tbuckley/cabot-search huggingface dataset:
Characterization of ovarian cancer long-term responders on olaparib.
Authors: Stephanie Lheureux, Jonathan A. Ledermann, Stanley B. Kaye, Charlie Gourley, Michael Friedlander, David Bowtell, Jacques De Greve, Anna deFazio, Ronnie Shapira-Frommer, Johann Sebastian De Bono, M. William Audeh, Elise C. Kohn, Kathryn Alsop, Clare L. Scott, Ursula Matulonis, Bella Kaufman, Brent Burger, Jane D Robertson, Tony Ho, Amit M. Oza
Journal: Journal of Clinical Oncology (2014)

5534 Background: BRCA1/2 mutations (BRCAm) appear to predict benefit from PARP inhibition. However, non-mutation carriers also benefit and not all patients (pts) with BRCAm respond to PARP inhibitors. The objective of this study was to identify and clinically characterize pts remaining on durable olaparib therapy for further molecular analyses to determine the features underlying long-term response. Methods: A retrospective meta-analysis comprised pts with recurrent ovarian cancer (OC) from trials in the olaparib clinical program. Long- and short-term benefits were defined as olaparib treatment for > 2 years and < 6 months respectively, segregated by monotherapy or maintenance. Results: 372 OC pts, 323 with BRCAm have been already treated with olaparib 400 mg bid capsule as monotherapy at time of relapse (Studies D0810C000001-02-09-12-20-24-42). In these trials, 197 pts (53%) were treated < 6 months from which 169 pts (52.3%) had BRCAm. Conversely, there were pts with long-term benefit from olaparib, such as 6 pts in the D0810C000020 study, treated for > 4 years. The table shows the OC pts treated with maintenance olaparib (n=136) and also with olaparib in combination with chemotherapy followed by maintenance (n=81), separating out the pts with BRCAm. Conclusions: Although many long-term responders to olaparib have BRCAm, there are several with no known BRCAm. Response durability may be related to a number of factors including germline and somatic BRCAmutations. The clinical and molecular characterization of these pts and comparison with short- or median-term disease control will improve understanding of response and resistance to PARP inhibitors. Treatment duration D0810C000019: Olaparib maintenance 400 mg bid capsule monotherapy* D0810C000041: Combination with carboplatin/paclitaxel followed by maintenance 400 mg bid capsule monotherapy* Pts All (n=136) BRCAm (n=74) BRCA wt/vus (n=57) BRCA missing (n=5) All (n=81) BRCAm OC subgroup (n=20) BRCA wt/vus OC subgroup (n=34) BRCA missing OC subgroup (n=27) < 6 months 49 (36%) 21 (28.4%) 25 (43.9%) 3 (60%) 19 (23.5%) 0 11 (32.4%) 8 (29.6%) > 24 months 32 (23.5%) 21 (28.4%) 11 (19.3%) - 17 (21%) 11 (55%) 3 (8.8%) 3 (11.1%) Abbreviations: wt, wild type; vus, variant unknown significance. *Data cut off: November 2012.
Systematic education and utilization of volunteer patient advocates for cancer clinical trial information dissemination at NCCTG community sites
Authors: C. Chauhan, W. Eppard
Journal: Journal of Clinical Oncology (2004)

1031 Background: Cancer patients are often unaware of cancer clinical trials or fearful of participation because of mistrust and misunderstanding of cancer clinical trial methods and protocols. Methods: The Patient Advocacy Committee of NCCTG has developed a five-prong approach of education and support of volunteer community patient advocates who are cancer survivors. Trained, volunteer patient advocates intervening at the individual and community level may have a positive impact on cancer clinical trials accrual. This program includes: 1) Yearly two-day training symposium; 2) Regular individual mentor telephone contact; 3) Quarterly three-hour long conference calls; 4) Co-chair community site visits; 5) Listserv membership. Member patient advocates are educated and supported in working proactively in their communities to share general information about cancer clinical trials in a non-threatening, non-coercive environment, moving people to a more positive, receptive posture. Activities of trained advocates include but are not limited to meeting with newly diagnosed patients, presentation of general clinical trials information to community service groups, and speaking to cancer support groups. Results: Currently thirty-eight cancer survivor patient advocates represent twenty-five communities in the program, demonstrating active community involvement, high community visibility, innovative educational program development, and unflagging dedication to cancer education. Conclusions: Recruitment, training, and support of an affiliated group of volunteer community patient advocates provides positive, high visibility for cancer research through group and individual education initiatives. Volunteer peer educators facilitate the movement of clinical trials into mainstream consciousness.Community and individual education by trained volunteer patient advocates enhances public awareness and understanding of the purpose and process of cancer research . No significant financial relationships to disclose.
Respiratory Network Stability and Modulatory Response to Substance P Require Nalcn
Authors: Szu-Ying Yeh, Wei-Hsiang Huang, Wei Wang, Christopher S. Ward, Eugene S. Chao, Zhenyu Wu, Bin Tang, Jianrong Tang, Jenny J. Sun, Meike Esther van der Heijden, Paul A. Gray, Mingshan Xue, Russell S. Ray, Dejian Ren, Huda Y. Zoghbi
Journal: Neuron (2017)
Combination therapy with gefitinib and capecitabine in metastatic breast cancer (MBC): A phase I trial
Authors: E. L. Mayer, L. N. Harris, A. H. Partridge, R. S. Gelman, S. T. Schumer, R. S. Comanaru, M. Long, E. Sampson, H. J. Burstein, E. P. Winer
Journal: Journal of Clinical Oncology (2006)

10564 Background: Preclinical models have suggested synergy between the EGFR tyrosine kinase inhibitor gefitinib (G) and the 5-FU prodrug capecitabine (C), an active treatment for MBC. This phase I study was designed to explore the safety of this all-oral regimen in patients (pts) with MBC. Methods: Pts were treated in sequential cohorts (n = 3–6) using a fixed dose of G (250 mg qd continuously) and escalating doses of C (1500 mg/m 2 /day, 1750 mg/m 2 /day, and 2000 mg/m 2 /day) in a 21-day cycle. An additional 10 pts were enrolled in a validation cohort at the maximum tolerated dose (MTD). Dose limiting toxicity (DLT) was defined during the first cycle as any grade 3/4 toxicity or a delay &gt;3 weeks due to unresolved toxicity. The primary endpoint was safety; secondary endpoints included assessments of tumor response (using RECIST criteria), adherence to the oral regimen, and biomarker measurements. Results: 19 pts were enrolled; the mean age was 49 y, 58% of tumors were hormone receptor positive, and 10% were HER2 positive. The mean number of prior MBC chemotherapy regimens was 1.2 and 74% had visceral spread. No pts in dose escalation cohorts had DLT during cycle 1. The 10 pts in the validation cohort (MTD C 2000 mg/m 2 ) had 3 DLTs in cycle 1 and 1 DLT in cycle 2 (95% CI 12–74%). For all pts at C 2000 mg/m 2 (n = 13), there was no grade 4 toxicity, however 5 (38%) had grade 3 toxicity, 7 (54%) required a C dose reduction, and 2 (15%) came off study for persistent toxicity. 3 pts (23%) experienced grade 3 diarrhea, and 4 pts (31%) had moderate to severe hand/foot syndrome. There were no objective responses (PR or CR) observed out of 18 evaluable pts. The mean number of completed cycles of therapy was 4.8, and 3 pts (16%) were treated for &gt; 24 weeks. An exploratory analysis of serum EGFR measurements demonstrated no association of pre- or post-therapy values with lack of progression. Monitoring adherence to oral therapy using a microelectronic monitoring system (MEMS) was feasible, and detailed data will be presented. Conclusions: In this phase I dose escalation trial of G/C therapy in women with MBC, treatment was generally well tolerated, with a confirmed C MTD of 2000 mg/m 2 . Moderate toxicity and dose reductions were common. In this small cohort, the G/C combination did not appear to have substantial anti-tumor activity. [Table: see text]
A trial of gemcitabine (gems) in combination with cisplatin for treatment of recurrent/metastatic head and neck squamous cell carcinoma (HNSCC)
Authors: M. Yang, H. Wang, W. Wang, T. Chiou, P. Chen
Journal: Journal of Clinical Oncology (2006)

15505 Aims: To determine the efficacy of gemcitabine in combination with cisplatin, and to assess the safety profile of the regimen as the first-line treatment in patients with recurrent/metastatic HNSCC. Methods: An open-label, non-comparative, multi-center phase II study for patients with histologically proven recurrent/metastatic HNSCC without prior treatment for their recurrent/metastatic disease. In this trial, 1250 mg/m 2 gemcitabine was administered alone on day 1 and day 8 and 80 mg/m 2 cisplatin would follow gemcitabine on day 8, to be repeated in cycles of 21 days until disease progression, intolerable toxicity, or consent withdrawal. Results: Between 04/2004 and 09/2005, 34 patients were enrolled in this study. 33 patients have completed the study treatment. Characteristics of the 33 patients: male- 33; median age- 51 years (range 38–65); 30 pts had a performance status (PS) of 0 or 1 and 3 had a PS of 2 (ECOG scale); histology: recurrent/metastatic HNSCC in all cases. Of the 33 patients, 25 were evaluable for response assessment. Partial response was observed in 8, stable disease in 10, and progressive disease in 7 patients. Overall response rate was 32% (95% Confidence interval 12%–52%). Grade 3/4 hematological toxicities included neutropenia in 12 pts, leukopenia in 11 pts, thrombocytopenia in 2 pts and anemia in 8 pts. Grade 3/4 nausea or vomiting was observed in 2 pts. Other toxicity was mild in the treatment. Patient treatment and follow-up are still ongoing. Conclusion: This study, with an overall response rate of 32% and a rate of stable disease of 40%, has shown a good activity with mild and acceptable toxicities of gemcitabine/cisplatin regimen in patients with recurrent/metastatic HNSCC. Survival and response analyses will be presented at the meeting. No significant financial relationships to disclose.
John Hector Scotson
Authors: Edward Andrews, Christopher Harrison
Journal: BMJ (2017)

John Hector Scotson was a much loved general practitioner, known for his kind, gentle, unhurried, and calm approach. His great listening skills stemmed from a genuine interest in patients and their families. His cheerful disposition was rarely troubled, and he was always polite and self effacing. He was a partner in Timperley, near Altrincham, for 35 years and was a trainer for 20 of these. While he was in practice and well after retiring, many of his articles and letters were published in medical journals and national newspapers. Subjects that particularly engaged his interest included iatrogenic effects in medicine, delay in cancer diagnosis in primary care, and, especially, medical ethics, where he stood up for Christian and Hippocratic principles, opposing calls for euthanasia and embryo experimentation. His well known views on ethical principles …
Early results of a phase II multi-institutional trial of chemoradiation (CR) using weekly docetaxel (Doc) and erythropoetin (Epo) for high-risk postoperative head and neck cancer (HRPHNC) patients
Authors: A. J. Cmelak, B. A. Murphy, D. Raben, M. Kane, E. Weng, B. Burkey, B. Kish, J. Song, J. Netterville
Journal: Journal of Clinical Oncology (2004)

5552 Background: Postoperative radiation with concurrent cisplatin has shown improved efficacy over radiation alone in randomized trials for patients with HRPHNC: ≥2 involved nodes (N), extra-capsular nodal disease (EC), +margins (+M), N3 disease (N3). This phase II trial in HRPHNC evaluates the efficacy and toxicities of postop CR using weekly docetaxel, and with weekly Epo in patients with suboptimal Hgb (≤12 gm/dl). Methods: HRPHNC patients were enrolled 2–8 weeks after surgery with PS 0–1, no distant metastases, and no prior regional radiation or chemotherapy. Treatment consisted of conformal radiation (60Gy in 6 weeks) with weekly Doc 25mg/m2 and Epo 40,000U. Primary endpoints include local/regional control, DFS, and patterns of failure. Secondary endpoints include toxicity and QOL. Results: 15 HRPHNC (11 male, 4 female) ages 22–69 years (median 51) were enrolled. Characteristics include: Oropharynx=6, Oral Cavity=6, Hypopharynx=1, Larynx=1; AJCC stage III=2 pts, IV=13 pts. HRPHNC eligibility included: N=11, EC=8, +M=5. Doc was held for Gr4 mucositis (muc), Gr4 dermatitis, or allergy. Doc was reduced to 20mg/m2/wk after 5 pts had prolonged Gr≥3 muc; however, all 5 received 5 or all 6 weekly doses. At 20mg/m2, the number of Doc doses tolerated/prescribed were: 3/6=1 pt, 4/6=3 pts, 5/6=3 pts, 6/6=3 pts, and most often held for acute Gr4 muc. Median FU is 18 months (3–41): 12 (80%) remain NED, 1 patient died of local recurrence, 1 of distant mets, and 1 with both. No Gr≥3 late toxicities have been observed, although prolonged muc and taste loss (∼3 months) has been observed in a few patients. Only 1 pt requires PEG to date. QOL data will be analyzed at a later date. Conclusions: Postoperative radiation with weekly doc 20mg/m2 (+/- Epo) for HRPHNC is feasible. Early results suggest high locoregional control rates (80%). Weekly Doc doses > 20 mg/m2 appear to result in prolonged Gr≥3 muc. Accrual will continue using this regimen with intensity-modulated radiation therapy, and local/regional control, DFS, and toxicities will be evaluated with this approach. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Pfizer Pfizer Johnson & Johnson
Weekly bolus topotecan as first-line therapy for extensive stage small cell lung cancer in patients who are elderly, poor performance status, or have severe coexistent illness: A Minnie Pearl Cancer Research Network phase II trial
Authors: J. F. Patton, J. D. Hainsworth, D. R. Spigel, H. A. Burris, D. A. Yardley, L. H. Morrissey, L. Sylvester, C. Dannaher, D. L. Shipley, F. A. Greco
Journal: Journal of Clinical Oncology (2004)

7275 Background: Topotecan given intravenously for 5 consecutive days every 3 weeks is standard second-line therapy for patients (pts) with relapsed small cell lung cancer (SCLC) and ovarian cancer. Weekly bolus topotecan produces significantly less toxicity than the 5 day schedule, and appears as active as the standard schedule in pts with relapsed ovarian cancer. Methods: This ongoing phase II study was designed to evaluate the toxicity and response rate of weekly bolus topotecan in pts with previously untreated extensive stage SCLC who were elderly (> 65 years), poor performance status (PS), or had severe coexistent medical illness. Topotecan 4mg/m2 IV over 30 minutes for 12 consecutive weeks was planned. Dose modifications were made based on toxicity. Pts were evaluated for response after 4 weeks; at least 3 weekly treatments were required to be evaluable. Results: Seventeen pts of the required 40 pts have thus far been enrolled; 12 men, 5 women, ages 64–81 (median 71); PS 0=1, 1=4, 2=12). Thirteen pts are evaluable for response. Two pts have had partial responses (15%); 6 pts stable tumor (45%). Grade 3/4 neutropenia has been seen in 4 of 17 pts (24%), but no grade 3/4 thrombocytopenia was observed. Grade 2 fatigue was observed in 10 pts (56%) and grade 3 fatigue in 6 pts (35%). A total of 107 weeks of therapy have been administered. There were 15 weeks of treatment delay and 8% required dose reductions. Conclusions: Weekly bolus topotecan appears to have modest activity and is well tolerated in this poor prognostic group of pts with previously untreated extensive stage SCLC. We expect to evaluate 15 additional pts soon. Severe myelosuppression is seen less often than expected compared to the standard 5 day schedule of topotecan. Fatigue is an important toxicity and may be reduced by planned rest weeks. Studies of weekly topotecan in combination with other active cytotoxic agents should be considered in pts with extensive stage SCLC. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration GlaxoSmithKline GlaxoSmithKline GlaxoSmithKline
Surviving as a therapeutic target and biomarker for non-small-cell lung cancer
Authors: B. Lu, A. Gonzalez, P. Massion, Y. Shyre, D. Carbone, D. Hallahan
Journal: Journal of Clinical Oncology (2004)

7153 Background: Survivin inhibits apoptosis and promotes mitosis. Its expression has been restricted to malignant tissues. High levels of survivin expression are associated with poor survival of cancer patients. Both nuclear and cytoplasmic staining of survivin was observed. However, the prognostic value of cellular compartmentation of survivin has been a subject of debate. Methods: Antisense oligonucleotides (ASO) against survivin were used to examine the impact of survivin inhibition upon mitosis, apoptosis and viability of H460 lung cancer cells. Immunohistochemistry was used to determine whether nuclear or cytoplasmic localization of survivin predicts survival of 48 patients with resected NSCLC. Results: The anti-Survivin ASO specifically attenuated the protein expression of survivin in H460 cells. Survivin inhibition using antisense oligonucleotides resulted in increases of apoptosis and mitotic arrests of H460 cells. H460 cells had significantly decreased viability following the treatment of the antisense oligonucleotides. Patients with nuclear staining of survivin had significantly shorter overall survival (relative risk: 3.9, p=0.02). Conclusions: Our data suggest that survivin is a potential therapeutic target and a prognostic biomarker for NSCLC. No significant financial relationships to disclose.
Evaluation of renal function in children with solid tumors: Comparison between estimation with Schwartz formula and EDTA clearance.
Authors: Carole Serrano, Rana Benazzouna, Christophe Maritaz, Christelle Dufour, Dominique Valteau Couanet, Isabelle Borget, Jean Lumbroso, Herve Remy, Francois Lemare
Journal: Journal of Clinical Oncology (2012)

9560 Background: Using the [51Cr]-ethylenediamine tetra acetic acid ([51Cr]-EDTA) method provides an accurate measure of glomerular filtration rate (GFR) for each patient. However, this method is not always feasible in routine. Thus, several mathematical equations have been developed to predict creatinine clearance. The most widely used in pediatric patients is the Schwartz formula, based on patient height and serum creatinine. However, this method has not been validated in pediatric cancer patients. The aim of the present study was to compare GFR measured with the 51Cr-EDTA method to GFR estimated with the Schwartz formula in patients younger than 18 years of age and treated for solid tumors. Methods: Data have been retrospectively collected on consecutive children treated between 2001 and 2011 at Institut Gustave Roussy. All of the patients had undergone assessment of GFR via 51Cr-EDTA clearance and estimation of renal function by the Schwartz formula. Exclusion criteria were serum creatinine under 25µmol/L or no recent dosage available. GFR analysis was realized using the slope intercept method after a single injection of 51Cr-EDTA solution.. Values of the GFR were calculated by multiplying the volume of dilution by the slope of the single exponential fit to the three data points and then expressed in ml/min/1.73m². Student paired t-test (alpha = 0.05) was used to compare results obtained for each patient with the two methods. Results: 196 patients (120 males, 76 females), treated with various types of cancer (neuroblastoma, osteosarcoma, Ewing sarcoma, lymphoma…) Mean age was 6.7 years. Mean GFR was 127.5 ml/min/1.73m² with the 51Cr-EDTA method versus 148.1 ml/min/1.73m² with the Schwartz formula. Mean of difference was 20.7 ml/min/1.73m² with a confidence interval [-25.7 ; -15.6] (p &lt; 0.0001). Conclusions: GFR estimated with the Schwartz formula is statistically different from the isotopic method. In most cases, GFR estimated with the Schwartz formula is overestimated. This study highlights the lack of accuracy of this equation in pediatric population with cancer. The 51Cr-EDTA method must be preferred when a reliable and accurate evaluation of renal function is needed.
The morbidity and mortality conference (MMC) concept applied to contemporary oncology practice: Retrospective findings on management of 233 patients (pts) who died of ovarian cancer (OC), colorectal cancer (CRC), and wild-type (no identified targetable mutation) nonsquamous non-small cell lung cancer (WTLC).
Authors: Neil Love, Michael J. Birrer, J. Randolph Hecht, Heather A. Wakelee, Gigi Qiqi Chen, Margaret Ann Deutsch, Maria Eugenia Picton, Estelamari Rodriguez, Lyndsay Willmott, Gloria Kelly, Kirsten Miller, Jonathan Moss, Douglas Paley, Kathryn Ziel
Journal: Journal of Clinical Oncology (2017)

241 Background: MMC have traditionally evaluated pt management and potential areas for quality improvement. We hypothesized that this approach could be adapted and extrapolated to gain increased insight into how pts with common solid tumors are being treated in general oncology practice and how the approaches used align with evidence-based guidelines. Methods: 102 randomly recruited US-based general medical oncologists from a proprietary database of 4,019 agreed to consult their medical records and provide information on biomarkers assessed, systemic therapies administered and other treatment-related factors for the last pt in their practice to die from OC, CRC and/or WTLC. An IRB exemption was obtained and a modest honorarium was provided. Results: Pts with OC, CRC and WTLC received a median of 3, 3 and 2 lines of therapy, respectively, the majority of which were supported by guidelines, but in more than half of cases, the regimen administered required dose adjustment/discontinuation due to toxicity. Less than half of pts were offered trial participation and only 15 (6%) entered a trial. 19 pts with OC (25%), 25 pts with CRC (32%) and 58 pts with WTLC (73%) did not undergo BRCA, MSI and multiplex genomic testing, respectively, despite the recommendation of available guidelines. Conclusions: The MMC model may be an effective means to document variability as well as consistency in current oncologic care. Data generated via this assessment juxtaposed with current clinical evidence and available guideline recommendations could potentially serve as a powerful educational intervention. These findings require additional validation but provide initial support for future iterations of this exercise. [Table: see text]