tbuckley/cabot-search huggingface dataset:
Relationship between implementation of the American Society of Clinical Oncology/College of American Pathologists guideline recommendations for breast core-needle biopsies and delay in therapy for patients with breast cancer.
Authors: D. Rosen, M. A. Quraishi, L. P. Middleton, W. T. Yang, A. A. Sahin
Journal: Journal of Clinical Oncology (2011)

26 Background: Recently the ASCO/CAP suggested new guideline recommendations for immunohistochemical (IHC) testing of biomarkers in breast cancer. An algorithm that relies on accurate, reproducible assay performance was proposed and preanalytical, analytical and postanalytical standards suggested. One such recommendation is to have appropriate internal controls when assessing hormone expression. In this retrospective study we evaluated 242 breast core biopsy specimens to assess the impact of the recently proposed ASCO/CAP guideline recommendations and its possible impact on routine daily practice. In addition, we explore the impact of blindly selecting a random core for potential future studies. Methods: A total 988 cores from 242 specimens corresponding to 224 patients diagnosed between 2008 and 2009 were examined. Each core was examined for the presence of normal glands, percentage of tumor involvement, biomarker status, and diagnostic adequacy. Results: Absence of normal glands was found on 61/242 specimens (25%). Of these, expression of ER, PR and HER2 was seen in 44 (72%), 28 (46%), and 21 specimens (35%) respectively. Negative staining for ER, PR and HER2 was observed in 7 specimens (12%). A total of 148 cores (15%) showed absence of tumor and 275 cores (28%) had &lt;25% of tumor in them. 18 cores (2%) were insufficient for diagnosis due to either scant tumor present or crush artifact present. Conclusions: Although the presence of internal control glands is optimal, its presence may be unnecessary if proper IHC batch run controls are utilized and histologic/IHC concordance is performed. Tumor histology and IHC profile concordance is imperative specially in triple negative cases. The impact on patient health care of an “receptor uninterpretable” biopsy is yet to be determined, but likely would include assessment of the delay in care due to a repeat biopsy with procurement of additional tissue, additional heath care costs, and anxiety to the patient. Adequacy check using frozen section could be done to assess for the presence of tumor during the procedure.
Early drop of circulating tumor cells (CTC) and increase of circulating endothelial cells (CEC) during neoadjuvant chemotherapy (CT) combined with bevacizumab in HER2-negative inflammatory breast cancer (IBC) in multicenter phase II trial BEVERLY 1.
Authors: J. Pierga, F. Bidard, F. Andre, T. Petit, F. Dalenc, T. Delozier, G. Romieu, J. Bonneterre, J. Ferrero, P. Kerbrat, A. Martin, P. Viens
Journal: Journal of Clinical Oncology (2011)

10510 Background: CTC detection in blood is an independent prognostic factor in primary breast cancer with a detection rate from 20 to 25% (Pierga CCR 2008). Changes in the CTC HER2 status compared to primary tumor have been reported. Predictive value of CEC for response to anti-angiogenic agents is debated. Methods: CTC and CEC were detected in 7.5 ml and 4 ml of blood respectively in the neoadjuvant setting of HER2 negative IBC (T4d) patients (pts) enrolled in the phase II multicenter trial BEVERLY 1, evaluating bevacizumab (15mg/kg q3w) in combination with sequential neoadjuvant CT of 4 cycles of FEC followed by 4 cycles of Docetaxel. The CellSearch System, combining EpCAM immunomagnetic selection followed by anti-cytokeratin (A45B/B3) and anti-HER2 staining for CTC and CD146 IMS and CD105 staining for CEC. Results: From 12/08 to 09/10, 101 pts were included and 92 were evaluable for CTC and CEC. At baseline, 37 pts out of 92 had ≥ 1 detectable CTC (40%, 95%CI 30-50%). No correlation was found between CTC and CEC levels. A dramatic drop in CTC incidence (p<0.0001) was observed from baseline to the 1st follow-up analysis after 4 cycles (6%). There was a significant increase of CEC median number from baseline (12) to preoperative sample (130) (p <0.001) and a decrease (39) (p=0.04) when CT and bevacizumab were interrupted for surgery. In 40 patients, CTC HER2 status was analyzed at baseline: 18/40 had ≥ 1CTC and 12 had HER2 positive CTCs. Conclusions: We observed a high CTC detection rate of 40% in pts with HER2 negative IBC, including triple-negative tumor. Our study indicates that CT combined with bevacizumab causes significant but opposite changes in CTC and CEC. Our results confirm the discrepancy of the HER2 status in CTC and corresponding primary tumors. Changes in CTC and CEC will be correlated to the primary tumor response as indicator for clinical outcome. Baseline Pre-C5 Pre-surgery Post-surgery CTC ≥ 1CTC 37/92 (40%) 5/82 (6%) 5/63 (8%) 2/56 (3.5%) ≥ 5CTC 17/92 (18.5%) 1/82 (1%) 1/63 (1.5%) 0/56 (0%) Range 1-559 1-6 1-5 1-2 CEC Median 12 18 130 39 Range 1-696 1-505 1-635 1-1,243 +/-SD 85 68 133 170
PTEN expression in Palestinian women with breast cancer, particularly in triple-negative subtype.
Authors: A. A. Khatib, M. N. AL Abed
Journal: Journal of Clinical Oncology (2011)

27 Background: According to data from the Palestinian Ministry of Health, breast cancer is the most common malignancy affecting Palestinian women, being 30% of all cancers affecting female patients, 60% of them present with metastasis, very few studies were conducted to explore characteristics of this cancer in this population. Triple-negative breast cancer (TNBC) has distinct clinical and pathologic features. The fact that this type is more aggressive despite lacking the expression of growth promotion receptors, suggest other players, as defect in tumor suppressors such as PTEN gene. To our knowledge this is the first study in English literature correlating TNBC to loss of PTEN protein expression. The aim of this study is to establish data about the clinicopathological characteristics of breast cancer in Palestinian women, and to study the status of PTEN protein expression by immunohistochemistry in breast cancer and specifically in TNBC. Methods: 100 confirmed cases of breast cancer, were collected from different pathology centers, clinicopathological data; age, grade, stage for each case were specified. Each case was evaluated for the expression of hormone receptors, Her-2 status, and for PTEN protein expression by immunohistochemistry (IHC) to see if a certain pattern is noted. Results: Out of the 100 cases, the mean age at presentation was 53.3 years, 69.84% of the cases presented with advanced stage and 53% were high grade, 58% were ER positive and 46% were PR positive. HER-2 positive breast cancer were 26%. 30% of all breast cancer cases were TNBC subtype. Loss of PTEN expression was seen in 44% of cases. 60% of TNBC cases lost PTEN expression, which was statistically significant (p + 0.035), no significant correlation between PTEN loss and ER, PR, HER-2, grade or stage. Conclusions: Palestinian women have high incidence of TNBC in comparison to White population, and presented with high grade, and advanced stage tumors. There is a significant correlation between PTEN loss and TNBC that needs more research and study.
Prognostic clinical parameters to predict the necessity of reconstructive vascular surgery for patients who undergo postchemotherapy retroperitoneal lymph node dissection (PC-RPLND) for advanced nonseminatous germ cell tumors (NSGCT).
Authors: A. Heidenreich, M. Schrader, K. Dieckmann, C. Winter, D. A. Pfister
Journal: Journal of Clinical Oncology (2011)

229 Background: PC-RPLND remains an integral part of the multimodality treatment for advanced NSGCT. The need to resect and to replace the major retroperitoneal vessels must be known preoperatively to enable complete resection of the residual masses. Methods: PC-RPLND was performed in 411 patients with NSGCT and normalized (81%) or plateauing (19%) tumor markers following 3-4 cycles PEB/PEI. PC-RPLND was performed in 5 institutions with a variable surgical frequency of 14 to 158 PC-RPLNDs. Good, intermediate, and poor prognosis according to the IGCCCG criteria was identified in in 59.8%, 21.2%, and 19% respectively. Results: Resection of the inferior vena cava was performed in 28 (6.81%), resection of the abdominal aorta was necessary in 13 (3.16%) patients. In 29/41 (70.7%) adjunctive surgical procedures such as nephrectomy, small bowel resection, ureteral resection had to be performed to ensure complete resection of the residual masses. Histologically vital cancer or mature teratoma was identified in 78.1% of the resected vascular specimens. Mean time of surgery was 295 (243-615) Min., mean blood loss was 690 (350 – 3400) ml. Good prognosis was identified in 15.4%, intermediate and poor prognosis was present in 41%and 43.6%, resp. Of all 411 patients involvement of the major retroperitoneal vessels was found in 3.2%, 18.4% and 21.8% with good, intermediate, and poor prognosis, resp. The mean tumor diameter was 5.9 (1.0 – 32) cm for the entire cohort and 9.8 (4-32) cm for the cohort of patients with vascular surgery. Significant prognosticators to predict vascular involvement were identified by multivariate analysis: intermediate/poor prognosis, number of cycles of chemotherapy, tumor diameter &gt; 14cm, circumferential encasement of &gt; 50% of the vessel diameter. Conclusions: Complete resection of the inferior vena cava or the abdominal aorta during PC-RPLND is necessary in about 10% of patients. The identified predictors enable already preoperatively a risk adapted interdisciplinary approach for complete resection of the residual masses in an experienced centre. No significant financial relationships to disclose.
CMV-Replication After Allogeneic Stem Cell Transplantation Is Associated with a Gvhd-Independent Reduced Relapse Risk in Lymphoma
Authors: Ahmet H Elmaagacli, Michael Koldehoff, Nina K. Steckel, Yael Hegerfeldt, Markus Ditschkowski, Sandra Christoph, Tanja Gromke, Rudof Stefan Ross, Hellmut Ottinger, Dietrich Beelen
Journal: Blood (2012)
Predicting nipple-areolar involvement using preoperative breast MRI and primary tumor characteristics.
Authors: S. T. Steen, A. P. Chung, S. Han, A. Vinstein, J. L. Yoon, A. E. Giuliano
Journal: Journal of Clinical Oncology (2011)

40 Background: Preoperative assessment of the nipple-areolar complex (NAC) is invaluable when considering nipple-sparing mastectomy (NSM). We hypothesized that breast MRI could predict involvement of the NAC with tumor. Methods: We compiled clinical, pathologic and imaging data for patients who underwent preoperative breast MRI followed by mastectomy or NSM between 2006 and 2009. Blinded rereview of all MRI studies was performed by a breast MRI imager and compared to initial MRI findings. Multivariate analysis identified variables predicting NAC involvement with tumor. Results: Of 77 breasts, 18 (23%) had tumor involving or within 1 cm of the NAC. The sensitivity of detecting pathologically confirmed NAC involvement was 61% with history and/or physical exam, and 56% with MRI. Univariate analysis identified the following variables as significant for NAC involvement: large tumors close to the nipple on preoperative MRI, node-positive disease, invasive lobular carcinoma, advanced pathologic T stage, and neoadjuvant chemotherapy. On multivariate analysis, only tumor size &gt; 2 cm and distance to the NAC &lt; 2 cm on MRI maintained significance. Pearson correlation coefficient for MRI size compared to pathologic size was 0.53 (p&lt;0.0001). Conclusions: MRI is not superior to thorough clinical evaluation for predicting tumor in or near the NAC. However, MRI-measured tumor size and distance from the NAC are correlated with increased risk of NAC involvement. Preoperative history and physical examination, tumor characteristics, plus breast MRI can aid the surgeon in planning for successful NSM.
Use of extent surgery via intraperitoneal route to improve iliopsoas sarcoma local control.
Authors: A. Souadka, C. Le Pechoux, F. Rimareix, B. Boulet, P. Terrier, J. Domont, A. Cioffi, A. Blesius, A. Le Cesne, S. Bonvalot
Journal: Journal of Clinical Oncology (2011)

e20508 Background: Sarcomas of the iliopsoas compartment exhibit high local recurrence rates because it is one of the most inaccessible areas. Methods: We analyzed all iliopsoas soft tissue sarcomas addressed for surgery in our institution from 1997 to 2010 in a prospective data base. Surgical technique and histological specimens were prospectively evaluated. Concerning primaries, the endpoints were local recurrence, distant metastasis and overall survival (OS) analyzed by Cox model. Results: There were 32 patients (pts): 29 primaries (including 8 second extended resection after initial unplanned surgery) and 3 recurrences. Mean tumor size (cm) was 14.5 (12 -17) French Sarcoma Group grades were: 1 (n=10), 2 (n=9), 3 (n=12). Histological subtypes were liposarcoma n=12, leio and rhadomyosarcoma n=8, MPNST n=4, others n=8. Main symptoms were femoral palsy (n=10) and palpation of a mass (n=16). Twenty two pts received neoadjuvant treatment (17 chemotherapy, 5 radiotherapy), with 10 objective responses. Intraperitoneal route with chevron incision and section of the inguinal ligament was used for 30 pts. All patients had one bloc resection without intraperitoneal rupture. Femoral nerve resection, nephrectomy, colectomy and vascular resection with bypass were added to the myomectomy for 21, 4, 7 and 6 pts respectively. Mean blood loss (ml) was 540 (200-4000). One pt died post operatively of heart attack, 3 pts had percutaneous drainage of post operative collection. Quality of resection was R0 n=19 pts, R1 n=13 pts. After re excision, residual tumor was found in all the pts (microscopic n=2 pts, macroscopic n=6 pts). Clear median minimum margin was 2 mm (1-30). With a median follow up of 38 months, 3 pts developed local recurrence and sarcomatosis: all the 3 concerned re excision after inadequate initial surgery with tumor rupture. Six high grade pts developed metastasis. The 5-year local recurrence metastatic rate and OS were 16.3% and 31.5% and 61.8% respectively. Conclusions: Intraperitoneal route allows complete monobloc resections of large iliopsoas sarcomas, associated with adjacent organs when necessary. It improves local control compare to extra peritoneal route and historic data.
Likelihood of high volume renal surgeons to offer elective partial nephrectomy in high complexity tumors as classified by the nephrometry scoring system.
Authors: C. J. Weight, S. P. Kim, P. L. Crispen, R. H. Breau, S. A. Boorjian, R. H. Thompson, B. C. Leibovich
Journal: Journal of Clinical Oncology (2011)

354 Background: Partial nephrectomy (PN) has demonstrated equivalent cancer control to radical nephrectomy (RN) and has been associated with lower rates of all-cause mortality. Nevertheless, there continues to be wide variability in practice pattern in the treatment of renal masses. Specifically, the decision to perform PN or RN often depends on patient, surgeon and renal mass characteristics. By quantifying the renal tumor using the R.E.N.A.L. nephrometry scoring system, collecting surgeon information, and providing defined clinical scenarios we attempt to evaluate factors important in surgeon decision-making. Methods: In June 2009, all members of the American Urological Association with a listed email address were invited to participate in a survey evaluating the management of renal masses. Respondents were asked their preferred treatment for 8 clinical scenarios. Each of these renal masses was given a nephrometry score (NS). The propensity to offer PN was evaluated by NS and surgical volume. High volume was defined as &gt; 50 renal cases per year and low volume was defined as £ 10 cases per year. Results: 764 attending level urologic surgeons responded to each of the 8 scenarios providing 6112 evaluable clinical scenarios. NS ranged from 4-10; each unit increase was associated with 2-fold increased odds of a surgeon offering radical nephrectomy (OR 1.99, 95% CI: 1.93,2.06). PN was the preferred treatment for approximately 95% of patients with low complexity tumors (NS &lt; 8) regardless of surgical volume. However, proposed treatment of high complexity tumors (NS ³ 8) demonstrated considerable heterogeneity in treatment choice. Controlling for all patient characteristics, high surgical volume significantly predicted whether PN would be offered to patients with high complexity tumors (OR 3.04 95% CI: 2.34,9.95), but not those with low complexity tumors (OR 1.95 95% CI: 0.87,4.38) compared to low volume surgeons. Conclusions: Increasing NS correlated with increased use of radical nephrectomy, particularly after a score of 8 among all surgeons. As renal surgical volume increased, surgeons were more willing to offer PN in high complexity tumors. No significant financial relationships to disclose.
CXCL-8/IL8 Produced by Diffuse Large B-cell Lymphomas Recruits Neutrophils Expressing a Proliferation-Inducing Ligand APRIL
Authors: Benoit Manfroi, Thomas McKee, Jean Francois Mayol, Sebastien Tabruyn, Sebastien Moret, Christian Villiers, Christian Righini, Martin Dyer, Mary Callanan, Pascal Schneider, Alexandar Tzankov, Thomas Matthes, Nathalie Sturm, Bertrand Huard
Journal: Cancer Research (2016)

Tumor-infiltrating neutrophils have been implicated in malignant development and progression, but mechanisms are ill defined. Neutrophils produce a proliferation-inducing ligand APRIL/TNFSF13, a factor that promotes development of tumors from diverse origins, including diffuse large B-cell lymphoma (DLBCL). High APRIL expression in DLBCL correlates with reduced patient survival, but the pathway(s) dictating APRIL expression are not known. Here, we show that all blood neutrophils constitutively secrete APRIL, and inflammation-associated stimuli, such as TNF, further upregulate APRIL. In a significant fraction of DLBCL patients, tumor cells constitutively produced the ELC-CXC chemokine CXCL-8 (IL8), enabling them to recruit APRIL-producing blood neutrophils. CXCL-8 production in DLBCL was unrelated to the cell of origin, as APRIL-producing neutrophils infiltrated CXCL-8+ DLBCL from both germinal center (GC) and non-GC subtypes. Rather, CXCL-8 production implied events affecting DNA methylation and acetylation. Overall, our results showed that chemokine-mediated recruitment of neutrophils secreting the tumor-promoting factor APRIL mediates DLBCL progression. Cancer Res; 77(5); 1097-107. ©2016 AACR.
Long-term survival and competing causes of death in men with stage I seminoma.
Authors: C. Beard, M. Chen, N. D. Arvold, P. L. Nguyen, A. K. Ng, K. E. Hoffman
Journal: Journal of Clinical Oncology (2011)

226 Background: To better understand the impact of RT on mortality, we analyzed long-term survival and patterns of excess mortality in men with stage I seminoma. Methods: 9,045 men with stage I seminoma were identified in the Surveillance Epidemiology and End Results database. Time to testicular-cancer mortality (TCM), death from second malignancy (SM), cardiovascular mortality (CVM) or suicide (SUIC) and all-cause mortality (ACM) were calculated. Survival estimates were calculated using the Kaplan-Meier method. Gender- and age-adjusted standardized mortality ratios (SMR) were calculated using U.S. population data. Cox and Fine and Gray multivariable analysis were used to evaluate the effect of RT on mortality outcomes. Results: 7,025 men (78%) received RT. After a median follow-up of 11.7 years, 869 men (9.6%) had died: sixty-five from TCM, 279 from SM, 169 from CVM and 37 from SUIC. 10-year rates of ACM and TCM were 4.24% and 0.52% among men who received RT and 7.14% and 1.22% among men who did not. Compared to the adjusted general population, men with seminoma had increased risk of ACM (SMR 1.12; 95% confidence interval [CI] 1.12-1.28), SM (SMR 1.78; 95% CI 1.58-2.00) and SUIC (SMR 1.40; 95% CI 1.02-1.94) and decreased risk of CVM (SMR 0.73; 95% CI 0.62-0.84). Rates of ACM, SM and SUIC (SMR, all p &lt; 0.05) were increased whether RT was used or not. Men who received RT were less likely to die (adjusted hazard ratio [AHR] 0.76; 95% CI 0.65-0.89; p &lt; 0.001) and had a lower risk of TCM (AHR 0.39; 95% CI 0.24-0.65; p &lt; 0.001). There was no difference in CVM between men who did and did not receive RT (AHR 0.89; 95% CI 0.60-1.15; p = 0.230) and a numerical increase in SM in men who received RT as compared to others (AHR 1.25; 95% CI 0.90-1.72; p=0.180). Conclusions: Compared to the general population, men with a history of stage I seminoma had increased risks of all-cause mortality, death from second malignancies, and suicide. Our data suggest that 15 years after diagnosis, men who did receive RT may be more likely to die from a second malignancy than men who did not. Although not receiving RT was associated with higher testicular-cancer mortality, the results may reflect decreased access to care or follow-up as active surveillance protocols were not common during the study era. No significant financial relationships to disclose.
Integrated genomic analysis of survival outliers in glioblastoma
Authors: Sen Peng, Harshil Dhurv, Brock Armstrong, Bodour Salhia, Christophe Legendre, Jeffrey Kiefer, Julianna Parks, Selene Virk, Andrew E. Sloan, Quinn T. Ostrom, Jill S. Barnholtz-Sloan, Nhan L. Tran, Michael E. Berens
Journal: Neuro-Oncology (2016)

To elucidate molecular features associated with disproportionate survival of glioblastoma (GB) patients, we conducted deep genomic comparative analysis of a cohort of patients receiving standard therapy (surgery plus concurrent radiation and temozolomide); "GB outliers" were identified: long-term survivor of 33 months (LTS; n = 8) versus short-term survivor of 7 months (STS; n = 10). We implemented exome, RNA, whole genome sequencing, and DNA methylation for collection of deep genomic data from STS and LTS GB patients. LTS GB showed frequent chromosomal gains in 4q12 (platelet derived growth factor receptor alpha and KIT) and 12q14.1 (cyclin-dependent kinase 4), and deletion in 19q13.33 (BAX, branched chain amino-acid transaminase 2, and cluster of differentiation 33). STS GB showed frequent deletion in 9p11.2 (forkhead box D4-like 2 and aquaporin 7 pseudogene 3) and 22q11.21 (Hypermethylated In Cancer 2). LTS GB showed 2-fold more frequent copy number deletions compared with STS GB. Gene expression differences showed the STS cohort with altered transcriptional regulators: activation of signal transducer and activator of transcription (STAT)5a/b, nuclear factor–kappaB (NF-κB), and interferon-gamma (IFNG), and inhibition of mitogen-activated protein kinase (MAPK1), extracellular signal-regulated kinase (ERK)1/2, and estrogen receptor (ESR)1. Expression-based biological concepts prominent in the STS cohort include metabolic processes, anaphase-promoting complex degradation, and immune processes associated with major histocompatibility complex class I antigen presentation; the LTS cohort features genes related to development, morphogenesis, and the mammalian target of rapamycin signaling pathway. Whole genome methylation analyses showed that a methylation signature of 89 probes distinctly separates LTS from STS GB tumors. We posit that genomic instability is associated with longer survival of GB (possibly with vulnerability to standard therapy); conversely, genomic and epigenetic signatures may identify patients where up-front entry into alternative, targeted regimens would be a preferred, more efficacious management.