tbuckley/cabot-search huggingface dataset:
Effect of change of body mass index (BMI) during therapy on the efficacy of endocrine therapy in premenopausal patients with breast cancer: An analysis of the ABCSG-12 trial.
Authors: G. Pfeiler, R. Königsberg, B. Mlineritsch, H. Stoger, C. F. Singer, S. Poestlberger, G. G. Steger, M. Seifert, P. C. Dubsky, R. Jakesz, H. Samonigg, V. Bjelic-Radisic, R. Greil, C. Marth, C. Fesl, M. Gnant
Journal: Journal of Clinical Oncology (2011)

514 Background: Aromatase inhibitors (AIs) are effective as adjuvant endocrine treatment in breast cancer (BC) patients. Recently, it has been argued that BMI at BC diagnosis impacts on the efficacy of endocrine therapy. Interventional trials try to identify a benefit on outcome by BMI change after BC diagnosis. As endocrine therapy may lead to an increase of body weight, we investigated the impact of BMI change during therapy on BC outcome. Methods: ABCSG-12 examined the efficacy of ovarian suppression using goserelin (3.6 mg q28d SC) in combination with anastrozole (ANA) or tamoxifen (TAM) ± zoledronic acid (ZOL 4 mg IV q6mo) in premenopausal women with endocrine-responsive BC. BMI was calculated using prospectively collected data on weight and height at study entry as well as every three months up to 3 years of endocrine treatment. Comparisons between BMI at study entry and BMI during therapy were done by Wilcoxon signed rank test. Comparisons of BMI changes between ANA and TAM were done by Kruskal-Wallis test. Cox regression models were used to analyse the impact of BMI change as a time dependent covariate on disease free survival (DFS). Results: BMI significantly increased in both treatment arms after 1, 2 and 3 years of therapy. The increase of BMI was significantly higher in patients treated with TAM compared to ANA after 1, 2 and 3 years (0.68 vs. 0.38 kg/m², 1.06 vs. 0.71 kg/m² and 1.10 vs. 0.74 kg/m², p<0.05). None of the Cox regression models showed an impact of BMI as a time dependent covariate on DFS. No difference regarding DFS could be observed comparing patients with an increase of weight by >0.5kg after 1 year to patients with no such increase in weight (HR 1.25, 95%CI 0.886 1.76, p=0.2). Increase or decrease of BMI could not be correlated to the amount of adverse events at any time during therapy. Conclusions: BMI significantly increases in premenopausal patients during endocrine therapy, especially in those treated with TAM. As the change of BMI during therapy does not impact on disease outcome, the BMI at BC diagnosis seems to be much more important than any short-term change thereafter.
Prognostic value of hemoglobin level increase during axitinib treatment for metastatic renal cell carcinoma.
Authors: Alison Claire Johnson, Margarida Matias, Elodie Coquan, Pierre-Emmanuel Brachet, Audrey Emmanuelle Dugue, Alicia Molinier, Loic Mourey, Helen Jane Boyle, Brigitte Laguerre, Carole Helissey, Bernard J. Escudier, Florence Joly
Journal: Journal of Clinical Oncology (2016)

580 Background: Axitinib is used after failure of first line treatment for metastatic renal cell carcinoma (mRCC). A common side effect of axitinib is the increase of hemoglobin level (HbL) during treatment with a suspected correlation with better outcome. We examined whether HbL increase during the first 3 months of axitinib treatment is associated with better prognosis. Methods: Retrospective multicenter analysis including patients with mRCC treated with axitinib for at least 3 months from 2012 to 2014 as part of the French temporary use authorization cohort. Progression-free survival (PFS) was analyzed according to the following factors: gender, International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) prognostic score at axitinib initiation, polycythemia (HbL above 16.5/18.5 g/dL or hematocrit above 56/60% for women/men), and maximum increase in HbL within the first 3 months of treatment. Results: 97 patients were analyzed (71% men; median age at diagnosis: 54.7 years [22; 80]; IMDC: 23%, 49%, and 27% in the favorable, intermediate, and poor-risk group, respectively). Patients received axitinib for a median of 8 months [3; 30]. Grade 2-3 toxicities were observed in 81% of patients. Objective response rate was 32%. The median PFS and OS were 8.9 [7.4; 9.3] and 22 [19.4; not reached] months, respectively. During the first 3 months, 81 patients (84%) experienced HbL increase with a median increase of +2.3g/dL [-1.1; 7.2] and 40 of them (51%) had an increase above this median. Eight patients (8%) presented polycythemia. In univariate analysis, significantly longer PFS was observed for men (p = 0.02), for patients who had a better IMDC prognostic score (p = 0.004), and for patients who experienced an increase of HbL ≥ 2.3 g/dL (with a median PFS of 11.7 vs. 7.4 months; p = 0.025), but not for patients with polycythemia. In a multivariate analysis, after adjustment for IMDC score (p &lt; 0.0001) and gender (p = 0.029), an increase in HbL ≥ 2.3 g/dL was significantly associated with a longer PFS (HR = 0.57, 95%CI [0.34; 0.95]). Conclusions: HbL increase ≥ 2.3g/dL in the first 3 months of axitinib treatment was associated with longer PFS. These results require validation in a prospective trial setting.
The impact of spatial distribution patterns of tumor foci on biochemical recurrence in prostate cancer.
Authors: Okyaz Eminaga, Reemt Hinkelammert, Axel Semjonow
Journal: Journal of Clinical Oncology (2015)

130 Background: The influence of spatial distribution patterns of organ-confined Prostate Cancer (PCa) on the biochemical recurrence (BCR) remains unclear. Therefore, we conducted a study investigating the association between distribution patterns and BCR-free rate in organ-confined PCa. Methods: The anatomical distribution of PCa in 743 men with pT1-pT3N0 and without neoadjuvant therapy was analyzed to determine 20 groups with similar distribution patterns of PCa. Then, 245 men with pT2N0R0 were considered for prognostic evaluation. Spatial distribution patterns of PCa were evaluated using a cMDX-based map model of the prostate. A comparison analysis including 552,049 compare operations was performed to assist the similarity levels of the distribution patterns. K-mean cluster analysis was applied to determine 20 groups with similar distribution patterns. A decision tree-Analysis was performed to divide these groups according to BCR. BCR-free survival was compared. Predictors of progression were investigated using a Cox proportional hazards model. Results: BCR was occurred in 8.2% men with pT2N0R0 PCa. In decision tree analysis, certain PCa distribution patterns revealed no BCR at a median follow-up of 60 mo. (IQR: 42.3-77.0) In univariate and multivariate analysis, the prostate volume, the distribution patterns were an independent predictor for BCR in univariate and multivariate, whereas tumor stage, Gleason score, PSA, relative tumor volume were not. When patients with pT2R0 were stratified according to PCa distribution patterns, the presence of BCR-negative PCa distribution patterns was significantly associated with no risk of BCR by comparison to BCR-associated PCa distribution patterns (P=0.001). Conclusions: PCa distribution patterns provide a prognostic value for BCR. Distribution patterns of PCa can be applied to create more meaningfully predictive pathological T2 sub-divisions than current pT2 prostate cancer sub-stages.
Tumor site, clinicopathological characteristics, and survival of patients undergoing primary elective colorectal cancer resection.
Authors: James Hugh Park, Joanne Edwards, Campbell S.D. Roxburgh, Donald C. Mcmillan, Paul G. Horgan
Journal: Journal of Clinical Oncology (2016)

585 Background: Cancers arising in the proximal and distal colorectum differ in embryological origin, predisposing genetic and epigenetic mutations, clinicopathological characteristics and survival. However, the effect of tumor site on the prognostic value of clinicopathological characteristics and systemic inflammatory responses (SIR) is not known. The present study aims to examine the relationship between tumor site, clinicopathological characteristics and cancer-specific survival (CSS) in patients undergoing elective colorectal cancer (CRC) resection. Methods: Patients who had undergone elective, primary resection of stage I-III CRC (1997-2013) were included. Tumors were categorized as proximal (cecum to splenic flexure) or distal (splenic flexure to rectum) based on pathological reports. SIR was assessed using modified Glasgow Prognostic Score (mGPS; 0-CRP &lt; 10mg/L, 1-CRP &gt; 10mg/L, 2-CRP &gt; 10mg/L and albumin &lt; 35g/L). Results: 796 patients were included; 302 tumors were proximal and 494 were distal to the splenic flexure. Proximal location was associated with advanced age, T stage, poor differentiation, greater lymph node yield, peritoneal involvement and an increased mGPS (all P&lt; 0.01). In all patients, on multivariate survival analysis, distal tumor site, advanced age, T stage, N stage, venous invasion, margin involvement and mGPS were independently associated with reduced CSS (all P&lt; 0.05). In patients with proximal cancer, only age (HR 1.8, P= 0.001), T stage (HR 1.9, P= 0.009), N stage (HR 1.9, P&lt; 0.001) and mGPS (HR 1.6, P= 0.004) were associated with CSS, whereas in patients with distal CRC, T stage (HR 1.4, P= 0.024), N stage (HR 1.5, P= 0.001), venous invasion (HR 1.5, P= 0.038), margin involvement (HR 4.1, P&lt; 0.001) and mGPS (HR 1.5, P= 0.003) were associated with survival. Conclusions: In the present study, tumor site was associated with distinct clinicopathological characteristics. Furthermore, the prognostic value of pathological characteristics currently employed in tumor staging, such as venous invasion and margin involvement, differed with tumor site, whereas evaluation of the SIR was similarly prognostic in patients with proximal and distal CRC.
Cetuximab plus chemoradiation with cisplatin and 5-fluorouracil (5-FU) in locally advanced unresectable esophageal squamous cell carcinoma.
Authors: P. Sunpaweravong, S. Sunpaweravong, D. Sangthawan, S. Pinaikul, S. Attasaranya, A. Dechaphunkul, W. Mitarnun, T. Fungthammasarn
Journal: Journal of Clinical Oncology (2011)

e14548^ Background: Cisplatin and 5-FU combined with radiation is standard for locally-advanced esophageal squamous cell carcinoma. Cetuximab has shown synergism with cisplatin and radiation. This study was aimed to evaluate the efficacy and safety of the addition of cetuximab to chemoradiation. Methods: Patients with unresectable stage III-IVa squamous cell carcinoma of the esophagus were enrolled and received 2 cycles of cisplatin (80 mg/m2 every 3 weeks) and cetuximab (400 mg/m2 then 250 mg/m2 weekly for 7 weeks) plus radiation 50 Gy (2Gy/d x 25 fractions), followed by 4 cycles of cisplatin and 5-FU (800 mg/m2/d for 5 days). Tumor assessment was performed every 6 weeks (RECIST and endoscopic ultrasonography). Results: From January to Decmber 2010, 20 patients were enrolled. Patients characteristics were: female/male 2/18 and median age 62 (44-78). Overall response rate was achieved in 12 patients (80%), 2 patients (13.3%) had stable disease, and 1 patient (6.7%) had disease progression (5 patients were not evaluable). Major treatment-related grade 3-4 toxicities were anemia (25%), renal impairment (20%), hyponatremia (20%), neutropenia (15%), fatigue (15%), febrile neutropenia (10%), diarrhea (10%), vomiting (5%), and esophagitis (5%). Conclusions: Cetuximab added to chemoradiotherapy with cisplatin and 5-FU is active and has an acceptable toxicity profile in patients with locally-advanced unresectable esophageal squamous cell carcinoma. Major toxicities are hematologic and metabolic disturbances, but mostly not severe and manageable.
Pathologic complete response after neoadjuvant paclitaxel and carboplatin chemotherapy for stage II-III breast cancer: A community cancer center experience.
Authors: Anuradha Belur, Arun Kumar Arumugam Raajasekar, Susan Burdette-Radoux
Journal: Journal of Clinical Oncology (2015)

43 Background: To evaluate the efficacy and safety of neoadjuvant carboplatin and weekly paclitaxel in locally advanced breast cancer. Methods: In a retrospective study, 15 patients receiving neoadjuvant chemotherapy with carboplatin and paclitaxel from 2008 to 2013 were identified with breast cancer stages IIA to IIIB. Patients received carboplatin at 6 times the area under the curve (AUC 6) every 4 weeks and paclitaxel 80 mg/m2 weekly for 16 weeks. Weekly trastuzumab was added for human epidermal growth factor receptor 2 (HER2) positive status. The primary endpoint was pathologic complete response (pCR) rate, defined as the absence of invasive cancer in breast and axillary lymph nodes. Partial response was defined as downstaging from clinical to pathologic stage. Results: 15 patients were identified. Median age was 57 years (range, 33 to 80 years). 6 women were African American, 3 Hispanic, 2 Asian and 3 Caucasian. 4 patients had stage IIIB disease, 5 had stage IIIA, 5 had Stage IIB and one had stage IIA. 2 patients had inflammatory cancer. 8 patients underwent modified radical mastectomy, 2 bilateral mastectomy and 4 lumpectomy. The tumor was estrogen receptor positive (ER+) in 8 patients, triple negative in 7 patients and HER2 positive in 2 patients. There were two episodes of febrile neutropenia and one death from sepsis. There was one episode of grade 4 thrombocytopenia requiring dose reduction of carboplatin to AUC 4. There were two instances of grade 3 peripheral neuropathy. One of these patients received a dose reduction of paclitaxel to 70 mg/m2. 10 patients received additional dose dense chemotherapy with doxorubicin and cyclophosphamide. Overall, the pCR rate was 0. Partial response was seen in 9 patients (60%). 14 patients received postoperative radiation; one patient declined radiation therapy. Conclusions: In cooperative group trials, neoadjuvant carboplatin and paclitaxel has been shown to achieve high pCR rates in patients with triple negative and HER2 positive breast cancer without exposure to an anthracycline. In our ethnically diverse patient population at a community cancer center, no pathologic complete responses were seen.
A hypoxic niche to protect human colon carcinoma stem cells from chemotherapy.
Authors: Q. Mao, Y. Zhang, X. Fu, J. Xue, L. Wang, T. Chen, W. Guo, X. Mo, Y. Lu
Journal: Journal of Clinical Oncology (2011)

e14096 Background: Recent evidence suggests that a subpopulation of tumorigenic CD133+ cells from human colon carcinoma be termed as colon cancer stem cells (cCSCs). Our earlier study demonstrated that most of human cCSCs located in hypoxic niche, and the hypoxic human cCSCs resisted radiotherapy to some extent. However, little was known whether hypoxia niche could protect cCSCs from chemotherapy in vivo. Methods: Each of 23 fresh samples of human colon adenocarcinoma was transplanted into nude mice. The tumor-bearing mice derived from five primary tumors were randomized to 4 groups when xenografts reached 100mm3~250mm3: A: saline, B: 5-FU, C: oxaliplatin, and D: oxaliplatin plus 5-FU. After 2 weeks' treatment, the percentages of hypoxic CD133+ and CD133- population were quantified by flow-cytometry marked by pimonidazole (PIM). CD133+ and CD133- cells were sorted and detected for ki67 and PIM via immunofluorescence double staining. Results: Mice xenografts were successfully established from 17 of 23 samples. The average ratio of CD133+ cells was 2.58% (0.42~11.3%). Hypoxic subpopulation of CD133+ and CD133- cells was 66.5% (31.92~90.43%) and 26.4% (1.9~ 65.7%), respectively. The treatment elevated the CD133+ portion in all treatment groups compared to the saline (p<0.001). Although there was not markedly change for the hypoxic subpopulation of CD133+cells, hypoxic fraction of proliferative CD133+ cells was increased by 14.62% (6.44%~20.05%), 16.45% (10.45~24.23%) and 20.46% (9.79~33.12%) in groups B, C and D, respectively. Furthermore, even though proliferative cells in CD133+ and CD133- cells was reduced by 29.93% and 62.5% in group C, 25.26% and 68.22% in group D. However in group B, the CD133+ cells was increased by 37.09% and the CD133- cells was not changed. Conclusions: More CD133+ cCSCs than CD133- cells locate in hypoxic niche, where cCSCs are better at retaining proliferating property under chemotherapy pressure, producing resistance. Oxaliplatin rather than 5-Fu inhibits proliferation of cCSCs, which maybe the possible mechanism underlying better outcome by oxaliplatin in colon cancer patients.
Clinical and genetic risk factors for bone loss in breast cancer survivors after adjuvant chemotherapy
Authors: J. Matro, C. Stankiewicz, M. Horn, W. Hwang, J. Green, I. Su, L. Velders, L. Sherman, A. DeMichele
Journal: Journal of Clinical Oncology (2008)

578 Background: Premature ovarian failure and accelerated bone loss are common late effects of adjuvant chemotherapy for breast cancer. Polymorphisms (SNPs) in bone metabolism and estrogen biosynthesis genes associated with osteoporosis in the general population have been identified (COL1A1 Sp1, IL6_634, VDR fok1 & taq1, ESR1_397, ESR1_325, ESR Xba1, TGF-B 509 & 869). Little is known about clinical and genetic risk factors for osteoporosis in breast cancer survivors. Methods: We performed a cohort study at the Abramson Cancer Center of the University of Pennsylvania. Eligible patients were female, premenopausal at breast cancer diagnosis, AJCC stage I, II or III, had recent follow-up with no recurrence, and received adjuvant chemo one to four years prior to enrollment. Subjects signed informed consent, completed questionnaires, provided blood samples for genomic DNA, and underwent bone density measurement via DEXA scan as part of usual clinical care. Single nucleotide polymorphisms were identified via pyrosequencing and SNPlex assays. Results: We enrolled 132 breast cancer survivors with an average age at chemo start of 43 (range 26.7–57.8); 89% were Caucasian, 5% black. DEXAs were obtained on 118 (89%) at 1.9 years post-chemo (range 0–4.7). Most patients (94%) were treated with anthracycline-based regimens; 57% received a taxane. Hormone therapy was given to 76%; 12% received an aromatase inhibitor. Chemo-related amenorrhea occurred in 47% and was significantly associated with increasing age at chemo (p<0.0001). DEXAs were obtained at 41 facilities. Osteopenia/porosis (T-score < -1.0) at hip and/or spine occurred in 44 patients (33%). Increasing age at chemo was associated with a nonsignificant increase in the risk of osteopenia/porosis (OR 1.03, 95%CI 0.97, 1.1). Significant protective effects were found among women treated with a taxane (OR 0.45; 95%CI 0.21, 0.98), but dose density (q2 vs. q3wk) was not significant (OR 1.44, 95%CI 0.66, 3.2). SNP frequencies ranged from 16–96%; none were associated with osteopenia/porosis at this early timepoint. Conclusions: Age, dose density, and presence of high-risk SNPs were not associated with osteopenia/porosis among breast cancer survivors in the early post-chemotherapy period. Taxanes may have a protective effect. No significant financial relationships to disclose.
Metformin use and outcome of sunitinib treatment in diabetic patients with metastatic renal cell carcinoma.
Authors: Daniel Keizman, Maya Ish-Shalom, Avivit Peer, Maya Gottfried, Hans J. Hammers, Mario A. Eisenberger, Victoria J. Sinibaldi, Victoria Neiman, Eli Rosenbaum, David Sarid, Eli Gez, Wilmosh Mermershtain, Keren Rouvinov, Raanan Berger, Michael Anthony Carducci
Journal: Journal of Clinical Oncology (2015)

440 Background: Sunitinib (Su) is a standard treatment (tx) for metastatic renal cell carcinoma (mRCC). Pre-clinical and clinical studies in several cancer types suggest that the antidiabetic agent metformin (Met) has antitumor activity. Met may negatively regulate mTOR activity. Its effect on the outcome of targeted therapies in mRCC is poorly defined. We analyzed the effect of Met use on the outcome sunitinib tx in diabetic patients (pts) with mRCC. Methods: We performed a retrospective study of an unselected cohort of diabetic pts with mRCC, who were treated with Su in 7 centers across 2 countries. Pts were divided into 2 groups: (1) Met users and (2) Met naive. The effect of Met use on response rate (RR), progression free survival (PFS) and overall survival (OS), was tested with adjustment of other known confounding risk factors using a chisquare test and partial likelihood test from Cox model. Furthermore, univariate and multivariate analyses of association between clinicopathologic factors and Met use, and outcome were performed using the entire pt cohort. Results: Between 2004-2014, 108 diabetic pts with mRCC were treated with sunitinib. There were 52 Met users (group 1) and 56 nonusers (group 2). The groups were balanced regarding the following clinicopathologic factors: age, gender, HENG risk, past nephrectomy, mRCC histology, ≥2 metastatic sites, lung/liver/bone metastasis, prior targeted tx, smoking status, use of angiotensin system inhibitors (ASIs), pre-tx neutrophil to lymphocyte ratio (NLR) &gt;3, Su-induced hypertension (HTN), and Su dose reduction/tx interruption. Clinical benefit (partial response + stable disease) in group 1 vs. group 2 was 96% vs. 84%, while 4% vs. 16% had disease progression within the first 3 months of tx (p=0.054). Median PFS was 15 vs. 11.5 months (p=0.1). Median OS was 32 vs. 21 months (p=0.001). In multivariate analyses of the entire pt cohort (n=108), factors associated with PFS were active smoking (HR=2.7, p&lt;0.0001) and pre-tx NLR &gt;3 (HR 1.8, p=0.012). Factors associated with OS were Met use (HR 0.2, p&lt;0.0001), HENG risk (HR 3.3, p=0.008), active smoking (HR=2.9, p&lt;0.0001), liver metastases (HR 1.8, p=0.004), and pre-tx NLR &gt;3 (HR 3.3, p&lt;0.0001). Conclusions: Met use may improve the OS of diabetic pts with mRCC that are treated with Su.