tbuckley/cabot-search huggingface dataset:
Correlation between PI3K/PTEN/AKT/mTOR pathway genetic variations and clinical outcome in patients with squamous cell carcinoma of the head and neck receiving cetuximab-docetaxel treatment.
Authors: Alberto Fusi, Katharina Pfisterer, Konrad Friedrich Klinghammer, Maren Knoedler, Anika Nonnenmacher, Ulrich Keilholz
Journal: Journal of Clinical Oncology (2012)

5572 Background: The PI3K/PTEN/AKT/mTOR pathway is one of the most targeted in human cancers and alterations in the axis are frequent events in squamous cell carcinoma of the head and neck (HNSCC). Specific genetic variations in this pathway have been associated with variation in recurrence, survival and response in lung cancer and esophageal cancer. The aim of this study was to determine whether single nucleotide nucleotide polymorphisms (SNPs) in AKT1, AKT2, FRAP1, PI3KCA and PTEN identified in other cancers were associated with treatment response and clinical outcome in patients with HNSCC. Methods: Genomic DNA was extracted from FFPE tissue specimens of 45 patients with recurrent or initially metastatic HNSCC who received a combined treatment with docetaxel and cetuximab in a phase II study. Eleven single SNPs in the genes AKT1, AKT2, FRAP1 (mTOR), PIK3CA and PTEN were genotyped by means of Real Time PCR system or by direct sequencing and analysed for association with response to therapy and survival. Results: None of the SNPs was related to treatment response. Two SNPs (AKT2:rs8100018 and PTEN:rs12569998) were associated with variation in progression risk. The AKT2:rs8100018 homozygous variant resulted in increased risk, with a HR of 4.83 (95% CI, 1.11-21.03) and the PTEN:rs12569998 homozygous variant in an increased risk, with a HR of 2.36 (95% CI, 1.24-4.50). AKT2:rs8100018 and PTEN:rs12569998 genetic variation had an additive effect on risk of tumor progression. The AKT2:rs8100018 homozygous variant was significantly associated with overall survival (OS) with HR of 3.57 (95% CI, 1.06-12.00) while presence of one of the two variant alleles of AKT1:rs3803304 with a lower risk of death (HR: 0.51; 95% CI, 0.27-0.97). Conclusions: We found significant associations between common genetic variants in the PI3K/PTEN/AKT/mTOR pathway and outcome in patients with HNSCC. Despite the small sample size, patient cohort and treatment were homogeneous. As a consequence, evaluation of SNPs as a host factor may be considered in addition to tumor-specific mutations for personalized treatment development.
IMPAIRED CORONARY FLOW RESERVE ON 82RUBIDIUM POSITRON EMISSION TOMOGRAPHY IMAGING PREDICTS ADVERSE EVENTS IN PATIENTS WITH AUTOIMMUNE DISEASE
Authors: Attila Feher, Nabil Boutagy, Evangelos Oikonomou, Edward Miller, Albert J. Sinusas, Monique Hinchcliff
Journal: Journal of the American College of Cardiology (2020)
Objective assessment of sentinel node tumor burden and its impact on sentinel node localisation in breast cancer
Authors: A. Goyal, A. Douglas-Jones, R. G. Newcombe, R. E. Mansel
Journal: Journal of Clinical Oncology (2006)

605 Background: Extensive tumor infiltration of the draining lymph nodes may prevent the migration of tracer to the sentinel node(SN), adversely affecting SN identification. Methods: A total of 202 breast cancer patients underwent SN biopsy using 99mTc albumin colloid and Patent Blue V injected peritumorally. This was followed by standard axillary clearance in all patients at the same operation. Tumor burden in the SN was assessed by measuring the size of metastasis, percentage replacement(PR) of the SN by tumor and by documenting extranodal invasion(EI). Digital images of the marked slides were acquired and measurements were made using Image Pro Plus software. Results: The overall SN identification rate was 94.6% (191/202), of which 5 were false negatives. Only 18% (2/11) of patients with failed SNB had evidence of nodal metastases on completion axillary clearance. A total of 83 positive SNs were removed from 64 patients. Radioisotope count in the SNs decreased with increasing PR of the SNs by tumor (p=0.005). 30% (24) of the nodes removed were not hot (counts&lt;10 times the background count). The mean PR by tumor of these nodes was 55% (SD 36) as compared to 33% (SD 33) for hot nodes (p=0.009). 20% (16/81) of the positive SNs showed EI. 69% (11) of nodes with EI were not hot (radioisotope count ratio &lt;10) and would not be localised if the radioisotope was used alone. SNs with EI had a lower radioisotope count compared to SNs without EI (p&lt;0.0001). The mean PR by tumor of nodes with EI was 70% (SD 26) compared to 32% (SD 33) of nodes without EI. This shows that extranodal growth of the tumor would occur once the node is &gt;50% replaced with tumor. There was no correlation between radioisotope uptake and size of metastasis in the SN. There was no correlation between blue dye uptake and tumor burden in the positive SN. Conclusion: In an individual SN, the PR by tumor and EI are markers of lymphatic obstruction and significantly associated with reduced radioisotope uptake. These results suggest that &gt;50% replacement of the node by tumor will compromise the lymphatic flow and may lead to failed localisation of the node if the radioisotope is used alone. However, the SN tumor burden does not affect blue dye uptake. This result provides an argument for using a combination of blue dye and radioisotope for SN biopsy. No significant financial relationships to disclose.
PERI-PROCEDURAL RIGHT CORONARY ARTERY OCCLUSION BY CALCIUM EMBOLUS CAUSING ACUTE MYOCARDIAL INFARCTION DURING TRANSCATHETER AORTIC VALVE IMPLANTATION
Authors: Balaji Natarajan, Srishti Nayak, Suneel Kumar, Anisha Rastogi, Prabhdeep Sethi
Journal: Journal of the American College of Cardiology (2020)
PREDICTORS OF INCREASED MORTALITY RISK IN PATIENTS WITH NEGATIVE STRESS ECHOCARDIOGRAPHY
Authors: Rayan Jo Rachwan, Fakilahyel S. Mshelbwala, Rody G. Bou Chaaya, Edward A. El-Am, Mohammad Sabra, Zeina Dardari, Omar Batal
Journal: Journal of the American College of Cardiology (2020)
RELATIONSHIP BETWEEN T-WAVE HETEROGENEITY IN RESTING 12-LEAD EKGS AND TROPONIN LEVELS IN PATIENTS EVALUATED FOR ACUTE CORONARY SYNDROME
Authors: Sofia A. Medeiros, Fernanda Tessarolo Silva, Giovanna C. Pedreira, Bruce Nearing, Edward A. Ullman, Ernest Gervino, Richard Verrier
Journal: Journal of the American College of Cardiology (2020)
Polydopamine-coated nucleic acid nanogel for siRNA-mediated low-temperature photothermal therapy
Authors: Fei Ding, Xihui Gao, Xiangang Huang, Huan Ge, Miao Xie, Jiwen Qian, Jie Song, Yuehua Li, Xinyuan Zhu, Chuan Zhang
Journal: Biomaterials (2020)
THE WOMEN IN CARDIOLOGY TWITTER NETWORK
Authors: Neha Chandra, Ruth Hsiao, Hilary Shapiro, Shire Beach, Sarah Snow, Karol E. Watson, Marcella Calfon-Press, Tamara Horwich, Martha Gulati, Gina Price Lundberg, Sherry-Ann Brown, Purvi Parwani, Janet K. Han
Journal: Journal of the American College of Cardiology (2020)
Race/ethnicity, literacy, and prostate cancer: Initial findings from the COMPARE registry
Authors: O. Sartor, C. L. Bennett, S. Halabi, M. Kattan, P. Scardino
Journal: Journal of Clinical Oncology (2006)

4620 Background: Comprehensive Multicenter Prostate Adenocarcinoma Registry (COMPARE) evaluates variations in initial prostate cancer (PCa) therapy according to race/ethnicity. Similar studies for prostate cancer patients with PSA failure following radiation therapy or radical prostatectomy are unreported. Poor health literacy and African American race are predictive of advanced stage prostate cancers at diagnosis. Methods: COMPARE includes 778 men (62% &gt;70 yr; 80% white and 13% AA) with rising PSA post-localized PCa therapy. Median follow-up post-registry entry is 5 months. Enrollment at 146 sites to date: urology (N = 129), radiation oncology (n = 12), other (n = 5). Most sites are private practice (n = 132) vs academic (n = 14). Health literacy was tested with a 7-item validated word recognition test; scores of ≥4 correlate with ≥6 th grade literacy. Variations in therapy, both initial and after PSA failure, were assessed as a function of patient/regional factors. Results: Initial therapy included radical prostatectomy (RP) 44.5%, external beam radiation therapy (EBRT) 30.7%, brachytherapy (BT) 13.1%, other (11.5%). Literacy data are available for 725 men, one fifth had poor literacy skills (&lt;4); higher rates of low literacy were present in AA vs white men (p &lt; 0.05). Significant variations in initial care were associated with poor vs normal literacy skills (brachytherapy: 8% vs 16%; radical prostatectomy: 52% vs 44%, p &lt; 0.05). Watchful waiting was the most common management for PSA failure patients, 82% for men aged ≤70 yr and 77% for men &gt;70 yr. Among prostate cancer patients &gt;70 yr, after adjustment for literacy and Gleason score, African American men were only 41% as likely as whites to undergo watchful waiting (95% CI, 19% to 92%). Conclusions: Poor health literacy is common among men with prostate cancer; these men are more likely to receive radical prostatectomy. With men &gt;70 yr with PSA failure post-radical prostatectomy or post-radiation therapy, African American men were 2.5× more likely than white men to choose therapy (primarily castration) over watchful waiting. Findings from smaller cohorts found that urologic symptoms were the most important factor associated with use of castration versus watchful waiting for PSA failure. No significant financial relationships to disclose.
ASSOCIATION OF SERUM HOMOCYSTEINE LEVEL AND CORONARY MICROVASCULAR ENDOTHELIAL DYSFUNCTION IN PATIENTS WITH ANGINA AND NON-OBSTRUCTIVE CORONARY ARTERY DISEASE
Authors: Amir Lerman, Ali Ahmad, Michel Toni Corban, Takumi Toya, Ji Young Park, Lilach Lerman
Journal: Journal of the American College of Cardiology (2020)
Predicting factors for early and long-term mortality after thoracotomy in patients with primary lung cancer.
Authors: Cynthia van Arkel, Daphne Dumoulin, Bart van Straten, Joost ter Woorst, Saskia Houterman, Ben van den Borne
Journal: Journal of Clinical Oncology (2013)

e18562 Background: To determine factors predicting early and long term mortality in patients who underwent a thoracotomy because of primary lung cancer. Methods: Data of patients who underwent a thoracotomy in the Catharina Hospital Eindhoven between 1 January 1995 and 1 January 2011 have been collected retrospectively from the medical files. Early mortality was defined as mortality &lt;30 days after surgery. Last date of follow up was 1 January 2013. Patients were divided in three periods according to date of surgery (1: 1995-1999, 2: 2000-2004 and 3: 2005-2010). Predicting factors for early mortality were assessed with uni- and multivariate logistic regression analysis. For long term mortality and survival predicting factors were assessed using the Cox proportional hazards model and Kaplan-Meier survival curves. Results: In total 501 patients underwent a thoracotomy due to primary lung cancer. Overall 30 day mortality was 5.8% (n=29). Early mortality was 3.0% for lobectomy (n=289), 0.2% for bilobectomy (n=29) and 11% for pneumonectomy (n=109). Multivariate analysis showed that age over 70 (p=0.002), pneumonectomy (p=0.008) and a pre-operative VO2max of &lt;15 ml/kg/min (p=0.02) were significant predictors of early mortality. With respect to long term survival, 308 (62%) patients had died at the end of the follow-up period. Median survival time was 44 months, with an overall 5- and 10- year survival of 45% and 27% respectively. The 5- and 10-year survival for stage I, II and III-IV was 61% and 37%; 46% and 30%;16% and 6.6%, respectively (p&lt;0.0001, log rank test). Finally Cox regression analysis showed that stage (stage I (HR 0.30; 95% CI 0.22-0.42), stage II (HR 0.38; 95% CI 0.26-0.57) compared to stage III-IV, FEV1% ≤70% (HR 1.57; 95% CI 1.61-2.11), a history of cerebrovascular disease (CVD) (HR 1.97; 95% CI 1.20-3.23) and surgery in an earlier time period (1 (HR 1.50; 95% CI 1.04-2.17); 2 (HR 1.46; 95% CI 1.05-2.02) compared to 3) were significant predictors of long term mortality. Conclusions: In this cohort age, pneumonectomy and pre-operative VO2max are significant predictors of early mortality. Significant predictors of long term mortality are disease stage, FEV1%, a history of CVD and surgery in an earlier time period.
CYP3A4 phenotyping with midazolam to predict sunitinib exposure.
Authors: Nielka P van Erp, Djoeke de Wit, Alex Sparreboom, Jan den Hartigh, Margret den Hollander, Jacqueline M.C. Konig-Quartel, Trees Hessing, Henk-jan Guchelaar, Hans Gelderblom
Journal: Journal of Clinical Oncology (2013)

2592 Background: Patients treated with sunitinib show high inter-patient variability in drug exposure (40-60%), which is largely unexplained. Since sunitinib is metabolized by CYP3A4, variability in the activity of this enzyme may explain a considerable proportion of the observed variability. We therefore prospectively studied the relationship between CYP3A4 activity and systemic exposure to sunitinib. Methods: In fifteen patients treated with sunitinib in a four weeks “on” – two weeks “off” regimen the pharmacokinetics of sunitinib and its active metabolite SU12662 were assessed. To determine sunitinib+SU12662 steady-state exposure, samples were collected over 24hrs after at least 14 days of sunitinib therapy. To assess CYP3A4 activity, midazolam 7.5mg orally was administered on the final day of the two weeks “off”. Plasma concentrations were measured over a period of 7hrs to determine midazolam exposure. Exposures (AUC) were calculated using a trapezoidal approach (Phoenix WinNonlin v6.3). The relationship between CYP3A4 activity (midazolam exposure) and sunitinib+SU12662 exposure was determined by linear regression analysis. The percentage of variability in sunitinib+SU12662 exposure that could be explained by CYP3A4 activity was calculated by Pearson’s correlation. In addition, the correlation between sunitinib+SU12662 C trough levels and sunitinib+SU12662 exposure was assessed. Results: A strong correlation between midazolam exposure (AUC 0-7hr ) and steady-state sunitinib+SU12662 exposure (AUC 0-24hr ) was found (p= 0.002); CYP3A4 activity explained 55% of the observed inter-patient PK variability of sunitinib+SU12662. Furthermore sunitinib+SU12662 C trough levels were highly predictive (96%) for overall sunitinib+SU12662 exposure (AUC 0-24hr ). Conclusions: Midazolam as a phenotyping probe could be useful before start of sunitinib therapy to identify patients at risk for under- respectively overtreatment at a standard dosage regimen. Therefore, CYP3A4 phenotyping could be useful to individualize sunitinib therapy. Additionally, sunitinib+SU12662 trough levels are highly predictive for sunitinib+SU12662 exposure and thus can be used for monitoring and guiding sunitinib therapy in clinical practice. Clinical trial information: NCT01743300.
Full-dose irinotecan plus platinum (IP) with concurrent thoracic radiotherapy (C-TRT) in unresectable locally advanced non-small cell lung cancer (LA-NSCLC).
Authors: Jun Zhang, Tithi Biswas, Daniel B Fried, Julian Rosenman, Suzanne M. Russo, Wenimar Salvador, Stephen Tiley, Teresa Parent, Susan Eubanks, Zenith Nelson, Raid Aljumaily, Mark Bowling, Paul R. Walker
Journal: Journal of Clinical Oncology (2012)

e17547 Background: Weekly paclitaxel-carboplatin or cisplatin-etoposide with C-TRT is the standard of care for unresectable LA-NSCLC, with median survival time (MST) of 16-24 months and 3 year overall survival (OS) of 17-27%. Irinotecan plus platinum with C-TRT has been studied in LA-NSCLC with similar outcomes and no undue toxicities (Langer et al J Thorac Oncol 2007; Bastos et al J Thorac Oncol 2010). We reviewed our multi-disciplinary thoracic oncology program experience of full dose IP with C-TRT in LA-NSCLC. Methods: All patients with unresectable LA-NSCLC treated between January 2007 and December 2011 were searched through our program database and included. 26 patients treated with definitive IP and C-TRT were identified. Treatment consisted of irinotecan 65mg/m 2 , plus cisplatin 30mg/m 2 or carboplatin AUC 3, on days 1 and 8, every 21 days for four cycles. C-TRT started on day 22 at 2 Gy/day for 6-7 weeks. (Total 60-70Gy.) Survival curves were estimated by Kaplan-Meier analysis. Primary end point was OS. Secondary endpoints were overall response rate (ORR), progression free survival (PFS), and toxicities. Results: Patient characteristics: Median age 61 (range 44-82); 73% males; 50% squamous, 31% adenocarcinoma, 19% other histology; 30% Stage IIIA/ 62% IIIB/8% IIB. 1 patient died early without evaluation. ORR was 69%, 5 (19%) complete response, 13 (50%) partial response, 7 (27%) stable disease. Median PFS 10.1 months. MST 31.4 months. One year OS 67.8% (95% CI 52-89) and three year OS 35.7% (95%CI 15-87). 12 (46%) patients had G3/4 hematologic toxicities: 7 neutropenia, 6 thrombocytopenia, 6 anemia, 2 lymphopenia. 9 (34.6%) patients had G3/4 non-hematologic toxicities: 4 radiation esophagitis, 3 elevated creatinine, 2 pneumonia, 2 nausea/vomiting. 1 G5 radiation pneumonitis. Two patients died of pneumonia and sepsis. 18 (69%) patients completed 4 cycles IP with concurrent TRT. Conclusions: Definitive treatment with full dose Irinotecan plus platinum and concurrent thoracic radiotherapy is effective and tolerable for unresectable LA-NSCLC with an enhanced MST of 31 months and 3 year OS of 35%.
INTEGRATING SOCIAL DETERMINANTS OF HEALTH IN CLINICAL CARE DELIVERY
Authors: Anekwe E. Onwuanyi, Diane Wirth, Faith Works-Fleming, Andrea Cafarelli, Michael Knauss, Modele Ogunniyi, Brandi Quinn, Jeff Herald, Amy Bick, Eva Gourrier, Tara Shropshire
Journal: Journal of the American College of Cardiology (2020)
A Randomized Phase II Preoperative Study of Autophagy Inhibition with High-Dose Hydroxychloroquine and Gemcitabine/Nab-Paclitaxel in Pancreatic Cancer Patients
Authors: Herbert J. Zeh, Nathan Bahary, Brian A. Boone, Aatur D. Singhi, Jennifer Lee Miller-Ocuin, Daniel P. Normolle, Amer H. Zureikat, Melissa E. Hogg, David L. Bartlett, Kenneth K. Lee, Allan Tsung, J. Wallis Marsh, Pranav Murthy, Daolin Tang, Natalie Seiser, Ravi K. Amaravadi, Virginia Espina, Lance Liotta, Michael T. Lotze
Journal: Clinical Cancer Research (2020)

We hypothesized that autophagy inhibition would increase response to chemotherapy in the preoperative setting for patients with pancreatic adenocarcinoma. We performed a randomized controlled trial to assess the autophagy inhibitor hydroxychloroquine in combination with gemcitabine and nab-paclitaxel.Participants with potentially resectable tumors were randomized to two cycles of nab-paclitaxel and gemcitabine (PG) alone or with hydroxychloroquine (PGH), followed by resection. The primary endpoint was histopathologic response in the resected specimen. Secondary clinical endpoints included serum CA 19-9 biomarker response and margin negative R0 resection. Exploratory endpoints included markers of autophagy, immune infiltrate, and serum cytokines.Thirty-four patients in the PGH arm and 30 in the PG arm were evaluable for the primary endpoint. The PGH arm demonstrated statistically improved Evans grade histopathologic responses (P = 0.00016), compared with control. In patients with elevated CA 19-9, a return to normal was associated with improved overall and recurrence-free survival (P < 0.0001). There were no differences in serious adverse events between arms and chemotherapy dose number was equivalent. The PGH arm had greater evidence of autophagy inhibition in their resected specimens (increased SQSTM1, P = 0.027, as well as increased immune cell tumor infiltration, P = 0.033). Overall survival (P = 0.59) and relapse-free survival (P = 0.55) did not differ between the two arms.The addition of hydroxychloroquine to preoperative gemcitabine and nab-paclitaxel chemotherapy in patients with resectable pancreatic adenocarcinoma resulted in greater pathologic tumor response, improved serum biomarker response, and evidence of autophagy inhibition and immune activity.
Morbidity of staged proctectomy after hepatectomy for colorectal cancer: A matched case-control analysis.
Authors: Ching-Wei David Tzeng, George J. Chang, Steven A. Curley, Jean-Nicolas Vauthey, Lee M. Ellis, John Michael Skibber, Barry W. Feig, Eddie K. Abdalla, Thomas A. Aloia, Y. Nancy You, Miguel A. Rodriguez-Bigas
Journal: Journal of Clinical Oncology (2012)

629 Background: Proctectomy after hepatectomy, or the “reverse approach,” is an alternative to traditional sequencing for advanced liver metastases with asymptomatic colorectal primaries. However, perioperative morbidity from staged proctectomy remains uncharacterized. We sought to identify risk factors for morbidity in these patients. Methods: A single-institution colorectal database was queried for patients treated with proctectomy after previous hepatectomy from 2003-2011. Reverse approach patients (31) were matched 1:2 with a cohort of standard proctectomy patients (62), using operation, age, sex, and surgeon. Perioperative factors were analyzed by univariate/multivariate models for associations with complications graded by Dindo-Clavien criteria. Results: 31 patients with adenocarcinoma ≤20 cm from the anal verge underwent proctectomy after hepatectomy. Median time from hepatectomy to proctectomy was 5.1 mo. Median tumor distance was 8.5 cm from the anal verge. No patients with primary tumors in situ recurred in the liver while awaiting proctectomy after hepatectomy. Prior to proctectomy, there were 28 (90%) major hepatectomies and 7 (22%) portal vein embolizations. Grade ≥2 complications developed in 42% of reverse approach and 27% of standard proctectomies (p=0.17). Grade 3 complications developed in 10% and 8%, respectively (p=1.00). There were no perioperative deaths. Reverse approach patients did not differ from the control cohort in operation, demographics, body mass index (BMI), comorbidities, tumor distance, operative time, estimated blood loss (EBL), length of stay, or complication rates (p&gt;0.05). Independent predictors of Grade ≥2 complications were BMI ≥30 (p=0.007), operative time ≥300 min (p=0.012), intraoperative transfusion (p=0.044), concurrent procedures (p=0.024), and age ≥50 (p=0.030). Independent factors for Grade 3 complications were operative time ≥300 min (p=0.015), intraoperative transfusion (p=0.011), and EBL ≥300 ml (p=0.047). Conclusions: Risk factors for morbidity of staged proctectomy are similar to those for standard proctectomy. When applied to selected patients, the reverse approach is safe with acceptable morbidity.
CLO20-046: National Cancer Institute Experience With Generic Anastrozole (Anastrodex, Hikma) in Newly Diagnosed Postmenopausal Female Egyptian Patients With Low Burden Visceral Metastatic Breast Cancer
Authors: Mohamed Ali Maher, Abdelhamid Mohamed Fouad, Mariam Maged Elhaddad
Journal: Journal of the National Comprehensive Cancer Network (2020)

"CLO20-046: National Cancer Institute Experience With Generic Anastrozole (Anastrodex, Hikma) in Newly Diagnosed Postmenopausal Female Egyptian Patients With Low Burden Visceral Metastatic Breast Cancer" published on 20 Mar 2020 by National Comprehensive Cancer Network.