tbuckley/cabot-search huggingface dataset:
Immunohistochemical tumor markers do not predict response to neoadjuvant doxorubicin and docetaxel in breast cancer
Authors: A. M. Kallab, R. Dalton, R. Hessler, K. Yeh, T. Wang, P. Schoenlein, A. May, S. McKinnon, A. Jillella
Journal: Journal of Clinical Oncology (2004)

794 Background: Complete pathologic response (CPR) to preoperative chemotherapy is a powerful predictor of survival in breast cancer (BC). We initiated a phase II study to determine the efficacy of doxorubicin (D) and docetaxel (T) in the neoadjuvant treatment of BC. We also evaluated the ability of molecular markers to predict response to the combination. Methods: Eligible patients had biopsy proven early or locally advanced BC, adequate heart and organ functions and good performance status. The treatment consisted of D (50 mg/m2) and T (75mg/m2) intravenously every 3 weeks for 4 cycles, followed by surgery. Prophylactic dexamethazone 8 mg po bid for 3 days and ciprofloxacin 500 mg po bid days 5 to 14 were given with each cycle. Postoperative treatments were left at the discretion of the treating physician. Quantitative immunohistochemistry for ER, PR, Her2-neu, Ki-67, bcl-2, p53, p21, EGFR, and p-Gylcoprotein were performed on tissues before chemotherapy administration using the ChromaVision Automated Cellular Imaging System (ACIS). Results were correlated with clinical and pathological responses. Results: To date, 26 of 30 patients have been enrolled all of whom are evaluable for clinical response and toxicity (pathological response is available on the first 23). The mean tumor size was 7.5cm, 37% had early and 63% locally advanced BC, and 58% had positive axillary lymphadenopathy. The overall clinical response was 89% (37% complete and 52% partial). There were 3 stable diseases (11%) and 0% progression. Complete pathological response: 22% in breast. Neutropenic fevers were documented in 34% of patients (0% documented infection). There were no statistically significant differences in the total number of cells expressing markers between complete and non- complete responders. Conclusion: the combination of D and T is highly active in early and locally advanced BC. Unfortunately, none of the markers listed above correlated with positive or negative complete responses. Supported by Aventis Pharmaceuticals. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Aventis Pharmaceuticals
Sperm recovery and ICSI outcomes in Klinefelter syndrome: a systematic review and meta-analysis
Authors: Giovanni Corona, Alessandro Pizzocaro, Fabio Lanfranco, Andrea Garolla, Fiore Pelliccione, Linda Vignozzi, Alberto Ferlin, Carlo Foresta, Emmanuele A. Jannini, Mario Maggi, Andrea Lenzi, Daniela Pasquali, Sandro Francavilla
Journal: Human Reproduction Update (2017)

Specific factors underlying successful surgical sperm retrieval rates (SRR) or pregnancy rates (PR) after testicular sperm extraction (TESE) in adult patients with Klinefelter syndrome (KS) have not been completely clarified.The aim of this review was to meta-analyse the currently available data from subjects with KS regarding SRRs as the primary outcome. In addition, when available, PRs and live birth rates (LBRs) after the ICSI technique were also investigated as secondary outcomes.An extensive Medline, Embase and Cochrane search was performed. All trials reporting SRR for conventional-TESE (cTESE) or micro-TESE (mTESE) and its specific determinants without any arbitrary restriction were included.Out of 139 studies, 37 trials were included in the study, enrolling a total of 1248 patients with a mean age of 30.9 ± 5.6 years. The majority of the studies (n = 18) applied mTESE, 13 applied cTESE and in one case testicular sperm aspiration (TESA) was used. Additionally, four studies used a mixed approach and in one study, the method applied for sperm retrieval was not specified. Overall, a SRR per TESE cycle of 44[39;48]% was detected. Similar results were observed when mTESE was compared to cTESE (SRR 43[35;50]% vs 45[38;52]% for cTESE vs micro-TESE, respectively; Q = 0.20, P = 0.65). Meta-regression analysis showed that none of the parameters tested, including age, testis volume and FSH, LH and testosterone (T) levels at enrollment, affected the final SRR. Similarly, no difference was observed when a bilateral procedure was compared to a unilateral approach. No sufficient data were available to evaluate the effect of previous T treatment on SRR. Information on fertility outcome after ICSI was available for 29 studies. Overall a total of 218 biochemical pregnancies after 410 ICSI cycles were observed (PR = 43[36;50]%). Similar results were observed when LBR was analyzed (LBR = 43[34;53]%). Similar to what was observed for SRR, no influence of KS age, mean testis volume, LH, FSH or total T levels on either PR and LBR was observed. No sufficient data were available to test the effect of the women's age or other female fertility problems on PR and LBR. Finally, no difference in PR or LBR was observed when the use of fresh sperm was compared to the utilization of cryopreserved sperm.The present data suggest that performing TESE/micro-TESE in subjects with KS results in SRRs of close to 50%, and then PRs and LBRs of close to 50%, with the results being independent of any clinical or biochemical parameters tested.
Examining measurement properties of the consumer-based cancer care value index (CCCVI) survey: A measure to identify quality improvement priorities in cancer care.
Authors: San Keller, Manshu Yang, Kathleen J. Yost
Journal: Journal of Clinical Oncology (2017)

222 Background: Current approaches to measuring the quality of cancer care may not produce sufficient information to enable providers to structure care that aligns closely with their patients’ preferences. To close this gap, we developed the Consumer-based Cancer Care Value Index (CCCVI) survey, which assesses the aspects of cancer care that patients value the most and how their values align with their experience in receiving cancer care. Methods: The CCCVI field test included 721 adults who received cancer care in the last 12 months from 4 geographically diverse cancer care centers, including patients with varying stages of cancer, types of cancer, types of treatment (e.g., surgery, radiation, medical oncology), and demographic characteristics. The survey included items that asked patients to directly rate the “importance” of 24 aspects of cancer care, along with 24 corresponding items that measured the “frequency” with which they received each aspect of care. We evaluated the reliability and validity of the survey items, and developed “value grids” plots which visually depicted the “importance” scores against the “frequency” scores. We conducted subgroup analysis to examine income and racial/ethnic disparities in the extent of misalignment between patients’ values and experiences. Results: The survey demonstrated good internal consistency reliability (Cronbach’s alpha = 0.91) and acceptable-to-good construct and criterion validity. Value grids identified potential areas of improvement in the areas of how doctors communicate and how quickly patients get care. The subgroup analysis showed the most misalignments between patients’ values and experiences in the aspects of doctor communication for lower-income patients and in the aspects of getting care quickly for patients from racial/ethnic minority groups. Conclusions: The CCCVI survey is a reliable and valid tool for cancer care providers to identify top priority areas (i.e., high-importance but low-frequency areas) to facilitate their quality improvement efforts. It also recognizes subgroup variations in the misalignment between patients’ values and care experiences.
Is successful resection following neoadjuvant radiation therapy for borderline resectable pancreatic cancer dependent on improved tumor-vessel relationships?
Authors: Avani Satish Dholakia, Amy Hacker-Prietz, Aaron Tyler Wild, Siva P. Raman, Laura D. Wood, Daniel A. Laheru, Lei Zheng, Ana De Jesus-Acosta, Peng Huang, Dung T. Le, Richard D. Schulick, Barish H. Edil, Susannah G. Ellsworth, Timothy M. Pawlik, Christine A Iacobuzio-Donahue, Ralph H. Hruban, John L. Cameron, Elliot K. Fishman, Christopher Lee Wolfgang, Joseph M. Herman
Journal: Journal of Clinical Oncology (2013)

4057 Background: Margin-negative (R0) surgical resection is the only potentially curative therapy for pancreatic cancer. For patients deemed borderline resectable (BL), neoadjuvant chemoradiotherapy (NRT) increases the likelihood of subsequent R0 resection and improves overall survival. Prognostic factors for achieving resection following NRT have yet to be clearly identified. Methods: Fifty consecutive patients with BL-PDAC evaluated by a multidisciplinary tumor board who received NRT from 2007-2012 were retrospectively identified. Computed tomography (CT) scans pre- and post-radiation and surgical specimens were centrally reviewed. Results: 29 patients underwent resection following NCRT, while 21 remained unresectable. Between the two groups, age, gender, mean RT dose, and proportion of pancreatic head tumors were not significantly different. Smaller tumor volume and lack of the following factors was associated with selection for resection: superior mesenteric/portal vein encasement (p=0.01), superior mesenteric artery involvement (p=0.02), ascites (p=0.01), and questionable/overt metastases (p=0.01). Notably, celiac artery involvement/encasement, common hepatic artery encasement, and percentage change in tumor volume were not significant predictors of resection (all p&gt;&gt;0.05). Interestingly, tumor volume and degree of individual vessel involvement did not significantly change from scans before and after NCRT (all p&gt;&gt;0.05). Median OS was 22.9 vs.13.0 months in resected and unresected patients, respectively (p&lt;0.001). Of resected patients, 93% had negative margins, 28% had positive nodes, 27% demonstrated &lt;10% viable tumor, and 12% had pathologic complete response at surgery. Dpc4 expression was retained in 68% of specimens with viable tumor. Conclusions: Although the apparent radiographic extent of vascular involvement does not change significantly after NRT, subsequent R0 resection rates are high, nodal involvement is low, and outcomes are similar to resected patients who receive adjuvant therapy. Resection attempts should not be deferred solely based on lack of improvement in tumor-vessel interactions.
Glyco-optimized trastuzumab-GEX, a novel anti-HER2 monoclonal antibody with ADCC activity: A phase I clinical study in patients with HER2-positive tumors.
Authors: Hellmut Samonigg, Sara De Dosso, Antonella Perotti, Walter Fiedler, Guenther Gastl, Bruno Dietrich, Kelvin Eckert, Hans Baumeister, Marc Oliver Salzberg, Steffen Goletz
Journal: Journal of Clinical Oncology (2014)

2515 Background: TrasGEX is a glyco-optimized anti-HER2 antibody. It is designed to fully retain the antigen-binding properties of trastuzumab. It is manifold improved by fully human glycosylation and optimized for its antibody dependent cellular cytotoxicity (ADCC)-mediated anti-tumor efficacy for all FcɣRIIIa genotypes as well as for lower HER2 expressing tumors. In vitro studies showed an approximate 10 to 140 fold improvement of ADCC-mediated anti-tumor activity for TrasGEX depending on the level of HER2 expression and of the FcɣRIIIa receptor status. Methods: This is a phase I, dose-escalation trial of TrasGEX 12 to 720 mg IV flat-dose q3w in patients progressive with advanced or metastatic cancer for whom no effective standard treatment is available and ErbB2 (HER2) positivity (at least 1+). The primary objective of this first-in-human study was to determine the optimal dose and regimen of TrasGEX in the study population. Results: A total of 37 patients were treated with up to 720 mg TrasGEX IV flat-dose q3w in 5 cohorts of 3 to 6 patients each and an extension group of 16 patients who received 720 mg. No DLT was observed, the MTD was not reached. Infusion-related reactions (IRR) were the most frequently observed drug-related AEs (51.4%) all but two of grade 1 or 2. Premedication with paracetamol and steroids reduced the frequency and intensity of IRRs. The pharmacokinetic properties were dose-dependent with a maximal half-life of 263 h ± 99 h at 720 mg. One patient with HER2+++ salivary duct tumor developed a CR, two HER2+++ patients reached strong PR (breast: 240 mg, FcɣRIIIa allotype: FF, prior trastuzumab non-responder; colon: 480 mg, FV allotype) and 12 (32.4%) showed SD (HER2+ = 4; HER2++ = 3; HER2+++ = 5), of which 40% had been exposed to trastuzumab at earlier therapies. Conclusions: TrasGEX at doses of up to 720mg IV q3w was well tolerated. No DLT was observed. The pharmacokinetic properties support a q3w infusion scheme. Evidence of activity was seen in 40.6% of patients, including one CR and 2 PRs in patients with progressive disease at study entry. Clinical trial information: NCT01409343.
Prevalence of COPD in a lung cancer case-control study: Variability by assessment method and by race.
Authors: Ann G. Schwartz, Shirish M. Gadgeel, Chrissy Lusk, Angie Wenzlaff, Stephanie Pandolfi, Garrett Walworth, Antoinette J. Wozniak, Christine Neslund-Dudas, Amy Ardisana, Michael Flynn, David Spizarny, Thomas Song, Paul Kvale, Michael Simoff, Robert Chapman, Zane T. Hammoud, Ayman Soubani
Journal: Journal of Clinical Oncology (2014)

1609 Background: The association between lung cancer risk and a history of self reported COPD (Chronic Obstructive Pulmonary Disease) is well established, but the association is less consistent when based on CT scan evidence of emphysema. We evaluated the effect of COPD ascertainment method on lung cancer risk estimates in a case-control study focused on genomic variation in lung cancer patients with and without COPD. Methods: A total of 899 participants (280 lung cancer cases and 619 controls) have been enrolled; 45% are African American (AA). Participants completed a questionnaire, spirometry and CT scans to assess COPD by radiology assessment and quantitative imaging analysis. Enrollment to the study to analyze genomic variation is ongoing. Results: 20% of cases and 10% of controls reported a physician diagnosis of emphysema; lung cancer risk was significantly associated with self-report (OR=2.1; 95%CI 1.4-3.1). A larger percentage of cases (63%) and controls (53%) were classified as having emphysema based on radiology assessment, reducing the association with lung cancer (OR=1.5, 95% CI 1.1-2.1). The percentage of false positives (“yes” on self-report and “no” on the CT) at ~ 3% and false negative reports (self-report “no” and “yes” on CT) at ~ 45% were consistent across racial groups. Risk of lung cancer based on self reported COPD compared to spirometry defined COPD (FEV1/FVC < 70%) was similar. 40% of cases self reported COPD as did 24% of controls (OR = 2.0; 95% CI 1.4-2.7), while 52% of cases and 35% of controls had a COPD diagnosis based on spirometry (OR = 2.0; 95% CI 1.4-2.7). Significant differences in self-reported versus spirometry-defined COPD were observed in both cases (p=0.03) and controls (p<0.001), driven by findings in AA. AA cases (p=0.01) and controls (p<0.001) had evidence of under-reporting of COPD. ORs associated with emphysema on CT were 1.2 (95% CI 0.7-1.8) for whites and 2.1 (95% CI 1.3-3.5) for AA ( p=0.053). Quantitative imaging for COPD is underway. Conclusions: These results indicate participants under-report emphysema and COPD, under-reporting differs by race, and regardless of measurement method, there is a significant effect of emphysema and COPD on lung cancer risk.
A Class of Reactive Acyl-CoA Species Reveals the Non-enzymatic Origins of Protein Acylation
Authors: Gregory R. Wagner, Dhaval P. Bhatt, Thomas M. O’Connell, J. Will Thompson, Laura G. Dubois, Donald S. Backos, Hao Yang, Grant A. Mitchell, Olga R. Ilkayeva, Robert D. Stevens, Paul A. Grimsrud, Matthew D. Hirschey
Journal: Cell Metabolism (2017)
Blinded assessment of radiological changes after stereotactic ablative radiotherapy (SABR) for early-stage lung cancer: Local recurrences versus fibrosis.
Authors: Suresh Senan, Kitty Huang, Sashendra Senthi, Femke Spoelstra, Andrew Warner, Ben J. Slotman, David Palma
Journal: Journal of Clinical Oncology (2013)

7520 Background: Stereotactic ablative radiotherapy (SABR) is a guideline-recommended treatment for unfit patients with early-stage lung cancer. The 5-year local recurrence rates are approximately 10% but fibrotic changes are common during follow-up, leading to difficulty with timely detection and salvage therapies. Previously reported high-risk features (HRFs) on computed tomography (CT) are 1) enlarging opacity at the primary site; 2) sequential enlarging opacity; 3) enlarging opacity after 12 months; 4) bulging margin; 5) loss of linear margin and 6) loss of air bronchograms. We performed a blinded assessment of CT imaging of patients with and without local recurrences. Methods: Patients treated with SABR for early stage lung cancer between 2003 and 2012, who developed pathology-proven local recurrence (n=12), were matched 1:2 to patients without recurrences (n=24), based on baseline factors. The median age at diagnosis was 68 years and median post-SABR imaging follow-up was 24 months (range 6 to 67 months). Patients were well-matched in the recurrence and non-recurrence groups. A total of 153 CT scans were available. Serial CT images were assessed by 3 radiation oncologists blinded to outcomes, viewing anonymized images projected onto a large screen. Results: All established HRFs were significantly associated with local recurrence (p&lt;0.01), and one additional HRF was identified: cranio-caudal growth (p&lt;0.001). The best individual predictor of local recurrence was opacity enlargement after 12 months(100% sensitivity, 83% specificity, p&lt;0.001). The odds of recurrence increased 4-fold for each additional HRF detected in an individual patient. The presence of ≥3 HRFs in an individual patient was highly sensitive and specific for recurrence (both &gt;90%). The HRFs enlarging opacity and cranio-caudal growth were each detected ≥3 months prior to the actual diagnosis of local recurrence in 42% of patients. Conclusions: Local recurrences following SABR can be accurately predicted by the presence of HRF’s on post-treatment CT scans. This approach may reduce unnecessary diagnostic procedures, and ensure earlier use of salvage therapies.
Abstract 19911: Bystander Cardiopulmonary Resuscitation and Bystander Defibrillation Associated With Increased Return to Work in Out-of-Hospital Cardiac Arrest Survivors
Authors: Oleh Dorosh, Kirsten Fonager, Rikke N Mortensen, Mads Wissenberg, Steen M Hansen, Carolina M Hansen, Shahzleen Rajan, Freddy Lippert, Fredrik Folke, Signe Riddersholm, Gunnar Gislason, Bodil S Rasmussen, Svend E Jensen, Christian Torp-Pedersen, Kristian Kragholm
Journal: Circulation (2016)

Introduction: Early defibrillation holds potential to improve survival following out-of-hospital cardiac arrest (OHCA). However, its association with return to work remains unknown.

Methods: Using nationwide data, we examined associations between bystander interventions (cardiopulmonary resuscitation [CPR] alone and defibrillation with and without bystander CPR) and return to work in 30-day survivors of OHCA in Denmark from 2001-2012. We included patients of presumed cardiac etiology, non-EMS-witnessed arrest, of working age (18-65 years) and previously employed in a five-week span prior to OHCA. Employment data was available from the Danish Labor Market Authority database containing weekly follow-up data on employment status since 1991.

Results: Of 665 eligible 30-day survivors, 19.3% (n=128) had not received bystander interventions, 12.9% (n=86) had missing status on bystander interventions, 59.2% (n=394) had received bystander CPR but not bystander defibrillation and 8.6% (n=57) were defibrillated by bystanders. Of 57 patients defibrillated by bystanders, 54 (94.7%) had also received bystander CPR. Relative to the no bystander resuscitation group, patients who received bystander CPR or defibrillation or had missing status on bystander interventions were more often older (P=0.01); men (P=0.008); of higher socioeconomic status (P=0.04); with public location of arrest (P<0.001) and witnessed arrest (P=0.02). In adjusted analyses, bystander CPR and bystander defibrillation were significantly associated with return to work (HR 1.46 [95% CI 1.14-1.87]; and HR 1.58 [95% CI 1.10-2.29], respectively). The cumulative incidence rates of return to work according to bystander intervention status are shown in the Figure.

Conclusion: Bystander CPR and bystander defibrillation were associated with increased return to work rates, suggesting a need for strategies to improve bystander CPR and public access defibrillation to further improve outcomes.

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Employment and quality of life (QOL) in human papillomavirus-related (HPV+) oropharynx cancer treated with definitive chemoradiation (CTRT).
Authors: Shrujal S. Baxi, Han Xiao, Matthew G. Fury, Coral L. Atoria, Lara Dunn, Talya Salz, Eric Jeffrey Sherman, Alan Loh Ho, Nancy Y. Lee, David G. Pfister
Journal: Journal of Clinical Oncology (2015)

9587 Background: HPV+ oropharynx cancer affects younger patients and is often treated with CTRT. We aimed to assess the impact of CTRT on employment and QOL in these patients. Methods: We completed a cross-sectional survey of clinically cancer-free patients with advanced, M0, HPV+ oropharynx cancer ≥ 1 year from primary CTRT. We assessed employment status using study-specific items. QOL was measured using the EQ5D and EORTC QLQ-H&N35. We examined the association between sociodemographic and clinical factors on employment outcomes and QOL at time of survey. Results: 129 patients (mean 23 months. post-CTRT) completed the survey. Median age was 57 years (range 25-76); 91% were male; 56% had an ECOG functional status score of 0 (vs1/2); 83% had stage IVA disease. High-dose cisplatin was the most common chemotherapy (63%). 53% reported at least one problem on the EQ5D, most commonly pain (29%) and anxiety (24%). Despite high rates of dry mouth (88%), thick saliva (69%), coughing (54%) patients reported high overall QOL, as measured by EQ5D. At diagnosis, 107 (83%) patients were employed including 23/23, 58/65 and 26/41 of patients ages < 50, 50-59, and > 60 years, respectively (p < 0.001); 80% were professionals or managers. Employment at diagnosis did not vary by pretreatment functional status. During CTRT, 10 (9%) stopped working and did not return, 74 (69%) took time off but returned to work, 20 (19%) reduced responsibilities but kept working, and 3 (3%) continued working. Of the 74 patients who took time off, median time to return to work was 14 weeks (interquartile range 8-24 weeks). There was no significant difference in time off by chemotherapy type, ECOG status, or age. At time of survey, 75% were employed. Current employment status did not vary by overall QOL at the time of survey. Conclusions: Despite persistent effects of CTRT, survivors of HPV+ oropharynx cancer reported good QOL. CTRT interrupted employment in the majority of these patients, but most returned to work. More efforts are needed to evaluate the determinants of employment, return to work and the socioeconomic burden of CTRT in this working-age population.