tbuckley/cabot-search huggingface dataset:
Toxicity in patients (pts) age 65 or older with dose-adjusted REPOCH (DA-REPOCH) for untreated diffuse large B-cell lymphoma (DLBCL).
Authors: Deborah Marie Stephens, Amy S. Ruppert, Beth Christian, Jeffrey Alan Jones, Joseph M. Flynn, Pierluigi Porcu, Robert A. Baiocchi, John C. Byrd, Emily K. Dotson, Brooke S. Crawford, Kristie A. Blum
Journal: Journal of Clinical Oncology (2012)

e18508 Background: ORR of 97-99% and 5-yr PFS of 75-79% are reported with front-line DA-REPOCH in pts age 19-85. In these prospective series, 72% of pts escalated ≥ 1 dose level (DL), febrile neutropenia (FN) occurred in 36-51% pts, and 3-4% died of toxicity. Methods: We performed retrospective analysis of pts ≥ 65 treated with DA-REPOCH front-line for DLBCL at Ohio State University from 2002-2011. PFS estimates were calculated by the Kaplan-Meier method. Logistic regression and proportional hazards models were fit to identify variables associated with ORR and PFS, respectively. Results: 69 pts ≥ 65 yrs (range, 65-92) received DA-REPOCH for de novo (n=42) or transformed (prior CLL=16, FL=9, HL=2) DLBCL, including 28 pts ≥ 75. Performance status (PS) was ≥ 2 in 43%, 86% were stage III-IV, 77% had an aaIPI ≥ 2, 19% had bulky disease ≥ 10 cm, 83% had extranodal disease, and median creatinine clearance (CrCl) was 64 ml/min. Median number of cycles was 5 (range 1-7). Max DL was 1, 2, and 3 in 72, 13, and 6% of pts, respectively, and 9% received all cycles below DL 1. Max DL and number of cycles were similar between pts 65-74 and &gt; 75. Dose reductions (DR), delays, FN, and hospitalization occurred in 48, 39, 38, and 42% of pts, respectively. DR were associated with age ≥ 75 (p=0.001) or reduced CrCl (p=0.02) and delays strongly associated with PS ≥ 2 (p=0.001). FN was associated with bulky disease (p=0.03); 31% of pts without bulky disease developed FN compared to 67% with bulk. Nine pts (13%, 3 pts ≥ 75) died of toxicity (7 pts at DL 1 and 2 at DL &lt; 1). ORR was 67% (95% CI 52-75%). Median PFS was 17 mos (95% CI 6-43). Increased LDH (p=0.008 and p&lt;0.001) and number of prior chemotherapies (p=0.04 and p&lt;0.001) were independently predictive for ORR and PFS, respectively. DR and age were not associated with ORR or PFS, controlling for LDH and number of prior regimens. In 42 pts with de novo DLBCL, ORR was 71% (95% CI 54-85%) and median PFS was 36 mos (95% CI 7-94). Conclusions: In this retrospective study, toxicity is increased with DA-REPOCH in pts ≥ 65 with DLBCL, compared to published results in a younger population. Age ≥ 75, impaired CrCl, and poor PS are associated with increased risk of DR and delays, although age and DR do not appear to impact ORR and PFS.
Claudin-1 as a novel transcriptional target of hedgehog signaling and a predictor for outcome in breast cancer.
Authors: Sanjay Warrier, Christina Sellinger, Jane McNeil Beith, Aurelie Cazet, Alex Swarbrick, Hugh Carmalt, Sandra O'Toole
Journal: Journal of Clinical Oncology (2013)

1053 Background: Hedgehog signaling is important in the development of a number of malignancies. We have recently shown that the Hedgehog (Hh) signaling pathway is associated with a poor outcome and is a novel therapeutic target in triple negative breast cancer. Gene expression profiling of M6 murine cell line mammary xenografts overexpressing Hh ligand revealed a series of genes potentially regulated by Hh in breast cancer. We explored the expression patterns of one of the candidates, Claudin-1, an adhesion molecule, and its association with Hh pathway markers and outcome in 292 invasive ductal carcinomas. Methods: Immunohistochemistry for Claudin-1 was performed and scored by two observers for membranous and cytoplasmic localization. Membranous or cytoplasmic expression were scored and its associations with patient outcome were assessed using Kaplan Meier and Cox Proportional hazard model analyses. Correlations with clinicopathological features and Hh pathway protein expression were undertaken using chi squared analysis. Results: Claudin-1 was expressed both in the cytoplasm and at the plasma membrane of breast carcinoma cells. Cytoplasmic predominant expression of Claudin1 was associated with a favorable prognosis (HR 0.59 (95% CI: 0.36, 0.97), p = 0.039. In contrast, membranous predominant expression was associated with larger tumors, histological grade 3, a high Ki67 index and a poor outcome (HR 1.66 (95% CI: 1.064, 2.60), p = 0.026). Importantly, membranous Claudin-1 directly correlated with Hh ligand (p &lt; 0.0001) and paracrine pathway activation as indicated by high epithelial Hh ligand expression (p &lt; 0.0001) and high Gli1in the peritumoral stroma (p=0.027). There is a strong correlation between paracrine hh/gli (p = 0.001) and membrane predominant claudin confirming our in vivo findings. Conclusions: Claudin-1 is an important component of the tight junction in epithelial cells. We have shown for the first time that Claudin-1 is a direct target of Hh pathway activation. Furthermore, we report that the subcellular localization of Claudin-1 shows distinct association with outcome in breast cancer. These findings provide insight into potential mechanisms of metastatic spread of breast cancer.
A meta-analysis comparing cisplatin-based to carboplatin-based chemotherapy in moderate to advanced squamous cell carcinoma of head and neck (SCCHN).
Authors: Qinyang Li, Jian Guan, Yue Zhang, Min Chen, Lu Li, Nanjie Xiao, Mi Yang, Yongmei Dai, Chi Zhang, Longhua Chen
Journal: Journal of Clinical Oncology (2015)

6036 Background: The cisplatin (CDDP)-based CT is considered as the standard regimen for the treatment of moderate to advanced SCCHN. Recently, an alteration is made to carboplatin (CBDCA) because of its similar mode of action. We conducted a meta-analysis to compare the efficacies and toxicities of these two treatments. Methods: The search strategy included Pubmed, Science Direct, the Cochrane Library, China National Knowledge Internet Web. Statistical analyses were performed using RevMan 5.2. The primary endpoint was overall survival (OS) with secondary endpoints of locoregional control (LRC) and severe toxicity (grade ≥ 3). Hazard ratio (HR) and risk ratio (RR) were calculated using random- or fixed-effect models. Kaplan-Meier curves were read by Engauge-Digitizer. Results: Overall 12 studies and 1165 patients were included. CDDP-based CT significantly improved 5-year OS (HR = 0.67,95%CI 0.49-0.91;P = 0.01) compared to the CBDCA group. No difference in 3-year OS/LRC was observed (P = 0.08;P = 0.64), but a subgroup analysis showed a better 3-year OS in the CDDP arm for non-nasopharynx carcinoma (non-NPC) SCCHN (HR = 0.66,95%CI 0.48-0.91;P = 0.01). The CDDP-based CT was associated with more gastrointestinal toxicities (RR = 4.58,95%CI 1.57-13.37;P = 0.005) and nephrotoxicity (4/110 = 3.6%) compared to the CBDCA group, but less hematologic toxicities (anemia, leukopenia and thrombocytopenia) with RRs of 0.27 (95%CI 0.12-0.63),0.71 (95%CI 0.52-0.96),0.28 (95%CI 0.15-0.54). Risk of skin toxicity was identical. Moreover, we found that for non-NPC SCCHN, mucositis occurred more frequently and severely in CDDP-based treatment (RR = 3.55,95%CI 1.42-8.88;P = 0.007), whereas less for NPC (RR = 0.20,95%CI 0.09-0.45;P < 0.0001). Conclusions: Patients with CDDP-based CT can achieve a higher OS, but there is no significant difference in LRC. The CDDP-based CT is associated with less hematologic toxicities but more gastrointestinal toxicities and nephrotoxicity compared to the CBDCA arm. Risk of mucositis in the CDDP group is higher for non-NPC SCCHN, but lower for NPC. The precise roles of CDDP and CBDCA in the management of SCCHN remain to be determined.
Bevacizumab plus chemotherapy in the treatment of metastatic breast cancer: Hospital of Cruces experience.
Authors: Josefa Ferreiro, Abigail Ruiz de Lobera, Aintzane Sancho, Sergio Carrera, Ines Marrodan, Itziar Rubio, Eluska Iruarrizaga, Eider Azkona, Alberto Munoz Llarena, Guillermo Lopez-Vivanco
Journal: Journal of Clinical Oncology (2012)

e11525 Background: Antiangiogenic therapies such as bevacizumab (BV), have proven to be effective in improving outcomes in metastatic disease from several tumor types. For metastatic breast cancer (MBC), combinations of BV and established chemotherapy regimens potentially offer new, more efficacious treatments without the significant toxicity associated with combining multiple cytotoxic agents. Methods: This is a retrospective chart review that reflects Hospital of Cruces experience with BV in combination with chemotherapy in patients with MBC. Demographic and treatment data were collected from diagnosis and follow-up period. Results: A total of 66 patients were included. Median age was 53(34-78) years. ECOG PS 0/1/2/3 was 35%/51.5%/10.5%/3%, respectively. Positive hormone receptor (66.7%) and negative hormone receptor (33.3%). Her2 negative and triple negative were 100% and 33.3% of the patients. Adjuvant treatment received was 81.8% chemotherapy and 56.1% hormone therapy. Most frequent metastasis locations: bone (68%), liver 54.5%, lymph nodes (51.5%) and lung (27.3%). Thirty-five patients reported two or 3 metastasis locations. Chemotherapy used with BV was docetaxel (68.2%) and paclitaxel (31.8%). Median of BV courses was 6 (1-20). Response rate was 57.5% (53% partial response) and 28.8% had stable disease. Median Progression Free Survival (PFS) was 11.7 months and median OS was 19.7 months. Statistical differences were observed between patients who received a maintenance therapy with BV vs patients who received no maintenance therapy (PFS: 9.34 vs 15.36 months, p&lt;0.001; OS: 13.81 vs 25.56 months, p&lt;0.001). Most frequent toxicities 3/4 were: neutropenia 31.8%, febrile neutropenia 21.2%, asthenia 21.2%, infection 9.1% and onycholysis 6.1%. Conclusions: BV in combination with chemotherapy improves clinical benefit in terms of increased PFS and OS in first-line treatment of metastatic breast cancer. Maintenance with BV revealed statistical differences. Toxicity profile was manageable and as expected for BV.
Frequency and Prognostic Significance of Cytogenetic Abnormalities in 1269 Patients with Therapy-Related Myelodysplastic Syndrome - a Study of the International Working Group (IWG-PM) for Myelodysplastic Syndromes (MDS)
Authors: Andrea Kuendgen, Heinz Tuechler, Meritxell Nomdedeu, Detlef Haase, Guillermo Garcia-Manero, Rami S. Komrokji, Francesc Sole, Mikkael A. Sekeres, Matteo Giovanni Della Porta, Alan F List, Mario Cazzola, Amy E. DeZern, Gail J. Roboz, David P. Steensma, Arjan A. van de Loosdrecht, Richard F. Schlenk, Xavier Calvo, Sabine Blum, Arturo Pereira, Arturo Pereira, Peter Valent, Dolors Costa, Dolors Costa, Aristoteles Giagounidis, Aristoteles Giagounidis, Luis Benlloch, Uwe Platzbecker, Carmen Pedro, Michael Lübbert, María Teresa Cedena, Julie Schanz, Sigrid Machherndl-Spandl, Maria Lopez-Pavia, María Díez-Campelo, Claudia D. Baldus, Montserrat Martínez de Sola, Reinhard Stauder, Brayan Merchan, Claudia Mende, Maria Teresa Voso, Maria Teresa Voso, Itziar Oiartzabal, Itziar Oiartzabal, Christina Ganster, Francesc Cobo, Thomas Schroeder, Jordi Esteve, Rainer Haas, Benet Nomdedeu, Peter Greenberg, Ulrich Germing, Guillermo Sanz
Journal: Blood (2016)
Microangiopathy, Arterial Stiffness, and Risk Stratification in Patients With Type 2 Diabetes—Reply
Authors: Benjamin M. Scirica, Eugene Braunwald, Deepak L. Bhatt
Journal: JAMA Cardiology (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Cardiology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Cardiology journal
Impact of cytoreductive nephrectomy on disease-specific survival (DSS) in the cytokine and targeted therapy eras: Age- and TNM-stage matched analysis of SEER data.
Authors: Rebecca A. Nelson, Nicholas J. Vogelzang, Sumanta Kumar Pal
Journal: Journal of Clinical Oncology (2013)

4579 Background: The role of cytoreductive nephrectomy (CN) for patients with mRCC was well-defined in the cytokine era. However, its role is controversial in the era of targeted therapies. Methods: The Survival, Epidemiology, and End Results (SEER) Database was queried to compare the relative benefit of CN in the cytokine era (defined as 1992-2004) as compared to the targeted therapy era (defined as 2005-2009). Patients with mRCC and clear cell, papillary or chromophobe histology were identified, and divided into cohorts with and without CN. Within each category, patients diagnosed during the cytokine era were matched by age and TNM stage to patients diagnosed during the targeted therapy era. Associations between clinicopathologic characteristics and DSS were explored through univariate and multivariate analyses. Results: Amongst matched pts who had received CN (n=2,218), no significant differences in age, gender, race, histology (clear cell v non-clear cell), T-stage, or N-stage were observed. Median DSS was superior in those patients diagnosed during the targeted therapy era as compared to the cytokine era (22 mos v 17 mos, P&lt;0.0001). On multivariate analysis including the aforementioned clinicopathologic variables and DSS, diagnosis during the targeted therapy era was an independent predictor of improved survival amongst patients who had received CN (HR 0.78, 95%CI 0.70-0.87; P&lt;0.0001). Amongst matched pts who had not received CN (n=4,214), there were no differences in clinicopathologic characteristics. Median DSS was similar in patients diagnosed during the targeted therapy era as compared to the cytokine era within this group (4 mos for each; P=NS). Conclusions: Patients who received CN during the targeted therapy era had a superior DSS as compared to patients who received the procedure during the cytokine era. In contrast, patients who had not received CN had a similar DSS across both time periods. While prospective trials mature (i.e., CARMENA and EORTC 30073), these data support the continued use of CN in the context of targeted agents.
PD-L1 is commonly expressed and transcriptionally regulated by STAT3 and MYC in ALK-negative anaplastic large-cell lymphoma
Authors: V Atsaves, N Tsesmetzis, D Chioureas, L Kis, V Leventaki, E Drakos, T Panaretakis, D Grander, L J Medeiros, K H Young, G Z Rassidakis
Journal: Leukemia (2017)
Risk-assessed exercise and diet in prostate cancer survivors: Consequences of cancer treatment on cardiopulmonary fitness and cardiovascular risk.
Authors: Sara Faithfull, Jonathan Aning, Karen Poole, John Saxton, Bruce Griffin, Ralph Manders, Agnieszka Lemanska, Sophie Gasson, Stephen Langley, Joe Wainwright, John Marshall, John Heyworth, Kerri M. Winters-Stone
Journal: Journal of Clinical Oncology (2017)

142 Background: Evidence from large observational studies suggests that men with prostate cancer have a higher risk of cardiovascular events due to accelerated atherosclerosis linked to androgen deprivation therapy (ADT). Adults &gt; 70 years of age have poorer outcomes from cancer treatment in the UK. However, it is not yet clear what might be contributing to poorer outcomes among older men with prostate cancer. Thus the purpose of this study was to assess the health and fitness of a cohort of prostate cancer survivors, from 2 regions in the UK, and identify factors that may influence cardiovascular health. Methods: Baseline assessments from 83 men with prostate cancer with no evidence of distant disease particpated. Men undertook a Cardiopulmonary Exercise Test (CPET), sit to stand, step test, grip strength, hip to waist ratio, self-reported exercise questionnaire (Godin), and co-morbidity index. Men were 1-3 years post diagnosis. Age-group comparisons were made using analysis of covariance against cardiac risk profile (QRisk2). Results: Men who were older ( &gt; 75) were more likely to have poorer cardiopulmonary fitness, as measured by VO 2 Peak , and worse grip strength than age standardised values. Increased obesity across all groups (raised BMI) and higher B/P all contributed to a raised QRisk2 (mean: 36.9±6.1), which is higher than men of a similar age. Older men perceived themselves to be less physically active and were more likely to be on ADT. Conclusions: In our sample, men older than 75 had greater CVD risk, poorer physical function and lower strength. Improvements in diet and physical activity could improve physical function and reduce cardiovascular risk factors. Older men were more likely to be on ADT so to reduce long term co-morbidities other risk factors need to be addressed. More comprehensive functional health assessment at point of treatment could help clinicians optimise therapy to reduce long term comorbidities. [Table: see text]
Persistent pain following breast cancer surgery: A case-control study.
Authors: Sara N. Edmond, Rebecca A. Shelby, Francis J. Keefe, Mary Scott Soo, Celette Sugg Skinner, Sandra Stinnett, Gretchen M. Ahrendt, Jessica Manculich, Jules H. Sumkin, Margarita L. Zuley, Dana H. Bovbjerg
Journal: Journal of Clinical Oncology (2014)

9579 Background: Persistent pain following surgery for breast cancer is increasingly recognized as an important clinical problem. The mechanisms responsible remain to be determined, but psychological factors have been implicated in studies of breast cancer survivors. However, case control studies that provide direct comparisons to matched samples of healthy women are rare in this literature. Methods: We recruited breast cancer survivors (n=200) at the time of their first postsurgical mammogram (approx 1 yr) and compared their responses on validated self-report measures of pain, and select psychological factors (symptoms of anxiety and depression) to a matched sample (n=150) of healthy women receiving mammograms on the same day. The majority of women were white, married, and well educated. Only racial representation differed between the groups, so all analyses controlled for that factor. Results: Women with a history of cancer were more likely to meet criteria for persistent pain and reported greater levels of pain intensity, pain unpleasantness, pain interference, and pain frequency (all p<0.01). They also reported using medication for pain more frequently (p<0.01). There were no statistical differences in BMI, caffeine consumption, or smoking status. Symptoms of depression, but not anxiety were significantly (p=0.01) higher in women with histories of breast cancer. Persistent pain was related to the severity of the women’s depressive symptoms (p=0.002). When persistent pain and symptoms of depression were included in multivariate analyses of case-control differences, there was no longer a significant difference between the groups in persistent pain (p=0.25). Conclusions: Women who have undergone breast cancer surgery have higher levels of persistent and current pain, as well as higher levels of depressive symptoms compared to women without histories of breast cancer. Analyses suggest that higher levels of depressive symptoms may make a substantial contribution to the higher levels of persistent pain in these women. Future research should test this causal assumption with randomized trials of behavioral interventions known to reduce the contribution of psychological factors to pain (e.g., targeted pain coping skills training).
Touch prep (TP) cytology as a tool for determining pulmonary parenchymal resection margin status
Authors: K. M. Brown, J. Flaherty, V. Ciocca, H. Ehya, W. Scott, M. Goldberg
Journal: Journal of Clinical Oncology (2007)

18095 Background: Accurate determination of parenchymal resection margins is critical in excision of primary and metastatic lung cancers. Complete microscopic examination of the entire margin is difficult and may not give timely results. Staple-line excision may compromise the accuracy of histologic margin exam (HME). TP offers a novel method to obtain pulmonary parenchymal margin status intraoperatively. Methods: Patients undergoing wedge resection for a known malignant lung lesion were studied prospectively. At the time of resection, the specimen stapled margin underwent TP on 3 glass slides for cytological analysis. The presence or absence of malignant cells on TP was correlated to final HME. Local recurrence and overall survival by TP and HME status were compared using logrank test. Results: Thirty specimens from 29 patients were studied between December 2002 and April 2006. Fifteen specimens (50%) were right- sided; 9/29 patients (31%) were male. Median age was 66 years (range 28 - 81). Histologies included non-small cell lung cancer (NSCLC) in 22 (73%), and metastases from colorectal cancer (4/30, 13%), sarcoma (2/20, 7%), and breast (1/30, 3%). All TP negative specimens had negative HME. TP was positive in 10 of 30 (33%) specimens, 6 of which had negative HME. These included 4 NSCLC and metastases from sarcoma (1) and colon (1). Mean margin distance was 4 ± 1.7 mm for TP/HME negative specimens, 0.5 ± 0 mm for TP/HME positive specimens, and 5 ± 1.7 mm for TP positive/HME negative patients. There was no difference in time to local recurrence between patients with positive margins by TP vs HME (18.6 and 18.63 months), or in TP and HME negative patients (30.1 and 30.6 months). Conclusion: TP analysis of lung parenchymal margins is safe and feasible. A negative TP is highly predictive of negative HME. Factors contributing to false-positive TP remain unresolved. Multi-institutional prospective studies are indicated for further characterization of this promising tool. No significant financial relationships to disclose.
MECHANISMS OF ANTERIOR CRUCIATE LIGAMENT INJURIES IN HIGH SCHOOL ATHLETES
Authors: Saeko Takahashi, Yasuharu Nagano, Wataru Ito, Toru Okuwaki
Journal: British Journal of Sports Medicine (2017)

Background Anterior cruciate ligament (ACL) injury is one of the most serious sports injuries. However, few studies have surveyed the details of ACL injury mechanisms in high school athletes. Objective To investigate the mechanisms of ACL injuries among 1,000 ACL injuries in high school athletes by retrospectively reviewing the Japan Sports Council notification data. Design Epidemiological survey and retrospective study. Setting Young athletes (15–18 years old) belonging to sports clubs (soccer, basketball, judo, handball, volleyball) in high school (10th–12th grade). These clubs had a high incidence of ACL injuries in young Japanese athletes. Patients (or Participants) We collected data on 100 ACL injuries for each sport and sex for 1,000 athletes with injured ACL. Interventions (or Assessment of Risk Factors) We divided these data according to mechanisms such as contact (direct and indirect) and non-contact (play- and surface-related). Indirect contact was defined as an external force applied to the athlete but not directly to the injured knee. External force was involved in the injury process. Main Outcome Measurements We compared the mechanisms of injury between sexes and specific sports. Results Non-contact injuries were greater than contact injuries in ball games, except in male soccer. Most judo players experienced contact injuries. Over half of contact injuries were indirect in ball games. Surface problems caused 2.4% of ACL injuries. Conclusions We clarified the mechanisms of ACL injuries in young athletes. Detailed investigations of ACL injury mechanisms and prevention programs are needed.