tbuckley/cabot-search huggingface dataset:
Concordance of HER2 status between local and central review in gastric and gastroesophageal junction cancers: A French observational study of 394 specimens (HERable study).
Authors: Genevieve Monges-Ranchin, Benoit Terris, Marie-Pierre Chenard, Frederic Bibeau, Frederique Madeleine Penault-Llorca, Mouna Bougrini, Emmanuele Conde Da Silva Fraga, Laurent Doucet
Journal: Journal of Clinical Oncology (2016)

30 Background: As some gastric (GC) and gastroesophageal junction adenocarcinoma (GEJC) overexpress HER2, HER2 testing should be part of routine assessment to decide target treatment initiation. Thus, the study objective was to assess the concordance of HER2 status between local and central laboratories. Methods: From July 2012 to February 2014, this observational study tested tumor samples from patients (pts) with GC or GEJC, regardless of disease stage. HER2 positive (+) status was defined as immunohistochemistry (IHC)3+ or IHC2+/In Situ Hybridization (ISH)+. The concordance was analyzed between HER2 status assessed by local laboratories (any technique) and centralized laboratory (IHC 4B5 and silver (S) ISH for all specimens). Results: 394 specimens from 367 pts were analyzed by 19 local laboratories. Pts' characteristics were: mean age 66±13 years, male 69%, GC 60%, intestinal type 55%. The specimens were surgical resections (52%), biopsies (41%), adenopathy (4%) and distant metastasis (3%). HER2+ status was found in 18% of locally tested specimens (69/394: 52 IHC3+; 17 IHC2+/ISH+) and in 19% of centralized specimens (73/394: 56 IHC3+; 17 IHC2+/SISH+). Among HER2+ specimens, 53% (39/73) were GC and 73% (53/73) were of intestinal histological type. Regarding amplification, 20% of centralized SISH tests (79/393) were amplified. The concordance between HER2 status (n = 393) assessed by local and centralized laboratories was acceptable according to Landis and Koch classification with a kappa coefficient of 0.69 (95%CI [0.60-0.78]). The discordance between HER2 status assessed by local and centralized laboratories was 9%. The rate of false negative was 27% and false positive 5%. Conclusions: The HERable study is the first large French study to evaluate concordance between HER2 status assessed by local and centralized laboratories. The cumulative rate of false negative and false positive in GC and GEJC is 9% (95% CI [6%; 12%]). Quality control should be setup to improve the quality of this test. [Table: see text]
Interest of systematic patient contact by phone call between two cycles of chemotherapy.
Authors: P. Afchain, N. Amiot, M. Bennamoun, S. Watson, A. Langlois, C. Louvet
Journal: Journal of Clinical Oncology (2011)

e19523 Background: Chemotherapy (CT) toxicity recording is usually performed when patients (pts) have recovered from previous cycle side-effects (SE), and could have therefore forgetten their incidence and/or seriousness. We investigated whether or not systematic phone calls between two cycles will 1- help pts to describe their CT tolerance, 2- prevent possible complications of an emerging toxicity and 3- check pt’s ability to overcome usual SE based on advice previously provided. Methods: 108 consecutive pts, treated for various cancer types, by various CT types benefited from phone calls performed by an oncologist or by the coordinating nurse. Calls were planned at D+7 for q2weeks regimens, and at D+14 for q3weeks regimens. During each call, toxicity and pt’s complaints were recorded. Calls were graded as follow: grade (gr) 0: no additional action; gr 1: additional advice provided; gr2: additional call after a lab test mandated; gr 3: fast GP intervention mandated; gr 4: fast visit in the oncology department proposed; and gr 5: emergency hospitalization required. After at least 3 months of follow-up, a satisfactory survey was carried out. Results: For 101 calls out of the 529 done (19.1%), pts did not answer, and a message was left suggesting to call back if necessary. Median time call was 3 minutes (range 1 to 18). Among the 428 evaluable calls, 331 (77.3%) were gr 0 (pts managed well their possible SE); 79 (18.5%) were gr 1, (additional advice was useful for non-severe SE management); and 18 (4.2%) were gr 2 to 5 - gr 2: 11; gr 3: 2; gr 4: 4; gr 5: 1 – (call was able to prevent and/or treat a serious SE). In addition, 23 pts anticipated the planned call, which was then not made. Survey resulted in a high rate of satisfied pts (89.9%), 93.2% found convenient the time of planned calls, and 96.6% were more confident after the call. Conclusions: Systematic phone calls between 2 cycles of CT are feasible, provide at least an appreciated psychological support, and can help in case of usual as well as of serious SE. Experiment is now extended to more pts, based on a modified information record sheet, to better assess the value of systematic calls, the need for GP implication, the need for additional pt education and to perform recommendations for this procedure.
Clinical Spectrum, Evolution and Management of Autoimmune Cytopenia Associated with Angioimmunoblastic T-Cell Lymphoma: A Retrospective, Multicenter Study
Authors: Etienne Crickx, Radjiv Goulabchand, Claire Fieschi, Lionel Galicier, Paul Coppo, Veronique Meignin, Richard Delarue, Olivier Casasnovas, Veronique Leblond, Guillaume Moulis, Marc Michel, Jehan Dupuis, Fabien Le Bras, Virginie Fataccioli, Corinne Haioun, Bertrand Godeau, Philippe Gaulard, Matthieu Mahevas
Journal: Blood (2016)
Automated bone scan index as a quantitative imaging biomarker indicative of efficacy to enzalutamide in patients with metastatic castrate resistant prostate cancer (mCRPC).
Authors: Aseem Anand, Michael J. Morris, Steven M. Larson, Mattias Ohlsson, Andreas Joseffson, John Thomas Helgstrand, Lars Edenbrandt, Peter Sander Oturai, M. Andreas Roeder, Anders Bjartell
Journal: Journal of Clinical Oncology (2016)

226 Background: The automated BSI (auto-BSI) is a computerized means of quantitatively expressing tumor burden in bone. Following the analytical validation of auto-BSI, we are now clinically qualifying the tool as a response biomarker in mCRPC. In the present study, we assess the association of auto-BSI and that of PSA with overall survival (OS) in mCRPC patients (pts) being treated with enzalutamide. Methods: All mCRPC pts who initiated enzalutamide treatment at Skåne Hospital, Sweden and at Rigshospitalet, Denmark, with a minimum of one year follow-up, were eligible for the study. Eligible mCRPC pts with baseline (BL) bone scan available before starting enzalutamide were enrolled in the study. PSA, hemoglobin (Hgb) and alkaline phosphatase (ALP) were obtained at BL. Treatment follow-up PSA and auto-BSI were obtained at week-12. auto-BSI was obtained using the analytically validated EXIN bone BSI version 2.0. Cox regression and concordance index (c-index) were used to evaluate the association with OS. Results: 80 mCRPC pts with BL bone scans were enrolled in the study. Treatment follow-up bone scans were available from 62 pts. Univariate analysis demonstrated that auto-BSI, PSA, ALP and Hgb at BL were associated with OS (p &lt; 0.0001). In the multivariate analysis, only auto-BSI and HgB were significantly associated with OS. The auto-BSI showed the highest c-index in prediction of OS (c-index 0.72, SE 0.03). Adding auto-BSI to the BL covariate model significantly improved the discrimination from c-index 0.67 to 0.72 (p &lt; 0.05). At treatment follow-up, the univariate analysis of the change in auto-BSI and the percent change in PSA were strongly associated with OS with c-index 0.76 and 0.72 (SE 0.05), respectively. In bivariate analysis, the change in auto-BSI remained strongly associated with OS (p &lt; 0.0001) whereas the percent change in PSA appeared to be less so (p = 0.07). Conclusions: Auto-BSI and its change demonstrated an independent and a strong association with OS in mCRPC pts being treated with enzalutamide. The study serve as a foundation for prospective validation of auto-BSI as an imaging biomarker indicative of efficacy to enzalutamide.
Additional imunohistochemical evaluation and detection of micrometastasis in the sentinel lymph nodes of patients with endometrial cancer.
Authors: G. Favero
Journal: Journal of Clinical Oncology (2011)

e15564 Background: The presence of lymph node (LN) metastases has a major impact on the prognosis of women with endometrial cancer. Sentinel lymph node (SN) biopsy can potentially help to avoid extensive dissection, however, current data show insufficient diagnostic accuracy. The objective of the study is to evaluate the effect of immunohistochemical (IHC) staining of the SN in order to increase accuracy. Methods: From January 2008 to December 2009, 30 consecutive patients with endometrial cancer were labeled by hysteroscopic injection of Tc-99and underwent SN biopsy . All sentinel lymph nodes were submitted to immunohistochemical (IHC) staining using Pan-cytokeratin antibody combined with a set of three 4 mm thick sections cut every 250 μm. Results: 59 SN obtained from 25 patients were available for IHC staining. Significantly more metastases were detected compared to H&E staining. Ten out of 59 SN (17%) had detectable micrometastasis or isolated tumor cells (ITC).This had a positive impact on the diagnostic accuracy of the sentinel node biopsy. Sensitivity increased from 67% to 100% (p=0,01) since 2 false negative patients out of 6 patients with LN metastases were positive for micrometastasis in the H&E negative SN. In addition, 2 patients with H&E tumor-free LNs were diagnosed with ITC in their SN. These additional micrometastasis or ITC were equally distributed among the pelvic and para-aortic area. Conclusions: We could demonstrate that additional immunohistochemistry staining can substantially improve the diagnostic accuracy of SN biopsy. If this is associated with a false positive rate of 7% has to be shown by careful follow up of IHC SN positive patients.
Left ventricular and left atrial function in patients with borderline and established hypertension.
Authors: Takashi Natsume, Katsuhiko Nakajima, Hajime Shibata, Masatoshi Yokouchi, Fujio Deguchi, Katsuro Shimomura, Masao Ikeda
Journal: Circulation (1983)

To evaluate left ventricular (LV) and left atrial (LA) function in patients with borderline and established hypertension, 7 indexes of LV systolic function (cardiac index, end-diastolic volume index, ejection fraction, LV network, mean VCF, Vmax and peak dp/dt), 7 indexes of LV diastolic properties (specific compliance, LV mass index, LV wall thickness, stiffness constant, time constant T, end-diastolic pressure and peak negative dp/dt) and 3 indexes of LA function (volume index, chamber stiffness constant and muscle stiffness constant), all obtained form the data of cardiac catheterization and cineangiogram, were analyzed in patients with normotension (N, n=12), borderline hypertension (BH, n=13) and established hypertension (EH, n=17). LV systolic function was not impaired in the BH and EH groups. In the BH group, LV diastolic function was not affected, but LV wall thickness and stiffness constant were significantly greater in the EH group than in the N group. There was no significant difference in LA volume index among the 3 groups, but a significant increase of LA chamber stiffness constant was found only in the EH group as compared to the values of the N group. On the other hand, LA muscle stiffness constant was significantly greater in the BH group than in the N group, and significantly greater in the EH group than in the BH group. From these results it seemed that LV systolic and diastolic functions were not impaired in patients with borderline hypertension, and that LV systolic function was not affected, but LV diastolic function was possibly impaired in patients with established hypertension. Moreover, it was suggested that LA compliance was impaired already not only in patients with established hypertension, but also in patients with borderline hypertension.
A Phase 1b, Open-Label, Dose Escalation and Expansion Study Evaluating the Safety and Efficacy of Entospletinib (GS-9973) with Vincristine and Dexamethasone in Adult Subjects with Relapsed or Refractory Acute Lymphoid Leukemia (ALL)
Authors: Mark D. Minden, Wendy Stock, Howland Crosswell, Robert D Siegel, Patrick Chun, Steve Abella, Jing He, Clarence Eng, Dan Douer
Journal: Blood (2015)
Differential expression of small ubiquitin-like modifier family of proteins in patients with colorectal adenocarcinoma.
Authors: R. Wiatrek, M. P. Duldulao, Z. Chen, W. Li, J. Kim, Y. Li, Y. Chen, J. Garcia-Aguilar
Journal: Journal of Clinical Oncology (2011)

420 Background: The cytotoxic effects of radiation and chemotherapy are mediated in part by DNA damage. The small ubiquitin-like modifier (SUMO) family of proteins regulates DNA repair pathways by activating factors involved in homologous recombination (HR) or non- homologous end joining (NHEJ). Our objective was to determine the potential role of SUMO proteins in patients with colorectal cancer. Methods: We first assessed two established colorectal cancer cell lines (HCT116 and HT29) and two normal colonic mucosa cell populations utilizing ultra high-throughput expression analysis (Solexa) to examine differential expression of genes involved in SUMOylation (SAE1, SAE2, PIAS-1, and DNAPKcs). To verify the clinical relevance of SUMOylation in colorectal cancer, we obtained archived specimens from patients with colorectal cancer (n=51) and examined the expression of these proteins in both benign and malignant tissue by immunohistochemistry (IHC). Results: Ultra high-throughput expression analysis of cancer and normal cells revealed a 10 to 15-fold upregulation of SAE2 (heterodimer of the E1 activation enzyme in SUMOylation), a 10 to 11-fold upregulation of DNAPKcs (catalytic subunit in NHEJ repair pathway), and a 6-fold upregulation of SAE1 in cancer cells. In contrast, PIAS-1 showed similar expression levels between cancer and normal colonic cells. By IHC, SAE1 and SAE2 were highly expressed in 65% and 53% of tumor specimens, respectively; but only in 7% and 0% of normal tissues, respectively. DNAPKcs was also highly expressed in tumor tissues (63%) with corresponding low expression (0%) in normal tissues. Corroborating the cell line results, PIAS-1 was infrequently expressed in both tumor (10%) and normal tissues (0%). Conclusions: We are the first to demonstrate the differential expression of SUMO proteins in colorectal cancer cell lines and in clinical specimens. SUMO proteins have a role in DNA repair and their expression in colorectal cancer may modify tumor response to chemoradiotherapy. No significant financial relationships to disclose.
BCR Responsiveness is Associated with Time to First Treatment (TTFT) in B-Cell Chronic Lymphocytic Leukemia (B-CLL): Results From a Single Cell Network Profiling (SCNP) Verification Study
Authors: Alessandra Cesano, Erik Evensen, Jason Ptacek, James Cordeiro, Rachael E. Hawtin, Jodi R. Ware, Ilaria Nichele, Maria Teresa Scupoli
Journal: Blood (2011)
Oncologists', physicians' and surgeons' opinions on the perceived value and appropriateness of the speciality to inform patients on adjuvant chemotherapy after radical surgery for non-small cell lung cancer.
Authors: K. S. Khor, D. Tai, S. Popat, M. Beckles, M. Leung, M. Al Sahaf, E. K. S. Lim
Journal: Journal of Clinical Oncology (2011)

7011 Background: The benefit of chemotherapy after surgery for lung cancer is established, but roles and responsibilities of discussing adjuvant chemotherapy are not established. Whilst risks are straight forward to convey, difficulties in conveying the benefit results from published hazard ratios as the benefit varies with stage and therefore needs to be calculated individually and conveyed in a language that is understood by the patient. Methods: From 2010 to 2011, a survey was conducted of cancer physicians, oncologists and surgeons in the UK. Clinicians asked to rank the most appropriate speciality to discuss adjuvant chemotherapy with patients, to calculate expected survival given baseline survival probability of 80% and a hazard ratio of 0.80, and then surveyed for the additional expected gain in cohorts with a 5 year survival probability of 40%, 60% and 80% respectively before they would recommend adjuvant chemotherapy Results: A total of 202 responses were received from 27 surgeons, 77 physicians, 87 oncologists (11 unstated). The majority of 56% of surgeons, 79% of physicians and 61% of oncologists felt an oncologist as the most appropriate initial clinician to discuss adjuvant chemotherapy with patients after surgery. In total 33% of surgeons, 53% of physicians and 73% of oncologists were able to correctly calculate the expected survival of patients. When asked about perceived value before considering recommending adjuvant chemotherapy with 5 year survival probabilities of 40%, 60% and 80%, clinicians reported an expected a mean gain (SE) of 20.8% (2.7), 15.6% (2.4) and 13.2% (2.1) against an expected of 12%, 8% and 4% respectively with a hazard ratio of 0.80. Conclusions: Our survey suggest oncologists as the clinicians best able to calculate the individual benefit of adjuvant chemotherapy and the majority of specialities polled agreed oncologists as the most appropriate initial person to discuss adjuvant chemotherapy with patients after radical surgery for lung cancer. The perceived value prior to recommending adjuvant chemotherapy in clinicians greatly exceeds current published results.
Is there an intermediate risk group of nonseminoma?
Authors: Jaroslav Hajek, Jakub Cvek, Jana Jackaninova, Eva Skacelikova, Jan Krhut, Ondrej Havranek, David Feltl
Journal: Journal of Clinical Oncology (2013)

323 Background: To evaluate predictive factors of testicular nonseminoma cancer. Methods: Between 2000 and 2012, 189 patients with testicular nonseminoma cancer were evaluated. Stages according to TNM classification were I, II, and III for 84 patients (60%), 49 (26%), and 56 (30%). The median age of the patients was 31 years (range 18-77 years). Treatment was based on orchiectomy plus chemotherapy (bleomycine/etoposide/cisplatin and vinblastine/ifosfamide/cisplatin) and retroperitoneal lymphadenectomy in residual disease. Treatment protocol was updated regularly according to international standards. Overall survival (OS) was evaluated according to the stage, Karnofsky index (KI), and dose intensity of chemotherapy with the Kaplan-Meier method at 5% significance level. Results: There was a significant difference between OS in patient with the different stages (log-rank test, p=0.000), however, detailed analysis revealed that there is significantly worse survival in stage IIIC only (10-years OS for IIIC vs. IIIA+B, 35% vs. 88%, p=0.001) while the difference among IIIB and lower stages was not significant (p=0.383) and 10-years OS was 94%. Dose intensity of chemotherapy proved to be a significant predictive factor for OS in stage IIIA+B patients. Patients with no dose reduction had a significantly higher OS than those with any kind of dose reduction (10-years OS 96% vs. 0%, log-rank test, p=0,000). In stage IIIC, however, the dose intensity had no influence on OS (log-rank test, p=0.167). Unlike dose intensity, in stage III disease KI had no prognostic significance for OS (KI&lt;80 versus KI≥80, Log-rank test, p=0,627) and this is true both for stages IIIA+B and for stage IIIC. Conclusions: Standard of care in testicular nonseminoma cancer offers excellent prognosis with no significant differences in OS for good and intermediate risk groups. On the other hand, outcomes for stage IIIC are poor and further intensification of treatment is warranted. We have found no impact of performance status on OS neither for stage IIIA+IIIB nor stage IIIC. Reduction of chemotherapy dose has a negative impact on OS in patients with stage IIIA+IIIB and should be avoided if possible.
Are VO<sub>2PEAK</sub> prediction equations accurate in predicting VO<sub>2PEAK</sub> in presurgical oncology patients?
Authors: J. S. Scheetz, G. S. Morris, K. E. Brueilly, C. E. Hightower
Journal: Journal of Clinical Oncology (2011)

e19578 Background: Quantitative presurgical fitness status (VO2PEAK) provides very useful but difficult to obtain patient information. The purpose of this study therefore was to determine if equations that use anthropometric measures to predict VO2PEAK might accurately predict VO2PEAK in recently diagnosed, presurgical cancer patients. Methods: After receiving physician clearance, 111 subjects (83 males, 28 females) with abdominal, gastrointestinal, and urinary tract tumors underwent a standard ramp bicycle ergometer cardiopulmonary exercise test within two weeks of scheduled surgery. The exercise protocol sequentially entailed 3 min of quiet resting, 3 min of unloaded cycling, ramp protocol to peak exercise tolerance, and 3 min of recovery. Ramp rates (5-25 W/min) were individually chosen to achieve standard test durations of 8-12 min per patient. Tests were symptom limited and considered peak if the subject achieved >85% of predicted heart rate and a respiratory exchange ratio > 1.1. Measured VO2PEAK results (ml/min) were compared with VO2PEAK values predicted by the equations of Neder et al, Eur. Respir. J. 1999; Fairborn et al, Chest. 1994; Storer et al, Med Sci. Sport Exer. 1990, Jones et al. Am. Rev Respir. Dis. 1985. The UT M. D. Anderson Cancer Center Institutional Review Board approved this study. Statistical analysis: The strength of the relationship between measured and predicted VO2PEAK values was measured by correlational analysis. Similarity between the means of the measured vs. predicted VO2PEAK values was determined using a paired t-test (p < 0.05). Results: Only the results from the Storer et al equation were found to be both highly correlated with and statistically similar to the measured values. Conclusions: Results suggest that the Storer et al equation provides accurate estimates of VO2PEAK in this particular patient population. Such information would provide insight into 1) the presurgical fitness status of this group of cancer patients, 2) their need for presurgical reconditioning and 3) their postsurgical risk for adverse outcomes. Measured Neder et al Fairborn et al Storer et al Jones et al Pearson r 0.2168 0.7444 0.9347 0.7002 P value 0.0000 0.0355 0.5801 0.0000