 (2%), hepatitis -2 (2%) patients, neuropathy-4 (4%) and diarrhea-8 (7.2%). 86/110 (78%) were evaluable for response out of which 4 (5%) had CR, 31(36%) had PR, 13(15%) had SD, and 38 (44%) had progressive disease. 32/110 (29%) pts received 2 nd -line chemotherapy (majority capecitabine -irinotecan based). Conclusions: This is the single largest study to show tolerance and efficacy of Gem-P in Indian pts with advanced GB cancer. Compared to the ABC 02 study, the clinical benefit rate is low at 56% suggesting that the biology of advanced GB cancers in Indian pts is likely to be aggressive and needs to be studied in prospectively designed studies.
Incidence of testicular cancer in the United States from 1992 to 2009.
Authors: Manas Nigam, Brisa Aschebrook-Kilfoy, Sergey Shikanov, Scott E. Eggener
Journal: Journal of Clinical Oncology (2013)

339 Background: The incidence of testicular cancer (TC) increased in the US through 2003. However, little is known about these trends after 2003. We sought to determine trends in TC incidence based on race, ethnicity and tumor characteristics. Methods: TC incidence and tumor characteristic data from 1992-2009 were extracted from the Surveillance, Epidemiology, and End Results-13 (SEER) registry. Trends were determined using JoinPoint. Results: TC incidence in the US increased from 1992 (5.7/100,000) to 2009 (6.8/100,000) with annual percentage change (APC) of 1.1% (p &lt; 0.001). TC rates were highest in non-Hispanic white men (1992: 7.5/100,000; 2009: 8.6/1000) followed by Hispanic men (1992: 4.0/100,000; 2009: 6.3/100,000) and lowest among non-Hispanic black men (1992: 0.7/100,000; 2009: 1.7/100,000). Significantly increasing incidence rates were observed in non-Hispanic white men (1.2%, p &lt; 0.001) but most prominently among Hispanics, especially from 2002-2009 (5.6%, p &lt; 0.01). A significant increase was observed for localized TC (1.21%, p &lt; 0.001) and metastatic TC (1.43%, p &lt; 0.01). Increased incidence occurred in localized tumors for non-Hispanic white men (1.56%, p &lt;0.001), while Hispanic men experienced an increase in localized (2.6%, p &lt; 0.001), regionalized (16.5% from 2002-09, p &lt; 0.01), and distant (2.6%, p &lt; 0.01) disease. Conclusions: Through 2009, testicular cancer incidence continues to increase in the United States, most notably among Hispanic men. [Table: see text]
Relationship between pain and depression among patients with cancer at a community teaching hospital.
Authors: Uri Goldberg, Damoun Safarpour, Khin N. Aung, Neil Pasco, Benjamin Levron, Amy Fung, Atefah Kalantary, Mario Hernandez, Byron Cary, Ratesh Khillan, Kalpana Panigrahi, Madhumati R. Kalavar
Journal: Journal of Clinical Oncology (2016)

81 Background: While depression is often under-diagnosed in the general population, the rate of under-diagnosis among patients with cancer may be far higher. The American Cancer Society reports that a quarter of all patients with cancer may suffer from depression. We seek to identify a link between pain and depression among patients with cancer which may signal an enhanced need both for the involvement of mental health services and for more effective pain management. Methods: This is an observational cross-sectional study evaluating depression among patients with cancer in an outpatient setting. From June of 2015 to January of 2016, 29 patients from our institution’s affiliated cancer clinics were interviewed by study staff members about their pain and various other cancer-related concerns. Subjects were also administered the depression screening tool Patient Health Questionnaire 9 (PHQ-9). Data was collected and analyzed using Spearman’s rho. Results: The inclusion criteria included a confirmed cancer diagnosis and willingness to participate in a clinical study. There were no exclusion criteria. Age ranged from 43 to 87 and women comprised 75% of participants. Of the 18 patients who complained of pain (62.1% of the total), 14 reported pain of at least 7 of 10 in severity (77.8%). Severity of pain was found to correlate positively with the questions of “Poor appetite or overeating” as well as “Moving or speaking so slowly...Or the opposite — being so fidgety or restless...” (R = 0.41, P = 0.03; R = 0.40, P = 0.03, respectively). Presence of pain likewise correlated positively with the latter question (R = 0.46, P = 0.01). Conclusions: The effects of depression on patients with cancer may contribute to life-shortening complications related to reduced compliance with treatment and lifestyle modifications, as well as the exacerbation of heart disease and other comorbid conditions. Our findings demonstrate that pain, particularly severe pain, may signal an elevated risk of depression and call for the swift involvement of mental health services. Likewise, the high proportion of patients complaining of pain in general and severe pain in particular suggests a need for more aggressive pain management among patients with cancer within our cohort.
Outcomes from placebo/best supportive care-controlled trials (PBSCT) in the era of molecular targeted therapy: A meta-analysis.
Authors: M. C. Miranda, A. B. Fede, N. Magalhaes, N. Fraile, V. Ayres, M. B. Santos, S. Gonzaga, K. Brunetti, A. Del Giglio, R. Riechelmann
Journal: Journal of Clinical Oncology (2010)

6127 Background: The increasing number of experimental anticancer agents to be tested in clinical trials has led to many PBSCT. And while the “placebo effect” may improve certain patient-reported outcomes, antitumor effects induced by placebo/best supportive care are unlikely. In the era of cytostatic molecular targeted agents, PBSCT are needed to better evaluate time-to-event endpoints. The extent to which such new therapies benefit patients over placebo/best supportive care (no anticancer treatment [NACT]) is subject to questioning. We performed a meta-analysis of PBSCT of targeted agents to pool the outcomes of experimental therapies versus NACT. Methods: Systematic review of randomized phase II and III trials of anticancer targeted agents fully published in PubMed in English or Spanish in the last ten years and which used an exclusive best supportive care control group with or without placebo. Because we were interested in the antitumor effects of NACT against cytostatic agents in time-to-event outcomes, we selected only trials of advanced cancer. Results: Twenty-four trials were eligible, comprising 7936 patients: the median number of patients per study was 234, nearly 80% (16) used placebo, 20 (83%) were entirely or partially funded by for-profit organizations, 13 (54%) used overall survival as the primary endpoint and half had positive results for the primary endpoint. Progression-free survival was improved by targeted therapies (n = 14; 5,314 patients; HR: 0.89, CI 95% 0.87-0.91; p < 0.00001). When limiting to trials without group crossover (n = 13; 5,692 patients) targeted agents led to improved overall survival when compared to NACT (HR: 0.93; CI 95% 0.89-0.96; p < 0.00001). The overall proportion of patients experiencing any grade 3/4 adverse event was 32.1% versus 23.7% among those receiving molecular agents and NACT, respectively (OR: 1.42, CI 95% 1.32-1.53, p < 0.00001). Conclusions: While half of PBSCT were reportedly negative, which demonstrates the need for such trials, time-to-event outcomes from NACT are clearly inferior to those provided by targeted antitumor agents. Future trials should develop alternative designs to prevent patients from receiving exclusive NACT. No significant financial relationships to disclose.
Population pharmacokinetics and pharmacogenomics of erlotinib: Effect of drug exposure on treatment outcomes in Japanese patients with non-small cell lung cancer.
Authors: M. Fukudo, Y. Ikemi, Y. Togashi, K. Masago, Y. H. Kim, T. Mio, M. Mishima, K. Inui, T. Katsura
Journal: Journal of Clinical Oncology (2011)

2549 Background: Erlotinib is a potent EGFR tyrosine kinase inhibitor, currently used to treat non-small cell lung cancer (NSCLC). Erlotinib shows a significant pharmacokinetic (PK) variability and has various adverse reactions including fatal interstitial lung disease (ILD). We aimed to investigate population PK of erlotinib and to explore the relationship between early drug exposure and the safety and antitumor activity in clinical practice setting. Methods: A total of 60 patients with NSCLC treated with erlotinib (150 mg/day) were enrolled in this study. Full PK profiles of erlotinib and its active metabolite OSI-420 were evaluated on day 1 and at steady state (ss) on day 8. The CYP3A5*3 and ABCG2 421C>A polymorphisms were genotyped, and EGFR mutation status in tumors (exons 18-21) was obtained from medical records if available. Population PK analysis was performed with NONMEM program. The objective response rate (ORR) was assessed using RECIST criteria. Results: The metabolic ratio of erlotinib to OSI-420 was correlated with the CYP3A5*3 genotype. The apparent clearance of erlotinib and OSI-420 were significantly decreased in patients with the ABCG2 421A allele. The cumulative incidences of grade > 2 rash and diarrhea during the first month were significantly higher in patients with high AUCss (> 37.2 µg*h/mL) than others (50% v 18%, P < .01 and 29% v 4%, P < .01, respectively). Furthermore, the ABCG2 genotype was related to the incidence of diarrhea but not rash. In 2 patients with ILD-like events, trough levels were extensively elevated on the day of the events (> 3.0 µg/mL). The ORR in patients with EGFR mutations did not correlate with AUCss (low group, 82%; high group, 90%), whereas there appeared to be a greater response for high group versus low group within the wild-type patients (33% v 11%). Conclusions: Erlotinib disposition can be affected by CYP3A5 and ABCG2, and early drug exposure would be associated with the development of adverse events while having a less impact on tumor response particularly in NSCLC patients with EGFR mutations. Genome-based and PK-guided erlotinib therapy should be valuable to minimize toxicity and maximize clinical efficacy.
Utilizing network quality committees to improve reporting and adherence to evidence-based clinical pathways.
Authors: Debra A. Patt, J. Russell Hoverman, Gay Lindsey, Deedra Jastrzembski, Cynthia Taniguchi, Brian Turnwald, Janet L. Espirito, Jody S. Garey
Journal: Journal of Clinical Oncology (2012)

76 Background: In an era of evidence based medicine, several different evidence based pathways for cancer treatment exist. Few, however, contain decision support, are implemented into an electronic health record (EHR) or have demonstrated their effectiveness to provide value-based care. Providing systems to make a Pathways program operational and improve adherence supports a culture of value-based care. Methods: Physician designed evidence based pathways for a large network of community oncologists was rolled out over a statewide practice. A team of pharmacists and data managers designed a program to support implementation of this pathways initiative. Physician-led quality committees were created at the practice level to troubleshoot and characterize the process of making adherence operational and improving upon other quality metrics, variance reporting, and patient satisfaction. Treatments were charted in the EHR and available for reporting. Documentation of rationale for off-pathway exceptions was also captured. Assessable data, adherence, and exception documentation were measured prior to the onset of the committees and again with follow-up for 1 year after initiation of the committees from March 2011 through February 2012. Results: Within this large practice of 342 physicians, there were 39 quality committees created. During this time assessable data, adherence, and justification of exceptions to evidence-based pathways changed. At the beginning of the time period, assessable data was 84% and improved to 90% after a year. Adherence to pathways was 60% and improved to 68% over the same time interval. Exception documentation also improved from 14% to 25%. Conclusions: Formalizing an internal physician-driven operational procedure to improve upon quality can increase the reporting and adherence to physician created evidence-based pathways across a network of community oncologists and moves to change a culture of value-based excellence within community oncology practices. Continuous and internally driven adherence to value-based metrics improve compliance over time. Internal systems such as these are essential to make evidence-based pathways operational.
Detection of HER2 status of circulating tumor cells and disseminated tumor cells using a microfluidic platform (cell enrichment and extraction technology [CEE]).
Authors: S. Krishnamurthy, F. Z. Bischoff, J. A. Mayer, K. Wong, S. Mikolajczyk, T. Pham, H. M. Kuerer, A. Lodhi, A. Bhattacharyya, C. Hall, A. Lucci
Journal: Journal of Clinical Oncology (2011)

613 Background: Evaluation of HER2 status of circulating tumor cells (CTCs) and disseminated tumor cells (DTCs) can provide valuable information to make therapy changes. We report here the utility of a microfluidic platform for evaluation of HER2 gene amplification in CTCs and DTCs by fluorescent in situ hybridization (FISH). Methods: Blood (10ml) and BM (1–2ml) were collected from patients with operable breast cancer. Mononuclear cells were recovered, incubated with a mixture of 10 primary capture antibodies(Abs), introduced into CEE microchannels ( Biocept, Inc,San Diego), stained with fluorescent cytokeratin (CK) and CD45 Abs and then processed for FISH using probes specific to centromere 8 (spectrum aqua), 17 (spectrum green) and HER2 (spectrum orange). The ratio of HER2:CEP17 >2.2 in any CD45 negative cell was regarded as positive for HER2 gene amplification. Results: Blood and BM from 50 patients with T1N0(26),T1N1(5),T2N0(6),T2N1 (3),T2N3(3),T3N0 (2),T3N1(1),T4N1(2),T4N3(2) with 7 HER2+ and 43 HER2 - invasive tumors were studied. HER2+ CTCs were noted in 4/49 (8.0%) patients with HER2 + (1) and HER2 - (3) tumors. HER2+ DTCs were noted in 14/50 (28%) patients with tumors that were HER2+ in 2 and HER2- in 12 patients. Six of the 7 patients with HER2 amplified tumors did not show any HER2 amplified CTCs and 5 of the same patients did not contain HER2+ DTCs. Overall, HER2 gene amplified CTCs and DTCs were noted in blood and BM simultaneously in only 2 patients and in either the blood (2) or BM (12) in the remaining patients. Conclusions: 1. The cell enrichment and extraction microfluidic technology (CEE) provides a sensitive platform for evaluation of HER2 by FISH in intact CTCs and DTCs. 2. HER2 + CTCs and DTCs were encountered in HER2 + as well as in HER2 - primary tumors. 3. Discordant HER2 status was contributed mainly by HER2 + DTCs occurring in HER2 -primary breast tumor. 4. The clinical implications of evaluating HER2 in CTCs and DTCs in patients with invasive breast cancers needs further investigation.
Sorafenib (Soraf) and bevacizumab (Beva) for recurrent metastatic hepatoblastoma (HB).
Authors: A. Marsh, L. Lo, J. H. Feusner
Journal: Journal of Clinical Oncology (2011)

9575 Background: Few effective treatment options exist for patients with HB who fail to respond to standard chemotherapeutic agents. Soraf has shown activity in treatment of advanced hepatocellular carcinoma (HCC); its use in HB has not been reported. Beva (combined with other agents) is used to treat several types of metastatic cancers. We report the use of Soraf and Beva in combination for a patient with recurrent metastatic HB recalcitrant to traditional agents. Methods: A 2-year old male with a left-sided abdominal mass and AFP of 33,608 ng/ml had a left hepatectomy to remove a large embryonal HB. Adjuvant chemotherapy of cisplatin, 5-flurouracil, and vincristine was given. The AFP level fell gradually (nadir of 76 ng/ml) after surgery but began to rise during the third cycle of chemotherapy. Computed tomography (CT) of the lung revealed numerous bilateral pulmonary nodules that were proven at biopsy to be HB. Over the next nine months, the following chemotherapeutic regimens were used: 1.Vincristine with irinotecan. 2. Doxorubicin with ifosfamide. 3. Carboplatin with etoposide. 4. Intensive cisplatin and doxorubicin (2 different regimens). 5. Cisplatin plus very high dose acetaminophen with N-acetylcysteine rescue. 6. Erlotinib and Beva for 8 weeks AFP levels continued to rise and serial CT scans demonstrated progressive disease, except for a brief period of stable disease after treatment # 4. Based on the efficacy of Soraf in HCC and the possibility that this tumor was acting more like a
Predictors of ovarian cancer survival: A prospective study at Mayo Clinic.
Authors: A. E. Wahner Hendrickson, E. L. Goode, K. L. Knutson, K. Kalli, P. Ramar, L. C. Hartmann, M. J. Maurer
Journal: Journal of Clinical Oncology (2011)

e15526 Background: Better prediction of outcome in ovarian cancer (OC) would help identify patients who could benefit from newer therapeutics. Using a well-defined patient cohort with detailed clinical-epidemiologic characterization, we sought to build a prognostic model for overall survival in OC. Methods: Women with newly diagnosed ovarian, primary peritoneal and fallopian tube cancers seen at Mayo Clinic were prospectively enrolled. Overall survival was defined as time from diagnosis until death or last follow-up. Cox proportional hazards models were used to generate survival models; time dependent AUC were used to assess the prognostic utility of models. Results: 843 patients diagnosed between 1999-2010 were analyzed. The median age at diagnosis was 62 years with median follow-up of 26 months. The most prognostic variables in univariate analyses were stage and ascites. A backwards selection approach yielded a multivariable model containing prior oral contraceptive use, prior pregnancy, age >70, stage, grade, ascites, and debulking extent. Multivariable AUC was improved over univariable models. Conclusions: While standard features such as stage and tumor debulking are highly associated with outcome, host exposures also contribute information. A multivariable model of prognosis in OC may enhance individualization of treatment strategies. N (%) Univariate HR (95% CI) Multivariate HR (95% CI) Stage I-II 165 (20%) Ref III-IV 663 (80%) 5.29 (3.52-7.93) 2.83 (1.65-4.83) Grade Low 110 (14%) Ref High 698 (86%) 3.67 (2.40-5.59) 2.11 (1.36-3.28) Debulking extent Optimal 675 (83%) Ref Suboptimal 139 (17%) 2.33 (1.86-2.92) 1.78 (1.41-2.24) Age <50 122 (14%) 0.61 (0.43-0.85) 0.83 (0.59-1.18) 50-69 472 (56%) Ref 70+ 249 (30%) 1.69 (1.37-2.09) 1.50 (1.20-1.88) Ascites No 226 (34%) Ref Yes 447 (66%) 2.71 (2.05-3.57) 1.72 (1.29-2.30) Oral contraceptive use No 330 (44%) Ref Yes 428 (57%) 0.67 (0.54-0.82) 0.82 (0.65-1.03) Prior pregnancy No 104 (14%) Ref Yes 655 (86%) 1.60 (1.14-2.24) 1.45 (1.03-2.04)
Racial and gender disparities in renal cell carcinoma.
Authors: Mohammad Mozayen, Anteneh Tesfaye, Khalil Katato
Journal: Journal of Clinical Oncology (2012)

461 Background: In spite of advancements in early diagnoses and better cancer treatments in the United States, ethnic and gender disparities still exist. In some types of cancer, African Americans and males generally tend to have higher disease frequency and worse outcomes. Studies about survival outcome among various racial groups in RCC are very scarce. Our study compared stage distribution and overall survival in relation to ethnicity and gender in patients with renal cell carcinoma (RCC). Methods: We retrospectively reviewed 205 patients diagnosed with RCC between 1995 and 2008 in a community hospital setting. Patients with additional malignancies, lymphoma of the kidneys, or no follow up data were excluded from the study. Demographics, pathology, disease stage, operative note, and subsequent follow up data were reviewed. Patients were divided into groups according to race and gender. Results: A total of 205 patients were included, Caucasians were 176 (85.9%), African Americans were 13.7% and Asians were 1 (0.5%). Males (M) were 127 (62.3%) and females (F) were 77 (37.7%). The median age of the study population was 65 (22-91). Clear cell histology was seen in 79%. Stage I was seen in 53.9%, II in 23.5%, III in 13.7% and IV in 8.8% of the study population. Advanced stages (III, IV) were seen in 18% of African American and in 23% of Caucasians (p=0.45). Advanced disease (III, IV) was seen in 22% of Females compared to 24% in Males (p=0.6). The 3 year overall survival for the study population was 67.3% (95% CI: 60.4-73.7). The 3 year overall survival for African Americans was 50% compared 71.5% in Caucasians (p=0.02). The 3 year overall survival for Females was 68.4% compared to (68.8%) (p=0.54). Conclusions: Our study showed that in patients with RCC, African Americans had worse survival outcome compared to Caucasians in spite of similar stage distribution. Our study didn’t show any gender based disparity in overall survival. Large studies are necessary to determine the causes of poor survival outcome in African American population in RCC.