tbuckley/cabot-search huggingface dataset:
Evaluation of two-dimensional response to predict overall survival in patients with metastatic colorectal cancer treated with the first-line bevacizumab-based chemotherapy.
Authors: Goro Nakayama, Nao Takano, Chie Tanaka, Daisuke Kobayashi, Masahiko Koike, Michitaka Fujiwara, Yasuhiro Kodera
Journal: Journal of Clinical Oncology (2015)

539 Background: The evaluation of the quantitative analyses for tumor response, such as early tumor shrinkage (EST) or depth of response (DpR), could be useful to serve the surrogate for survival benefits in chemotherapies for patients with mCRC. However, these analyses might be insufficient to explain an individual-level surrogacy of long-term survival outcomes in anti-angiogenic agents, because patient tumor dynamics might be highly diverse. In this study, we defined ‘2-DR’ by both tumor shrinkage and time factors as a new efficacy outcome measure to explain the impact of chemotherapy with BEV on long-term survival outcome. Methods: All patients included in this analysis had participated in phase II clinical trial (CCOG-0801, UMIN000006818). Forty-seven patients with previously untreated mCRC were treated with mFOLFOX6 plus BEV, followed by FOLFIRI plus BEV. The median PFS and OS were 7.3 and 30.8 months, respectively. ETS and DpR are defined as the ratio of tumor shrinkage observed at 8 week after initiation of treatment and the nadir to baseline. 2-DR, that is the area enclosed by the coordinate points including ETS, DpR and 20% increase over nadir at progression disease, is calculated as follows: 2-DR (week×%) = (0.5 TR+1.1 TP-4)×DpR+0.5 TR×ETS–10 TP, where TR is the time duration from the date of initiation of therapy to maximum tumor shrinkage and TP is the time duration from the date of observation of maximum tumor shrinkage to 20% increase over nadir. Results: Median ETS, DpR and 2-DR were 23% (range, -33 to 72), 31% (range, -33 to 100) and 10.3 (week×%) (range, -4.4 to 92.6), respectively. The Spearman rank correlation coefficients were 0.27 between ETS and OS, 0.28 between DpR and OS, and 0.46 between 2-DR and OS, respectively. There was strong relationship between 2-DR and OS (p&lt;0.01). Median OS in the higher and lower 2-DR groups was 21.5 months (95% CI, 20.4 to 29.8) and 32.9 months (95% CI, 24.5 to 41.3), respectively (p&lt;0.01). A Cox regression model revealed that 2-DR was the only independent prognostic factors for OS (HR 0.26, p&lt;0.01). Conclusions: 2-DR could be a new surrogate marker of OS in the BEV-based first-line chemotherapy for mCRC.
Dose intensity: a critique of a critical review.
Authors: W M Hryniuk
Journal: Journal of Clinical Oncology (1989)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1989.7.5.681 Journal of Clinical Oncology - published online before print September 22, 2016 PMID: 2651583 Dose intensity: a critique of a critical review. W M HryniukxW M HryniukSearch for articles by this author https://doi.org/10.1200/JCO.1989.7.5.681 First Page PDF © 1989 by American Society of Clinical Oncology
Consolidation hemibody radiotherapy following induction combination chemotherapy in high-tumor-burden multiple myeloma.
Authors: M R MacKenzie, H Wold, C George, D Gandara, G Ray, S Schiff, J Shields, R Artim, H Davidson, F Meyers
Journal: Journal of Clinical Oncology (1992)

PURPOSE Curative therapy for multiple myeloma continues to be an elusive goal. This report discusses the Northern California Oncology Group (NCOG) phase I and II trial in high-tumor-burden disease that used a strategy that consisted of induction chemotherapy (vincristine, melphalan, cyclophosphamide, and prednisone [VMCP]) for eight cycles followed by sequential hemibody radiation therapy (RT) and subsequent chemotherapy for an additional eight cycles. PATIENTS AND METHODS Seventy-two previously untreated stage III myeloma patients were entered onto the study. Sixty-nine received induction chemotherapy, 40 received induction chemotherapy and hemibody RT, and 23 received induction chemotherapy, hemibody RT, and consolidative chemotherapy. RESULTS Twenty-two complete responses (CRs) were obtained by induction chemotherapy, with four additional CRs after RT and consolidative chemotherapy. Nineteen patients developed grade 4 hematologic toxicity primarily after upper hemibody RT. Eight of these developed long-standing neutropenia or thrombocytopenia. Median survival of the group was 134 weeks, which was not significantly different from other approaches. CONCLUSIONS Hemibody RT can be combined with chemotherapy as induction therapy and can be safely administered in a community setting. However, as administered here no survival advantage was demonstrated.
Survival analysis according to disease subtype in AVAGAST: First-line capecitabine and cisplatin plus bevacizumab (bev) or placebo in patients (pts) with advanced gastric cancer.
Authors: Manish A. Shah, Eric Van Cutsem, Yoon-Koo Kang, Shaker R. Dakhil, Taroh Satoh, Keisho Chin, Yung-Jue Bang, Lilian Bu, Grozdana Bilic, Atsushi Ohtsu
Journal: Journal of Clinical Oncology (2012)

5 Background: Gastric cancer (GC) is a heterogeneous disease that may be divided into distinct subtypes with different epidemiology, risk factors, and molecular expression profiles: proximal non-diffuse GC (type 1), diffuse GC (type 2), and distal non-diffuse GC (type 3). In clinical practice, GC subtypes are treated as a single disease. Regional efficacy differences were seen in AVAGAST: pts in Americas and Europe showed more evidence of benefit than Asia-Pacific pts. We analyzed outcomes in the phase III AVAGAST study according to GC subtype and region in order to test if GC subtype was prognostic of outcome and predictive of bev benefit. Methods: Pts were randomized and treated as previously described. The effect of treatment on overall survival (OS), measured by hazard ratio, was examined in an unplanned exploratory analysis using Cox proportional hazards models. Median OS was estimated using the Kaplan-Meier method. Results: 733 of 774 AVAGAST pts were included. Type 2 GC (52.1%) was more common than type 1 (9.5%) or type 3 (38.3%). Irrespective of treatment, pts with type 2 GC had worse outcome than type 3 GC (median OS 10.3 vs 11.7 mo; HR=0.82; 95% CI 0.68–1.00); non-Asian pts had the most dismal prognosis (8.0 vs 11.1 mo; HR=0.68; 95% CI 0.53–0.89). The table below describes the bev effect according to subtype. Non-Asian pts with GC type 2 and 3 appear to benefit from bev. Conclusions: In all regions, pts with type 3 GC had a better prognosis than type 2 GC. Bev therapy appeared to improve outcomes in non-Asian pts with type 2 and 3 GC. These data suggest that GC subtypes may be important predictors of pt outcome and warrant further prospective evaluation. [Table: see text]
The clinical and biological correlates of coagulopathy in children with acute leukemia.
Authors: R C Ribeiro, C H Pui
Journal: Journal of Clinical Oncology (1986)

We determined the clinical and biological correlates of coagulopathy in a large series of patients with untreated childhood acute leukemia. Twenty-five of 805 children with acute lymphoblastic leukemia (ALL) (3.1%) and 27 of 195 with acute myeloid leukemia (AML) (13.8%) met any two of three requirements for a coagulation disorder: fibrinogen level less than 150 mg/dL; fibrin degradation products greater than 10 micrograms/mL; and prolongation of prothrombin time (PT) greater than 12 seconds, activated partial thromboplastin time (PTT) greater than 45 seconds, or thrombin time (TT) greater than 18 seconds. Patients with ALL complicated by abnormal coagulation were more likely to be boys and to have a T-cell immunophenotype, a high leukocyte count, a mediastinal mass, leukemic involvement of the CNS, hepatosplenomegaly, and L2 blast cell morphology. These features were highly interrelated, with only T-cell markers and CNS involvement achieving independent significance in a multivariate logistic regression model. Hepatomegaly, blast cell morphological subtype (French-American-British [FAB] M3, M4, and M5) and age less than 2 years were each associated with coagulopathy in patients with AML, although age failed to retain importance after logistic regression analysis. The presence of coagulopathy at diagnosis of ALL did not influence the rate of remission induction (P = .55). By contrast, only 14 of 27 children with coagulopathy at diagnosis of AML achieved a complete remission (CR), compared with 129 of 168 other patients who lacked this complication (P = .003). After multivariate analysis, coagulopathy remained independently associated with failure to attain remission in AML (P = .02). Fatal hemorrhagic complications arising in the CNS or lungs accounted for nine of the 13 induction failures in this group. The presence or absence of coagulopathy had no discernible influence on treatment outcome among patients with either ALL or AML who attained a CR. Laboratory evidence of a coagulation defect may be useful in identifying patients with AML who have a greater risk of induction failure and, hence, require close surveillance and intensive replacement therapy to prevent fatal hemorrhagic complications.
Targeting human melanoma neoantigens by T cell receptor gene therapy
Authors: Matthias Leisegang, Thomas Kammertoens, Wolfgang Uckert, Thomas Blankenstein
Journal: Journal of Clinical Investigation (2016)

In successful cancer immunotherapy, T cell responses appear to be directed toward neoantigens created by somatic mutations; however, direct evidence that neoantigen-specific T cells cause regression of established cancer is lacking. Here, we generated T cells expressing a mutation-specific transgenic T cell receptor (TCR) to target different immunogenic mutations in cyclin-dependent kinase 4 (CDK4) that naturally occur in human melanoma. Two mutant CDK4 isoforms (R24C, R24L) similarly stimulated T cell responses in vitro and were analyzed as therapeutic targets for TCR gene therapy. In a syngeneic HLA-A2-transgenic mouse model of large established tumors, we found that both mutations differed dramatically as targets for TCR-modified T cells in vivo. While T cells expanded efficiently and produced IFN-γ in response to R24L, R24C failed to induce an effective antitumor response. Such differences in neoantigen quality might explain why cancer immunotherapy induces tumor regression in some individuals, while others do not respond, despite similar mutational load. We confirmed the validity of the in vivo model by showing that the melan-A-specific (MART-1-specific) TCR DMF5 induces rejection of tumors expressing analog, but not native, MART-1 epitopes. The described model allows identification of those neoantigens in human cancer that serve as suitable T cell targets and may help to predict clinical efficacy.
Research to Publication e-learning
Authors: Trish Groves
Journal: BMJ (2016)

What should we think about researchers who use the wrong techniques (either wilfully or in ignorance), use the right techniques wrongly, misinterpret their results, report their results selectively, cite the literature selectively, and draw unjustified conclusions?We should be appalled.Yet numerous studies of the medical literature, in both general and specialist journals, have shown that all of the above phenomena are common...This is surely a scandal."This extract from an editorial in The BMJ by statistics professor Doug Altman is more than 20 years old. 1 Sadly, things haven't improved all that much, and we know that health research efforts and resources continue to be wasted in high and lower income countries alike. 2 There's waste in publishing too.Editors reject papers because research questions and methods are inadequate, and papers get retracted because they are unusable or untrustworthy.
Paclitaxel/gemcitabine versus paclitaxel/vinorelbine in advanced non-small cell lung cancer (NSCLC): A phase III randomized study
Authors: P. A. Kosmidis, E. Timotheadou, A. Koutras, G. Pentheroudakis, C. Christodoulou, A. M. Dimopoulos, D. Bafaloukos, E. Samantas, D. Pectasides, K. Syrigos
Journal: Journal of Clinical Oncology (2009)

8038 Background: Paclitaxel and vinorelbine (PV) have shown synergism of cytotoxic effect in vitro (Cancer Invert, 2000, 18(8): 804-5). This combination was compared prospectively to the paclitaxel/gemcitabine (PG) regimen in non-operable NSCLC. Methods: 415 stage IIIb wet and IV chemotherapy-naïve for metastatic disease patients with PS 0–1 were randomized to paclitaxel 200mg/m 2 on day 1 plus either gemcitabine 1gm/m 2 (Group A) or vinorelbine 25mg/m 2 (Group B) on days 1 and 8 every 3 wks as first line chemotherapy. Results: A total of 398 out of 415 patients were eligible for analysis on the intent to treat basis (group A: 196, group B: 202). All patient and disease characteristics were well balanced. Overall response rate (RR) was 27% for group A and 24% for group B (P=0.57). Median progression free survival (PFS) was 5.2 months (m) (95% CI, 4.4 - 5.9) and 4.7m (95% CI, 4.1 - 5.3) for groups A and B respectively (P=0.51). Median survival (OS) was 11.5m (95% CI, 9.5 - 12.6) and 9.3m (95% CI, 7.7 - 10.9) for groups A and B respectively (P=0.25). Grade 3/4 neutropenia was worse (P&lt;0.001) in group B. Febrile neutropenia and severe infections were more prominent (P&lt;0.001, P=0.005 respectively) in group B. Conclusions: Although RR, PFS, OS are similar in both groups, toxicity is significantly worse in group B and therefore further investigation of PV is of no value. No significant financial relationships to disclose.
Phase I / II study of ASP8273 in patients with non-small-cell lung cancer (NSCLC) harboring EGFR activating mutations
Authors: Toshio Shimizu, Hiroshi Nokihara, Haruyasu Murakami, Takashi Seto, Makoto Nishio, Koji Takeda, Akira Inoue, Katsuyuki Kiura, Koichi Azuma, Anne Keating, Andrew Krivoshik, Koichi Uegaki, Kentaro Takeda, Kanji Komatsu, Satoshi Morita, Masahiro Fukuoka, Kazuhiko Nakagawa
Journal: Annals of Oncology (2015)
Abstract 287: What Is the Optimal Chest Compression Depth During Resuscitation from Out-of-Hospital Cardiac Arrest in Adult Patients?
Authors: Ian G Stiell, Siobhan Brown, Clifton W Calloway, Tom P Aufderheide, Sheldon Cheskes, Christian Vaillancourt, David Hostler, Daniel P Davis, Ahamed Idris, James Christenson, Laurie Morrison, John Stouffer, Cliff Free, Graham Nichol
Journal: Circulation (2012)

Introduction: The 2010 AHA/ILCOR recommendations suggested an increase in CPR compression depth for adults, with a target &gt;50 mm and no upper limit. This target is based upon limited evidence and, hence, we sought to determine the optimal compression depth range for adult patients. Methods: We studied emergency medical services treated OOHCA patients from the Resuscitation Outcomes Consortium ROC PRIMED clinical trial and Epistry - Cardiac Arrest database for whom electronic CPR compression depth data were available, from June 2007 to December 2010. We calculated anterior chest wall depression in millimeters for each minute of CPR. We controlled for 10 covariates including compression rate and calculated adjusted odds ratios for survival to hospital discharge, 24-hour survival, and any return of circulation (ROSC). Smoothing splines were used to explore the relationship between average compression depth and outcome for all patients as well as men and women separately. Results: We included 9,142 adult patients from 9 U.S. and Canadian cities with these characteristics: mean age 67.5 years; male 64 %; bystander witnessed 44%; bystander CPR 42%; initial rhythms - VF/VT 24%, PEA 20%, asystole 49%, other non-shockable 6%; outcomes - ROSC 31.3%, 1-day survival 22.8%, survival to hospital discharge 7.3%. For all patients, mean compression rate was 108 per minute; mean compression fraction 0.68; mean compression depth 41.9 mm with ranges: &lt;38 mm 37%, 38-51 mm 45%, &gt;51 mm 18%. Adjusted odds ratios for survival to discharge, with depth &gt;51mm as reference, were &lt;38 mm - 0.69 (95% CI 0.53, 0.90) and 39-51 mm - 1.03 (0.81, 1.30). Results were similar for the intermediate outcomes of ROSC and 1-day survival. Covariate-adjusted spline curves revealed that the maximum survival was associated with a depth of 45.8 mm followed by a decline in survival by 50 mm (optimal interval 44-49 mm). We also found no differences in the spline curves between males and females. Conclusions: This study found that more than one-third of patients received very low compression depth. The optimal CPR compression depth for survival appears to be 46 mm (44-49) for both males and female adults but falls off after 50 mm. These findings conflict with the 2010 international guideline recommendations.
The Integration of Early Palliative Care With Oncology Care: The Time Has Come for a New Tradition
Authors: Jessica R Bauman, Jennifer S Temel
Journal: Journal of the National Comprehensive Cancer Network (2014)

The past decade has brought forth innovative research that questions the traditional oncology care model for patients with advanced cancer. Through integrating palliative care (PC) early into the disease course for patients with a poor-prognosis cancer, 3 seminal studies showed improvements in outcomes, ranging from quality of life, mood, patient satisfaction, prognostic understanding, health service use, and possibly survival. The results of these paradigm-changing studies generate questions about the mechanisms through which early PC improves patient outcomes and about how best to disseminate early PC models. This article reviews the 3 studies, examines challenges to conducting PC research, and considers future directions in the field.
Early Changes Induced in Rat Liver by Methylazoxymethanol Acetate: Mitotic Abnormalities and Polyploidy2
Authors: Morris S. Zedeck, Stephen S. Sternberg, Xenophon Yataganas, Jane McGowan
Journal: JNCI Journal of the National Cancer Institute (1974)

Within 24–48 hours after a single dose of methylazoxymethanol (MAM) acetate, the livers of rats showed extensive hemorrhage and necrosis; however, by the 4th day the liver showed little pathology other than irregularities in the size and shape of the hepatocytes. Significantly increased thymidine incorporation into hepatic DNA at this time, relative to controls, suggested that the replacement of necrotic cells was not yet complete. Seven days after treatment, when DNA synthesis had returned to control levels, the number of polyploid cells increased significantly. In addition, ≈ 11% of the hepatocyte anaphase and telophase mitotic figures contained chromosomal bridges and acentric fragments. The mitotic abnormalities and the increase in polyploid cells were evident as late as 1 month after treatment.
Esophageal cancer treatment in our institute from 1999 to 2005
Authors: Y. Miyazaki, H. Imamura, T. Kishimoto, K. Yamamoto, H. Furukawa
Journal: Journal of Clinical Oncology (2007)

15183 Background: 5 year survival rate of esophageal cancer in Japan reported to the Japanese Society for Esophageal Diseases from 1988 to 1994 (9,143 cases) was improved to 35.5% comparing to the rate of the beginning of 1980 which remained around 20%. This result was given by the increase of early cancer cases attributed to the progress of the ability of diagnosis, the improvement of the postoperative management, and the 3 field lymph node dissection introduced from the middle of 1980. Biological malignant potential and the modality of treatment for esophageal cancer in Japan differs from those in the United States. Methods: We studied clinicopathological characteristic and treatment results of 63 esophageal cancer patients in our institute from 1999 to 2005. Results: 63 patients consisted of 47 males and 16 females with mean age of 63.4±11.4. Out of 47 patients who underwent surgical treatment, 6 and 4 patients underwent neoadjuvant chemoradiotherapy and chemotherapy, respectively. 15 patients without surgical treatment consisted of 12 patients, including one patient after endoscopical mucosal resection, undergoing chemoradiotherapy, 2 patients undergoing chemotherapy, and 3 patients undergoing radiotherapy, respectively. Most common histological type was squamous cell carcinoma (55 patients), followed by adenocarcinoma (3 patients), small cell carcinoma(3 patients), others(2 patients), and unknown(1 patients). There was 1 surgical treatment-related death. The major complications were SSI (18 patients), anastomotic leakage(7 patients) and recurrent nerve palsy (5 patients). The 2-year survival rate of patients with surgical resection was 68.1%, while the rate of the unresectable patients was 38.9%.Since 2002, we have adopted posterior mediastinal route as a prime choice, rather than retrosternal route. The median amount of blood loss, rate of complications and duration of post operative hospital stay of each routes are 650/415(ml), 65/45(%), 35/22(day), respectively. These results suggested that posterior mediastinal route showed superiority comparing to restrosternal route. Conclusions: Backed by these outcomes, we will aim to establish a logical strategy for esophageal cancer therapy which could accompany fewer complications, respect quality of life and prolong survival time. No significant financial relationships to disclose.
Large bowel mucosal metastases from breast cancer.
Authors: H K van Halteren, H Peters, P G Gerlag
Journal: Journal of Clinical Oncology (1998)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1998.16.11.3711 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 9817292 Large bowel mucosal metastases from breast cancer. H K van HalterenxH K van HalterenSearch for articles by this author , H PetersxH PetersSearch for articles by this author , P G GerlagxP G GerlagSearch for articles by this author Show More St. Joseph Hospital, Veldhoven, The Netherlands. https://doi.org/10.1200/JCO.1998.16.11.3711 First Page PDF © 1998 by American Society of Clinical Oncology
Reduced Lower-Limb Muscle Strength and Volume in Patients With Type 2 Diabetes in Relation to Neuropathy, Intramuscular Fat, and Vitamin D Levels
Authors: Monirah M. Almurdhi, Neil D. Reeves, Frank L. Bowling, Andrew J.M. Boulton, Maria Jeziorska, Rayaz A. Malik
Journal: Diabetes Care (2016)

Muscle weakness and atrophy of the lower limbs may develop in patients with diabetes, increasing their risk of falls. The underlying basis of these abnormalities has not been fully explained. The aim of this study was to objectively quantify muscle strength and size in patients with type 2 diabetes mellitus (T2DM) in relation to the severity of neuropathy, intramuscular noncontractile tissue (IMNCT), and vitamin D deficiency.