tbuckley/cabot-search huggingface dataset:
Does 8-guage stereotactic core needle biopsy improve the accuracy over 11-gauge devices? Evaluation of pure DCIS on stereotactic biopsy and the rate of upstaging.
Authors: Deepa R. Halaharvi, Mark H. Cripe
Journal: Journal of Clinical Oncology (2014)

97 Background: Ductal carcinoma in situ (DCIS) accounts for 25% of newly diagnosed breast cancers. Core needle biopsy (CNB) has replaced open surgical biopsy for mammographic calcifications. We compare our experience with 8-gauge vs. 11-gauge vacuum assisted core needle biopsy in pure DCIS. We hypothesize that the diagnosis of DCIS with use of an 8-gauge vacuum-assisted core needle will lead to a lower rate of upstaging to invasive cancer at definitive surgical excision compared to 11-gauge vacuum-assisted core needle biopsy. Methods: A retrospective study was performed evaluating all patients who underwent a stereotactic core needle biopsy at our institution for DCIS during 2008-2012.We then compared the upstaging rates between patients biopsied using 8 or 11-gauge biopsy devices. Results: A total of 580 patients underwent STCNB during 2008-2012 at our institution, there were 461 patients excluded as they did not meet inclusion criteria and 119 patients were included. The most common mammographic finding was calcifications in 104/119 (87.4%) and a mammographic mass in 15/119 (12.60%). Biopsy with the 11 gauge needle was utilized in 60 patients and 59 patients with 8-G needle. Factors associated with upstaging were using a smaller 11 gauge needle and a mass on imaging, higher grade and more than four cores obtained on biopsy. There was an upstaging rate of 17/60 (28%) in patients who underwent stereotactic biopsy using a11-gauge needle versus upstaging rate of 7/59 (11.8%) in patients who underwent stereotactic biopsy using 8 gauge needle. We obtained a statistically significant p-value of 0.025. Conclusions: This is one of the few studies comparing upstaging rates from pure DCIS on STCNB using 8 and 11-gauge stereotactic vacuum assisted needles. Our results show that there is a statistically significant decrease in upstaging of pure DCIS to invasive malignancy at excision using the larger 8-gauge needle devices. The clinical implication is that SLNB need not be performed secondary to the low upstaging rate. We recommend that all stereotactic core needle biopsies be performed using the 8-gauge needle devices, and that SLNB generally be omitted for DCIS.
The usefulness of serum X-linked inhibitor of apoptosis protein (XIAP) for predicting recurrence of renal cell carcinoma.
Authors: Fumiya Hongo, Daisuke Toiyama, Takashi Ueda, Yasunori Kimura, Terukazu Nakamura, Kazuya Mikami, Natsuki Takaha, Tsuneharu Miki
Journal: Journal of Clinical Oncology (2012)

396 Background: The X-linked Inhibitor of Apoptosis protein (XIAP) is associated with cell survival by blocking caspase-mediated apoptosis. We have reported the expression and prognostic value of XIAP in human prostate cancer using prostate tissue microarrays (Clin Cancer Res 2007). The expression and prognostic significance of XIAP in renal cell cancer (RCC) has been rarely studied. To our knowledge, no report on the serum XIAP levels from RCC patients has been published. In this study, we examined serum XIAP levels of RCC patients and normal individuals and evaluated its utility as biomarker. Methods: Peripheral blood samples were obtained from 99 patients (68 men and 31 women, median age; 60.7 years [36–85]) with RCC before surgery. All the patients underwent radical or partial nephrectomy. Blood samples were also collected from 52 healthy controls. The histological grade was as follows: Grade1; n= 5, Grade2; n=72, Grade3; n= 22. The serum XIAP levels were measured by a sandwich enzyme-linked immunosorbent assay. Cut off value was calculated by ROC analysis. Results: The serum XIAP levels in patients with RCC were higher than those of normal control individuals (328.3 pg/ml vs 156.2 pg/ml, P&lt;0.001). At a median follow up of 33 months (1-105M), tumor with low serum XIAP showed significantly longer progression free survival (PFS) than those with high serum XIAP in Grade 1-2 group (P&lt;0.001). Conclusions: Serum XIAP level is associated with recurrence and prognosis. These results suggest that it may be used as a novel prognosticator and a potential target for renal cell cancer diagnosis and therapy.
Preoperative treatment to modify the immune microenvironnement of liver colorectal metastases.
Authors: Marc Van Den Eynde, Bernhard Mlecnik, Jean-Pascal H. Machiels, Daphne Debetancourt, Gabriela Bindea, Geraldine Pairet, Anne Jouret-Mourin, Christine Sempoux, Jean Francois Gigot, Catherine Hubert, Yves Humblet, Javier Carrasco, Nacilla Haicheur, Florence Marliot, Franck Pages, Jerome Galon
Journal: Journal of Clinical Oncology (2015)

602 Background: We previously reported that an adaptive Th1 immune response (CD3/CD8/CD45RO T-cells) observed in resected primary colorectal tumor and liver colorectal metastases (LCM) is an important prognostic factor. B and FoxP3 regulatory lymphocytes participate to the modulation of this response. We aimed to investigate whether the preoperative treatments influenced the quality and the density of the immune infiltrates previously reported in the LCM. Methods: We used a cohort of metastatic colorectal patients (n=107) engaged for curative liver surgery with available FFPE blocks for all resected LCM to confirm the prognostic impact of the immune response. Among this cohort of 338 LCMs, 46 were completely resected after chemotherapy (CT) alone, 130 after CT + anti-VEGF, 118 after CT + anti-EGFR and 44 after surgery alone. LCMs were analyzed for histological response according the Tumor Regression Grade (TRG) and regrouped as Response (R, TRG1-3) or No Response (NR, TRG4-5). The density of CD3+ (T-cells), CD8+ (cytotoxic), CD45RO+ (memory), CD20+ (B-cells) and FoxP3+ (regulatory) in the core (CT) and invasive margin (IM) of all LCM was quantified on immunostained slides. The mean density value (CT/IM) was calculated for each marker with a dedicated image analysis software on whole-slide imaging. Comparisons were made using the Wilcoxon-Mann-Whitney test. Results: LCMs showing R (compared to NR and untreated LCM) were more frequently associated with a high immune infiltrate for CD3+ (CT: p&lt;0.005; IM: p&lt;0.05), CD8+ (CT: p&lt;0.005; IM: p&lt;0.005) and CD20+ (CT: p&lt;0.05). Conversely, high FoxP3+ density in the CT and IM was related to NR and untreated LCMs (p&lt;0.01). LCMs treated with an anti-EGFR therapy showed higher densities of CD3+ (CT: p&lt;0.005; IM: p&lt;0.01), CD8+ (CT: p&lt;0.005), CD45RO+ (CT: p&lt;0.005), CD20+ (CT: p&lt;0.005) and FoxP3+ (CT: p&lt;0.05; IM: p&lt;0.005) compared to other treatments and untreated LCMs. Conclusions: Preoperative treatment modifies the LCM immune microenvironnement. LCMs with a histological response show a cytotoxic immune response (CD3+/CD8+) with associated B-cells (CD20+) and downregulated Tregs (FoxP3+). The use of an anti-EGFR therapy significantly increases immune infiltration in the CT.
Reporting of subgroup analyses (SGA) in phase III randomized trials in gastrointestinal (GI) cancer.
Authors: Sarah Rachel Barton, Ian Chau, Clare Peckitt, Francesco Sclafani, David Cunningham
Journal: Journal of Clinical Oncology (2013)

78 Background: Correct interpretation of SGA is important as it influences selection of therapeutic interventions for patient subsets. We aimed to evaluate the association of prospectively determined study characteristics with reporting of SGA and claims of subgroup effects in GI cancer trials. Methods: We performed a systematic literature review and extracted data from all articles meeting the following criteria: published 01/01/2003-01/09/2012 in peer-reviewed journal; reporting results of phase III randomised controlled trial; n≥150; testing investigational medicinal product in GI cancer. The primary aim was to compare reporting of SGA between industry and nonindustry sponsored trials. Results: 145 trials were identified. SGA were reported in 100 (69%). A significantly larger median number of SGA were reported in industry than in non-industry sponsored trials (6 vs 2, p=0.004). In the 52 trials claiming subgroup effects, significant test of interaction was evident in only 25%, with no difference between industry and non-industry trials (Table). There was an association between larger number of trial subjects and more SGA reported (p&lt;0.001). Trials of targeted therapy compared to cytotoxic (median 6 vs 2, p=0.004) and trials with significant primary endpoint (median 6 vs 2, p=0.006) reported more SGA. Industry sponsored trials with a significant primary endpoint reported more SGA (median 8) than others (p&lt;0.001). Conclusions: Industry sponsored trials with positive result and trials of targeted therapy appear to report SGA more frequently. Since only quarter of trials claiming subgroup effects had evidence of significant test of interaction, circumspection should be adopted when using SGA as the basis for variance in GI cancer treatment. Conference abstracts may contain more SGA, and these will be incorporated into further analyses. [Table: see text]
Validation of a Prognostic Model and the Impact of SF3B1, DNMT3A, and Other Mutations in 289 Genetically Characterized Lower Risk MDS Patient Samples
Authors: Rafael Bejar, Kristen Stevenson, Bennett Caughey, Omar Abdel-Wahab, Naomi Galili, Guillermo Garcia-Manero, Hagop M Kantarjian, Azra Raza, David P. Steensma, Ross L Levine, Donna Neuberg, Benjamin L. Ebert
Journal: Blood (2011)
Survival investigation in patients with colorectal liver metastasis: A single-institution analysis.
Authors: Jianmin Xu, Dexiang Zhu, Li Ren, Ye Wei
Journal: Journal of Clinical Oncology (2012)

617 Background: To investigate survival in patients with colorectal liver metastasis (CRLM) and identify risk factors associated with survival. Methods: Clinical, pathologic, treatment and complete follow-up data were retrospectively collected from 1613 consecutive patients with CRLM in Zhongshan Hospital between 2000 and 2010. The prognostic value of different factors was studied through univariate and multivariate analyses. Results: The median survival was 22.0 mo and 5-yr survival rate was 16%. Survival of synchronous liver metastases (SLM) (21.2 mo and 16%) was lower than that of metachronous liver metastases (MLM) (30.1 mo and 23%, p&lt;0.01). Survival after resection of liver metastases was 49.8 mo and 37%, higher than that after chemotherapy (22.2 mo and 0%), that after intervention(19.0 mo and 11%), that after chemotherapy combined with intervention(22.8 mo and 10%)and that after local regional treatment (28.5 mo and 0%). Expansion of the indications for liver resection (38.0 vs 48.0 mo, 32% vs 40%), simultaneous or staged resection of primary colorectal tumor and liver metastases (47.0 vs 44.0 mo, 33% vs 35%) and preoperative neoadjuvant therapy (44.0 vs 48.0 mo, 38% vs 36%) had no significant effect on survival. 64 initially irresectable patients could undergo surgery after convertible therapy, with the median survival 36.9 mo and 5-yr survival 30%, better than that of unresectable patients (18.2 mo and 8%). Five factors were found to be significant and independent predictors of poor survival by multivariate analysis: SLM, poorly differentiated primary, number of liver metastases &gt;= 4, largest liver metastases &gt;= 5 cm, and no surgical treatment of liver metastases. Giving one point to each above factor, the population was divided into six groups with 5-yr survival rates: 0 (64%), 1 (44%), 2 (29%), 3 (4%), 4 (4%) and 5 (1%) (p&lt;0.01). Conclusions: Survival of SLM was lower than that of MLM. Resection of liver metastases provides good long-term survival benifit for patients with resectable and initially irresectable liver metastases. Expansion of the indications for liver resection is acceptable. Long-term survival outcome can be predicted from a risk factor scoring system.
Tumor boards among physicians caring for lung and colorectal cancer patients.
Authors: Kenneth L. Kehl, Mary Beth Landrum, Katherine Leslie Kahn, Stacy W. Gray, Clifford Y. Ko, Aileen B. Chen, Nancy Lynn Keating
Journal: Journal of Clinical Oncology (2014)

179 Background: Multidisciplinary tumor board meetings are an important part of cancer care, but few data are available about their benefits. We assessed the association of tumor board participation and structure with patient outcomes. Methods: We surveyed a population and health system-based cohort of patients with lung or colorectal cancer diagnosed in 2003-05 (N=9732) and their physicians (N=1601). We asked physicians how often they participated in tumor boards and whether those meetings served a treatment planning function, evaluated prior treatment decisions, reviewed only challenging cases, reviewed &gt;1 cancer site, and/or served only as teaching sessions. Using logistic and Cox regression, we assessed associations of tumor board participation and tumor board features with patient clinical trial enrollment, receipt of guideline-concordant care, patient-reported quality, and survival. We adjusted for patient demographic and clinical characteristics and physician traits, including specialty. In this exploratory analysis, P values were not adjusted for multiple comparisons. Results: Patients treated by the 54% of physicians participating in tumor boards weekly (vs. less often/never) were more likely to enroll in clinical trials (OR 1.6, 95% CI 1.1-2.2). Patients of physicians whose meetings reviewed &gt;1 cancer site had lower likelihood of trial enrollment (P=0.04) and, among patients with stage I/II non-small cell lung cancer (NSCLC), of curative-intent surgery (P&lt;0.001). Patients with stage I NSCLC, extensive-stage small cell lung cancer (SCLC), or stage IV colorectal cancer had lower mortality if treated by physicians participating in tumor boards weekly (vs. less often/never, P&lt;0.05). Stage I NSCLC patients whose physicians’ tumor boards reviewed &gt;1 cancer site had higher mortality (P=0.04), as did patients with SCLC whose physicians’ tumor boards served only as teaching sessions (P=0.004 for limited SCLC, &lt;0.001 for extensive SCLC). Conclusions: Frequent physician tumor board engagement was associated with patient clinical trial participation and lower mortality for colorectal, small cell lung, and early non-small cell lung cancer, diseases that may benefit from coordinated treatment delivery among specialists.
uPAR and mTORC2 as coupled targets for therapeutics development in bladder cancer.
Authors: Andrew M. Hau, Andrew Gilder, Jing-jing Hu, Steven L. Gonias, Donna E. Hansel
Journal: Journal of Clinical Oncology (2016)

447 Background: Bladder cancer currently ranks as the fifth most common and the single most expensive cancer to manage in the United States. Although it is established that invasive behavior is a major predictor of diminished outcomes for patients with bladder cancer, the molecular mechanisms governing bladder cancer cell invasion are not well understood. The urokinase receptor (uPAR) and mammalian target of rapamycin complex 2 (mTORC2) represent two powerful pro-invasion candidates that have increased expression in high-grade, invasive bladder cancer, though the former has not been characterized in detail in bladder cancer. Therefore, the aims of this study are to characterize the uPAR signaling network and delineate the signaling interplay between mTORC2 and uPAR in bladder cancer. Methods: Using immunoblot and RT-qPCR analyses, we evaluated uPAR expression in a panel of immortalized bladder cancer cell lines: UROtsa, RT4, UMUC3, T24 and J82. uPAR influence on mTORC1 and mTORC2 signaling was determined by immunoblot analysis following targeted gene-silencing of uPAR using siRNA. Additionally, the effects of uPAR knockdown on cell migration and invasion were investigated using modified scratch-wound migration and transwell invasion assays. Lastly, signaling interplay between uPAR and mTORC2 was investigated by evaluating the effects of uPAR and mTORC2 silencing on Rac1 activity. Results: uPAR knockdown in a subset (T24 and J82) of invasive bladder cancer cell lines inhibited mTORC2, but not mTORC1, activity as measured by P-AKT S473 and P-S6 levels. We found that uPAR silencing in T24 and J82 cells resulted in significant reductions in cell migration and invasion through Matrigel. This is likely attributed to inhibition of Rac1 and decreased lamellipodia formation. Conclusions: Collectively, our results identify uPAR and mTORC2 as major regulators of bladder cancer cell invasion and that these two systems are linked through Rac1. Further investigation of uPAR and mTORC2 inhibition using uPAR-targeting antibodies and mTOR inhibitors in an in vivo mouse model of bladder cancer will determine if these signaling pathways are therapeutically beneficial for the treatment of bladder cancer.
The ADEBAR-trial: The sequencing of regional radiotherapy and chemotherapy does not influence cytostatic dose intensity
Authors: H. L. Sommer, W. Janni, B. Rack, D. Steinfeld, D. Augustin, W. Simon, M. Heinrigs, K. Gauger, N. Harbeck, M. Kiechle
Journal: Journal of Clinical Oncology (2005)

744 Background: ADEBAR is a multicenter phase III trial to evaluate whether breast cancer (BC) pts with > 3 axillary lymph metastases benefit from a sequential anthracycline-docetaxel regimen (E90C-D: 4 cycles epirubicin [E] 90 mg/m2 plus cyclophosphamide [C] 600 mg/m2 q21 days followed by 4 cycles docetaxel [D] 100mg/m2 q21 days) compared to dose-intensive anthracycline-containing polychemotherapy (FE120C: 6 cycles E 60 mg/m2 d 1+8, 5-FU 500mg/m2 d 1+8 and C 75 mg/m2 d 1–14, q4 weeks). We analyzed the influence of timing of regional radiotherapy on the cytostatic dose density. Methods: As of June 1st 2004, 176 actively participating centers recruited 994 patients (29.2 patients/month, median) in the ADEBAR-study. Participating centers opted to time the mandatory regional radiotherapy, including breast or chest wall and infra-/supraclavicular irradiation, within a sandwich setting after half of the chemotherapy cycles, or after completion of the entire cytostatic treatment. Complete treatment data were evaluable of 435 patients. Results: In 336 pts (77.2%), radiotherapy was performed after the completion of all chemotherapy cycles, in 99 pts radiotherapy was performed after completing half of the chemotherapy cycles. At least one serious adverse event occurred in 86 pts (19.8%), and in 2.8% of the chemotherapy cycles. The interval between cycles was prolonged at least once in 142 pts (32.6%) and dose reduction was performed at least once in 75 pts (17.2%). Hospitalisation was necessary at least once in 125 pts (28.7%). The sequencing of radiotherapy and chemotherapy did not correlate with the incidence of serious adverse events (0.65), interval prolongation (p=0.29), and hospitalisation (p=0.71). There was a non-significant trend for more frequent dose reduction in patients with sequential treatment (19.0% vs. 11.1%, p=0.07). Conclusions: The sequencing of regional radiotherapy and chemotherapy - sandwich or sequential - does not influence cytostatic dose density. However, because of the predominant risk for life threatening distant metastasis, we recommend to complete the chemotherapy before starting radiotherapy in patients with more than three axillary lymph node metastases. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Aventis, Novartis, Pierre Fabre Aventis, Novartis, Pierre Fabre
UGT1A1 promoter genotype and toxicity in patients with advanced colorectal cancer treated with irinotecan-containing chemotherapy
Authors: S. Chiara, M. Serra, P. Marroni, S. Lastraioli, A. Ponzanelli, L. Tomasello, F. Leonardi, E. Franzini, M. Paganuzzi, R. Notaro
Journal: Journal of Clinical Oncology (2005)

2016 Background: Inherited variation in the activity of enzymes involved in drug metabolism are likely to be responsible for most inter-individual variability in the toxicity and the efficacy of the drugs themselves. The topoisomerase-I inhibitor irinotecan may have unpredictable severe toxicity: mainly diarrhea and myelosuppression. Its active metabolite, SN38, is inactivated through glucuronidation by uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1). The UGT1A1 promoter includes, in the TATA box region, a well known polymorphism containing either 7 or, more commonly, 6 TA repeats. The (TA)7 allele has been associated with a reduced rate of SN-38 glucuronidation and more severe toxicity in patients treated with irinotecan. Methods: UGT1A1 was genotyped by PCR on samples obtained under an institutional review board-approved protocol from 66 patients with advanced colorectal cancer treated, 24 in first and 42 in second line, with irinotecan-containing chemotherapy. Toxicity has been graded according to NCI common toxicity criteria. Results: The median age of patients was 63 years (range: 31–82 years); median performance status was 0 (range: 0–2). 31 patients are homozygotes (TA)6, 8 are homozygotes (TA)7 and 27 are heterozigotes: allele frequencies are 0.674 for (TA)6 and 0.326 for (TA)7, similar to that observed in the Italian general population. Severe gastrointestinal or/and hematological toxicity, leading to dose reduction in 12 cases and treatment withdrawal in 3, has been observed in 26 patients (two of which had both toxicities): diarrhea, grade 3 in 13 cases; neutropenia, grade 3 in 11 cases and grade 4 in 4. In addition, in 6 patients the treatment was discontinued on account of other toxicity (including 4 cases of thromboembolism). Grade ≥3 diarrhea or/and neutropenia has been observed in 32.3% of homozygotes (TA)6, in 50% of homozygotes (TA)7 and in 44.4% of heterozigotes. Conclusions: The relationship between UGT1A1 genotype and irinotecan toxicity has been investigated and these data confirm that UGT1A1 (TA)7 allele is associated with a slight, but not yet statistically significant, higher frequency of severe toxicity. No significant financial relationships to disclose.