tbuckley/cabot-search huggingface dataset:
Human epidermal growth factor receptor 2 (HER2) positivity shown by fluorescence in-situ hybridization in patients with advanced gastric cancer: A multicenter study in Taiwan.
Authors: K. Yeh, Y. Chen, J. Chen, W. Su, M. Liu, K. Rau, C. Yen, L. Chen, Y. Chao, C. Tsao
Journal: Journal of Clinical Oncology (2011)

e14576 Background: Based on the results of ToGA (Trastuzumab for Gastric Cancer) study, trastuzumab in combination with chemotherapy can be considered as a new standard option for patients with human epidermal growth factor receptor 2 (HER2)-positive advanced gastric or gastro-esophageal junction (GEJ) cancer (Lancet 2010;376:687-97). In ToGA study, overall HER2-positivity rate was 22.1%; however, exceptionally low HER2-positivity rate was observed in some countries, including Taiwan (only 3%; ASCO-GI 2008:A11). The underlying factors contributing to low HER2-positivity rate in Taiwan remain obscured. Re-evaluation of HER2-positivity for Taiwanese GC patients in a larger sample size is highly warranted. Methods: We tested HER2-positivity by gene amplification using fluorescence in-situ hybridization (FISH) in formalin-fixed paraffin-embedded gastric or GEJ cancer samples. The testing was centralized to a single laboratory (Quest, UK). The PathVysion HER2 DNA probe Kit (Vysis, Abbott Molecular Inc., Germany) was used, which is FDA approved to detect the HER2 gene amplification. Results of hybridization on enumeration of 20 interphase nuclei from tumor cells are reported as the ratio of average HER2 copy number to that of CEP17, a specific region of the Chromosome 17’s centromere. Specimens with amplification showed a HER2 and CEP17 signal ratio of >/= 2.0. If the final ratio is calculated by the primary observer as near/at the cut-off point (1.8-2.2), an additional 20 cells is counted. The second observer will count an additional 20 cells. Results: Between Sep. 2007 and Nov. 2010, 180 patients (M:109, F:71) with gastric or GEJ adenocarcinoma from 8 medical centers in Taiwan were enrolled and evaluated by FISH testing. Among them, 47 patients (M:34, F:13) showed a HER2/CEP17 signal ratio of >/= 2.0, the overall HER2-positivity for Taiwanese GC patients was 26.1% (19.7%-32.5%, 95% CI). Conclusions: More than a quarter of Taiwanese advanced GC patients showed HER2-positivity by FISH, comparable with that of ToGA study. Novel HER2-targeted agents are justified for future active investigation in Taiwanese GC patients.
Prediction of progression-free survival (PFS) adjusted by continuous platinum-free interval (PFI) at fixed timepoints in patients with recurrent ovarian cancer (ROC): Results from OVA-301.
Authors: A. Poveda, B. J. Monk, S. B. Kaye, J. B. Vermorken, I. B. Vergote, I. B. Runnebaum, E. Pujade-Lauraine, T. V. Parekh, A. Nieto, J. Gomez, Y. C. Park, N. Colombo
Journal: Journal of Clinical Oncology (2011)

5067 Background: OVA-301, a randomized, open-label phase III study comparing trabectedin plus pegylated liposomal doxorubicin (PLD) vs. PLD alone in 672 patients with ROC, showed significant and clinically relevant longer PFS in patients treated with the combination. In ROC the efficacy of re-treatment is broadly accepted to be highly correlated with the extension of PFI. A PFI ≥ 6 months (n=430) predicts platinum sensitivity, but within this group, a PFI of 6-12 months (n=214) is considered to indicate a partially platinum-sensitive (PPS) disease. Kaplan-Meier unadjusted survival estimates are widely used for plotting time-to-event curves. Allmer and Sargent (SUGI-2003) proposed an alternative method to plotting survival estimates at a specified point in time, adjusted by a continuous explanatory variable that may be of interest. Methods: In this study adjusted estimates of PFS by continuous PFI at fixed timepoints (3, 6 and 12 months) according to Allmer and Sargent method have been considered. Results: Trabectedin and PLD provided a 21% risk reduction for disease progression or death compared with PLD (HR = 0.79; p = 0.0190), with median PFS of 7.3 months for the combination and 5.8 months for PLD (Monk et al., 2010). With the adjustment by PFI, and PFI by treatment interaction, plots representing the PFS rate prediction at 3, 6 and 12 months showed a significant difference along PFI axis favoring the combination of trabectedin and PLD. In the PPS subgroup, no PFI imbalance was observed, and the interaction term was not significant. Median adjusted estimates for main effects in PFS were 7.7 months vs. 5.5 months (adjusted HR = 0.63; p = 0.0115), again favoring the combination. Conclusions: ROC relapse outcome of subsequent re-treatment is largely influenced by the PFI extension. Therefore, it is important to adjust this variable in the analysis of PFS. In accordance with previously published estimates for PFS, the new estimation approach for presenting predicted survival data based on the continuous PFI showed an improved PFS in patients treated with the combination of trabectedin and PLD.
Evaluation of patient's versus hematologist/oncologist's office visit agenda.
Authors: Cory Patrick, Kaitlin McIntyre, Rakesh Singal, Damien Mikael Hansra
Journal: Journal of Clinical Oncology (2016)

125 Background: Few studies have been reported in oncology regarding elements of physician agenda. We aim to compare elements of a doctor office visit agenda between hem/onc physicians (MD) and patients (pts). Methods: Pts and MDs were enrolled to completed a five question survey. Pts were asked: “My doctor” Focuses more on quantity of life and less on quality of life, spends enough time with me, addresses symptoms, addresses chemo side effects, and addresses prognosis. MDs were asked the same questions but worded: "I” spend enough time with pts for example. Answers were recorded on a 5 point scale (1 = highly disagree, 2 = disagree, 3 = neutral, 4 = agree,5 = highly agree) and converted into 2 categories (1,2,3 = neutral/disagree vs 4,5 = agree). Fisher’s exact test with 2 sided p-value was used to compare significance between MD &amp; pts. Results: 1008 pts and 55 MDs were enrolled between 06/2013 - 10/2015. Pt mean age 55 (18-88) with 45% male and 55% female. Racial profile: 16% white, 14% black, 2% Asian/Pacific Islander. Ethnicity: 62% of pts were Hispanic vs. 38% not Hispanic, &amp; 6% other. A significant number of pts feel MDs focus more on quantity of life vs. quality of life (64% pt vs 26% MD p &lt; 0.0001) and MD spend enough time (94% pt vs 82% MD p &lt; 0.05). No differences were seen for symptoms (92% vs 87% p = 0.2), side effects (92% vs 94% p = 1.0), or prognosis (91% vs 96% p = 0.3) pt vs MD respesctively. Conclusions: Pts feel MDs focus more on quantity of life vs. the quality of life. MDs feel they focus more on quality of life vs. quantity of life. Perhaps bridging the gap in what constitutes “quality of life” may improve patient satisfaction. Furthermore MDs underestimate the time spent with their patients. Perhaps MD are spending too much time with some patients resulting in inefficient office visits.
Adjuvant chemotherapy for upper-tract urothelial carcinoma: A systematic review and meta-analysis of available studies.
Authors: Jeffrey J. Leow, Steven L. Chang, Toni K. Choueiri, Joaquim Bellmunt
Journal: Journal of Clinical Oncology (2014)

330 Background: Upper-tract urothelial carcinoma (UTUC) accounts for less than 5% of all urothelial cancers. Adjuvant chemotherapy (AC) for UTUC may improve survival outcomes, but currently available evidence is limited. Methods: A comprehensive literature review was performed to identify all studies comparing AC with control for patients with UTUC. The search included the Medline, Embase, Cochrane Central Register of Controlled Trials databases, and abstracts from the American Society of Clinical Oncology meetings up to June 2013. An updated systematic review and meta-analysis was performed. Results: A total of 9 retrospective cohort studies were identified (Table). For disease-specific survival, 6 studies had sufficient data (AC: n=406, control: n=1,227), with a pooled hazard ratio of 0.64 in favor of AC over control (95% CI: 0.41 to 0.99; p=0.047). Between-trial heterogeneity was not significant based on the Cochran Q statistic (p=0.14) and I 2 = 40% (95% CI=0-76). Four studies had sufficient data for overall survival (AC: n=228, control: n=685), with a pooled hazard ratio of 1.06 (95% CI: 0.52 to 2.13; p=0.88). Between-trial heterogeneity was observed based on the Cochran Q statistic (p=0.03) and I 2 (68%, 95% CI: 7-89). There were no randomized trials investigating the role of AC for UTUC. Conclusions: There appears to be a significant benefit in disease-specific survival, but not overall survival, for AC in UTUC. While limited by the retrospective nature of studies and relatively small sample size, this analysis may be helpful in guiding the oncologic management of UTUC. [Table: see text]
Interim safety data on the ZICE trial: A randomized phase III, open-label, multicener, parallel group clinical trial to evaluate and compare the efficacy, safety profile, and tolerability of oral ibandronate versus intravenous zoledronate in the treatment of patients with breast cancer with bone metastases.
Authors: P. J. Barrett-Lee, N. Murray, J. Abraham, A. Casbard, H. Clements, T. S. Maughan, G. Griffiths
Journal: Journal of Clinical Oncology (2010)

1085 Background: The IV bisphosphonate zoledronate is widely used in the UK to treat metastatic bone disease from breast cancer. Oral bisphosphonates may have advantages over IV but this has not been formally assessed. Bisphosphonates are associated with renal toxicity and with osteonecrosis of the jaw (ONJ), reported to affect approximately 1% of patients, which is linked to dental infection and tooth extraction. Methods: The Roche Product Limited supported National Cancer Research Institute ZICE trial, coordinated by the Wales Cancer Trials Unit and sponsored by Velindre NHS trust, will determine whether the oral bisphosphonate ibandronate is noninferior to IV zoledronate in terms of preventing skeletally related events (SREs) over 96 weeks in 1,400 patients. Eligible participants must have bone metastases from histologically proven breast cancer and an ECOG performance status 0-2. The primary outcome is frequency and timing of SREs. Secondary outcome measures include time to SRE, proportion with SREs, pain scores, QoL, survival, health resource usage, and serum bone marker levels. Serious adverse events (SAEs) are assessed for expectedness and causality to the bisphosphonate i.e. whether a serious adverse reaction (SAR) or suspected unexpected serious adverse reaction (SUSAR). Results: Recruitment opened in January 2006 and 1,074 patients have been recruited from 98 centers. 231 patients have completed 96 weeks of treatment, an additional 44 have withdrawn and 311 have died. 32 SARs (including 3 ONJ) and 15 SUSARs have been reported. Conclusions: This is the biggest metastatic breast cancer trial conducted in the UK. The IDMC has reviewed all the safety data including the SAE data and has recommended that there are currently no safety concerns. So far, the reported incidence of ONJ is lower than anticipated. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Roche Roche
Challenges with insurance and finances: Results from the 2012 Livestrong survey.
Authors: Stephanie Nutt, Carla Bann, Sarah R. Arvey, Linda Squiers, Ruth Rechis
Journal: Journal of Clinical Oncology (2014)

208 Background: More than 1.5 million new cancer cases occur each year in the U.S., and accessing health care is critical for mortality as well as for improving survivorship outcomes for cancer survivors. Methods: LIVESTRONG conducted an online survey of cancer survivors from June to December 2012. The current analyses include 4,320 respondents who were U.S. residents and diagnosed in 2002 or later. Results: Survivors in this study reported that for those who did not receive all of the medical care they needed they did not receive care because the insurance company wouldn’t pay for the care (41%) or they couldn’t afford the care (23%), with nine percent being denied health insurance coverage due to a cancer diagnosis. Other challenges reported included insurance not paying for a second opinion (8%) or the doctor/facility of the survivor’s choice (18%). Controlling for demographic and cancer-related factors, those diagnosed most recently (2010-2012) were less likely to report experiencing these challenges. Compounding insurance issues was the financial burden. Thirty percent of survivors reported that they or their family members had to borrow money or go into debt because of their cancer and five percent of survivors reported spending down their assets to qualify for Medicaid or a cancer-related program. Conclusions: In previous studies, patients who lack sufficient health insurance coverage tend to have poorer health outcomes. Overall, the data highlights that more can be done to connect survivors with the needed insurance and financial resources they need to access adequate cancer care during their treatment and beyond. [Table: see text]
Analysis of response to chemotherapy with subsequently emerging surgical potential in the initially locally advanced and/or metastasized gastric carcinoma.
Authors: P. Stuebs, T. Krause, K. Zierau, P. Habermann, K. Schuette, B. Garlipp, J. Fahlke, H. Lippert
Journal: Journal of Clinical Oncology (2011)

e14587 Background: Multimodal treatment of the advanced gastric carcinoma is associated with an improved oncological outcome. There is a chance for improved time of survival for a selected group of patients even in a palliative setting by achieving secondary resectability. Methods: Within the setting of multicentered phase II studies on chemotherapy of the advanced gastric carcinoma we analyzed patients (pts) with secondary resectability treated in our centre. In an initially purely palliative setting 84 (53.8%) pts were treated with cisplatin/docetaxel (C/D), 45 (28.8%) pts received cisplatin/5-FU/leucovorin (PLF), while 17 (10.9%) pts underwent a therapy combining C/D and cetuximab. A further 10 pts were treated according to differing chemotherapeutic protocols. A total of 45 out of 156 pts responded well to treatment and thus were treated surgically. After neoadjuvant therapy pts underwent D2 lymphadenectomy along with gastrectomy. A R0 situation was achieved in 35 pts (77.8%). Results: A significant advantage of 23.8 months (95% CI 16.85-30.75) was shown for pts receiving neoadjuvant therapy in regards to the overall survival (OS) versus 13.13. months (CI 9.99-16.28) in merely palliatively treated pts. Time to progression (TTP) showed significant improvement in the neoadjuvant setting with a median of 16.3 months versus 8.6 months. There was no significant difference in the overall survival or time to progression in regards to the chemotherapy administered (OS: C/D 23.8 vs PLF 19.77, TTP: C/D 18.9 vs PLF 16.3), however secondary resectability was not achieved in pts treated with a combination of C/D and cetuximab. Male gender and the histologically intestinal type were found to be initial positive prognostic factors. Conclusions: Results show that application of active chemotherapy in a multimodal concept of treatment can improve prognosis dramatically even in palliative settings for selected pts. In addition to the choice of therapy, excellent response evaluation and ambitious surgery are pivotal criteria. Developing valid predictive and prognostic parameters, like molecular signatures for instance, is a future necessity.
Phase II/pharmacodynamic trial of PD0332991 in patients with breast, colon, germ cell, and epithelial tumors containing amplification of CCND1.
Authors: R. F. Perini, A. DeMichele, D. J. Vaughn, M. Gallagher, W. Sun, B. J. Giantonio, U. R. Teitelbaum, S. Randolph, J. G. Christensen, R. D. Courtney, D. A. Pryma, C. R. Divgi, P. J. O'Dwyer
Journal: Journal of Clinical Oncology (2011)

3088 Background: The cell cycle is dysregulated in most patients with epithelial cancers, through activating mutations or overexpression of cell cycle proteins, or loss of cell cycle inhibitors such as p53, p16, etc. A proportion of tumors also have amplification of CCND1, which encodes cyclin D1. In a Phase I trial of the cdk4/6 inhibitor PD0332991 we found prolonged stable disease in patients with several types of epithelial cancer. We now report a phase II trial of PD0332991 in patients with four disease types: breast cancer, Kras-mutant colorectal cancer, resistant germ cell malignancies, and any tumor demonstrated to have amplification of cyclin D1, as assessed by FISH. Methods: Eligible pts were treated with PD0332991 125 mg daily for 21 of 28 days. The primary objective was to determine the progression-free survival in cohorts of 15 patients per tumor type. Secondary objectives include anti-tumor activity, pharmacodynamics (PD) and pharmacokinetics (PK). Results: We screened 79 patients with these characteristics for Rb positivity: 26 had positive staining and were treated. Toxicity was limited to myelosuppression, mainly neutropenia, as had been observed in the phase I study. Of nine patients with colorectal cancer, five had 18F-FLT PET/CT performed before and after about 5 weeks of therapy as a pharmacodynamic marker. Maximum SUV values were computed for tumor (up to five lesions) and lumbar vertebral bodies (sum of five) as a marker of marrow effect. Bone marrow SUV values varied by a factor of three between patients, but intrapatient variability was minimal. Following treatment, marrow SUV values declined by a mean of 21.3% (range +1.7 to -55%). A similar decrease in tumor SUV values was observed (mean 27.5% decrease, range -7.3 to -47.5%), and four of the five patients had a decrease of > 25%. Pharmacokinetic studies are in progress to relate to PD markers of toxicity and activity, and to expand a model derived from Phase I data. Conclusions: PD0332991 is a well-tolerated cell cycle inhibitor with evidence of disease control in patients with various tumor types. Preliminary data in colorectal cancer suggest that FLT PET may provide a pharmacodynamic measure of drug activity.
Microparticles in nasal lavage fluids in chronic rhinosinusitis: Potential biomarkers for diagnosis of aspirin-exacerbated respiratory disease
Authors: Toru Takahashi, Atsushi Kato, Sergejs Berdnikovs, Whitney W. Stevens, Lydia A. Suh, James E. Norton, Roderick G. Carter, Kathleen E. Harris, Anju T. Peters, Kathryn E. Hulse, Leslie C. Grammer, Kevin C. Welch, Stephanie Shintani-Smith, Bruce K. Tan, David B. Conley, Robert C. Kern, Bruce S. Bochner, Robert P. Schleimer
Journal: Journal of Allergy and Clinical Immunology (2017)
Gemcitabine plus oxaliplatin (GemOx) in advanced hepatocellular carcinoma (HCC): A multicenter study of over 200 patients.
Authors: N. Williet, A. Zaanan, M. Hebbar, V. Boige, L. Fartoux, T. Mansourbakht, O. Dubreuil, O. Rosmorduc, F. Bonnetain, J. Taïeb
Journal: Journal of Clinical Oncology (2011)

4033 Background: The standard treatment for advanced HCC is sorafenib. However this treatment does not induce tumor shrinkage and allows a modest improvement in overall survival (OS) and progression-free survival (PFS). For 10 years, we have developed a regimen of combined systemic chemotherapy with gemcitabine and oxaliplatin (GemOx regimen) which provides adequate control of the disease with manageable toxicity. We report our experience on > 200 patients (pts) consecutively treated with this regimen. Methods: This retrospective multicenter study included all consecutive pts treated for advanced HCC with GemOx. Survival curves were drawn with the Kaplan-Meier method and compared by the log-rank test. Models of univariate and multivariate analyses were used to search for prognostic and predictive factors of therapeutic efficacy and OS. Results: 210 pts were enrolled from 2001 to 2010. 190 pts are currently with complete data collection. Average age: 60 years (20-83), M / F: 164/26, metastatic stage: 36%, underlying cirrhosis: 86%, Child Pugh score A: 75 % B: 21%, C: 4%, median CLIP score: 3 (0-5), WHO Performance status 0/1/2/3: 34/49/15/2 %. The objective response rate (OR: complete response + partial response) was 21% (WHO criteria) and disease control rate (DCR: OR + stable disease) was 62 %. The median PFS and OS were 6 (95% CI: 4.5 to 10) and 10.5 (95% CI: 9-13) months, respectively. Ten pts were eligible for curative surgery and 5 for secondary
A prospective study evaluating stereotactic body radiation therapy in unresectable, recurrent, or residual pancreatic adenocarcinoma.
Authors: Lauren M. Rosati, Shalini Moningi, Amy Hacker-Prietz, Dan Laheru, Lei Zheng, Ana De Jesus-Acosta, Dung T Le, Joseph A. Moore, Elliot K. Fishman, Siva P. Raman, Todd R. McNutt, Timothy M. Pawlik, Fred E Eckhauser, Matthew J. Weiss, Joseph M. Herman
Journal: Journal of Clinical Oncology (2016)

454 Background: The purpose of this prospective, non-randomized phase II single-institution study was to evaluate if local control can be achieved with reasonable acute and late GI toxicity using fractionated SBRT in patients with unresectable, recurrent, or residual locally advanced pancreatic cancer (LAPC). Methods: A total of 24 patients with LAPC were enrolled from June 2013 to August 2014. Eligibility required stability after induction chemotherapy or residual disease or local failure after surgery. Induction chemotherapy regimens consisted of: (1) gemcitabine alone (8%); (2) gemcitabine-based regimens (17%); (3) FOLFIRINOX-based regimens (63%); or (4) combination regimens (13%). Chemotherapy was discontinued one week prior to SBRT. Patients received a median cumulative dose of 33 Gy in 5 fractions (5-6.6 Gy/fraction). Patients were permitted to resume chemotherapy one week post-SBRT. Toxicity was assessed using the NCI CTCAE version 4.0. Results: Of the 24 patients, 58% were male and 50% had tumors in the head of the pancreas. Median age at diagnosis was 66.8 years, and median follow-up from the date of diagnosis was 11.9 months (range, 7.4-29.7 months). There have not been any acute or late grade ≥ 2 gastritis, enteritis, fistula, or ulcer toxicities (primary endpoint). Median OS has not yet been reached, median LPFS was 19.3 months (95% CI, 12.3-14.8), median DMFS was 13.6 months (95% CI, 9.2-17.9) and median PFS was 13.6 months (95% CI, 13.5-25.2). Plasma CA 19-9 level was non-significantly reduced after SBRT, displaying a -9.15 average percent change from baseline (median time after SBRT, 1.2 months). FFLP at 1 year was 83.9%. Eight (33%) patients underwent successful surgery following SBRT, with rates of both margin- and node-negative resection being 75%. Conclusions: Chemotherapy followed by fractionated SBRT results in favorable local control and survival with minimal acute and late GI toxicity. A notable proportion of patients initially deemed unresectable underwent successful resection. This study suggests that SBRT can be safely given following more aggressive multiagent chemotherapy in patients with LAPC. Clinical trial information: NCT01781728.