tbuckley/cabot-search huggingface dataset:
Outcome analyses of patients with metastatic cervical cancers in a phase I clinic.
Authors: Ming-Mou Hou, Xiaochun Liu, Jennifer J. Wheler, Aung Naing, David S. Hong, Diane C. Bodurka, Kathleen M. Schmeler, Apostolia Maria Tsimberidou, Filip Janku, Ralph Zinner, Sarina Anne Piha-Paul, Karen H. Lu, Robert A. Wolff, Razelle Kurzrock, Siqing Fu
Journal: Journal of Clinical Oncology (2013)

e13534 Background: Patients with metastatic cervical cancers have a poor prognosis and few effective therapies available. Thus, access to a phase I trial may provide a viable option. Methods: Outcomes of 54 consecutive patients with metastatic cervical cancers seen in a phase I clinic at MD Anderson Cancer Center from 1/1/2006 to 12/31/2012 were reviewed in accordance with the MD Anderson IRB guidelines. Results: The 54 patients included Caucasians (n=34, 63%), Hispanics (n=9, 17%), African Americans (n=7, 13%), and others (n=4, 7%). Pathological diagnoses were squamous cell carcinoma (n=33, 60%), adenocarcinoma (n=12, 22%), adenosquamous (n=3, 6%), poorly differentiated carcinoma (n=2, 4%), small cell carcinoma (n=2, 4%), clear cell carcinoma (n=1, 2%), and melanoma (n=1, 2%). Initial staging was as follows: I (n=16, 30%), II (n=11, 20%), III (n=11, 20%), and IV (n=16, 30%). Prior treatment included surgery (n=23, 43%), radiotherapy (n=41, 76%), and systemic chemotherapy (n=54, 100%) including one regimen (n=30, 55%), two (n=15, 28%) and more (n=9, 17%). At their initial visit to the phase I clinic, the median age was 47 years. The majority of patients had ECOG PS 0-1 (n=45, 83%), and MDACC prognostic scores 0-1 (n=48, 89%). Almost all the 54 referred patients were enrolled into a phase I trial (n=52, 96%). Initial phase I trials these patients had received led to one CR, five PR, and 12 SD ≥ 6 months (CR/PR/SD≥6 months=35%). Of the patients who progressed on their first protocols, 11 patients (21%) were enrolled into a second protocol, leading to 36% of PR/SD≥6 months (n=4). Among those enrolled into a third (n=4) and a fourth (n=1) study, no CR/PR/SD≥6 months was achieved. The median overall survival in these 54 referred patients was 10.6 months. Among 36 patients who underwent molecular marker studies, 15 were found to harbor PIK3CA mutations and/or PTEN loss (42%) and achieved 60% of CR/PR/SD≥6 months (3 PR and 6 SD≥6 months). Conclusions: Aberrant PI3K pathway was frequently identified in advanced cervical cancers, and the high rate of CR/PR/SD≥6 months was observed in these patients treated under a phase I trial, suggesting that phase I trials, especially mutation matched regimens, may provide potential benefits to these patients.
Exposure-response relationship of open-label (OL) AMG 386 monotherapy in patients (pts) with recurrent ovarian cancer.
Authors: Beth Karlan, Jianfeng Lu, Lynn Navale, Erik Rasmussen, Yu-Nien Sun, Ignace B. Vergote, Mita Kuchimanchi, Douglas Warner, David M. Weinreich
Journal: Journal of Clinical Oncology (2012)

5072 Background: AMG 386, an investigational peptibody, inhibits tumor angiogenesis by preventing angiopoietins 1/2 and Tie2 receptor interaction. A phase II, double-blind, controlled study (NCT00479817) evaluated toxicity and efficacy of AMG 386 + paclitaxel (P) in recurrent ovarian cancer pts. Increased AMG 386 exposure in that study was associated with longer progression-free survival (PFS; Lu et al., JCO 2010; 28 [Suppl]: 5042). Here, these analyses were applied to pts electing OL AMG 386 monotherapy after progression in the placebo group. Methods: Pts with recurrent epithelial ovarian, fallopian tube, or peritoneal cancer (≤3 prior anticancer therapies, GOG ≤1) were randomized 1:1:1 to P IV QW (3 on/1 off) + AMG 386 (3 or 10 mg/kg) or placebo IV QW. In the placebo group, pts who progressed and stayed eligible could receive OL AMG 386 10 mg/kg IV QW monotherapy. In pts receiving AMG 386 monotherapy, post-hoc analyses evaluated PFS per RECIST, objective response rate (ORR), adverse events (AEs), and the relationships between high and low AMG 386 exposure (based on a median AUC SS of 10.6 mg*hr/mL) and efficacy (PFS per RECIST, ORR). Results: 161 pts were randomized. 18 pts received OL AMG 386 monotherapy (range: 1-56 infusions). At the time of analysis, PFS was 3.2 mo. ORR was 0%. 6 pts had stable disease (SD), 7 had progressive disease (PD). Common AEs were abdominal pain (n = 6), fatigue (n = 5), peripheral edema (n = 5), nausea (n = 5), urinary tract infection (n = 5), and vomiting (n = 5); grade ≥ 3 AEs in more than 1 pt were pleural effusion (n = 2; all grade 3), small intestinal obstruction (n = 2; all grade 3), and ovarian cancer (n = 2; all grade 5). PFS was longer in the high- (n = 9) vs low-exposure (n = 9) group (7.2 vs 1.8 mo; HR = .266, p = .041). Precrossover PFS was similar between high- and low-exposure groups (5.5 vs 4.5 mo; HR = 1.146, p = .812). For both groups, ORR was 0%. In the high-exposure group, 4 pts had SD, 3 had PD. In the low-exposure group, 2 pts had SD, 4 had PD. Conclusions: In line with results from a phase II study of AMG 386 + P, pts with recurrent ovarian cancer who received AMG 386 monotherapy and had high AMG 386 exposure had longer PFS than pts with low exposure. Toxicity was similar in both groups.
A retrospective study evaluating safety and feasibility of adjuvant chemotherapy with 6-week cycles versus 3-week cycles S-1 for patients with advanced gastric cancer curatively resected with D2 lymph node dissection.
Authors: Young Saing Kim, Sun Jin Sym, Junshik Hong, Hee Kyung Ahn, Inkeun Park, Jinny Park, Eun Kyung Cho, Jae Hoon Lee, Woon Ki Lee, Min Chung, Dong Bok Shin
Journal: Journal of Clinical Oncology (2014)

e15080 Background: Adjuvant chemotherapy with 6-week cycles S-1 was confirmed to improve overall survival and relapse-free survival in patient with advanced gastric cancer curatively resected with D2 lymph node dissection. We conducted a retrospective trial evaluating safety and feasibility of adjuvant chemotherapy with 6-week cycles versus 3-week cycles S-1 in patients with stage II/III gastric cancer who had undergone D2 gastrectomy. Methods: We retrospectively evaluated medical records of 83 patients with gastric cancer who had received adjuvant S-1 following curative D2 gastrectomy. Adjuvant S-1 was administered at a dose of 40 mg/m2 twice daily for 4 weeks followed by 2 weeks of rest (6-week cycles) or 2 weeks followed by 1 week of rest (3-week cycles) for 1 year. Results: 6-week cycles and 3-week cycles included 39 and 44 patients, respectively. Median number of cycles was eight (range, 1-9) in the 6-week cycles and 15 (range, 1-17) in the 3-week cycles. The number of patients who completed the prescribed S-1 treatment for 1 year was 27 (69%) in the 6-week cycles and 32 (73%) in the 3-week cycles (P = 0.73). The reasons for discontinuation of treatment were adverse events (10 vs 11%), recurrence within 1 year (15 vs 9%), and others (5 vs 7%) for 6-week cycles and 3-week cycles, respectively. More patients in the 6-week cycles than in the 3-week cycles experienced stomatitis (28 vs 9%, P = 0.02), diarrhea (54 vs 30%, P = 0.03) and elevated aminotransferase (44 vs 23%, P = 0.04). However, there was no significant difference in grade 3 or 4 adverse events (41 vs 43%, P = 0.84). Multivariate logistic regression analysis demonstrated that female (odds ratio [OR], 9.25; 95% CI, 1.48-57.65), creatinine clearance <60 mL/min (OR, 8.15; 95% CI, 1.23-54.07) and poor performance status (OR, 14.83; 95% CI, 1.87-117.45) were significant risk factors of treatment discontinuation due to adverse events. Conclusions: Our study showed that 3-week cycles of adjuvant S-1 for patients with stage II/III gastric cancer are feasible and might be superior to the conventional 6-week cycles with regard to non-hematological toxicities.
Improved renal function in patients switched from zoledronic acid to ibandronate: A retrospective review of medical records
Authors: I. J. Diel, R. Weide, H. Köppler, L. Antràs, M. Smith, J. Green, N. Wintfeld, M. Neary, M. Duh
Journal: Journal of Clinical Oncology (2007)

11500 Background: The renal safety profile of ibandronate (IA) was assessed retrospectively across a spectrum of oncology patients including multiple myeloma, breast, prostate, and non-small cell lung cancer. Patient groups were classified as IA switchers (with prior zoledronic acid (ZA) therapy) (n=34) or early IA (without prior ZA therapy) (n=72). Renal impairment rates and trends in renal function were compared during ZA and IA treatment periods in patients switching from ZA to IA (n=32 observable in both treatment periods). Methods: Medical records from two German oncology clinics, spanning May 2001 to March 2006, were reviewed. Serum creatinine (SCr) was analyzed from baseline to last evaluation. Renal impairment was defined as a SCr increase of =0.5mg/dL or =1.0mg/dL from baseline values of &lt;1.4mg/dL or =1.4mg/dL, respectively; or =25% decrease in glomerular filtration rate (GFR) from baseline. Results: Both groups had similar baseline renal function. Physicians reported that renal-related problems led to 22 patients (69%) switching from ZA to IA. Patients switched from ZA therapy to IA showed a significant trend towards renal function deterioration during the ZA treatment period (p=0.016) but experienced a trend towards improved renal function after switching to IA (p=0.082). Patients receiving IA with prior ZA therapy exhibited significantly higher renal impairment rates versus those without prior ZA therapy (50.0% versus 11.1%, relative risk (RR)=4.5, p&lt;0.0001 [SCr] and 70.6% versus 38.9%, RR=1.8, p=0.0024 [GFR] for patients with and without prior ZA therapy, respectively). Cox proportional hazards models, adjusted for significant covariates, found significantly higher hazards ratios (HRs) in the IA switchers group versus the early IA group (HR=7.7, p&lt;0.01 [SCr] and HR=4.3, p&lt;0.01 [GFR]). Conclusions: ZA naïve patients had a significantly lower renal impairment risk compared to those who received ZA followed by IA. Patients switching from ZA to IA showed recovery of renal function, suggesting that patients may benefit from IA early in the treatment cycle or by switching to IA treatment. A prospective randomized study is warranted. No significant financial relationships to disclose.
<i>FLT3</i> Mutation Testing in Acute Myeloid Leukemia
Authors: Arjun Gupta, David S. Viswanatha, Mrinal M. Patnaik
Journal: JAMA Oncology (2017)

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PRECISIÓN DIAGNÓSTICA DE LA ENDOSCOPIA CON LUZ BLANCA Y CROMOENDOSCOPIA VIRTUAL I-SCAN EN LA DETECCIÓN DE SIGNOS ENDOSCÓPICOS DE ESOFAGITIS EOSINOFÍLICA
Authors: B López Viedma, J Rodriguez Sanchez, M Peña Gomez, E De La Santa Belda, J Molina Infante, J Olmedo Camacho
Journal: Endoscopy (2015)

Introducción: La descripción y graduación de la severidad de signos endoscópicos de esofagitis eosinofílica (EE) se ha estandarizado mediante el índice EREFS (EoE Endoscopic Reference Score), demostradando reducir la variabilidad interobservador en estudios unicéntricos, aunque no ha sido evaluada de forma multicéntrica ni comparando diferentes técnicas de imagen.
Lipids in exosomes: Current knowledge and the way forward
Authors: Tore Skotland, Kirsten Sandvig, Alicia Llorente
Journal: Progress in Lipid Research (2017)

Lipids are essential components of exosomal membranes, and it is well-known that specific lipids are enriched in exosomes compared to their parent cells. In this review we discuss current knowledge about the lipid composition of exosomes. We compare published data for different lipid classes in exosomes, and what is known about their lipid species, i.e. lipid molecules with different fatty acyl groups. Moreover, we elaborate on the hypothesis about hand-shaking between the very-long-chain sphingolipids in the outer leaflet and PS 18:0/18:1 in the inner leaflet, and we propose this to be an important mechanism in membrane biology, not only for exosomes. The similarity between the lipid composition of exosomes, HIV particles, and detergent resistant membranes, used as lipid rafts models, is also discussed. Furthermore, we summarize knowledge about the role of specific lipids and lipid metabolizing enzymes on the formation and release of exosomes. Finally, the use of exosomal lipids as biomarkers and how the lipid composition of exosomes may be of importance for researchers aiming to use exosomes as drug delivery vehicles is discussed. In conclusion, we have summarized what is presently known about lipids in exosomes and identified issues that should be taken into consideration in future studies.
Biomarker analysis from a Phase I study of copanlisib with expansion cohorts in solid tumors with and without PIK3CA mutations and NHL.
Authors: Carol Elaine Pena, Michael Jeffers, Isabelle Genvresse, Leonard Joseph Appleman, Ramesh K. Ramanathan, Amita Patnaik
Journal: Journal of Clinical Oncology (2015)

2548 Background: Copanlisib is a novel, selective, reversible, pan-Class I phosphatidylinositol-3-kinase (PI3K) inhibitor with potent activity against both the δ and α isoforms. Safety and tumor response data from the first-in-man phase I trial have been reported (Patnaik et al., 2012, ASH), with two patients with follicular lymphoma ongoing as of January 2015, with partial responses lasting 1380 and 909 days. A secondary objective of the study was to identify biomarkers associating with copanlisib response. Methods: After dose escalation, expansion cohorts were enrolled and treated at the maximum tolerated dose (0.8 mg/kg, iv, on days 1, 8 and 15 of a 28-day cycle), including solid tumors (n = 25) with and without PIK3CA mutations, and non-Hodgkin lymphoma (NHL; n = 9). PIK3CA, BRAF, and KRAS mutations were tested using digital PCR on archival tumor samples and circulating tumor (ct) DNA from plasma (BEAMing). Next generation sequencing (NGS) of tumor genes and IHC for PTEN were performed on archival tumor samples. Results: Ten of 25 solid tumor patients (40%) had mutations in PIK3CA in tumor (BEAMing: 5/22; NGS: 4/9) and/or ctDNA (7/25), of which 8 had breast cancer; 2 of 22 tested (9%) had KRAS mutations. None of the NHLs tested had PIK3CA or KRAS mutations. PTEN loss was identified by IHC in 9 of 18 (50%) solid tumors, and in 1 of 7 (14%) NHLs tested. PTEN mutations were detected in 2 of 11 cases; both had PTEN loss. Of the 9 solid tumor patients with PTEN loss, 1 had a complete radiological response (CR) lasting more than one year and 2 had extended stable disease (SD) ( ≥ 4 cycles); conversely, of the 9 without PTEN loss, none had an objective response (OR) or extended SD. The CR was in an endometrial cancer patient with PTEN loss and both PTEN and PIK3CA mutations. However, PIK3CA mutations alone did not seem to enrich response rate, as 3 of 10 (30%) patients with PIK3CA mutations and 4 of 15 (27%) without had either an OR or extended SD. Conclusions: PTEN loss, but not PIK3CA mutations alone, may enrich for response to copanlisib in this mixed solid tumor expansion cohort. The CR to copanlisib in the presence of both PTEN and PIK3CA aberrations may be due to multiple mechanisms leading to PI3K pathway activation. Clinical trial information: NCT00962611.
Overcoming barriers in incorporating evaluation of quality of life (QL) and symptoms by using the ePRO version of the LCSS (eLCSS-QL) in a large-scale multinational NSCLC trial (AP-QL Trial).
Authors: Sumitra Thongprasert, Richard J. Gralla, Patricia J Hollen, Hoon-Kyo Kim, Te-Chun Hsia, Shi Yuankai, Karenza M. Alexis, Nina Kohn, Martin Lesser
Journal: Journal of Clinical Oncology (2013)

8092 Background: Survival and QL improvements are primary treatment goals in advanced NSCLC. Few trials evaluate both of these major endpoints well: typically only a minority of patients (pts) have QL followed over time, preventing such data from assisting in key decisions concerning the effectiveness and value of treatment. To overcome barriers, we used a computer-assisted version of the validated LCSS measure and tested this prospectively in a large study. Prior trials indicated that the eLCSS-QL requires only 2 minutes to complete the pt version and is highly acceptable. Methods: 622 pts received initial docetaxel (D)-based chemo, at 65 sites in 9 Asian countries. 70% male; 65% adenocarcinoma; median: KPS = 90; ECOG = 1 (27% ECOG 0). Stages: IV (72%), IIIB (28%). 84% had &gt; two major symptoms. 80% had combination chemo with cisplatin (52%) or carboplatin (28%). Computer skills were low in 73%. eLCSS-QL was completed every 3 weeks at the clinic. We also surveyed 98 physicians (MD) and nurses (RN) treating these pts regarding communication, usefulness and acceptability of the eLCSS-QL. Results: 97% of pts completed the eLCSS-QL at baseline; 90% completed follow-up evaluations. Over 90% found the eLCSS-QL easy to use, acceptable to complete at each visit; &gt;80% reported increased awareness of symptoms; making it easier to speak with MDs / RNs. 1% refused eLCSS-QL completion. Of MDs/RNs: &gt;90% found the eLCSS-QL easy to use and increased symptom awareness; &gt;80% reported improved communication, enhanced satisfaction with the pt visit, and recommend its use. Nearly 90% of MDs reported they could identify benefit from chemo earlier; 76% would order fewer imaging tests and 80% said the eLCSS-QL could save time. Major response rate 37%; median survivals: 13.9 months (D + cisplatin), 12.7 months (D + carboplatin). Conclusions: Patients, MDs, RNs all found the eLCSS-QL to be highly acceptable and easy to use with 90% of pts doing repeated QL measures. This large prospective trial demonstrates the potential for QL / symptom evaluation to aid in decision making and to guide appropriate use of chemotherapy and imaging while enhancing staff and pt satisfaction.
Incidence of venous thromboembolic events and effect on survival in patients with lung cancer
Authors: J. Shah, S. Donegan, D. Wang, F. Robert
Journal: Journal of Clinical Oncology (2007)

18017 Background: Venous thromboemboli (VTE) is a known complication in patients with cancer, however the true incidence and effect on survival in patients with lung cancer is not clear. Methods: We retrospectively reviewed a cohort of 388 patients with lung cancer from 1997 to 2006 seen at the University of Alabama in Birmingham. Results: Median age was 62 and the male (n=227) to female (n=160) ratio was 1.41:1. Small cell lung cancer (SCLC) was the histology in 50 patients (13%) and non small cell lung cancer (NSCLC) in 331 patients (87%). Among NSCLC, the distribution of various subtypes was: 144 (37%) adenocarcinoma, 93 (24%) squamous cell, 7 (2%) large cells and 93 (24%) non-small cell, not otherwise specified(NOS). Metastatic disease was present in 29% (96/337) of NSCLC and extensive disease in 54% (27/50) of SCLC patients. 73% had a performance status of 0/1 and 29% had weight loss ( &gt; 5% body weight). The overall incidence of VTE was 17 % (n=64); 9 patients prior to the diagnosis and 55 patients (86%) during the course of their disease. The incidence of VTE in SCLC was 10% (n=5) and in NSCLC 19% (n=59). VTE events in patients with non-small cell histologies were: 18% in adenocarcinoma, 25% in NSCLC-NOS, and 8% in squamous cell carcinoma. In patients with SCLC the incidence of VTE in limited stage disease (3/23) was similar to extensive stage disease (2/27). In NSCLC, patients with stage 1–3 disease had an incidence rate of 16% (39/241) compared to 21% (20/96) with metastatic disease. The median survival (MS) in SCLC patients with VTE was 21 months and without DVT was 17 months (P = 0.28). The MS in patients with NSCLC with VTE was 15 months and without VTE was 18 months (P = 0.12). Conclusions: There is a high incidence of VTE in patients with both NSCLC and SCLC with a trend to increased incidence in specific histologic subtypes and increased disease burden. Despite the potential anti-neoplastic benefit of anticoagulants there was a minimal difference in overall survival between cohorts, although this study was not designed to evaluate differences in survival. This data supports trials evaluating the role of prophylactic use of anticoagulants as a means to reduce the morbidity/mortality associated with VTE in this high risk population. No significant financial relationships to disclose.
Duration of lapatinib (L)-based therapy in HER2+ metastatic breast cancer (MBC) in a single institution.
Authors: Serafin Morales, Ariadna Gasol Cud"s, Antonia Salud, Elena Maria Aguirre Ortega, NoemÃƒÂ Tuset Der-abrain
Journal: Journal of Clinical Oncology (2014)

e11544 Background: Lapatinib (L) plus capecitabine is a standard regimen for patients with HER2+ MBC who have previously received trastuzumab. The aim of this study was to evaluate duration of L in different combinations for the treatment of advanced breast cancer. Methods: Retrospective analysis was undertaken to assess duration of L therapy for patients treated in our institution from July 2006 to September 2013. Results: A total of 41 patients were evaluated. Median age: 51 years. All patients were ECOG 0-1. 12 patients were diagnosed as metastatic disease, 19 with locally advanced and 10 with only local disease. Chemotherapy as neoadyuvant setting was performed in 15 patients. 39 patients received Trastuzumab previous to L with 9 patients in the adjuvant setting (23%), and the median of duration of Trastuzumab was 20 months (3-84). When treatment with L was initiated, 19 patients had metastases progression in the same site and 14 in de central nervous system. L was administered as first line in 6 patients (15%), 20 (49%) patients as a second line and 15 in more than 2 lines of treatment. The median duration of L was 7 months (1-73), however 25% of patients were treated for more than 15 months. Patients with previous neoadjuvant treatment had a median duration of L of 23 vs 9 months (Log Rank 0,034). The duration of L treatment was not influenced by prior Trastuzumab neither in the adjuvant nor metastatic setting, length of treatment with Trastuzumab, line of L treatment, and site of metastasis (included CNS). Positive progesterone receptor status was associated with more than 15 months period of L (p=0,026). Conclusions: Duration of Lapatinib treatment is not influenced by prior Trastuzumab, line of treatment and site of metastases. Variables associated with more than 15 months of Lapatinib were neoadjuvant treatment and progesterone receptor positive.