tbuckley/cabot-search huggingface dataset:
Questionable value of attribution when interpreting adverse event data: A joint evaluation by North Central Cancer Treatment Group (NCCTG) and American College of Surgeons Oncology Group (ACOSOG)
Authors: S. L. Hillman, D. J. Sargent, B. M. Bot, R. P. DeMatteo, E. A. Perez, K. V. Ballman, S. J. Mandrekar
Journal: Journal of Clinical Oncology (2007)

6511 Background: In March 1998, the Common Toxicity Criteria (CTC) version 2.0 introduced the collection of attribution of adverse events (AE) to study drug. Collection of attribution adds time and cost to the clinical trial process, and reporting in the literature has varied. At ASCO 2006 results were presented from NCCTG trial 97–24–51 that showed ∼ 50% of events on the placebo arm were reported as attributed to study drug and 25% of the time the same event was not consistently attributed. We sought to validate these results in a second placebo controlled trial. Methods: Patients on the placebo arm of the phase III ACOSOG trial Z9001 (imatinib mesylate vs. placebo after resection of primary gastrointestinal stromal tumors) were evaluated since the reported AEs could not be due to study drug. Attribution was collected per CTCv3.0 as not related, unlikely, possibly, probably, or definitely related, and categorized as “unrelated” (not related or unlikely) and “related” (possible, probable, or definite). Patterns were evaluated using generalized estimating equations adjusting for multiple events per patient. Results: 202 patients and 2871 AEs were included. 52% of AEs were reported as “related”. Known imatinib AEs were more likely to be reported as “related”. The reported rate of AE relatedness varied by AE type. No patterns were observed by gender, age, PS, severity or visit of AE. When the same event was reported on the same patient on multiple visits, the attribution category changed at least once 33% of the time with 19% changing from “related” to “unrelated” or vice versa. Conclusion: 52% of events on the placebo arm of Z9001 were reported as attributed to study drug and 19% of the time the same event was not consistently attributed. These data provide further evidence that attribution is difficult to determine, unreliable, and of questionable value in interpreting randomized clinical trials. No significant financial relationships to disclose. [Table: see text]
Long-term complications of neuroblastoma: A report from the Childhood Cancer Survivor Study
Authors: C. Laverdiere, Q. Liu, Y. Yasui, P. C. Nathan, J. Gurney, M. Stovall, L. Diller, N. K. Cheung, S. Wolden, L. L. Robison, C. A. Sklar
Journal: Journal of Clinical Oncology (2007)

9544 Background: Neuroblastoma (NB) survivors can develop many complications from their treatment. We evaluated long-term morbidity and mortality in a large cohort of NB survivors. Procedures: Late effects data from 5-year NB survivors diagnosed between 1970–1986 enrolled in the Childhood Cancer Survivor Study (CCSS) were collected from self-administered questionnaires. 832 survivors and 3,899 siblings were included. Treatment data were abstracted from the medical records of all survivors. Late mortality, second malignant neoplasm (SMN), and chronic health conditions were analyzed in relation to treatment factors. Results: 42 survivors (6%) died more than 5 years after their diagnosis (standardized mortality ratio [SMR]:4.8; 95% CI 3.5–6.5). Causes of death included: disease recurrence (n=23), SMN (n=6) (SMR: 8.5; 95% CI 3.1–18.4), cardiac (n=1) (SMR 2.9; 95% CI 0.04–16.0), pulmonary (n=1) (SMR 4.8; 95% CI 0.1–26.5), external causes (n=4), other and unknown (n=11). 33 developed a SMN (standardized incidence ratio [SIR] 8.6; 95% CI 5.9–12.1): thyroid (n=7), renal (n=6), soft tissue sarcomas (n=3), acute myeloid leukemia (n=2), breast cancer (n=2) and other (n=13). Exposure to radiation therapy (RT) (p=0.003) and to VP-16 (p=0.04) were significant risk factors for SMN. 38% of the survivors reported at least one chronic health condition. Compared to siblings, they were more likely to report any chronic condition (risk ratio [RR] 14.7; 95% CI, 12.4–17.6). The most common prevalent conditions included: musculoskeletal (RR 49.8; 95% CI, 27.9–88.8), endocrine (RR 36.2; 95%CI 24.1–54.5), sensory (RR 21.5; 95%CI, 14.6–31.7) and neurological (RR 13.1; 95% CI 10.8–16). A multivariable Poisson regression analysis revealed the following associations: laminectomy (RR 8.6; 95% CI 3.5- 21) and chest RT (RR 2.8; 95% CI 1.3–6.5) as risk factors for scoliosis; age &lt; 1 year at diagnosis (RR 1.9; 95% CI 1.4–2.6) and laminectomy (RR 3.5; 95% CI 2.4–5.3) for neurological complications; for hearing loss, increasing cumulative dose of cisplatin (for ≥ 600 mg/m 2 RR 52.8; 95% CI 10.2–272.5); and RT to the neck (RR 6.6; 95% CI 2.4–18) for hypothyroidism. Conclusions: NB survivors are at risk of developing chronic conditions. Long-term surveillance is required for early detection of these complications. No significant financial relationships to disclose.
Randomized comparison of every-two-week v. every-three-week chemotherapy in Ewing sarcoma family tumors (ESFT)
Authors: R. B. Womer, D. C. West, M. D. Krailo, P. S. Dickman, B. Pawel
Journal: Journal of Clinical Oncology (2008)

10504 Background: Chemotherapy with alternating cycles of vincristine-doxorubicin-cyclophosphamide and ifosfamide-etoposide, and primary tumor treatment with surgery and/or radiation therapy, is the usual approach to localized ESFT in North America. We conducted a trial asking whether chemotherapy intensification through interval compression could improve outcome. Methods: This was a prospective randomized-controlled trial for patients less than 50 y old with extra-dural ESFT, without distant metastases or prior chemotherapy or radiation therapy; and with adequate renal, cardiac, and hepatic function. Patients were treated with vincristine (2 mg/sq.m, max. 2 mg), doxorubicin (75 mg/sq.m) and cyclophosphamide (1.2 g/sq.m) alternating with ifosfamide (9 g/sq.m) and etoposide (100 mg/sq.m/), for 14 cycles, with filgrastim (5 mg/kg/day, maximum 300 mg) between cycles. Patients assigned to Regimen A were scheduled to begin chemotherapy cycles every 21 days, and patients assigned to Regimen B were scheduled to begin cycles every 14 days, or when ANC ≥ 750 and platelets ≥ 75. Primary tumor treatment (surgery, radiation, or both) was scheduled to begin week 13 (after 4 cycles in Regimen A and 6 cycles in Regimen B). The primary endpoint was event-free survival using a two-sided log-rank test with size 0.05 and power 0.8 to detect a 13% change in EFS from 60%, with 264 patients in each arm. Results: 587 patients were enrolled and randomized, and 568 were eligible, 284 in each regimen. For all courses, the median cycle interval for Regimen A was 21 days, mean 23.3 days; in Regimen B, the median interval was 15 days, mean 18.5 days. Event-free survival at a median of 3 years was 65% in Regimen A and 76% in Regimen B, p=0.028. The occurence of specific toxicities and the number of hospital days were similar for the two regimens. Conclusions: Every-2-week chemotherapy is more effective than every-three-week chemotherapy for localized ESFT, with no increase in toxicity. No significant financial relationships to disclose.
Leukocyte Migration in Ovarian Carcinoma: Comparison of Inhibitory Activity of Tumor Extracts 2
Authors: Isidore Faiferman, Norbert Gleicher, Carmel J. Cohen, David Koffler
Journal: JNCI Journal of the National Cancer Institute (1977)

Inhibition of migration of leukocytes from patients with serous cystadenocarcinoma of the ovary was studied by the use of several different types of ovarian carcinoma extract as antigen. KCI extract of an ovarian carcinoma was found to be the most effective antigen preparation in comparison with saline, deoxycholate, and perchloric acid extracts. Low concentrations of KCI ovarian carcinoma extract significantly inhibited migration of leukocytes from 11 of 17 patients with ovarian carcinoma (migration index, <0.74). Leukocytes from patients with breast, colon, or endometrial carcinoma showed minimal reactivity with ovarian carcinoma KCI extract, and leukocytes from patients with ovarian carcinoma showed minimal reactivity with KCI extracts of breast, colon, and endometrial carcinoma. These results suggested that the 3 m KCI procedure is superior for the isolation of antigens active in the leukocyte migration inhibition test and that this test may be of use for the isolation of tumor-associated antigen and the immunodiagnosis of ovarian carcinoma.
A Case-Control Study of Oral Contraceptive Use and Breast Cancer23
Authors: Charles H. Hennekens, Frank E. Speizer, Robert J. Lipnick, Bernard Rosner, Christopher Bain, Charlene Belanger, Meir J. Stampfer, Walter Willett, Richard Peto
Journal: JNCI Journal of the National Cancer Institute (1984)

Journal Article A Case-Control Study of Oral Contraceptive Use and Breast Cancer Get access Charles H. Hennekens, Charles H. Hennekens Search for other works by this author on: Oxford Academic PubMed Google Scholar Frank E. Speizer, Frank E. Speizer Search for other works by this author on: Oxford Academic PubMed Google Scholar Robert J. Lipnick, Robert J. Lipnick Search for other works by this author on: Oxford Academic PubMed Google Scholar Bernard Rosner, Bernard Rosner Search for other works by this author on: Oxford Academic PubMed Google Scholar Christopher Bain, Christopher Bain Search for other works by this author on: Oxford Academic PubMed Google Scholar Charlene Belanger, Charlene Belanger Search for other works by this author on: Oxford Academic PubMed Google Scholar Meir J. Stampfer, Meir J. Stampfer Search for other works by this author on: Oxford Academic PubMed Google Scholar Walter Willett, Walter Willett Search for other works by this author on: Oxford Academic PubMed Google Scholar Richard Peto Richard Peto Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 72, Issue 1, January 1984, Pages 39–42, https://doi.org/10.1093/jnci/72.1.39 Published: 01 January 1984 Article history Received: 18 January 1983 Accepted: 28 June 1983 Published: 01 January 1984
FOUR-YEAR ENTECAVIR TREATMENT IN NUCLEOSIDENAiVE HBEAG(+) PATIENTS: RESULTS FROM STUDIES ETV-022 AND -901
Authors: Steven Han, Ting-Tsung Chang, You-Chen Chao, Seung-Kew Yoon, Robert G. Gish, Hugo Cheinquer, Flair Jose Carrillho, Hui Zhang, Helena Brett-Smith, Robert Hindes
Journal: Hepatology (2007)
Abstract 12609: Intracardiac Echo Findings Post Atrial Fibrillation Ablation Are an Important Predictor of Late Pericardial Effusion
Authors: Luigi Di Biase, J. David Burkhardt, Pasquale Santangeli, Prasant Mohanty, Sanghamitra Mohanty, Chintan Trivedi, Javier Sanchez, Rodney Horton, Patrick Hranitzky, Amin Al-Ahmad, G. Joseph Gallinghouse, Sakis Themistoclakis, Rong Bai, Jason Zagrodzky, Dhanujaya R. Lakkireddy, Madhu Reddy, Richard Hongo, Steven Hao, Salwa Beheiry, Maria Lucia Narducci, Claude S. Elayi, Giovanni Forleo, Gemma Pelargonio, Antonio Dello Russo, Michela Casella, Claudio Tondo, Robert Schweikert, Andrea Natale
Journal: Circulation (2014)

Introduction: Major bleeding are serious complications of catheter ablation for atrial fibrillation (AF). Late effusions following AF ablation procedures have been recently reported.

We sought to determine whether the presence of a trivial effusion detected by intracardiac echo at the end of AF ablation procedures performed without warfarin discontinuation predicts the development of late pericardial effusion.

Methods: A total of 2618 consecutive patients undergoing catheter ablation for AF with continuous warfarin have been enrolled in this prospective registry. All ablation procedures were performed under intracardiac echocardiography (ICE) guidance. At the end of each procedure ICE was utilized to detect any degree of effusions.

Results: In 510 out of 2618 (19%) patients, trivial pericardial effusion was detected by ICE at the end of the procedure. All 2108 patients with negative ICE did not show any late pericardial effusions. On the other hand, 8 of the 510 (1.5%) patients with trivial effusion developed late significant pericardial effusion requiring pericardial drainage. The incidence of delayed effusion was 0.31% in this series. In none of the patients requiring epicardial drainage, warfarin was discontinued. A negative ICE finding for trivial pericardial effusion had a negative predictive value (NPV) of 99.6%.

Conclusion: This study shows that the presence of trivial pericardial effusion detected at the end of the ablation procedure by ICE warrant further follow-up by echocardiogram to exclude late tamponade. On the other hand, the absence of any effusion by ICE has a very high negative predictive value for late effusion.
Sun exposure guidance should be tailored to individuals, says NICE
Authors: Jacqui Wise
Journal: BMJ (2016)

Doctors and nurses should offer one to one advice on sunlight exposure tailored to people’s individual level of risk, new guidance from the National Institute for Health and Care Excellence (NICE) has recommended.1

The guidance said it was important that the risk of skin cancer from too much time in the sun should be balanced with the risk of low vitamin D levels in people who are indoors for long periods or who cover up for cultural reasons. It said that health practitioners should make people aware that, although sunlight exposure is a normal part of everyday life and some sunlight is good for health, risks arise from excessive exposure. …
Synergism in Carcinogenesis&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Arnold E. Reif
Journal: JNCI Journal of the National Cancer Institute (1984)

Six examples of exposure of humans to two carcinogens were found that satisfied the minimum requirements for analysis of whether the carcinogens acted in synergism. In all instances, the risk ratio for cancer in the group exposed to both carcinogens was equal to or greater than the product of the risk ratios of the singly exposed groups. These findings underline the danger of double exposure, even though they imply that some and not all pairs of carcinogens act in this way. Because the six studies did not extend to the end of the life-spans of the exposed individuals, the data may be skewed by the life-shortening effect of promoters. Nevertheless, the findings have implications regarding the employment of people who already having been exposed to one recognized carcinogen are in a job where they may receive additional exposure from a second carcinogen known to multiply their risk of cancer. Analyses of animal tests on synergism indicated that most published studies lack dose-response data for each of the two carcinogens, which are vital for definitive proof of synergism. Suggestions for performance of such tests are given. The theoretical basis underlying the concept of synergism is examined, equations for its evaluation are given, and examples of statistical tests for its presence are presented. The conclusion regarding the mechanism of action was that synergism occurs if the rate-limiting step in the generation of a single type of tumor differs for each of two interacting carcinogens.
Prognostic value of preoperative serum tumor markers, including CEA, Cyfra21–1, SCC, CA19–9, SCC, CA125, TPA, NSE, and SLX, in patients with completely resected pathological stage I non-small cell lung cancer
Authors: H. Matsuguma, H. Suzuki, Y. Ishikawa, T. Kondo, R. Nakahara, Y. Kamiyama, K. Mori, T. Kodama, S. Honjo
Journal: Journal of Clinical Oncology (2007)

7681 Background: Recent randomized control trials have shown a survival benefit of adjuvant chemotherapy in patients with stage II or more advanced NSCLC, while surgery alone is still the standard therapy for stage I patients. There is, however, a subgroup of patients among the stage I patients who have a poor prognosis, for whom adjuvant chemotherapy can be as effective as has been observed for the patients with more advanced disease. Preoperative serum CEA level has been reported to be an independent prognostic factor for stage I NSCLC. However, many other tumor markers have also been reported as prognostic indicators in different studies using different tumor markers. It is unknown which tumor marker is the most effective for selecting poor prognostic subgroup of patients with stage I NSCLC for which adjuvant chemotherapy can be applied. Methods: A total of 355 patients underwent complete resection, and were diagnosed as having stage I NSCLC from 1995 to 2003. Analyzed tumor markers included CEA, Cyfra21–1, SCC, CA19–9, SCC, CA125, TPA, NSE, and SLX. Cut-off values for each tumor marker are listed in the table . Clinicopathologic factors including age, gender, histology, vessel invasion, pleural invasion, and pathologic T indicator are also analyzed in the multivariate analysis. Results: Among the 355 patients, 211 patients were male, 249 had adenocarcinoma, 82 had squamous cell carcinoma, and 253 had pathologic T1 tumors. Percentages of elevated value for each tumor marker are listed in the table in combination with related survival data. Cox proportional hazard model demonstrated age, pleural invasion, histology, and CEA were significantly independent prognostic factors. Conclusions: CEA is thought to be the best tumor marker for selecting the poor prognostic subgroup of patients with resected stage I NSCLC because of its high percentage of abnormal value and high ability to differentiate prognostic subgroups. No significant financial relationships to disclose. [Table: see text]
Effectiveness of high-dose combination chemotherapy and autologous bone marrow transplantation for patients with non-Hodgkin's lymphomas who are still responsive to conventional-dose therapy.
Authors: J G Gribben, A H Goldstone, D C Linch, G Taghipour, A K McMillan, R L Souhami, H Earl, J D Richards
Journal: Journal of Clinical Oncology (1989)

We commenced a study in September 1981 to investigate the role of high-dose combination chemotherapy in the management of patients with non-Hodgkin's lymphomas who had failed conventional therapy. Fifty patients with diffuse intermediate- and high-grade non-Hodgkin's lymphomas were treated with high-dose combination chemotherapy with autologous bone marrow rescue (ABMT) and have a minimum follow-up of 1 year. Twenty patients had disease that was still responsive to conventional-dose chemotherapy, 15 had achieved a partial response (PR) to first-line therapy, and five were showing PR to salvage therapy after relapse. Twelve of these patients (60%) achieved complete remission (CR) (two following boost radiotherapy) and three patients have nonprogressive masses on computed tomographic (CT) scan as the only abnormality. None of these patients died during the procedure. Twenty-nine patients had disease not responsive to chemotherapy at conventional dosages: 19 had no response to first-line therapy and 10 showed no response to salvage therapy given after relapse. Only three of these patients achieved CR, all of short duration only. Only two patients in this group remain alive more than 2 years after the procedure and both have nonprogressive abnormalities on CT scan. Nine patients (31%) died of sepsis during the procedure. In those patients with disease not responsive to conventional-dose therapy, dose escalation is associated with a high procedure-related mortality and a low response rate. In those patients who still have chemotherapy-responsive disease the response rate is high and mortality is low.(ABSTRACT TRUNCATED AT 250 WORDS)
Feasibility of metastasectomy in patients treated with bevacizumab in first-line mCRC - Preliminary results from the First Beat-study
Authors: M. Michael, E. Vancutsem, A. Kretzschmar, S. Berry, F. Rivera, M. Dibartolomeo, M. Mazier, B. Lutiger, D. Cunningham
Journal: Journal of Clinical Oncology (2006)

3523 Background: In a phase III pivotal trial in patients (pts) with mCRC, bevacizumab (BEV) increased overall survival by 30% when added to first-line irinotecan, 5FU and leucovorin. The study reported 10% of pts having wound healing complications after major unplanned or elective surgery. The study had limited data on the feasibility and safety of metastastasectomies. First BEAT was opened to evaluate safety events of BEV in a broader pt population using a variety of chemotherapy (CT) regimens. Methods: First BEAT started in June 2004 and aims to enrol up to 2000 mCRC pts in 41 countries. Eligible patients starting with first-line CT are treated until progression with BEV (5mg/kg q2w (5FU based CT) or 7.5mg/kg q3w (Capecitabine (CAP) based CT). In case of major elective surgery, BEV should be stopped 6–8 weeks prior to the planned surgery and could be restarted 28 days after surgery and complete wound healing. At protocol visits, bleeding and wound healing data was collected according to CTC AE grading (v3.0). Results: By Dec 20th, 2005, 31 pts (13 male; median age 55 years; PS 0/1 90%/10%) had undergone metastasectomies. 27 were liver (1 pt had two operations), 3 lung, 1 peritoneal and 1 other resections. 27 were curative, 3 palliative and 2 other resections. 17 reported no residual disease, 5 had residual disease and for 8 resections the outcome was missing or unknown. Median time from first BEV treatment to surgery was 167 days and 54 days from last BEV administration to surgery, respectively. Median follow-up was 12.4 months. One pt died due to disease progression 5.5 months after surgery. CT regimens used with BEV included FOLFOX (N=9), CAPOX (N=9) and FOLFIRI (N=7). No wound healing or bleeding were reported. 21/31 pts reported no complications at all, for 3/31 data was currently missing and 7/31 pts reported the following complications: stomach perforation, right pleural effusion, surgical area infection, thrombosis portal vein/myocardial infarct, bowel-obstruction, ascites, ileus/cornea infection. Updated data will be available in June 06. Conclusions: Preliminary data suggest metastasectomies are feasible after treatment with BEV and CT. Stopping BEV 6–8 weeks before major surgery resulted in no bleeding or wound healing complications. [Table: see text]
Long-term effects of tiotropium in COPD
Authors: N Pareek
Journal: Thorax (2009)

Long-acting inhaled anticholinergic agents are a mainstay of treatment in chronic obstructive pulmonary disease (COPD) and have a beneficial effect on many clinical outcomes. This study examined the long-term benefits and safety of tiotropium in COPD, particularly the rate of decline of forced expiratory volume in 1 s (FEV1).

In a multinational double-blind …