tbuckley/cabot-search huggingface dataset:
Preliminary results of efficacy and tolerability of first-line bevacizumab in combination with carboplatin/paclitaxel in patients with advanced epithelial ovarian, fallopian tube or primary peritoneal cancer in clinical practice - a German cohort study.
Authors: Alexander Mustea, Sven Mahner, Gülten Oskay-Özcelik, Pauline Wimberger, Peter Jungberg, Wolfgang Meinerz, Dietmar Reichert, Helmut Forstbauer, Maren Keller, Rolf Richter, Melanie Frank, Sandra Klawitter, Claudia Kiewitz, Marianne Mueller, Jalid Sehouli
Journal: Journal of Clinical Oncology (2015)

e16574 Background: The phase III trials ICON 7 and GOG-0218 both have reported significant improvement in progression free survival (PFS) for the addition of bevacizumab to carboplatin and paclitaxel as first-line therapy in patients (pts) with advanced ovarian cancer. However, prospectively assessed efficacy in clinical practice has not been reported yet and data on elderly pts ( ≥ 70 years) are limited. Methods: The first interim analysis evaluated the efficacy and safety of this observational study. Pts are followed up to 27 months. PFS and duration of therapy were evaluated using the Kaplan-Meier method. Results: A total of 808 pts from 197 centers were included in the study since February 2012. 671 pts were evaluable for efficacy. Median age was 63 years (27% ≥ 70 years). Most of the pts were diagnosed with ovarian cancer (81%), 13% with primary peritoneal cancer and 6% with fallopian tube cancer. 73% of pts had FIGO stage IIIB/C. 28% had no residual disease after cytoreductive surgery. 36% of pts had a preexisting hypertension. After 12 months, more than 75% of pts (both all pts and in the subgroup of elderly) were without progression. In total, 20% PFS events were reported until data cut. Within a median treatment duration of 14 months (95%-CI 13.4-14.3) a cycle delay was documented for 12% of pts for carboplatin, 12% for paclitaxel, respectively, and 20% for bevacizumab (11%, 10% and 17% in the group of elderly pts). Dose reductions were documented in 11%, 10% and 5% of pts (15%, 12% and 7% for elderly). At data cut, discontinuation of treatment was documented for 316 pts (47.1%), 16% of these (49 pts) following adverse drug reactions. 734 pts were evaluable for safety. Fatigue (17%) was the most frequent adverse event. Intestinal perforation was reported for 0.5% of pts, thromboembolic events for 3%. Conclusions: Data are consistent with results from ICON 7 and GOG-0218 regarding outcome and toxicity profile. Elderly pts show no clinical relevant differences in PFS or tolerability although interpretation is yet limited. A second study phase has been opened to focus on pts ≥ 70 years.
A French multifactorial prospective study of tumor protein and genetic markers in stage I-III colorectal cancer (CRC): Highlight on molecular characteristics related to mismatch repair (MMR) status.
Authors: Gerard Milano, Maurice Chazal, Pierre Laurent-Puig, Sylviane Olschwang, Marie-Pierre Gaub, Jean-Louis Formento, Patricia Formento, Anissa Abderrahim-Ferkoune, Daniel Benchimol, Thierry André, Sydney Houry, Jean-Luc Faucheron, Christian Letoublon, Francois-Noel Gilly, Jean-Robert Delpero, Philippe Lasser, Bernard Pradere, Denis Pezet, Marie-Christine Etienne-Grimaldi
Journal: Journal of Clinical Oncology (2013)

3596 Background: There is still a need to identify prognostic markers in stage II CRC for setting up adjuvant treatment. The prognostic value of tumor genetic and protein markers was analyzed in CRC patients, as well as relationships between markers. Given the strong prognostic and predictive value of deficient MMR (dMMR), we examined whether dMMR tumors had a distinct protein profile as compared to proficient (pMMR) tumors. Methods: This prospective multicentric study involved 251 stage I-II-III CRC patients with complete surgical resection. Primary end-point was disease free survival (DFS, 60 events, median follow-up 88 months). Biomarkers analyzed on frozen primary tumors were: MMR status (bat 25, bat 26), mutations of KRAS (codons 12-13), BRAF (V600E), PIK3CA (exons 9 and 20), APC (exon 15) and P53 (exons 4-9), CIMP status, ploidy, S-phase fraction, LOH (8p, 17p, 18q), EGFR (ligand-binding assay), VEGFA expression (Elisa), thymidylate synthase (TS) enzyme activity and expression (RT-PCR), thymidine phosphorylase (TP) and dihydropyrimidine dehydrogenase (DPD) expressions (RT-PCR). Results: 30 stages I, 116 stages II and 105 stages III were included (FUFOL adjuvant treatment in 30 stages II and 61 stages III). 14% were dMMR. Multivariate Cox analyses showed that tumor staging was the only significant predictor of DFS. Log Rank analyses restricted to stage III showed tendencies for a shorter DFS in KRAS-mutated (p=0.005), BRAF wt (p=0.009) and pMMR tumors (p=0.036). dMMR tumors significantly expressed elevated TS (median 3.1 vs 1.4) and TP (median 5.8 vs 3.5) expression relative to pMMR (p&lt;0.001) and tended to express higher DPD expression (median 14.9 vs 7.9, p=0.027) and EGFR content (median 69 vs 38, p=0.037) relative to pMMR. Conclusions: The present data, suggesting for the first time that both TS (5FU target) and DPD (FU catabolism enzyme) are overexpressed in dMMR tumors, bring strong arguments to explain the resistance of dMMR CRC tumors to FU-based therapy. The fact that dMMR tumors tend to express elevated EGFR levels and are prone to be KRAS wt suggests that anti-EGFR may be a relevant therapy in these patients. Clinical trial information: 1997.CHUNice-948.
Active8: A randomized, double-blind, placebo-controlled study of chemotherapy plus cetuximab in combination with VTX-2337 in patients with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN).
Authors: Ezra E.W. Cohen, Robert L. Ferris, Kelly Gash, Kristi Manjarrez, Gregory Dietsch, Robert Mark Hershberg, James Kyle Bryan
Journal: Journal of Clinical Oncology (2014)

TPS3123 Background: The potential for synergy between cytotoxic and immunologic agents is an exciting area of exploration in oncology. Many chemotherapeutics like platinum and 5-FU can induce immunogenic antitumor effects. Natural killer (NK) cell-mediated antibody-dependent cellular cytotoxicity (ADCC) is an important mechanism of IgG1 monoclonal antibodies (MAb). VTX-2337 is a novel Toll-like receptor 8 (TLR8) agonist with preclinical data demonstrating synergistic effects with chemotherapy and increased ADCC with MAbs. For recurrent or metastatic SCCHN, the EXTREME regimen adding cetuximab to platinum and 5-FU improved median overall survival (OS) by 2.7 months. While a significant advance, further improvement is needed. Synergy with immunotherapy is one option. A phase Ib study of cetuximab and VTX-2337 in recurrent or metastatic SCCHN patients showed the combination to be tolerable and active. TLR8 activation and NK cell stimulation and mobilization provided a rationale to further assess this combination in SCCHN patients. Methods: This randomized, double-blind, placebo-controlled, phase 2 study evaluates the safety and efficacy of VTX-2337 with EXTREME vs. EXTREME alone for first-line treatment of recurrent or metastatic SCCHN. Patients must have a confirmed diagnosis with at least one measurable lesion and no previous systemic therapy for recurrence. Approximately 175 pts will be randomized 1:1 to receive VTX-2337 + EXTREME or placebo + EXTREME for 6 cycles (q3wk), followed by weekly cetuximab with biweekly VTX-2337/placebo. The primary objective is to compare progression-free survival (PFS) according to immune-related response evaluation criteria between the 2 treatment arms as determined by an independent review facility. Secondary objectives include comparisons of safety, OS, objective response rate, duration of best response, disease control rate, and duration of disease control of the two treatment groups. Pharmacodynamics and pharmacokinetics of VTX-2337 as well as translational medicine correlatives will also be evaluated. Enrollment began in October 2013.
Hemorrhage and/or Microaneurysm Severity and Count in Ultrawide Field Images and Early Treatment Diabetic Retinopathy Study Photography
Authors: Paolo S. Silva, Hala El-Rami, Rasha Barham, Aditi Gupta, Alan Fleming, Jano van Hemert, Jerry D. Cavallerano, Jennifer K. Sun, Lloyd Paul Aiello
Journal: Ophthalmology (2017)
Initial results of CALGB 80803 (Alliance): A randomized phase II trial of PET scan-directed combined modality therapy for esophageal cancer.
Authors: Karyn A. Goodman, Donna Niedzwiecki, Nathan Hall, Tanios S. Bekaii-Saab, Xing Ye, Michael O. Meyers, Kisha Mitchell-Richards, Daniel J Boffa, Wendy L Frankel, Alan P. Venook, Howard S. Hochster, Christopher H. Crane, Eileen Mary O'Reilly, David H. Ilson
Journal: Journal of Clinical Oncology (2017)

1 Background: To determine whether changing chemotherapy (CT) during pre-op chemoradiation (CRT) based on response to induction CT by 18 F-fluoro-deoxyglucose PET imaging can lead to improved pathologic complete response (pCR) in patients (pts) with resectable esophageal and gastroesophageal junction (GEJ) adenocarcinomas. Methods: 257 eligible pts were enrolled, underwent baseline PET scan, and were randomized to one of 2 induction CT arms: Modified FOLFOX-6 (oxaliplatin, leucovorin, 5-FU), days 1, 15, 29 or Carboplatin/Paclitaxel (CP), days 1, 8, 22, 29. Repeat PET was performed days 36-42; change in max standardized uptake value (SUV) from baseline was assessed. PET non-responders (≤35% decrease in SUV – PET-NR) crossed over to alternative CT regimen during CRT (50.4Gy/28 fractions). PET responders (&gt;35% decrease in SUV – PET-R) continued on same CT during CRT. Pts underwent surgery 6 wks post-CRT. Pts evaluable if had surgery, disease progression (PD), death due to disease, were unresectable or had adverse event (AE). Primary endpoint was pCR in PET-NR who crossed over to alternative CT (expected 5% under H 0 to 20% under H a ). Results: Pre-audit PET response data after induction CT and pCR rates after CRT and surgery are shown in the table. For PET-NR who crossed over to alternative CT during CRT, pCR was 15.6%; 95% CI (0.08, 0.26). Conclusions: Efficacy criteria were met for an improvement in pCR rates among pts who were PET-NR after induction CT and received alternative CT during CRT for esophageal and GEJ adenoca. Pts receiving induction and concurrent CP had an unexpectedly low pCR. Support: U10CA180821, U10CA180882 Clinical trial information: NCT01333033. [Table: see text]
Phase I study of OPB51602, a small molecule inhibitor of STAT3 phosphorylation, in patients with refractory solid malignancies.
Authors: Boon C. Goh, Andrea LA Wong, Ross A. Soo, Li-Ren Kong, Ying Kiat Zee, Benjamin Chuah, Soo-Chin Lee, Tomomi Mikami, Miyuki Yuasa, Patrick Marban, Wei-Peng Yong, Thuya Win Lwin, Qian Zhu
Journal: Journal of Clinical Oncology (2012)

3002 Background: STAT3 is constitutively activated by growth signaling pathways in many malignancies; in many cell lines inhibition of STAT3 leads to cell death. OPB51602 is a small molecule inhibitor of STAT3 phosphorylation (Tyr705) and activation. Methods: A phase I study of OPB51602 administered for 2 weeks every 3 weeks was initiated to determine the maximum tolerable dose (MTD), evaluate pharmacokinetics (PK), and assess pharmacodynamics effects on STAT3 in peripheral blood mononuclear cells (PBMCs). The starting dose was 2mg/day, and dose escalations to 5mg/d, 10mg/d, 20mg/d, were planned. Single dose PK was done on the first day of administration for 4 days. Dose escalation was based on the “3+3” design, MTD was defined as the dose with at least 2/6 dose limiting toxicities (DLTs) in the first cycle and toxicities were graded by NCICTCv4.0. Results: 32 patients (pt) were treated at doses of 2mg/d (n=7), 4mg/d (n=18), 5mg/d (n=7). The main toxicities observed included nausea/vomiting, diarrhea, peripheral neuropathy and fatigue. 5 mg/d was the MTD, where cycle 1 DLTs of grade 3 diarrhea/dehydration and hyponatremia occurred in 1 patient respectively. One pt developed grade 3 peripheral neuropathy at 4mg/d cohort. PK showed maximal drug levels 2-3 hours after administration, bi-exponential decay, with mean oral clearance of 316.5 +/- 638.9 L/h and long terminal mean half-life of 61.8 +/- 15.9 h on day 17. STAT3 phosphorylation in PBMCs assessed in 6 pts receiving 4mg/d was reduced from 67.4 +/- 17.4% at baseline to 53.0 +/- 18.1% (p=0.001) after administration on day 1. Interestingly, reduction in tumor metabolism by PET CT on day 15 was observed in 4/8 pts receiving 4mg/d. A pt with heavily pretreated adenocarcinoma of lung at 5mg/d dose had partial response; another pt with metastatic endometrial cancer at 4mg/d dose experienced stable disease for 6 cycles. Conclusions: OPB51602 has an MTD of 5mg/d on this schedule, demonstrates inhibition of STAT3 phosphorylation, and evidence of clinical activity. Further proof of concept studies of OPB51602 are warranted.
Factors and trends in cancer screening in the United States from 2004 to 2010.
Authors: Thanyanan Reungwetwattana, Julian R. Molina, Jeanette Y. Ziegenfuss
Journal: Journal of Clinical Oncology (2012)

1565 Background: Understanding the prevalence of cancer screening in the US and the factors associated with its accessibility is important for public health promotion. Methods: The 2004 and 2010 Behavioral Risk Factor Surveillance Systems were used to ascertain cancer screening rates among populations indicated for each test by age, gender, and the American Cancer Society recommendation for cancer screenings [fecal occult blood test (FOBT) or endoscopy for colorectal cancer (CRC) screening, digital rectal examination (DRE) or prostate specific antigen (PSA) for prostate cancer screening, clinical breast examination (CBE) or mammogram for breast cancer screening, and Papanicolaou (Pap) test for cervical cancer screening]. Results: Over this period, CRC and breast cancer screening rates significantly increased (15.9%, 13.9%) while prostate and cervical cancer screening rates significantly decreased (1.2%, 5.2%). Race/ethnicity might be an influence in CRC and cervical cancer screening accessibility. Prostate cancer screening accessibility might be influenced by education and income. The older-aged populations (70-79, &gt;79) had high prevalence of CRC, prostate and breast cancer screenings even though there is insufficient evidence for the benefits and harms of screenings in the older-aged group. Conclusions: The disparities in age, race/ethnicity, health insurance, education, employment, and income for the accession to cancer screening of the US population have decreased since 2004. The trajectory of increasing rates of CRC and breast cancer screenings should be maintained. To reverse the trend, the causes of the decreased rate of cervical cancer screening and the high rates of screenings in older-aged populations should, however, be further explored. [Table: see text]
Treatment effectiveness in advanced breast cancer patients in Italy: Ten years experience.
Authors: Sandro Barni, Ilaria Vallini, Marta Bonotto, Antonella Brunello, Monica Indelli, Stefania Gori, Chiara Saggia, Maria Cristina Petrella, Daniele Giulio Generali, Marzia Di Pietro Paolo, Anna Moretti, Francesco Massari, Valentina Fausti, Graziella Pinotti, Fabio Puglisi, Karen Borgonovo, Vittorina Zagonel, Luca Porcu, Elena Collovà
Journal: Journal of Clinical Oncology (2013)

e11573 Background: Several studies suggest that newer therapies can improve survival in MBC, but a different impact on overall survival (OS) is observed according to histology, extension of disease and prognostic factors. This survey was performed for evaluate Italian experience in cancer treatment in the last ten years. Methods: We collected data from 13 Italian Medical Oncology Unit; we registered all consecutive patients (pts) with breast cancer who have developed metastasis between 2000 and 2008. Demographic data, pathological characteristics and treatment were reported. OS was calculated from time of recurrence and stratified according to biological characteristics and to recurrence date. Results: 1542 pts was suitable for analysis; median age 61,7 (range 22-94); MBC at diagnosis 21,8%. Site of disease recurrence: bone 26,2%, visceral 25,4%, bone and visceral 20,7%, soft tissue 11,5%, soft tissue and visceral 8,4%, bone and soft tissue 7,8%. Molecolar classification: luminal A 66,3%, luminal B 14,5%, triple negative 11,5%, HER2+ like 7,7%. Pts received a median of 2 lines of chemotherapy (range 0-10) and 1 line of hormonal therapy (range 0-7); 22,5% received biological drugs. 15,5% of metastatic pts were enrolled in clinical trials. After a median follow up of 7.1 years 84,1% pts died (1297/1542 pts) and median OS was 2,7 years (range 2,6-2,9). We did not observe difference in OS for pts divided into 3 groups according to recurrence date (2000-2002, 2003-2005, 2006-2008). A longer median OS was observed in luminal B (3,8 years) versus luminal A and HER2+ like (2,8 years) and triple negative disease (1,2 years). Conclusions: Our survey describe a large number of MBC pts treated in 13 Italian Oncology Unit. OS analysis did not show significant differences according to recurrence date, but for different prognostic factors. OS data are superimposable to literature ones, showing a good transfer from clinical trials to clinical practice.
A multicentric study of interval compressed multiagent chemotherapy and metronomic chemotherapy for patients with Ewing sarcoma family of tumors: The Latin American Pediatric Oncology Group trial.
Authors: Lauro José Gregianin, Marcelo Scopinaro, Adriana Rose, Erica Boldrini, Sima Ferman, Antonio Sergio Petrilli, Cecilia M. J. Costa, Daniela Kirst, Gustavo Dufort, Milena Villarroel, Carmem Salgado, Maria Teresa A Almeida, Miguel Valero, Marcelo Rizzatti, Luis Alberto Castillo, Laurice Siqueira, Daniel Lustosa, Maria Pizza, Guadalupe Rey, Algemir Brunetto
Journal: Journal of Clinical Oncology (2015)

TPS10079 Background: Large cooperative group studies have shown the efficacy of risk-adapted treatment for Ewing sarcoma (ES). However, validation and local adaptation by national cooperative groups is needed. A multicenter protocol to determine the efficacy and safety of adapted regimen was developed by the Latin American cooperative group (GALOP). The primary endpoint is investigate the feasibility and progression free survival (PFS) of combined modality therapy that incorporates interval-compressed VDC/IE as shown by the AEWS0031 study, and metronomic chemotherapy (CT). Secondary endpoints include safety, overall survival and duration of response. Methods: Induction (Indct) CT consisted of alternating cycles of VDC (vincristine 1.5 mg/m2 d1, doxorubicin 37.5 mg/m2 d1 and d2, cyclophosphamide 1.2 g/m2 d1) and IE (ifosfamide 3 g/m2 d1, d2 and d3, and etoposide 165 mg/m2 d1, d2 and d3), followed by local control. Pts with localized disease received 6 cycles at Indct and 8 at consolidation (Cons), and pts with metastasis received 9 at Indct and 5 at Cons. The time interval between cycles at Indct and Cons are 14 and 21 days, respectively. After Cons, pts with metastasis received metronomic CT, which consisted in oral cyclophosphamide (25 mg/m2/day, continuously) and vimblastin (3 mg/m2, weekly), for 1 year, while pts with localized disease are randomized (1:1) to receive or not metronomic CT according to the following risk factor: , age above versus (vs) below 14-years-old, pelvic vs non-pelvic primary tumor, tumor size more vs less than 8 cm, and male vs female. Toxicity is assessed following cycles of CT according to the CTC criteria. Enrollment began in April 2010, and, as of January 2011, 234 pts (107 with metastasis) have been recruited across 37 centers from Argentina, Brazil, Chile, and Uruguay. Statistical design: Target enrollment is 500 subjects; 200 pts with metastasis, and 300 pts with localized disease, of which 150 is randomized to the metronomic CT arm and 150 receive no further CT, in order to identify a difference in 5-years PFS of 15% (power 0.80, 2-tail type 1 error of 0.05).
Erratum: (Journal of Clinical Investigation (February 1995) 95:2 (688))
Authors: H. A.G. Rosanelli, H. Blaszyk, J. M. Cunningham, R. M. McGovern, J. J. Schroeder, D. J. Schaid, J. S. Kovach, S. S. Sommer
Journal: Journal of Clinical Investigation (1995)
Validation of the 12-gene colon cancer recurrence score (RS) in NSABP C07 as a predictor of recurrence in stage II and III colon cancer patients treated with 5FU/LV (FU) and 5FU/LV+oxaliplatin (FU+Ox).
Authors: Michael O'Connell, Mark Lee, Margarita Lopatin, Greg Yothers, Kim Clark-Langone, Carl Millward, Soonmyung Paik, Saima Sharif, Steven Shak, Norman Wolmark
Journal: Journal of Clinical Oncology (2012)

3512 Background: Standardized clinical tools which accurately quantify recurrence risk are needed for optimal adjuvant treatment of colon cancer. The 12-gene RS has been validated in stage II colon cancer pts from QUASAR and CALGB 9581. We conducted a large prospectively-designed clinical validation study of RS, w/ pre-specified endpoints, methods, and analysis plan, in stage II and III colon cancer pts randomized to FU or FU+Ox in NSABP C-07. Methods: 50% of C-07 pts w/ tissue were randomly selected, stratified on stage (AJCC 6 th ) and recurrence. Gene expression was quantitated by RT-PCR on 25 µm manually microdissected fixed colon tumor tissue. Data were analyzed by Cox regression controlling for stage and treatment (TRT). Results: RT-PCR was successful in 892/921 pts (97%): 449 FU, 443 FU + Ox; 264 st II, 409 st IIIA/B, 219 st IIIC. The primary endpoint was met: RS predicted recurrence (HR/25 units=1.96, 95% CI 1.50-2.55 p&lt;.001). RS also predicted disease-free survival (p&lt;.001) and overall survival (p&lt;.001). RS predicted recurrence (p=.001) independent of T and N stage, MMR, nodes examined, grade, and TRT. Predefined high RS group (26% of pts) had higher recurrence risk than low RS group (39% of pts): HR=2.11, p&lt;.001. Cox model 5 yr recurrence risk (95%CI) in FU treated pts by RS group (low, int, high): st II 9% (6-13%), 13% (8-17%), 18% (12-25%); st IIIA/B 21% (16-26%), 29% (24-34%), 38% (30-46%); st IIIC 40% (32-48%), 51% (43-59%), 64% (55-74%). RS did not have significant interaction w/ stage (p=0.90) or age (p=0.76). Relative benefit of Ox was similar across range of RS (interaction p=0.48); accordingly, in Cox model and Kaplan-Meier analyses, absolute benefit of Ox increased w/ higher RS. Conclusions: RS predicts recurrence risk in stage II and III colon cancer, capturing underlying biology and providing risk information beyond conventional factors. RS is not predictive of relative benefit of Ox added to adjuvant FU but enables better discrimination of absolute Ox benefit as a function of risk. Incorporating RS into the clinical context may better inform adjuvant therapy decisions for pts w/ stage III as well as stage II colon cancer.