tbuckley/cabot-search huggingface dataset:
Phase II trial of weekly docetaxel and carboplatin as first line chemotherapy in advanced or metastatic non small cell lung cancer (NSCLC)
Authors: G. Y. Chahine, F. L. Nasr, J. G. Kattan, F. S. Farhat, M.-E. El Seoudi, M. Bachour, W. T. Moukadem, F. C. Younes, M. G. Ghosn
Journal: Journal of Clinical Oncology (2005)

7330 Background: Single-agent platinum therapy has been the backbone treatment in NSCLC. With the emergence of new cytotoxic agents such as Docetaxel, new combinations were evaluated. The concomitant use of taxanes and platinum derivatives has been shown to induce high response rate with moderate toxicity. To further improve the therapeutic index of this combination, we performed a phase II study associating weekly Docetaxel to Carboplatin. Methods: This is a prospective multicenter national phase II study enrolling thirty chemotherapy-naïve patients with advanced or metastatic NSCLC. Treatment consisted of a combination of Carboplatin (AUC=5 at day 1) and Docetaxel (35 mg/m2 IV day 1 and 8) with cycles repeated every 21 days. Eligible Patients were aged between 18 and 75 years; ECOG PS between 0–2; no prior chemotherapy for advanced or metastatic disease; measurable lesion according to RECIST; adequate hematologic, hepatic and renal function. Primary objective was determination of objective response rate (ORR). Secondary objectives were response duration, time till progression, treatment tolerability and overall survival. Results: Thirty eligible patients were included. 18 had stage III B and 12 had stage IV diseases. The median age was 63 (39–75) with a sex ratio of 3:1. 112 cycles were delivered with a median of 3.7 cycles per pt (1–9). 27 were evaluable for response since 3 patients are still ongoing. 10 pts responded partially (37% ORR) and 10 had stable disease. Mean OR duration was 5 months (extremes: 2 - 9). The median time to progression was 4 months and varied between 1 and 9 months. As for the safety profile, the serious toxicities of grade III and IV consisted of: leucopenia (1 pt), lymphopenia (1 pt), alopecia (1 pt) and 1 pt with allergic reaction. Survival data will be presented at the meeting. Conclusions: Our weekly schedule proved to be extremely tolerated enhancing the therapeutic index of this combination. No significant financial relationships to disclose.
Chemotherapy influence EGFR mutation status for Chinese patients with regionally advanced non-small cell lung cancer.
Authors: J. Wang, K. Chen, H. Bai, J. Zhao, Z. Wang, M. Zhuo, T. An, J. Duan, L. Yang, M. Wu, Q. Guo, X. Liu, S. Wang, Y. Wang
Journal: Journal of Clinical Oncology (2011)

7031 Background: EGFR-TKI has been recommended as standard second-line therapy for advanced non-small cell lung cancer (NSCLC) in China. However, it remains unclear whether there is a need to detect EGFR mutations before using second-line EGFR-TKI therapy. The key to answer this question is to identify whether chemotherapy may change EGFR mutation status. Methods: Total of 61 (stage IIb–IIIa) NSCLC pts were included in this study. All patients received neoadjuvant chemotherapy 2-4 cycles before surgery. The surgical specimen were microdissected before detection. EGFR mutation were detected by denaturing high performance liquid chromatograph (DHPLC) in tumor samples from both pre- and post- neoadjuvant chemotherapy. Results: The EGFR mutation ratio in all pts are 41.0% (25/61) before chemotherapy and dropped to 29.5% (18/61) after chemotherapy. 46 pts remained the same EGFR status after chemotherapy (including 32 cases of wild-type and 14 cases of mutant-type), 24.6% pts (15/61) were discordant for EGFR mutation, including 4 pts (6.6%) switch from negative to positive and 11 pts (18.0%) switch from positive to negative. Evalutation of the chemotherapy showed 1 case of CR, 41 cases of PR, 18 cases of SD and 1case of PD. There is no significant difference in the RR rate between the pre-chemotherapy EGFR mutant and wild type pts (24/61 39.3% vs 18/61 29.5%, P=0.781). The ratio of the pts remaining the same EGFR genetype after chemotherapy in the PR subgroup was higher than that in the SD subgroup (33/42, 78.6% vs 13/19 68.4%) but did not reach statistically significance. (p=0.172). The other factors, including the chemotherapy regimen, cycles, sex, smoke and pathological type (adeno vs non-adeno) are not related with the EGFR alternation. Conclusions: Our data indicated that EGFR mutation status was changed after chemotherapy in the Chinese NSCLC pts. The finding should be considered in future studies designed to elucidate the predictive role of EGFR mutations for second-line TKI therapy for NSCLC patients.
Expanding patient-reported outcomes to oral health complications from systemic cancer therapy.
Authors: Rebecca A. Miksad, Rohit Goyal, G. Scott Gazelle, J. Shannon Swan
Journal: Journal of Clinical Oncology (2012)

60 Background: Cross-disciplinary patient reported outcomes (PROs) assess the full range of side effects from systemic cancer therapy. For oral health complications, however, the validity of oral-health specific and generic health-related quality-of-life (QoL) instruments is unknown for cancer patients. This study evaluates the performance, measurement, and prediction characteristics of the Oral Health Impact Profile (OHIP–14) and EQ–5D in cancer patients with bisphosphonate-associated Osteonecrosis of the Jaw (ONJ). Methods: 34 cancer patients assessed the QoL of their own ONJ with the OHIP–14 and evaluated the QoL of 4 standardized ONJ Health States with the EQ–5D, as previously published. For each instrument, the standard response mean (SRM), effect size (ES), and ability to distinguish minimally important differences (MID) were evaluated for ONJ compared to baseline (longitudinal responsiveness). Instrument MIDs (cross-sectional responsiveness) were also calculated. Performance of a published general dentistry algorithm to predict EQ–5D values from OHIP–14 results was tested. Results: The OHIP–14 and EQ-5D instruments demonstrated moderate to large longitudinal and cross-sectional responsiveness. Pain was one of the most responsive domains for both instruments. Ceiling/floor effects were most prominent for OHIP–14. A general dentistry algorithm did not adequately predict EQ–5D values for cancer patients. Conclusions: This study provides the first empirical evidence for the performance, measurement, and prediction characteristics of oral-health specific and generic QoL instruments for the oral health side effects of systemic cancer treatment. Instrument validity is supported for oral health complications in cancer patients. These results provide benchmarks for PROs at the intersection of oral medicine and surgery, dentistry, and oncology. [Table: see text]
Prevalence of use of herbal therapies in adult cancer patients: Potential for herb-drug interactions
Authors: D. L. Citrin, D. Gupta, T. C. Birdsall, A. Aslam, J. F. Grutsch, T. Wodek, C. G. Lis
Journal: Journal of Clinical Oncology (2005)

6086 Background: The use of herbs is very common among cancer patients undergoing chemotherapy. The risk for herb-drug interaction is emerging as a growing concern in these patients because of a narrow therapeutic index of chemotherapy agents. A few herbs such as Garlic, Ginkgo, Echinacea, Ginseng, Valerian, Kava, grape seed extract and St. John’s Wort have been identified to have potentially adverse interactions with some commonly used chemotherapy agents. We investigated the prevalence of use of these herbs at our cancer center. Methods: A survey of 80 adult cancer patients presenting for treatment at Cancer Treatment Centers of America, Zion, IL was completed between 11/01 and 10/03. All patients had undergone chemotherapy within the last 30 days. Patients completed McCune Questionnaire, a validated instrument that captures information on the use of 56 dietary supplements in cancer, at admission to the hospital. Results: Of 80 patients, 35 (44%) were males and 45 (56%) females. 23 (29%) had breast cancer, 22 (27.5%) colorectal cancer, 10 (12.5%) lung cancer while 25(31%) had a variety of other cancers. Overall prevalence of use of herbs was 65% (52/80) while the prevalence of use of herbs suspected to have adverse interactions with chemotherapy was 25% (20/80). Of 20 patients who used one or more suspected herbs, 3 patients used 2 and 1 patient used 4 herbs. The most commonly used herbs were Garlic and Echinacea. Table 1 describes the prevalence of use of individual herbs. Conclusions: These findings have important implications for potential herb-drug interactions, and confirm the need for better patient-physician communication on the use of herbal therapies during cancer treatment. In addition, comprehensive research strategies are urgently needed to more accurately establish the nature and extent of interactions between herbs and chemotherapy drugs. Table 1. Prevalence of Use of Herbs Suspected to have Adverse Interactions with Chemotherapy (N = 80) No significant financial relationships to disclose.
Improving anti-emetics in chemotherapy induced nausea and vomiting.
Authors: Sandra Toutounji, Ron Fung, Katherine Enright
Journal: Journal of Clinical Oncology (2016)

220 Background: Chemotherapy induced nausea and vomiting (CINV) remains one of the most feared treatment-related toxicities in cancer patients. CINV has been shown to decrease quality of life and to increase dose modifications and unplanned hospital visits. Cancer Care Ontario (CCO) and the American Society of Clinical Oncology (ASCO) updated their CINV guidelines in 2013. These changes included a reclassification of many regimens from moderate (MEC) to highly emetogenic (HEC) and a decrease in the duration of serotonin inhibitors (5HT3i). Uptake of the new guidelines at Trillium Health Partners has been slow. We aimed to improve CINV by increasing the percentage of patients who received guideline concordant anti-emetics with their first cycle of HEC/MEC chemotherapy. Methods: The first 25 patients started on MEC/HEC chemotherapy during 3 time periods (pre-guidelines, 6 months post guidelines, 1.5 years post guidelines) were identified. The primary measure of interest was the percentage of patients receiving MEC/HEC who were treated in concordance with the updated CINV guidelines. Secondary measures included the percentage of MEC/HEC patients who experienced grade 2+ CINV. The collected data was used with quality improvement techniques to guide the development of interventions to improve guideline concordance. Results: The concordance of anti-emetics on the day of chemotherapy improved over time, but post-chemotherapy concordance remained at 0% (table). The primary driver for concordance was the use of NK1inhibitors on chemotherapy day, and the duration of 5HT3i post-chemotherapy. Using quality improvement methodology, the highest impact intervention was identified as changing the default settings in the computerized order entry system (CPOE) to reflect the updated guidelines. These changes are currently in progress and a test of this change will be presented. Conclusions: Concordance with CINV guidelines improved over time resulting in lower CINV and less need for reactive CINV interventions. Further work to target duration of 5HT3i is ongoing. [Table: see text]
Identification of prognostic value of lymphocyte-to-monocyte ratio in patients with advanced HBV-associated hepatocellular carcinoma.
Authors: Zhan-Hong Chen, Yingfen Hong, Xiao-kun Ma, Xing Li, Dong-hao Wu, Qu Lin, Min Dong, Jie Chen, Li Wei, Tian-tian Wang, Dan-yun Ruan, Jingyun Wen, Xiang-yuan Wu
Journal: Journal of Clinical Oncology (2016)

206 Background: Inflammatory microenvironment plays an important role in the progression of HCC. Peripheral blood LMR, as a novel inflammatory biomarker combining an estimate of host immune homeostasis and tumor microenvironment, has been found to be a predictor for clinical outcomes in various malignancies. There have been no reports regarding the prognostic value of LMR in advanced HCC until now. We want to investigate the prognostic value of LMR in patients with advanced HBV-associated hepatocellular carcinoma. Methods: From September 2008 to June 2010, a total of 174 patients with HBV-associated advanced HCC without fever or signs of infections were analyzed. Clinicopathological parameters, including LMR, were evaluated to identify predictors of overall survival. Univariate and multivariate analyses were performed, using the Cox proportional hazards model. The best cutoff was determined with time-dependent receiver operating characteristic curve. Results: Univariate and multivariate analyses showed that LMR was an independent prognostic factor in overall survival in patients with advanced HCC(P &lt; 0.01 ). The best cutoff point of LMR was 4.52. All patients were dichotomized into either a low LMR group( ≤ 4.52) or a high LMR group( &gt; 4.52). Overall survival(OS) of high LMR group was significantly longer than that of low LMR group(P &lt; 0.01 ). High LMR group patients had significantly higher 6-month OS rate(50% vs 23%, P &lt; 0.01) than that of low LMR group patients. Higher LMR level was significantly correlated with the presence of metastasis and larger tumor size(P &lt; 0.05). Conclusions: LMR is an independent prognostic factor of advanced HCC patients. Higher Baseline LMR levels indicates better prognosis.
Association of gender-related tumor recurrence with a polymorphic variant of LMTK3 in stage II and III colon cancer.
Authors: Wu Zhang, Armin Gerger, Melissa Janae Labonte, Dongyun Yang, Pierre Oliver Bohanes, Yan Ning, Thomas Winder, Peter M.D. Wilson, Leonor Benhaim, Rita El-Khoueiry, Anthony B. El-Khoueiry, Syma Iqbal, Georgios Giamas, Justin Stebbing, Heinz-Josef Lenz
Journal: Journal of Clinical Oncology (2012)

454 Background: Recent evidence suggests that Lemur Tyrosine Kinase 3 (LMTK3) activates estrogen receptor alpha (ERα) transcriptional activity in breast cancer. The mutant variants of two single nucleotide polymorphisms (SNPs) in LMTK3 (rs8108419 and rs9989661) were independently associated with reduced time to tumor recurrence (TTR), suggesting these SNPs were functionally significant. In colon cancer (CC), ERβ expression has been shown to be predominant with low levels of ERα also expressed. ERα stimulates cell proliferation, while ERβ negatively regulates the estrogen-dependent activity of ERα. Based on these previous findings, we hypothesized that LMTK3 rs808419 and rs9989661 may predict TTR in stage II and III CC. Methods: Either blood or FFPE tissue specimens were obtained from 234 patients (107 females and 127 males; median age 59 yrs (range 22–78 yrs)) with stage II (105 pts) or III (129 pts) CC at the University of Southern California. The median follow-up was 4.4 years. LMTK3 rs8108419 and rs9989661 were determined by PCR-RFLP. The primary endpoint of the study was TTR. This study was conducted adhering to the reporting recommendations for tumor marker prognostic studies (REMARK). Results: The minor allele of LMTK3 rs9989661 (C; frequency=30.5%) showed significantly longer median TTR (5.9 vs 12.2+ yrs; HR: 0.41, 95%CI: 0.15-1.18, log-rank p=0.086; univariate analysis) in female CC patients. After Cox proportional hazards model adjustment for stage and type of adjuvant chemotherapy, this result remained significant (HR: 0.25, 95%CI: 0.077-0.778, Wald test p=0.017). No significant association was found between TTR and LMTK3 rs9989661 in men and rs8108419 in both genders. Conclusions: This is the first report demonstrating LMTK3 rs9989661 associations with gender-related TTR in CC. We hypothesize that there is an ERα-dependent loop mechanism with higher estrogen levels in females exerting the effect on ERβ. Larger prospective trials are warranted to confirm these findings, and in vitro and in vivo studies are needed to identify the underlying biological mechanism.
Association of SF3B1 with Ring Sideroblasts in patients, In Vivo, and In Vitro models of Spliceosomal Dysfunction
Authors: Valeria Visconte, Hideki Makishima, Anna M Jankowska, Fabiola Traina, Hadrian Szpurka, Heesun J. Rogers, Andres Jerez, Christine L. O'Keefe, Sara Cohen Slatkin, Manoj Bupathi, Kathryn M Guinta, Michael J Clemente, Yogen Saunthararajah, Anjali S. Advani, Matt Kalaycio, Haruhiko Koseki, Kyoichi Isono, Jarnail Singh, Richard A Padgett, Mikkael A. Sekeres, Jaroslaw P Maciejewski, Ramon V Tiu
Journal: Blood (2011)
Comparison between two prognostic index: Nottingham index (NPI) and an alternative index based on log of nodal involvement (Lpi)
Authors: C. Abrial, X. Durando, P. Chollet, O. Tacca, I. Raoelfils, M. Mouret-Reynier, P. Gimbergues, F. Penault-Llorca
Journal: Journal of Clinical Oncology (2008)

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The female self-advocacy in cancer survivorship scale: Validating a new measure to support patient voice and engagement.
Authors: Teresa Hagan, Susan M. Cohen, Margaret Quinn Rosenzweig, Kristin Kelley Zorn, Clement Stone, Heidi AS Donovan
Journal: Journal of Clinical Oncology (2016)

96 Background: The Female Self-Advocacy in Cancer Survivorship (FSACS) Scale is a new measurement tool designed to address the increasing need for cancer survivors to lead their care in face of barriers. Based on previous input from female cancer survivors and other stakeholders, the purpose of this study is to evaluate the construct validity of the FSACS Scale. Construct validity is supported by evidence from: (I) Internal structure consistent with the underlying model of self-advocacy; (II) Sensitivity to differences between known groups; (III) Relationships between self-advocacy and key predictors (openness and conscientiousness; information engagement; social support) and outcomes (symptom distress and healthcare utilization); (IV) Relationships between self-advocacy and related concepts (patient activation; self-advocacy within the HIV/AIDS population); and (V) Relationships between self-advocacy and criterion measures. Methods: A mixed-mode cross-sectional survey design was used. Women with a history of an adult diagnosis of invasive cancer were recruited from two patient registries and seven advocacy organizations. Analyses included an exploratory factor analysis, t-tests, and bivariate correlations. Results: 315 adult female cancer survivors completed the survey. Evidence from all five construct validity hypotheses supports the construct validity of the FSACS Scale. The factor analysis confirmed the three underlying dimensions of self-advocacy resulting in a 20-item measure explaining 45.87% of the variance in responses with subscales’ Cronbach’s alphas between 0.791 and 0.850. Conclusions: Results support that the FSACS Scale is a theoretically-grounded measure of self-advocacy that can be used by clinicians and researchers to identify women at-risk for poor outcomes associated with low self-advocacy.
Tesetaxel: Development of a weekly dosing schedule for an oral advanced-generation taxane.
Authors: M. Beeram, A. W. Tolcher, K. P. Papadopoulos, A. Lang, L. Smith, R. Drengler, A. Qureshi, A. Patnaik
Journal: Journal of Clinical Oncology (2011)

e13045 Background: Tesetaxel, a novel, orally absorbed taxane that is not a substrate for P-glycoprotein, has demonstrated antitumor activity in pts with breast, gastric, and other solid tumors. Neutropenia is the most common dose-limiting effect. To date, tesetaxel has solely been administered using a once every 3 weeks schedule with an MTD of 27 mg/m2. Since other taxanes such as docetaxel and paclitaxel exhibit schedule-dependent effects, we evaluated a weekly dosing regimen of tesetaxel in escalating fixed doses. Threshold models predict taxane pharmacodynamics, and times above a threshold concentration (tC) correlate with both tumor response and toxicity; for paclitaxel, for instance, tC > 0.05 micromol/L was the best predictor of objective response and severe neutropenia (Joerger et al., Clin Cancer Res, 2007). Methods: Eligible pts had advanced solid tumors, ECOG PS 0-2, and adequate organ function. Tesetaxel was given once weekly for 3 weeks in 28-day cycles, beginning at a flat dose of 25 mg per cycle (e.g., 10 mg in Weeks 1 and 2 and 5 mg in Week 3), with progressive increase in total dose per cycle to 30, 45, 60 mg, and continued escalation in 15-mg increments to the MTD. Serial blood samples were collected, and parent compound was assayed by HPLC. Results: To date, 12 pts (3 pts/level) have been treated. Weekly dosing has been well tolerated up to 60 mg. No dose-limiting reactions have been observed, and the MTD has not been reached. Tesetaxel has a long T1/2 (~180 hrs), and low plasma concentrations in the range of 0.3–2.5 nmol/mL were detectable prior to the next dose. There was no substantial drug accumulation over multiple cycles. Conclusions: Weekly oral administration of tesetaxel is feasible and provides long-term, low-level exposure to this taxane. Given threshold effects observed with other taxanes, this finding may similarly predict clinical outcome and toxicity with tesetaxel. The MTD of this weekly regimen has not been reached, but exceeds the MTD of the every-3-week regimen.
Inflammation-based prognostic scores to predict outcome in patients with cancer.
Authors: D. C. Mcmillan, D. S. Morrison, D. Talwar, P. G. Horgan, M. J. Proctor
Journal: Journal of Clinical Oncology (2011)

e21154 Background: There is increasing evidence that the host inflammatory response plays an important role in the development and progression of cancer. A number of inflammation-based prognostic scores have been associated with survival in patients with cancer. The aim of the present study was to compare the prognostic value of inflammation-based prognostic scores (mGPS, NLR, PLR and PI) and examine whether they can be used across all tumour types. Methods: Patients in the North Glasgow with a registered cancer, who had a single sample taken for C-reactive protein, albumin, white blood cell, neutrophil, lymphocyte and platelet counts between 2000 and 2007, were included. The modified Glasgow Prognostic Score (mGPS), neutrophil:lymphocyte ratio (NLR), platelet:lymphocyte ratio (PLR) and prognostic index (PI) were compiled from the above blood tests. Results: 8759 patients were studied and 5163 (59%) died. The median time from blood sampling to diagnosis 1.7 months. On survival analysis, stratified by tumour type, a raised mGPS (HR 1.74, p<0.001), NLR (HR 1.97, p<0.001), PLR (HR 1.46, p<0.001) and PI (HR 1.69, p<0.001) were associated with increased overall and cancer specific mortality independent of age, sex and deprivation. Conclusions: A number of inflammation-based prognostic scores are independently associated with survival in patients with cancer, independent of tumour type, and should be considered an important tool in predicting outcome.