tbuckley/cabot-search huggingface dataset:
Effect of weight loss intervention on inflammatory and metabolic markers in breast cancer survivors: The lifestyle, exercise, and nutrition (LEAN) study.
Authors: Erikka Loftfield, Maura Harrigan, Fangyong Li, Brenda Cartmel, Yang Zhou, Mary Playdon, Lingeng Lu, Tara Beth Sanft, Melinda Irwin
Journal: Journal of Clinical Oncology (2014)

1505 Background: Obesity and physical inactivity are associated with poorer prognosis among breast cancer survivors. Inflammatory and metabolic pathways may explain these associations. We hypothesized that diet- and exercise-induced weight loss would decrease insulin, glucose, IGF-I, C-reactive protein (CRP), TNF-α, IL-6 and leptin, but increase adiponectin in breast cancer survivors. Methods: Ninety-seven overweight or obese breast cancer survivors were identified from the Yale-New Haven Hospital Tumor Registry and randomized to usual care (n=33) or weight loss counseling by a registered dietitian (n=64) for 6 months. The usual care group was provided with AICR nutrition and physical activity brochures. Weight was measured and fasting blood samples were drawn at baseline and 6-months by trained staff. We conducted analyses using the intention-to-treat procedure with baseline values imputed for missing 6-month values (n=16). We used analysis of covariance, adjusted for baseline biomarker levels, to evaluate mean biomarker changes across groups. In secondary analyses, we evaluated the effect of weight loss on biomarkers among women randomized to intervention. Results: On average, women randomized to intervention and usual care groups lost 6% and 2% body weight (p=0.0003), respectively. Women in the intervention group experienced decreases in insulin, glucose, CRP, leptin and TNF-α and increases in adiponectin and IGF-I. CRP decreased by 30% in the intervention group and 1% in the usual care group (-1.05 mg/L vs. -0.06 mg/L, p=0.05). Compared to intervention women who lost <5% body weight, those who lost ≥5% body weight had larger decreases in CRP (-1.58 mg/L vs. -0.54 mg/L, p=0.02), insulin (-3.21 μU/mL vs. -0.59 μU/mL, p=0.048), leptin (11.08 ng/mL vs. -0.76 ng/mL, p=0.002) and IL-6 (-0.20 pg/mg vs. +0.59 pg/mg, p=0.02) but an increase in IGF-I (+9.19 ng/L vs. -11.11 ng/L, p=0.01). Conclusions: Weight loss resulting from a 6-month, 11-session counseling program had favorable effects on some inflammatory and metabolic biomarkers associated with breast cancer survival. IGF-I may not be a mechanism through which weight loss improves breast cancer survival.
Cetuximab (CTX) in first-line treatment of elderly patients with metastatic colorectal cancer (mCRC), KRAS wild type: French multicentre prospective community-based registry and results.
Authors: Laurent Mineur, Eric François, Jean Marc Phelip, Rosine Guimbaud, Carine Plassot, Denis Michel Smith, Laurent Miglianico
Journal: Journal of Clinical Oncology (2017)

760 Background: Pts included in clinical trials represent the unusual population in mCRC. This study aims to provide oncologist with a better understanding of the potential benefit of CT with CTX in older patients with mCRC KRAS wild type and evaluate prognostic variables on the PFS including the age. Methods: Premium cancer study is a French multicentre prospective community-based registry. 493 pts enrolled and 487 included between September 2009 to March 2012 from 94 French centers and physicians. Pts had to provide written informed consent and protocol submitted to regulatory authorities. Predefined efficacy endpoints was PFS. CTX was administrated at 250 mg/m2 weekly (n=100; 20.3%) or 500 mg/m2 every 2 weeks (n=380;77,2%), other n=13; 2.5%) CT regimen choice was at physician’s discretion.. The main analysis is PFS as well as analysis of prognostic factors of this PFS (29 items including age (&lt; 65 years n=229; 65-74 years n= 165.; ≥75years n=93). Univariate analysis was performed for each covariate, PFS was estimated by Kaplan-Meier curves and compared by log-rank test. univariable Cox regression analysis was used to assess the association between each variable and outcome. Multivariable stepwise Cox models were then fitted for final variable selection of prognostic factors on PFS. Results: Univariate significant prognostic factors for PFS are OMS (0-1 vs 2-3), Tobacco, Site of tumor (right vs other), Number of metastatic organ (1 vs 2-3), Resecability of metastatic disease defined before CT (definitively non resectable metastases vs possible resectable), Surgery of mCRC, folliculitis or xerosis or paronychia grade 0-1 vs 2-4. Age was unidentified as a prognostic factor in univariate analysis. Four factors were independently associated with a better PFS: xerosis [hazard ratio (HR0,651); 95% confidence interval (CI) 0,494-0,857], (WHO PS) 0–1 (HR0,519 ; 95% CI 0,371–0,726) and folliculitis (HR 0,711; 95% CI0,558–0,956) metastases surgery 0,287(CI 0,205-0,403). Conclusions: CTX in combination with standard CT is effective, age is not identified as a prognostic factor for the PFS. Both groups of pts based on age benefit from CTX.
Randomized phase III trial of pixantrone compared with other chemotherapeutic agents for third-line single-agent treatment of relapsed aggressive non-Hodgkin's lymphoma
Authors: R. Pettengell, G. Narayanan, F. H. Mendoza, R. Digumarti, H. Gomez, P. Cernohous, I. Gorbatchevsky
Journal: Journal of Clinical Oncology (2009)

8523 Background: Currently, treatment options for multiply relapsed aggressive NHL are limited, and response rates are disappointing. Pixantrone, a novel aza-anthracenedione with structural similarities to mitoxantrone, has potentially reduced cardiotoxicity and has demonstrated promising clinical activity in phase II studies in heavily pretreated NHL patients. Methods: PIX301 was a controlled, multicenter, open-label phase III study of ≥ third-line treatment of relapsed aggressive (de novo or transformed) NHL. All patients were required to have received ≥ 1 prior anthracycline-containing regimen, with the cumulative doxorubicin-equivalent dose limited to ≤ 450 mg/m 2 . Randomization was to pixantrone 85 mg/m 2 on days 1, 8 and 15 of 28-day cycles, for up to 6 cycles, or to investigator's choice of a single-agent comparator (vinorelbine, oxaliplatin, ifosfamide, etoposide, or mitoxantrone; in the US only, gemcitabine and rituximab were permitted). The primary study endpoint was CR/CRu rate. Secondary objectives included safety, OS, and ORR. Originally planned to enroll 320 patients, PIX301 was amended to 140 patients due to slow enrollment. Results: 140 patients (70 per arm) were randomized. Median age was 60 on the pixantrone arm, 58 on the control arm; patients on both arms had received a median of 3 prior chemotherapeutic regimens. Based on independent review in the ITT population, the CR/CRu rate in patients treated with pixantrone was significantly higher than in those receiving other agents (20.0% vs. 5.7%, p-value = 0.02), and there were no CRs in the control group compared to 8 CRs in the pixantrone group. Conclusions: In this study, single-agent therapy with pixantrone achieved significantly superior CR/CRu and ORR rates in ≥ third-line treatment of relapsed/refractory aggressive NHL. [Table: see text] No significant financial relationships to disclose.
Outcomes of patients with malignant pleural mesothelioma (MPM) following the approval cisplatin/pemetrexed: Experience of a comprehensive cancer center.
Authors: Deepa Jagtap, Harvey Pass, Frank Baciewicz, Antoinette J. Wozniak, Miguel Alvelo-Rivera, Andre A. Konski, Wei Chen, Daryn W. Smith, Shirish M. Gadgeel
Journal: Journal of Clinical Oncology (2012)

e17528 Background: Mesothelioma is a rare cancer that is estimated to occur in about 2,500 people in the United States every year. MPM is the most common type of mesothelioma. Until 2003 there was no chemotherapeutic regimen approved for the treatment of MPM. The combination of cisplatin/pemetrexed was approved based on improved survival in a randomized phase III study. We analyzed the data of all MPM patients treated at our center, since the approval of this combination, to evaluate the outcomes of these patients. Methods: This retrospective analysis included all patients with MPM evaluated at Karmanos Cancer Institute in Detroit, Michigan, between 2005 to 2010. We analyzed the demographic data, history of asbestosis exposure, histology, clinical stage of diagnosis, treatment received and survival. A multiple Cox regression model was built on age, sex, histology, surgery or not and stage (I&amp;IIvs.III&amp;IV). Results: Fifty-four MPM patients were evaluated between 2005-2010. The median age of patients was 65 years, 70% were males, 74% had known history of asbestos exposure, 76% had epitheloid histology and 63% had stage III/IV disease at diagnosis. Seventy eight percent of patients received pemetrexed based therapy, 50% underwent pleural surgery (EPP-30%, Pleurectomy- 20%) and 37% received radiation therapy as part of the initial therapy. Twenty-one patients underwent surgery following neo-adjuvant chemotherapy. Thirty-nine percent of patients went on to receive second line therapy. The median overall survival was 18 months (95% CI 14- 22). COX model analysis showed that patients with epitheloid histology had a HR of 0.40, p= 0.0168) and patients who were stage I/II had a HR of 0.42, p = 0.0282. Surgery resulted in a HR of 0.66, but it was not statistically significant (p=0.2637). Age and sex were not significantly associated with survival. Conclusions: The median survival of MPM patients in this series was 18 months. As expected epitheloid histology and early stage at diagnosis were associated with improved survival. Surgery did improve survival but this improvement was not statistically significant.
Genetic variants of TCF7L2 and AXIN2 predict gender and tumor location-dependent clinical outcome in FIRE-3 trial: A validation study.
Authors: Yan Ning, Sebastian Stintzing, Volker Heinemann, Wu Zhang, Dongyun Yang, Yu Sunakawa, Stefan Stremitzer, Ana Sebio, Shinichi Yamauchi, Satoshi Matsusaka, Rita Elkhoueiry, Afsaneh Barzi, Anthony B. El-Khoueiry, Heinz-Josef Lenz
Journal: Journal of Clinical Oncology (2014)

3602 Background: Wnt signaling pathway genes TCF7L2 and AXIN2 complex control the proliferation and differentiation of intestinal epithelial cells. Our previous study showed that TCF7L2 and AXIN2 polymorphisms(SNPs) were associated with clinical outcome of mCRC patients(pts) treated with first line FOLFIRI/BEV from TRIBE (arm A) and PROVETTA trials (n=455) (ASCO 2013#3566). Our data demonstrated that the association of TCF7L2rs7903146 and AXIN2 rs2240308 snps with PFS and OS is depended on gender and location. The goal of the current study was to prospectively validate our previous findings in mCRC pts enrolled in FIRE-3 clinical trial, which treated with either first line FOLFIRI/BEV or FOLFIRI/cetuximab. Methods: Genomic DNA was isolated from tissue samples of 592 pts (patient characteristics gender, median age median follow up) treated with first-line FOLFIRI/ bevacizumab (n=295) or FOLFIRI cetuximab (n=297) from the FIRE-3 trial (NCT00433927). All pts were KRAS exon 2 wild-type. The bevacizumab arm served as validation arm whereas the cetuximab arm served as control arm. Results: Our data validated that TCF7L2rs7903146 and AXIN2 rs2240308 snps could predict clinical outcome when adjusted by pts gender and tumor location. 1) In right-sided tumors, Female pts with any T allele of TCF7L2rs7903146 were associated with significantly longer PFS(median=13 mos) (HR: 0.38; 95% CI: 0.15, 0.97) in comparison to those carrying C/C genetype(median=5.7 mos, P = 0.04), which is consistent with our previous data. 2) In left-sided tumors, Female pts with AXIN2 rs2240308 any A allele had shorter OS(median=24.8 mos)(HR: 2.87; 95% CI: 1.07,7.76; P = 0.026) compared to those with G/G variants(median=44.3 mos), which validated our previous data. No significant difference in control arm. Conclusions: In this study, we prospectively validated the predictive value of TCF7L2 rs7903146 and AXIN2 rs2240308 snps in mCRC pts treated with first-line FOLFIRI/BEV. More importantly, This is first time confirmed that this predictive value is dependent on gender and tumor location in over 900 mCRC pts, suggesting Wnt signaling may play different role in female vs male and in right vs left side tumors.
Surgical staging and its prognostic impact on patients with borderline ovarian tumors (BOT): A subanalysis of the Arbeitsgemeinschaft Gynaekologische Onkologie (AGO) ROBOT study.
Authors: Fabian Trillsch, Sven Mahner, Linn Lena Woelber, Eik Vettorazzi, Alexander Reuss, Nina Ewald-Riegler, Nikolaus De Gregorio, Christina Fotopoulou, Barbara Schmalfeldt, Alexander Burges, Felix Hilpert, Tanja N. Fehm, Werner Meier, Peter Hillemanns, Lars Christian Hanker, Annette Hasenburg, Hans-Georg Strauss, Martin Hellriegel, Pauline Wimberger, Andreas Du Bois
Journal: Journal of Clinical Oncology (2014)

5562 Background: Incomplete surgical staging was shown to be a negative prognostic factor for patients with borderline ovarian tumors (BOT). However, little is known about the prognostic impact of each individual staging procedure. Methods: Clinical parameters of 950 patients with BOT (confirmed by central reference pathology) treated between 1998 and 2008 in 24 German AGO centers were analyzed. Staging quality was evaluated following German guidelines. In patients with adequate surgery regarding their reproductive organs (bilateral salpingo-oophorectomy or intended fertility preserving surgery in patients ≤55 years), other recommended staging procedures (omentectomy, peritoneal biopsies, cytology, and, for mucinous histology, appendectomy) were evaluated applying uni- and multivariate regression models with respect to progression-free survival (PFS), separately for serous and mucinous histology. Results: A total of 559 serous BOT (64.1%) were opposed to 268 mucinous BOT (30.7%). For patients with serous histology, each additionally skipped staging procedure raised the risk for recurrence by at least 25% (HR 1.25; 1.95; 2.37 respectively) becoming statistically significant in case of two or more missing steps. The most crucial procedures were omentectomy in serous and appendectomy in mucinous BOT with HR of 2.00 (p=0.004) and HR of 4.86 (p=0.012) in univariate analyses. Together with established prognostic factors as FIGO stage, tumor residuals, and fertility preservation, omentectomy (HR 1.91; 95%CI 1.15, 3.19; p=0.01) retained a statistically significant impact on PFS in multivariate analysis for serous BOT as did appendectomy in case of mucinous histology (HR 4.60; 95%CI 1.33, 15.86; p=0.02). Conclusions: Individual surgical staging procedures appear to have prognostic importance for BOT patients. Despite excellent overall prognosis, the risk for recurrence rises with each skipped surgical step. This should be considered when re-staging procedures following incomplete primary surgery are discussed.
Phase II trial of single-agent ganetespib (STA-9090), a heat shock protein 90 (Hsp90) inhibitor in heavily pretreated patients with metastatic castration-resistant prostate cancer (mCRPC) post docetaxel-based chemotherapy: Results of a Prostate Cancer Clinical Trials Consortium (PCCTC) study.
Authors: Elisabeth I. Heath, Mark N. Stein, Ulka N. Vaishampayan, Emmanuel S. Antonarakis, Glenn Liu, Shijie Sheng, Katherine Farrow, Daryn W. Smith, Lance K. Heilbrun
Journal: Journal of Clinical Oncology (2013)

5085 Background: Hsp90 is a molecular chaperone required for the proper folding and activation of numerous client proteins and is critical to cell survival and proliferation. Ganetespib (G), a synthetic small molecule that binds to the ATP pocket in the N-terminus of Hsp90 causes the degradation of cellular proteins and ultimately death of cancer cells dependent on these proteins. G displays potent anticancer activity in prostate cancer cells. Methods: Eligible patients were ≥ 18 yrs old with ECOG performance status ≤ 2. Adequate hepatic, renal, and bone marrow function was required. Patients were treated with G 200 mg/m 2 intravenously once weekly for 3 consecutive weeks followed by 1 off-week. The primary objective was to evaluate the 6-month progression-free survival (PFS). Secondary endpoints included overall safety and tolerability of G and overall survival. Exploratory markers including maspin, cytokeratins 8 and 18, and HDAC1 were obtained pre, during, and post G treatment. We sought ≥ 4 patients with ≥ 6 months PFS (a success) in Stage 1 of a 2-stage near-optimal Simon design. Results: 18 patients were enrolled at 4 institutions. The patients’ median age was 68 (range 51-82), 13 were Caucasian, 4 were African American, and 1 was Asian. Median PSA was 210.7 ng/mL (range 25.9 – 3,489 ng/mL). One patient never started therapy. Among the 17 treated patients, the median number of cycles was 2 (range 1-5). The most frequent Grade 3 toxicities were diarrhea (3 patients), fatigue (3), and dehydration (3). Prior therapy included abiraterone (8), sipuleucel-T (4), and other targeted therapy (4). With &lt; 4 successes in Stage 1, the trial was terminated early. Median PFS was 1.9 months (90% CI: 1.7 – 2.7 months); median OS was 10.2 months (90% CI: 2.3 – 18.3 months). Exploratory markers have been evaluated and will be presented. Conclusions: Our study represents the first clinical trial of G in treating mCRPC patients. As a single agent therapy, G did not prolong PFS. Combination therapy is a consideration to improve therapeutic efficacy. Clinical trial information: NCT01270880.
A phase I/II study of carfilzomib (CFZ) as a replacement for bortezomib (BTZ) for multiple myeloma (MM) patients (Pts) progressing while receiving a BTZ-containing combination regimen.
Authors: James R. Berenson, Ori Yellin, Robert Dichmann, Dipti Patel-Donnelly, Ralph V. Boccia, James D. Hilger, Youram Nassir, Regina A. Swift, Robert A. Vescio
Journal: Journal of Clinical Oncology (2012)

8098 Background: Recent data has shown that single-agent CFZ can produce responses among MM pts refractory to previous treatment regimens including those containing BTZ. We conducted an intrapatient Phase 1/2 trial investigating the safety and efficacy of CFZ as a replacement for BTZ in BTZ‑containing regimens to which pts have progressed. Methods: Eligible pts had to have progressed while receiving their most recent BTZ‑containing regimen after at least 4 doses of BTZ at &gt; 1.0 mg/m² in &lt; 4 weeks per cycle. Combination regimens containing an alkylating agent, anthracycline, or a glucocorticosteroid were eligible. CFZ replaced BTZ in each regimen via intravenous administration over 30 min on days 1, 2, 8, 9, 15, and 16 of each cycle. Treatment continued using the same dose(s) and schedule(s) of each drug administered in the BTZ‑containing regimen. CFZ doses were escalated on each of the first 4 cycles from 20 to 27, 36, and 45 mg/m² or until a maximum tolerated dose (MTD) was reached for that regimen. Results: Of 19 enrolled pts 13 are evaluable to date and 6 have recently started treatment. Pts received a median of 7 (range, 1-18) prior treatments and 5 (range, 1-5) different BTZ-containing regimens. Pts were treated with CFZ and the following different combinations: bendamustine (BEND) alone, BEND + methylprednisolone, dexamethasone (DEX) alone, DEX + pegylated liposomal doxorubicin, ascorbic acid + cyclophosphamide, and melphalan alone. Pts have completed a median of 3 cycles. Clinical benefit was seen in 10 (77%) pts (complete response = 8%; very good partial response = 8%; partial response = 31%; minor response = 31%) with another 23% showing stable disease. The median time to progression (range: 2-8 months) has not been reached and only 2 pts have progressed. The most common grade 3/4 adverse events were thrombocytopenia occurring in 5 pts (all = grade 3 except 1 event) and fever occurring in two pts (grade 3). Four pts experienced a serious adverse event but no regimen has reached a MTD. Conclusions: These early results suggest that CFZ is an effective and tolerable replacement for BTZ for pts who are refractory to BTZ-containing combination regimens.
What I wish I had known: Young breast cancer survivors reflect on their experiences after breast cancer surgery.
Authors: Shoshana M. Rosenberg, Mary Greaney, Andrea Farkas Patenaude, Meghan E Meyer, Ann H. Partridge
Journal: Journal of Clinical Oncology (2017)

180 Background: Breast cancer (BC) surgery can have a profound impact on aspects of quality of life (QOL) particularly for young breast cancer survivors, given their life stage. Using a series of focus groups (FG), we explored post-surgical experiences of young survivors who had elected lumpectomy, unilateral or bilateral mastectomy. Methods: Women who had surgery for their stage 0-3 BC and who were 1-3 years from their diagnosis (dx) at age ≤ 40 were recruited to participate. We conducted 4 FG: 2 with women who had bilateral mastectomy, 2 with women who kept their contralateral breast. FG were recorded and transcribed with identifiers removed. FG transcripts were coded using NVivo, and emergent themes were identified by thematic content analysis. At the end of the FG, participants completed a demographic/medical history survey. Results: Of 20 participants (4-6 per FG), median age at dx was 37 yrs; 10% (2/20) identified as Hispanic; most (19/20) were married/partnered; 70% had Stage 1 (4/20) or 2 (10/20) disease. Almost all women who had mastectomies also had reconstruction. Emergent themes included: the unexpectedness of certain physical experiences post-surgery (e.g., surgical drains, pain, numbness), psychological impact of surgery (e.g., vulnerability, self image changes), and short and long-term adjustment to a “new normal”, irrespective of which surgery they had. While participants generally felt their doctors communicated key information about surgery and recovery, some expressed dissatisfaction with how this information was communicated, including feeling pressured to choose a particular surgical option. Conclusions: Young BC survivors have many physical and emotional concerns after BC surgery for which they may not feel prepared. Communicating balanced and relevant information prior to surgery about what to expect afterwards is essential and can potentially help survivors with their transition to a “new normal,” as they move from active treatment to survivorship. Informational resources and decision aids may enhance patient-doctor communication in this setting and help young survivors manage expectations surrounding short and longer-term physical and emotional effects after surgery.