tbuckley/cabot-search huggingface dataset:
Perception of curability in an international cohort of advanced cancer patients receiving palliative care.
Authors: Sriram Yennu, Omar M. Shamieh, Luis Fernando Rodrigues, Columbe Tricou, Marilène Filbet, Kyaw Naing, Akhileswaran Ramaswamy, Mary Joycylyn S. Bautista, Pedro Emilio Perez-Cruz, Sarah Fakrooden, Mary Ann Muckaden, Sofia Bunge, Vikash Sewram, Antonio Noguera Tejedor, David Hui, Minjeong Park, Diane D Liu, Eduardo Bruera
Journal: Journal of Clinical Oncology (2016)

5 Background: There is limited data on the illness understanding and perception of cure among advanced cancer patients (ACP) receiving palliative care around the world. The aim of the study was to determine the frequency and factors associated with perception of curability in countries in North and South Americas , Europe, Asia and Africa. Methods: Secondary analysis of a study to determine the decisional control preferences in different countries. ACP receiving palliative care were surveyed to assess the patients’ Understanding of Illness using a Understanding Of Illness questionnaire. Descriptive statistics and Logistic regression analysis were performed. Results: A total 1390 ACPs were evaluated. The median age was 58, 55% were female, 59% were married, 47% were catholic, 36.2% were educated college or higher degree. 681/1390 (49%) reported that their cancer is curable, 60% felt perceived that the goals of therapy was “to get rid of their cancer,” 79% perceived that the goals of the therapy was to “make them feel better.” 62 % perceived they were relatively healthy. Logistic regression analysis (Table 1) shows that better Karnosfsky performance status (OR 1.009, P = 0.04), higher education (OR 0.52, P = 0.0001), ACP's belonging to Brazil, France and S. Africa were less likely and ACPs from Philippines, Jordan were more likely to have a perception of curability. Age, gender, marital status, religion and passive decision control preferences were not significantly associated with perception of curability. Conclusions: The perception of curability in ACP's is 49% and significantly differs by education, performance status, and country of origin. Integration of Palliative Care can be more complex in these patients. Further studies are needed to develop strategies to reduce this misperception so as to have early integration of palliative care. [Table: see text]
A phase II study of ganetespib (G) as second- or third-line therapy for metastatic pancreatic cancer (MPC).
Authors: Ramya Thota, Laura Williams Goff, Emily Chan, Jordan Berlin, C. Michael Jones, Pamela McClanahan, Gregory Dan Ayers, Dana Backlund Cardin
Journal: Journal of Clinical Oncology (2014)

297 Background: Heat shock protein 90 (HSP90) regulates folding, stability and function of signaling proteins such as EGFR, IGF-1R, c-Met, ERBB4, PDGFRα and c-Ret, several of which are key pathways for MPC pathogenesis. G prevents Hsp90 binding to client proteins leading to inactivation and degradation, disrupting signaling that promotes cancer progression. This phase II study is designed to evaluate the efficacy of G in patients (pts) with refractory MPC. Methods: Pts with MPC in the 2 nd or 3 rd line setting, with PS 0-1, received G 175 mg/m 2 intravenously once weekly for 3 weeks out of a 4 week cycle. Primary endpoint was disease control rate (DCR) at 8 weeks, with a goal of 70% DCR. Secondary endpoints were response rate (RR), overall survival (OS), and safety. 43 pts were planned for initial accrual. Simon’s optimal two-stage design was used to assess 8 week DCR. G was considered inactive if 8 or fewer pts among the first 15 treated had disease control after 8 weeks of treatment (tx). Results: Seventeen pts were enrolled, and 14 received G. Median age was 65 (range 33-77), 4 female and 10 male. Eight received 1 prior line of therapy, and 6 received 2 prior lines of therapy. Grade 3 related toxicities include abdominal pain (4), fatigue (4), diarrhea (4), hyponatremia (9), nausea (1) and vomiting (1). There were no Grade 4-5 related events. DCR at 8 weeks was 21%, and OS was 2.5 months. Three pts didn’t complete tx; 1 due to disease progression after first cycle, 1 due to tx related toxicity, and 1 withdrew after 2 tx’s. Early stopping rules for lack of clinical efficacy led to study closure. Conclusions: Single agent G was tolerable with modest disease control when used as a single agent in refractory MPC. This disease is resistant to chemotherapy, and given the emerging data in both lung and breast cancer suggesting improved activity of G in combination with cytotoxic agents, studies combining this agent with chemotherapy in MPC are under development. Supported by Vanderbilt-Ingram Cancer Center CCSG (P30CA68485) and Synta. Clinical trial information: NCT01227018.
Induction with cisplatin (C) and docetaxel (D) plus concurrent three-dimensional (3D) conformal radiotherapy and weekly C and D for locally advanced non-small cell lung cancer (NSCLC) patients (pts): Phase II trial
Authors: M. Poudenx, P. Bondiau, N. Venissac, J. Otto, N. Pourel, O. Castelnau, J. Berdah, B. De Surmont Salasc, E. Teissier, J. Mouroux
Journal: Journal of Clinical Oncology (2008)

7585 Background: Concurrent chemoradiotherapy (CT/RT) is a standard of care for pts with unresectable NSCLC. However, the optimal combination remains unclear in this setting. The aim of our study is to evaluate the feasibility of induction chemotherapy with C+D followed by weekly C/D and concurrent 3D-conformal radiotherapy for stage III pts. Methods: Locally advanced stage III NSCLC pts ( ECOG PS 0–1, weight loss < 5%, no pleural or pericardium effusion ) were eligible. Pts received 2 cycles of induction therapy (d1=d22) by C 75 mg/ m2 and D 75 mg/ m2 followed by a concurrent 3D-conformal RT + CT comprising : Involved-Field (IF) RT 66 grays in 33 fractions/ 61/2 weeks and C 20 mg/m2 + D 20 mg/m2 weekly. Intermediate evaluation was planned 4 weeks after the initiation of RT (40–44 grays) to access eligibility for surgery. Final evaluation was performed 30 to 45 days treatment completion. The primary endpoint was response rate assessed by RECIST criteria. Second objective was toxicity (NCI-CTC criteria). Results: From 2004/08 to 2007/11, 44 pts were included by 7 centers. 4 pts were ineligible. Median age 61 years (40–72), 75% males. Eighty-two % of pts had stage IIIB (T4 N0–2: 68.7%, T1–3N3: 15.6%, T4N3: 15.6 %) and 18 % stage IIIA (N2:100%). 6 patients (15%) underwent resection with 2/6 pathologic complete response. The others 34 pts completed the CT/RT treatment. Hematologic toxicity was as follows: grade 3 neutropenia 20%, grade 4 10%, grade 3 febrile neutropenia 5%. Esophageal toxicity was limited to grade 1/2 respectively in 17.5% and 15 % of pts and grade 3 in 5 %. Pulmonary toxicity was grade 1/2 pneumonitis 5%/5%. Other grade 3 significant side effects were nausea 5%, vomiting 5 %, diarrhea 2.5 %. One patient died 30 days after surgery (Septis). Objective response rate for the whole group (40 pts) was 65% CI 95% [50.2%-79.8%] (complete response 5%, partial response 60%, stable disease 17.5%, progressive disease 17.5%). Conclusions: Cisplatin/docetaxel induction chemotherapy followed by concurrent 3D conformal-IF RT and weekly C/D is a feasible protocol associated with a high response rate and acceptable toxicity. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration sanofi-aventis
Phase II study to determine response rate, pharmacokinetics (PK), pharmacodynamics (PD), safety, and tolerability of treatment with the humanized anti-epidermal growth factor receptor (EGFR) monoclonal antibody EMD 72000 (matuzumab) in patients with recurrent cervical cancer
Authors: J. Blohmer, M. Gore, S. Kuemmel, R. H. Verheijen, R. Kimmig, L. F. A. G. Massuger, A. Du Bois, W. M. Smit, S. Kaye, C. Deubelbeiss
Journal: Journal of Clinical Oncology (2005)

2534 Background: After chemotherapy failure, treatment options for advanced cervical cancer are limited. EGFR is expressed by 80–100% of cervical cancers, suggesting that inhibiting EGFR signaling may be beneficial. Matuzumab is a humanized IgG1 monoclonal anti-EGFR antibody with single-agent clinical activity. This study assessed the response rate to matuzumab in subjects with cervical cancer progressing after treatment with platinum-based chemotherapy. Methods: Subjects received matuzumab (800 mg) weekly for 6 months in 4-week cycles. Antitumor activity (RECIST criteria) was assessed by CT/MRI at screening and every 8 weeks. PK sampling was performed at days 1, 3, 5, 8, 15, 22, and 29, and at end of treatment. EGFR saturation and percentage of pEGFR and pMAPK were determined in biopsies (skin, tumor, vaginal tissue) at screening and after the 1st cycle. Safety and tolerability were monitored after each infusion and with weekly haematological assays and monthly laboratory assessments. Results: All subjects had prior chemotherapy; 39/41 prior radiotherapy. Tumors were 29 squamous cell, 11 adenocarcinomas, and 1 undifferentiated carcinoma, stages IVB (n=7), IIIB (n=8), IIIA (n=1), IIA-B (n=12) and IB (n=10) (3 missing). Median age was 44 (range 26–73) years. Subjects received a median of 8 matuzumab infusions (range 1–57). Among 38 evaluated subjects, best responses in the preliminary analysis were 2 PR and 9 SD (independent assessment pending). Matuzumab-related grade (gr) 3 adverse events included elevated γ-GT (1), hepatotoxicity (1), diarrhea (1), fainting and thrombocytopenia (1), anorexia and lethargy (1), abdominal pain (1), and skin peeling/dryness (1). One subject with gr 4 abdominal pain and blood amylase with gr 3 pancreatitis discontinued treatment. PK and biological marker evaluations will be presented. Conclusions: Based on preliminary observations, the level of activity in this phase II study merits further investigation of matuzumab after platinum-based chemotherapy in subjects with advanced cervical cancer. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Merck Merck, Merck KGaA Merck, Merck KGaA Merck, Merck KGaA
HER2 overexpression in patients with breast cancer: Comparative study carried out by two different groups of pathologists
Authors: N. Giacomi, A. Mainella, S. Vigo, M. Lamelza, P. Price, F. Mohamed, F. Marmissolle, J. J. Valerga Martin, M. Antonelli, M. Sansano
Journal: Journal of Clinical Oncology (2008)

22162 Background: c-erb-B2 is amplified in approximately 18–20% of breast cancers (BC). Her2 overexpression represents the determining factor for the potential use of trastuzumab. Immunohistochemistry (IHC) is the most used technique. Available evidence suggests that about 20% of current Her2 testing is inaccurate. There is no universal consensus about the technical aspects to be used in the definition of Her2 status. The objective was to evaluate the different results obtained by two groups of pathologists in the determination of Her2 and its impact in the therapeutic decision. Methods: Between June-December/07 64 clinical reports of pts with BC were analyzed. The original Her2 status analyzed by pathologists of group A was reviewed by a pathologist of reference (group B). For Her2 status review, IHC was used with a policlonal antibody (CB11–1/500), antigenic recovery, Diaminobenzidina (DAKO) and system of detection ENVISION. Manual method per protocol of work was used (National Plan Her2). The results were interpreted using score 0 to 3 +. Results: 64 biopsies were analyzed by group A. The determination of Her2 was score 0 in 2 pts (3,1%), score 1 in 38 (59,3%), score 2 in 16 (25%) and score 3 in 8 (12,5%). Later on, a review was performed by group B, 2 pts (3,1%) scored 0, 45 (70,3%) scored 1; 2 (3,1%) scored 2 and 15 (23,4%) scored 3. Of the 2 pts score 0 of group A, 1 pt turned out to be score 2 and the other score 3. After group B analysed those pts that for group A were score 1, the results were: 86% (33 pts) scored 1 and 14% (5 pts) scored 3. According to group A, 16 pts scored 2. Group B results were totally different: 10 pts turned out to be a score 1 and 6 score 3. Only 3 of the 8 pts score 3 for group A coincided with group B results. Of the remaining 5 pts, 2 scored 0, 2 scored 1 and 1 scored 2. Of 15 pts score 3 of group B, 5 were previously score 1, 6 score 2, 3 score 3 and 1 score 0. For group B, only 2 pts turned out to be score 2, that for group A have been score 3 and score 0. Conclusions: In our population of pts, the overexpression of Her2 score 3 determined by group B (23,4%) coincides with the results reported in the bibliography. Discrepancy exists in the determination of the Her2 between both groups of pathologists. The review of the biopsies increased the detection of Her2 score 3 of 12,5% to 23,4%. No significant financial relationships to disclose.
Effect of chemotherapy and/or TURBT on pathologic response in patients receiving neoadjuvant chemotherapy for muscle-invasive bladder cancer.
Authors: Aaron Brant, Max Kates, Meera Chappidi, Hiten D. Patel, Nikolai A. Sopko, Trinity J. Bivalacqua
Journal: Journal of Clinical Oncology (2016)

395 Background: Neoadjuvant chemotherapy (NAC) for muscle−invasive bladder cancer (MIBC) has been associated with a survival benefit in patients who achieve pathologic response. However, a smaller but significant group of patients who receive transurethral resection of bladder tumor (TURBT) without NAC will also be down−staged. We estimated the prevalence of pathologic response to TURBT in patients who receive NAC. Methods: Of 737 serial patients who received radical cystectomy (RC) at Johns Hopkins Medical Center from 2005–2014, 328 with cT2 urothelial carcinoma were identified. 172 patients received NAC and TURBT, while 156 received only TURBT prior to RC. Demographic, clinical, and pathologic information was compared between groups using Wilcoxon−Mann−Whitney for continuous and chi−squared for categorical variables. Pathologic response was defined as &lt; pT2 at RC. A Poisson regression model with robust error variance was used to determine relative risk (RR) of pathologic response in NAC vs. non−NAC patients, adjusting for age, body mass index (BMI), race, gender, Charlson score, smoking status, days from MIBC diagnosis to surgery, and history of prior non−MIBC (NMIBC). Results: Pathologic response was higher in NAC patients compared to non−NAC patients (62% vs. 21%, RR = 3.00). NAC patients were significantly younger than non−NAC patients (64.8 vs. 71.2 years, p &lt; 0.01), with higher BMI (28.1 vs. 26.7 kg/m 2 , p &lt; 0.01), lower frequency of Charlson score ≥ 3 (13.4% vs. 26.7%, p &lt; 0.01), and lower frequency of prior NMIBC (9.4% vs. 22.4%, p &lt; 0.01). Adjustment resulted in a RR of pathologic response in NAC vs. non−NAC patients of 2.50 (95% CI: 1.69−3.69, p &lt; 0.01). Assuming no interaction between NAC and TURBT, this adjusted model suggests that in a cohort of patients who receive NAC, 40% (95% CI: 27–59%) of pathologic response can be attributed to TURBT. Conclusions: An adjusted model suggests that in a cohort of patients who receive NAC and TURBT prior to RC, 40% of pathologic response can be attributed to TURBT. An understanding of which patients are true responders to chemotherapy and which receive a therapeutic TURBT is needed to select optimal candidates for NAC.
DRAFT: RAMSETE trial of everolimus (RAD001) in the treatment of silent (nonfunctioning) advanced neuroendocrine tumors.
Authors: B. Wiedenmann, S. Caglio, L. Decroix, C. May, K. E. Oberg
Journal: Journal of Clinical Oncology (2010)

TPS208 Background: Nonfunctioning (nf) neuroendocrine tumors (NETs) do not hypersecrete biogenic amines and peptidic hormones in the blood, ie, they are nonsyndromic. Nf NETS represent at least 50% of gastroenteropancreatic NETs. Nf NETs may have symptoms due to tumor mass effect, such as abdominal pain and jaundice. Surgery is the only curative option but is limited to early well-differentiated disease. For inoperable advanced disease, there are currently no standard tumor control therapies. Everolimus is an oral inhibitor of the mammalian target of rapamycin (mTOR; a central regulator of cell growth and proliferation, cellular metabolism, and angiogenesis) and interrupts insulin-like growth factor/phosphatidylinositol 3-kinase signaling that is integral to NETs growth. Everolimus plus octreotide LAR showed promising efficacy in a phase II study in pts with pancreatic NETs (Yao 2009). Few studies have specifically focused on nf NETs at other primary sites (eg, bronchial, rectal, etc). The RAMSETE (RAD001 in Advanced and Metastatic Silent Neuro-Endocrine Tumours in Europe)clinical trial is examining the efficacy and safety of daily oral everolimus therapy for the treatment of advanced nonsyndromic NET pts, excluding pts with pancreatic NETs. Methods: RAMSETE is a single-arm, multicenter, single- stage phase II trial (target enrollment: 60 pts) of everolimus (10 mg/day) monotherapy treating pts with advanced nonsyndromic NETs, not including pancreatic NETs or poorly differentiated NETs. Pts may have received 0-3 prior systemic treatments and must have progressed within 12 months prior to enrollment. Study initiation was June 24, 2009; accrual is expected to finish in mid-2010. Everolimus will continue until tumor progression. The primary efficacy endpoint is the proportion of pts with complete response (CR) or partial response (PR) according to response evaluation criteria in solid tumors (RECIST) criteria. Secondary endpoints include disease control rate (CR + PR + SD [stable disease]), biochemical response rate based on the tumor marker chromogranin A, progression-free survival, overall survival, and safety. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis Novartis Novartis Novartis Novartis
Discovery of Non-Peptidyl Small-Molecule Human GCSF Receptor Agonists for the Potential Treatment of Neutropenia,
Authors: Keith Marschke, Deepa Rungta, Daniela A Slavin, Jennifer Sanders, Steven L Roach, Jason C Pickens, Yixing Shen, Arjan van Oeveren, Mei Hua Hong, Hong Sun, Reid P. Bissonnette, Peter M Syka, Lin Zhi
Journal: Blood (2011)
Variation in national use of long-term ADT by disease aggressiveness among men with unfavorable-risk prostate cancer.
Authors: Vinayak Muralidhar, Brandon Arvin Virgil Mahal, Gally Reznor, Toni K. Choueiri, Christopher Sweeney, Neil E. Martin, Peter F. Orio, Yu-Wei Chen, Michelle Daniel Nezolosky, Karen E. Hoffman, Felix Yi-Chung Feng, Quoc-Dien Trinh, Paul L. Nguyen
Journal: Journal of Clinical Oncology (2016)

54 Background: Current National Comprehensive Cancer Network (NCCN) guidelines uniformly recommend long-term androgen deprivation therapy (ADT) for all men with high-risk prostate cancer. We sought to determine whether the use of long-term ADT varied by the subcategory of disease, including the recently-defined subcategories of high-risk disease (favorable, other, and very-high) versus intermediate-risk disease. Methods: We identified 5,836 patients with NCCN intermediate-, high-, or very high-risk prostate cancer diagnosed between 2004 and 2007 and managed with external beam radiation therapy (EBRT) using the Surveillance, Epidemiology, and End Results database linked to Medicare claims data. Patients were stratified by risk group: intermediate-risk, favorable high-risk (previously defined and validated as T1c, Gleason 4+4=8, PSA &lt; 10 ng/mL or T1c, Gleason 6, PSA &gt; 20 ng/mL), other high-risk, or very high-risk. We used competing risks regression to estimate the rates of long-term (≥ 2 years) ADT in each of these groups. Differences were compared using multivariable regression modeling, adjusting for year of diagnosis, race, marital status, income level, age, and comorbidity. Results: Men with favorable high-risk prostate cancer were significantly less likely to receive 2 years of ADT than others with high-risk disease (21.9% vs. 29.3%, adjusted hazard ratio [AHR] 0.78, 95% confidence interval [CI] 0.67-0.90, p = 0.001), and similarly likely as those with intermediate-risk disease (AHR 1.08, 95% CI 0.94-1.25, p = 0.288). Others with high-risk disease were less likely to receive 2 years of ADT than those with very high-risk cancer (29.3% vs 36.4%, AHR 0.84, 95% CI 0.74-0.96, p = 0.010). Conclusions: Patients with EBRT-managed high-risk prostate cancer received significantly different rates of long-course ADT based on subclassification. Despite NCCN guidelines recommending long-term ADT for all high-risk or very high-risk prostate cancer, our results might reflect the view that these patients represent a heterogeneous group, with favorable high-risk cancer possibly warranting less aggressive therapy than other high-risk or very high-risk disease.
Sequential addition of a semi-intensive anthracycline-based regimen (TNCF) to docetaxel as neoadjuvant treatment of operable breast cancer: An update at five years
Authors: P. Chollet, C. Abrial, X. Durando, M. Mouret-Reynier, O. Tacca, R. Delva, B. Coudert, B. Leduc, E. Villeneuve, H. Curé
Journal: Journal of Clinical Oncology (2008)

11516 Background: To update the results of a phase II combining sequentially neoadjuvant docetaxel to a semi-intensive anthracycline-based regimen (TNCF); to compare these results to those of a larger 710 patients database in which patients were treated between 1982 and 2004 by several neoadjuvant chemotherapy protocols. Methods: From 2001 through 2003, 53 patients received four cycles of docetaxel, followed by a maximum of four cycles of TNCF every 21 days (Amat et al, Clin Breast Cancer, 2006). On completion of chemotherapy, patients underwent surgery and radiotherapy, then adjuvant treatment. Forty-four tumors (83%) were stage II disease (18 stage IIA and 26 stage IIB) and 9 (17%) were stage IIIa disease. In all, 43 (81%) patients had a canalar and 4 (7.5%) a lobular invasive carcinoma. 30% of the tumours were grade III SBR and 64% had at least one-positive HR. Patients received up to 8 cycles (median: 6 [range, 4–8]) ea. 21 days. Results: Clinical objective response rate (ORR) was 79% [CI 95% : 68–90], (47% complete), mammographic ORR was 59% [CI 95%:46–72], (23.5% complete) and echographic ORR was 79% [CI 95%:68–90], (19% complete). A pathological complete response (pCR) was confirmed in 11.3% [CI 95% : 3–20] using Chevallier’s classification. After a median follow-up of 62 months, the rates of OS and DFS at five years were 90.1% and 83.9%, respectively. Five patients (9.5%) died and 8 (15.1%) have relapsed: local and/or metastatic relapse. Conclusions: Although this combination was thought to be optimal: intensified anthracyclin regimen, then sequential combination with an effective taxane, the pCR was lower than expected and than in our 710 patients database (11.3% versus 14.3%). Nevertheless, we want to emphasize that OS and DFS at five years were higher than in our 710 patients database: 90.1% versus 83.3% for OS and 83.9% versus 68.8% for DFS. Moreover, OS and DFS at five years were even higher than in the arm 3 FEC-3 TXT of PACS01, a comparable study (Roché et al. Journal of Clinical Oncology, 2006): same OS but 83.9% versus 78% for DFS. No significant financial relationships to disclose.