tbuckley/cabot-search huggingface dataset:
Phase II study of carboplatin and amrubicin with a biweekly schedule in patients with advanced squamous cell lung cancer: Interim analysis.
Authors: Masao Ichiki, Tsukasa Yoshida, Tomomi Kumano, Tomoaki Hoshino
Journal: Journal of Clinical Oncology (2014)

e19141 Background: Recent advances in targeted therapy for NSCLC have augmented treatment choices for non-squamous NSCLC, but chemotherapy remains the therapeutic mainstay for squamous NSCLC. This phase II study was conducted to investigate the efficacy and safety of carboplatin in combination with amrubicin administered according to a biweekly schedule as first-line chemotherapy for advanced squamous NSCLC. Methods: Eligibility criteria included histologically or cytologically confirmed squamous NSCLC (stage IIIb or IV), no prior treatment, and measurable or evaluable disease. Amrubicin (35mg/m2) was administered intravenously on day 1 and 2, in combination with carboplatin (on day1) at an area under the concentration time curve (AUC) of 3, every 2 weeks. Results: There were 23 pts at this moment. All pts had squamous cell carcinoma. Median age was 68 (range 55-74), male/female= 22/1, PS0/1=9/14, EGFR-mutation status; mutated/wild type/unknown=0/15/8. The response rate was 21.7% [95% confidence interval (CI): 7.4-43.7%], with 5 partial responses. The median progression free survival was 4.0months. Serious toxicities (grade3/4): leukopenia (11/5), neutropenia (3/13), anemia (2/0), febrile neutropenia (3/0), hypercalcemia (1/0), urticarial (1/0), liver dysfunction (1/0). Conclusions: This regimen is effective for pts with squamous NSCLC. The update date including PFS and OS will be presented at the meeting. Clinical trial information: 000007102.
Low-dose computed tomography lung cancer screening in the Medicare program: Projected clinical, resource, and budget impact.
Authors: Joshua A. Roth, Sean D Sullivan, Arliene Ravelo, Joanna Sanderson, Scott David Ramsey
Journal: Journal of Clinical Oncology (2014)

6501 Background: Based on evidence from the National Lung Cancer Screening Trial (NLST), the U.S. Preventive Services Task Force (USPSTF) recently recommended annual low dose computed tomography (LDCT) lung cancer screening in patients age 55-80 with a 30 pack-year smoking history who currently smoke or quit in the past 15 years. Under the terms of the Affordable Care Act, Medicare will cover this screening procedure. We project the clinical, resource, and budget impact of this policy. Methods: We developed a model to forecast the 5-year incremental outcomes of implementing USPSTF LDCT screening recommendations vs. no screening. The model simulates a Medicare cohort consistent with 2013 enrollment and age distribution statistics. Lung cancer detection rates and stage at diagnosis were derived from the NLST. Included costs were LDCT screening/follow up, confirmatory bronchoscopy/biopsy, and stage specific lung cancer treatment (initial, continuing, terminal care). We estimated lung cancers detected, LDCT scans, and the total and per member per month (PMPM) budget impact in two scenarios: 1) complete implementation, with all eligible patients offered screening in all years, and 2) phased implementation, with an additional 20% of eligible patients offered screening each year. Results: In the complete and phased implementation scenarios, screening resulted in 141,000 and 101,000 more lung cancers detected (mostly Stage I), 37.5 million and 22.4 million more LDCT scans, and increased overall expenditure of $27.4 billion (PMPM $8.80) and $17.6 billion (PMPM $5.70), respectively. The most influential inputs were the proportion of eligible patients electing to undergo screening, initial treatment cost of early-stage lung cancer, and the proportion of stage IV diagnoses in the no screening strategy. Conclusions: Our analyses suggest that LDCT screening is will increase lung cancer diagnoses, result in a greater proportion of cases diagnosed at an early stage, and substantially increase Medicare expenditure. Forthcoming analyses will evaluate the resource demands of complete and phased screening implementation relative to existing LDCT facility and health professional supply.
TRK Fusion Cancers in Children: A Clinical Review and Recommendations for Screening
Authors: Catherine M Albert, Jessica L Davis, Noah Federman, Michela Casanova, Theodore W Laetsch
Journal: Journal of Clinical Oncology (2018)

Chromosomal translocations involving the NTRK1, NTRK2, and NTRK3 genes (TRK fusions), which encode the neurotrophin tyrosine kinase receptors TRKA, TRKB, and TRKC, can result in constitutive activation and aberrant expression of TRK kinase. Certain cancers almost universally harbor TRK fusions, including infantile fibrosarcoma, cellular congenital mesoblastic nephroma, secretory breast cancer, and mammary analog secretory carcinoma of the salivary gland. TRK fusions have also been identified at lower frequencies across a broad range of other pediatric cancers, including undifferentiated sarcomas, gliomas, papillary thyroid cancers, spitzoid neoplasms, inflammatory myofibroblastic tumors, and acute leukemias. Here we review the prevalence and diseases associated with TRK fusions and methods of detection of these fusions in light of the recent development of selective TRK inhibitors, such as larotrectinib, which demonstrated a 75% response rate across children and adults with TRK fusion cancers. We provide recommendations for screening pediatric tumors for the presence of TRK fusions, including the use of immunohistochemistry or fluorescence in situ hybridization for patients with tumors likely to harbor TRK fusions. Further, we recommend next-generation sequencing for tumors that have a relatively low prevalence of TRK fusions, both to identify patients who may benefit from TRK inhibition and to identify other targetable oncogenic drivers that exist in the same tumor types.
Age-related change in breast cancer stage at diagnosis relative to increased mammography detection over time: 1990-2012.
Authors: Judith April Malmgren, Mary K. Atwood, Henry G. Kaplan
Journal: Journal of Clinical Oncology (2014)

1589 Background: The United States does not have a national mammography screening program and relies on recommendations from the United States Preventive Services Task Force (USPSTF), the American Cancer Society (ACS) and other organizations to encourage screening. It has been hypothesized that mammography screening has not reduced advanced stage breast cancer (BC) from analysis of stage III and IV BC in a national database. Methods: Using our institutional breast cancer registry database, we reviewed change in stage distribution (0-IV) over time (OT) related to changes in detection method in the same time period. We restricted our analysis to age groups that have or have had screening recommendations during the time period (age 40 to 74) (N=8754). Pearson chi square tests were used to assess significance. Method of detection was categorized as patient (PtD) (N=3171), physician (PhysD) (n=460) or mammography (MamD) (n=5123) detected as recorded by the physician at time of diagnosis. Patients with unknown or other method of detection were excluded (n= 140). Stage for all years was converted to AJCC 7. Results: From 1990-2012 mammography detection of BC increased from 8% in 1990 to 22% in 2012 (+14%) (p<.001). MamD BC differed by age, presenting more often among older than younger women (p<.001) [age 40-49 = 45%, age 50-64 = 62%, age 65-74 = 68%]. For all groups combined stage shifted increasing 14% for stage 0 and decreasing 15% for stage I/II/III BC combined [stage I -4%, stage II -4%, stage III -7 %] with no change in stage IV (p<.001). By the three age groups, stage 0 BC change over time was +16% age 40-49, +14% age 50-64, and +11% age 65-74, stage I was 0% age 40-49, -6% age 50-64, -5% age 65-74; stage II was -10% age 40-49, 0% age 50-64/65-74; stage III -9% age 40-49, -7% age 50-64, -5% age 65-74; with no significant change in stage IV. Conclusions: A significant shift to lower stage disease was observed concurrent with increased mammography detection not restricted to stage III BC or including stage IV BC. Evaluation of association between screening recommendations and stage shift have to include change in all BC stages (0-IV) adjusted to a single AJCC grading standard and stratified to account for age related differences.
Senescent Mesenchymal Stem Cells Present at the Early Post Allogeneic Hematopoietic Stem Cell Transplantation Period Are Associated with an Increased Incidence of Acute Graft-Versus Host Disease and Increased Plasma Levels of Fas Ligand
Authors: Daniel Rivera, Lika Osugui, Sandra Muntion, Miguel Alcoceba, Concepcion Rodriguez, Rebeca Ortega, Natalia Espinosa, Ana Gomez de la Torre, Ana Rico, Miriam López-Parra, Alba Redondo, Eva Villarón, Félix López Cadenas, Silvia Preciado, Maria Díez-Campelo, Lucía López Corral, Marcos González, Dolores Caballero, Fermin Sanchez-Guijo
Journal: Blood (2018)
2nd cycle Remission Achievement with 7+3 Is Associated with Shorter Survival in Adults with Newly Diagnosed Acute Myeloid Leukemia: Analysis of Recent SWOG Trials
Authors: Megan Othus, Elihu H. Estey, Guillermo Garcia-Manero, Brent Wood, Derek Stirewalt, John Godwin, James K. Weick, Jeanne E. Anderson, Frederick R. Appelbaum, Harry P. Erba, Roland B. Walter
Journal: Blood (2018)
Real World Data on the Efficacy and Safety of Daratumumab in Relapsed/Refractory Multiple Myeloma: Data Collected from the Hungarian Hematology Centers
Authors: Gergely Varga, Tamas Masszi, Péter Farkas, Nikolett Wohner, Ágnes Bereczki, Zita Borbenyi, Árpád Szomor, Hussain Alizadeh, Erika Szaleczky, Krisztina Wolf, Tamás Schneider, Mark Plander, Tamás Szendrei, László Váróczy, Árpád Illés, Ottó Csacsovszky, Zoltán Csukly, Miklos Egyed, Péter Rajnics, Nora Adamkovich, Szabolcs Kosztolányi, Gábor Mikala
Journal: Blood (2018)
Hearts too small for body size after doxorubicin for childhood ALL: Grinch syndrome.
Authors: Steven E. Lipshultz, Rebecca E. Scully, Kristen E. Stevenson, Vivian I Franco, Donna S. Neuberg, Steven D Colan, Lewis B. Silverman, Javid J. Moslehi, Susan Cheng, Stephen E. Sallan
Journal: Journal of Clinical Oncology (2014)

10021 Background: Cross sectional studies show that cardiac abnormalities are common in survivors of doxorubicin (DOX)-treated childhood cancers. Longitudinal data, however, are rare. Methods: Serial echocardiograms (N = 900) from 115 DOX-treated childhood ALL (DFCI protocols 72-01 – 85-01) survivors were reported as indexed Z scores, indicating SDs above or below the normal mean for body size. Central single observer remeasurement minimized variability. Median individual and cumulative DOX doses were 30 mg/m2/dose and 352 mg/m2, respectively. Results: During 21 yrs median follow up (range 3-39), left ventricular (LV) fractional shortening remained decreased after DOX (mean LVFS >24 yrs: -2.42 [P<.05]). Both reduced LVFS and wall thickness related to cumulative dose (P<.05). LV dimension was initially above normal, but fell to become significantly decreased by last follow up (≤ 3yrs: +.53 [P<.05], > 12, ≤ 15yrs: +.08, > 24yrs: -.62 [P<.05], change over time: P<.001). The LV thickness-dimension ratio was significantly reduced until 21 yrs of follow up, following which it increased secondary to a fall in dimension and increasing wall thickness. However, the rise in wall thickness was accompanied by a progressive significant reduction in LV mass (≤ 3yrs: -.09 [NS], ≤ 24 yrs: -1.65 [P<.05]), indicating that increasing wall thickness was secondary to decreasing chamber size rather than myocardial hypertrophy. Conclusions: Progressive DOX cardiotoxicity transitions from an early subclinical dilated cardiomyopathy to a potentially restrictive cardiomyopathy detectable by 15+ years after exposure. The restrictive phase manifests as a relative decrease in LV dimension with a geometrically consequent rise in wall thickness leading to a normal thickness-dimension ratio at latest follow up. There is also a progressive fall in LV mass and cavity size that becomes inadequate for body size. Cardiomyopathy marked by shrinking myocardial and cavity size (Grinch Syndrome) appears to be a long term risk in this population. Monitoring for late clinically significant cardiotoxicity is essential. Symptomatic restrictive cardiomyopathy medical management failures are common, requiring use of early surgical therapeutic options.
Docetaxel, cisplatin, and fluorouracil combination in neoadjuvant setting in the treatment of locally advanced gastric adenocarcinoma: A phase II NEOTAX study.
Authors: Nuriye Özdemir, Huseyin Abali, Murat Vural, Suayib Yalcin, Berna Oksuzoglu, Burak Civelek, Dilek Oguz, Birol Bostanci, Bulent Yalcin, Nurullah Zengin
Journal: Journal of Clinical Oncology (2014)

e15038 Background: Neoadjuvant chemotherapy may increase curative resection rate in locally advanced gastric adenocarcinoma. This phase II trial aimed to evaluate the efficacy and safety of docetaxel, cisplatin and fluorouracil (DCF) combination in neoadjuvant setting in patients with locally advanced gastric adenocarcinoma. Methods: A total of 59 patients gastric adenocarcinoma were recruited in this multicenter, single arm, open label, local clinical phase II study conducted at five centers from Turkey between June 2006 and March 2012. Patients were required to have T3-4 or lymph node positive disease. After staging with computerized tomography (CT), endoscopic ultrasound and laparotomy or laparoscopy, the patients received 3 cycles of DCF with lenograstim. After the 3rd cycle, patients were evaluated for surgery. Gastrectomy and D2 dissection was required. Toxicity and response were evaluated in accordance with NCI CTC v3.0 and RECIST 1.0 Results: 48 of the (81.4%) patients were male and median age was 59 years (Min-max: 32-70). At baseline, 66.1% and 22.0% of patients were considered to be resectable and unresectable, respectively and resectability was not evaluated in 11.9%. T3 disease in 69.5% and 57.6%, T4 disease 15.3% and 37.3%; and positive lymph nodes 76.3% and 67.8% were present by CT and endoscopic ultrasound, respectively. In evaluable 47 patients, partial response in 34.0%, stable disease in 57.5% and progressive disease in 8.5% were observed. A total of 46 patients underwent surgery. In 38 (64.4%) out of 59 patients, R0 resectability was obtained. Median OS was 19.1 months (95% CI: 13·5-24·7 months) and median DFS was 11·6 months (95% CI: 5·9-17·4). Median OS was significantly better in patients younger than 60 ages (NA vs. 13.9 months, p=0.017) and in those with R0 resection compared to others (20.1 vs. 11.0 months, p=0.03) in treated patients. The most frequent grade 3-4 adverse events were neutropenia (52.5%; 11.9% febrile neutropenia) and diarrhea (10.5%). Conclusions: Classical DCF triplet with lenograstim support efficacious in the treatment of locally advanced gastric cancer with a significant R0 resection rate and manageable toxicity. Clinical trial information: NCT00343239.
Phase 2 study evaluating efficacy and safety of everolimus with letrozole in advanced (unresectable or metastatic) non-small cell lung cancer (NSCLC) after failure of platinum-based treatment: A preliminary analysis of toxicity.
Authors: Sina Vatandoust, Nimit Singhal, Michael Paul Brown
Journal: Journal of Clinical Oncology (2014)

e19089 Background: Lung cancer is a common malignancy with NSCLC comprising the majority of the cases. Previous studies have demonstrated a role for both the estrogen pathway and mammalian target of Rapamycin (mTOR) in NSCLC. Methods: We initiated a single arm phase 2 study of Simon 2 stage design to assess the safety and efficacy of treatment with the combination of aromatase inhibitor, letrozole (2.5 mg/day) and mTOR inhibitor, everolimus (10 mg/day) in the treatment of patients (pts) with advanced (unresectable stage III or stage IV) NSCLC who had failed at least one line of platinum-based chemotherapy. The institutional human research ethics committee approved the study. All pts signed informed, written consent. Results: After enrolling 5 pts, the study was closed after several serious adverse events (SAEs) were observed. Four of the 5 pts had a heavy smoking history. Two of the 5 treated pts developed grade V pulmonary toxicity after 16 and 62 days of exposure to the study combination. Limited autopsy studies revealed multiple asynchronous thromboemboli, areas of pulmonary infarction, and secondary alveolar hemorrhage in the first patient, and pulmonary veno-occlusive disease, arterial hypertension, patchy alveolar hemorrhage, and occasional small thromboemboli in the second patient. In both cases, there was no evidence of interstitial pneumonitis, inflammatory reactions, vasculitis or infection. A third patient developed reversible grade IV pulmonary toxicity after 30 days of study drug exposure. The remaining 2 pts had progression of disease after 1 and 3 months of treatment. Conclusions: There is a probable causal relationship between the study combination and the reported SAEs; although in the two grade V cases there was no evidence of non-infectious interstitial pneumonitis which has been reported in previous studies using everolimus. In the absence of additional clinical data in lung cancer pts, we recommend that extreme caution be exercised in the use of combined letrozole and everolimus regimens in this group of pts.
Contemporary multi-modal management of colorectal cancer: Evolving patterns of care in an Irish cohort.
Authors: Megan Greally, Emily Harrold, Helen M Fenlon, Donna Eaton, Jim McCarthy, Karen C Redmond, John B Conneely, Gerry P McEntee, Ann E Brannigan, Conor J Shields, Jurgen Mulsow, David James Gallagher, Desmond N. Carney, Michaela Jane Higgins, Catherine Margaret Kelly, John McCaffrey
Journal: Journal of Clinical Oncology (2018)

827 Background: The last 15 years have seen significant improvements in the outcomes of patients (pts) with CRC. More effective systemic therapy (Rx) and wider use of surgery (Sx) in stage IV disease (Dx) are key drivers of this. We evaluated the impact of intense surveillance in concert with greater use of metastasectomy and improved systemic Rx on CRC outcomes. Methods: This is a retrospective review of the clinical, radiologic and histological records for consecutive pts with CRC who were referred to the multi-disciplinary CRC team from 2003-2016. Pts with stage I/II Dx were included when referred for adjuvant Rx for high-risk features. We recorded pt characteristics, Rx received and outcomes. Survival was assessed using Kaplan-Meier analysis. Results: We identified 600 pts. Median age was 65 (22-97 years). 71.2% (n=427) of pts had left sided CRC and 25.7% (n=154) had right sided Dx. 211 pts (35.2%) had de novo metastatic Dx. 163 of 389 pts (41.9%) with stage II/III disease relapsed. Median Dx-free interval was 16 months. Of 163 relapses, 121 (74%) were detected by radiologic surveillance and 14 (9%) by rise in CEA. Symptomatic relapse occurred in 20 pts (12%). Median overall survival (OS) was significantly improved in pts with relapse detected by CT, PET/CT or CEA rise (54, 53 and 54 months respectively) vs pts with symptomatic relapse (4 months, p&lt;0.001). Metastasectomy rates were higher in pts with image-detected relapse ( p=0.017). Median OS for pts with stage IV CRC who received any Rx was 27 months. Pts with right sided Dx had shorter median OS vs pts with left sided Dx (24 months vs 40 months, p=0.002). 195 pts (52.8%) underwent metastasectomy; median OS was 71 months vs 16 months in those who did not undergo Sx. 84 pts (14%) with stage IV CRC are currently Dx-free after Sx. Median OS was improved with increasing lines of Rx. Survival in pts receiving best supportive care was 5 months vs 17, 25, 34, 38 and 42 months for pts receiving 2, 3, 4 and 5 lines of Rx respectively ( p&lt;0.001). Conclusions: CRC outcomes are improving with effective multi-disciplinary care, close surveillance, sequencing of systemic Rx and judicious use of salvage Sx following relapse. Our findings support long-term benefit for surgical metatastectomy in stage IV CRC.
Retail Clinics Provide Important Antibiotic Stewardship—Reply
Authors: Rita F. Redberg, Michael Incze, Mitchell H. Katz
Journal: JAMA Internal Medicine (2019)

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 Internal Medicine 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 Internal Medicine journal
Patterns of Care and Outcomes in Mantle Cell Lymphoma in the Modern Immunochemotherapy Era
Authors: Alessia Castellino, Melissa C. Larson, Matthew J. Maurer, Susan L. Slager, Cristine Allmer, Jonathon B. Cohen, Andrew L. Feldman, Sergei Syrbu, Brian K. Link, Umar Farooq, David J Inwards, Thomas M. Habermann, Thomas E. Witzig, James R. Cerhan, Grzegorz S. Nowakowski
Journal: Blood (2018)