tbuckley/cabot-search huggingface dataset:
Validation of Joensuu risk criteria for primary resectable gastrointestinal stromal tumors.
Authors: P. Rutkowski, E. Bylina, A. Wozniak, Z. Nowecki, C. Osuch, M. Matlok, W. Michej, A. Pienkowski, H. Joensuu, W. Ruka
Journal: Journal of Clinical Oncology (2010)

10018 Background: Approval of imatinib for adjuvant treatment of gastrointestinal stromal tumors (GISTs) raised discussion about accuracy of prognostic factors in GIST and the clinical significance of risk criteria. Methods: We evaluated the influence of a new modification of the NIH consensus criteria, the Joensuu risk criteria (Hum Pathol 2008;39:1411), and several clinicopathological factors on disease-free survival (DFS) in a prospective tumor registry series consisting of 549 consecutive patients diagnosed with primary, resectable, CD117-immunopositive GIST. The patients were followed up for a median of 28 months after tumor resection; none received adjuvant imatinib. Results: The median DFS time after surgery was 50 months. In univariate analyses, a high Joensuu risk group (p<0.000001), mitotic count >5/50 HPF (p<0.00001), primary tumor size >5 cm (p<0.00001), non-gastric tumor location (p=0.00001), tumor rupture (spontaneously or at surgery, present in 6.6% of cases; p=0.0014) and male gender (p=0.002) had adverse influence on DFS. In a multivariate analysis a mitotic count >5/50 HPF (HR 2.3), primary tumor size >5 cm (HR 2.0), non-gastric primary tumor location (HR 1.54) and male gender (HR 1.49) were independent adverse single prognostic factors. According to the Joensuu criteria there were 31 (5.7%), 129 (23.5%), 77 (14.0%) and 312 (56.8%) patients in the very low (VL), low (L), intermediate (I) and high (H) risk groups, respectively. Five-year DFS for the high, intermediate, low and very low risk groups was 21%, 80%, 93% and 100%, respectively. Conclusions: The Joensuu risk criteria, which include 2 additional factors to those of the NIH consensus criteria – the primary tumor site and tumor rupture - were validated as a reliable tool for assessing prognosis of primary operable GISTs. The Joensuu criteria identified particularly well high risk patients, who are proper candidates for adjuvant therapy. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis Novartis, Pfizer, Schering-Plough
A randomized phase II study of estramustine phosphate versus estramustine phosphate plus etoposide in hormone refractory prostate cancer (HRPC)
Authors: F. Fulfaro, V. Serretta, G. Cicero, G. Morgia, V. Altieri, A. Siragusa, M. Falsaperla, M. Napoli, G. De Grande, D. Melloni
Journal: Journal of Clinical Oncology (2008)

20632 Background: Docetaxel-based regimens represent the treatment of choice of HRPC. However, in some patients toxicity may be a concern and the quality of life may be compromised. The aim of this phase II randomized study is to investigate the efficacy and safety of low-dose chemotherapy regimen adopting a combination of EMP and VP16 in patients affected by HRPC. Methods: 54 HRPC patients were randomized between: arm A, daily oral standard dose EMP (10mg/kg) and arm B, low-dose EMP (3mg/kg) plus VP16 (25mg/mq) for 2 weeks followed by 2-weeks’rest. Systemic toxicity and hematologic exams were monitored every 2 weeks. Performance status, pain and analgesic use were evaluated according to WHO scales. Quality of Life (QoL) was evaluated through a self-administered visual analog scale (VAS). Results: Median age was 75 years (range 65–83).The most common adverse event was mild to moderate gastrointestinal toxicity. No grade 4 toxicity was registered. Treatment interruption due to grade 3 toxicity was necessary in 6 patients (30%) of arm A and 5 (18.5%) of arm B. A statistical significant difference in favor of the combination arm (B) emerged in terms of tolerability (p=0.02). Improvement in PS, pain and QoL was observed in 14 (70%) and 21 (77%) patients of arm A and B respectively. Ten patients (50%) of arm A and 13 of arm B progressed (48%). Median time to progression was 6 and 14 months (p= 0.02) in arm A and arm B, respectively. Thirty-one (66%) patients are alive with a median survival of 17 months. No difference emerged in overall survival between the 2 treatment arms. Conclusions: Patients affected by HRPC may benefit from oral low-dose combination of EMP and VP16 as palliative treatment. No significant financial relationships to disclose.
Talks continue on intensity payments for consultants Revalidation will require a cultural change GPs issued with new sickness certification guidelines Students want random alcohol and drug testing of doctors
Journal: BMJ (2000)

# Talks continue on intensity payments for consultants {#article-title-2}

Consultants' negotiators and officials from the NHS Executive have been discussing criteria for the intensity payments which were due to be paid from 1 April under the agreement reached for the distribution of the £50m recommended by the Doctors' and Dentists' Review Body in 1999.

At the last meeting of the Central Consultants and Specialists Committee (CCSC), the chairman of the negotiators, Mr Derek Machin, invited the committee to try out a versionof a proforma. This involved three levels of supplement—one for day intensity of work and two for differing levels of disturbance outside normal working hours.

The committee welcomed the progress that had been made, but were concerned about the practical difficulties of implementing a scheme along the lines proposed, instead of an across the board enhancement of salary. They thought that it would be bureaucratic and depend on subjective judgments about doctors' workload.

Mr Machin agreed to report the CCSC's concerns to the NHS Executive. Negotiations on the other changes to the contract (1 January, p 63) will get underway when the issue of the supplements has been …
Integration of Hedgehog and mutant FLT3 signaling in myeloid leukemia
Authors: Yiting Lim, Lukasz Gondek, Li Li, Qiuju Wang, Hayley Ma, Emily Chang, David L. Huso, Sarah Foerster, Luigi Marchionni, Karen McGovern, David Neil Watkins, Craig D. Peacock, Mark Levis, Bruce Douglas Smith, Akil A. Merchant, Donald Small, William Matsui
Journal: Science Translational Medicine (2015)

Activation of the Hedgehog pathway drives FLT3-mutated leukemia, and dual pathway inhibition effectively inhibits tumor growth.
Does maternal or paternal inheritance of <i>BRCA</i> mutation affect the age of cancer diagnosis?
Authors: I. Shapira, R. J. Gralla, M. Akerman, L. R. Weiselberg, V. S. John, H. Raftopoulos, V. Vinciguerra, J. L. Lovecchio, A. Menzin, S. Cohen
Journal: Journal of Clinical Oncology (2011)

1510 Background: Genetic diseases may display parent-of-origin effects in which the risk of disease depends on the sex of the parent from whom the disease allele was inherited. Female carriers of their fathers’ Lynch syndrome gene mutations develop cancer at an earlier age than those inheriting mutations from their mothers suggesting that Lynch syndrome genes may be subject to imprinting effects. Imprinting effect is evident in autosomal dominant hereditary paraganglioma, leading to tumors only if inherited from paternal germline. Methods: From 2004-2010 we analyzed 1,351 consecutive patients presenting for genetic counseling. In 148 patients with BRCA 1 or 2 the parent of origin for the mutation was known. Of these 148 patients, 2 had both BRCA1 and BRCA2 mutated paternally inherited. 63 inherited the deleterious BRCA mutation from fathers (45 affected with cancer) and 83 individuals inherited the deleterious mutation from mothers (54 affected). No ovarian cancers were identified in our cohort of BRCA 2 mutations of maternal inheritance. Two-sample t-test was used to compare the mean age at diagnosis in patients with BRCA 1 or 2 mutations of paternal or maternal inheritance. Results: Paternal inheritance of BRCA resulted in an earlier age of diagnosis of breast and ovarian cancer. These differences were significant with paternal inheritance of BRCA2 mutations; a non-significant trend was found in paternally inherited BRCA1 mutations. Conclusions: Women with paternally inherited mutations in BRCA gene mutations have cancers diagnosed at earlier ages compared with women who inherit gene mutations from their mothers. Maternal and paternal inherited BRCA alleles may not be exchangeable. In this small sample clear differences at age of cancer diagnosis are apparent in paternal inheritance of BRCA 2 gene mutation. These findings have important implications for surgical risk reduction strategies if they are duplicated in larger cohorts. Maternal allele (mean ± SD yrs) Paternal allele (mean ± SD yrs) Two-sample t-test p value Breast cancer BRCA1 47.0 ± 11.6 41.1 ± 7.4 p<0.0778 BRCA2 49.4 ± 10.2 40.8 ± 5.7 p<0.0030 Ovarian cancer BRCA1 56.3 ± 7.0 44.4 ± 3.8 p<0.0080
Multicenter phase II study of docetaxel plus oxaliplatin combination chemotherapy in patients with advanced gastric cancer
Authors: J. Kim, H. Song, Y. Do, K. Lee, M. Kim, H. Ryu, S. Bae, G. Park, J. Baek, W. Lee
Journal: Journal of Clinical Oncology (2007)

15026 Background: The present study was conducted to evaluate the efficacy and safety of a combination regimen of docetaxel plus oxaliplatin in patients with advanced gastric cancer. Methods: Patients with previously untreated metastatic or recurrent, measurable gastric cancer received intravenous docetaxel 65 mg/m 2 plus oxaliplatin (Oxalpla®, Yuhan.Co. Seoul, Korea) 120 mg/m 2 on days 1 in a 3-week cycle. Treatment was continued until disease progression, patient refusal, or an unacceptable toxicity up to 9 cycles. Results: Forty-two patients were enrolled in the current study. Of these, 39 were assessable for efficacy and 41 assessable for toxicity. Seventeen partial responses were confirmed, giving an overall response rate of 40.5% (95% CI: 26.0% to 54.1%, intention-to-treat analysis). At a median follow-up of 160.5 days, the median time to progression was 6.1 months, whereas median overall survival was not reached yet. Grade 3/4 neutropenia occurred in 10 patients, plus febrile neutropenia was observed in 3 patients. Most common non-hamatologic toxicity was nausea (grade 1/2 56.9%). There were two treatment-related deaths. Conclusions: Docetaxel and oxaliplatin combination was found to be well-tolerated and effective in patients with advanced gastric cancer. Accordingly, this regimen can be regarded as an important first-line treatment option for advanced gastric cancer. No significant financial relationships to disclose.
N0377: Results of NCCTG phase II trial of the mTOR inhibitor RAD-001 in metastatic melanoma
Authors: R. D. Rao, J. B. Allred, H. E. Windschitl, W. J. Maples, R. R. McWilliams, E. T. Creagan, J. S. Kaur, L. A. Kottchade, M. K. Gornet, B. A. Pockaj, S. N. Markovic
Journal: Journal of Clinical Oncology (2007)

8530 Background: RAD-001 (Everolimus) is an oral inhibitor of mammalian target of rapamycin (mTOR). Interim analysis results from a phase II study of RAD-001 in patients with metastatic melanoma (MM) were presented at ASCO 2005. This study was re-opened using a higher dose based on an improvement in the 16 week progression free survival (PFS) rate and good tolerability. Methods: A two- stage, phase II multi-institutional trial was conducted in patients with MM to assess that 16 weeks PFS rate was at least 50%. Inclusion criteria: measurable disease, ECOG performance score of 0–2. Exclusion criteria: presence of intracranial metastases, concurrent use of inducers of cytochrome 3A4 and abnormal organ function. The dose of RAD-001 in the second cohort was increased to 10 mg daily (increased from 30 mg weekly) based on evidence of safety of the higher dose. Results: Twenty-nine patients were enrolled; baseline information is available on 27. Median age was 63 yrs; 15 (56%) had &gt;2 sites of metastatic disease. Most (48%) had stage M1c disease. PS was 0, 1 and 2 in 58%, 38% and 4%. All but 4 (15%) had received prior therapy. Grade 3 adverse events included stomatitis and fatigue (2 each), leukopenia, neutropenia, diarrhea, anorexia, dehydration, dyspnea, hyperglycemia, and hypersensitivity (1 each). Planned interim analysis was done after 20 patients were enrolled. 14 (70%) had progressed 16 weeks, failing to meet the decision rule needed (PFS &gt;30%) to restart accrual. The median PFS for all 29 patients was 56 days. The median overall survival (OS) has not been reached. For the entire cohort of 53 pts treated on this study (at both dose levels), the median PFS, median OS were 59 and 286 days respectively. Conclusion: Interim analysis after enrollment of 20 patients at a higher dose of RAD-001 demonstrated significantly more toxicity and no added clinical efficacy. The 16 week PFS rate target was not reached, and accrual was suspended. No significant financial relationships to disclose.
How much do the side effects of chemotherapy matter? Patients' attitudes to side effects versus a potential loss of duration of remission.
Authors: R. A. Buckman, H. K. Berman, S. S. Sridhar, A. M. Joshua
Journal: Journal of Clinical Oncology (2010)

e19585 Background: Side-effects of chemotherapy, including nausea, vomiting, alopecia, fatigue and potential infections may be burdensome to patients with incurable cancers. Some patients may be prepared to consider a shorter duration of tumour control if such side-effects were absent or minimal. Methods: We designed a brief questionnaire to assess the duration of tumor control that patients would be prepared to forego, if therapy for incurable cancer had negligible side-effects. Patients were asked if they would forego 0, 3, 6, and 12 months of tumor control if the average duration of remission were hypothetically 24 months, and if side-effects of chemotherapy were minimal. They also rated the questionnaire for intelligibility, ease of completion and whether or not they could express their feelings adequately. Results: 133 patients with a previous diagnosis of cancer (107 with breast and 26 with prostate cancer) completed the questionnaire. Thirty four patients (26%) were aged < 50, and 99 (74% %) >50. Forty four patients (33%) were currently receiving chemotherapy, 36 (27%) percent had had chemotherapy previously and 53 (40 %) had never had chemotherapy. Of all 133 patients 97%, 71%, 45% and 29% indicated they would choose to forego 0, 3, 6 and 12 months of tumor control respectively. There were no significant differences related to age, past or current experience with chemotherapy, or to tumour site. 94% of patients found the questionnaire easy to understand, 93% easy to complete and 86 % felt they could express their opinions in their answers. Conclusions: Significant proportions of patients would accept a potential loss of duration of tumor control in favour of lesser side-effects during chemotherapy treatment of incurable cancers. These findings suggest a way of opening discussions with patients on this important topic. No significant financial relationships to disclose.
GW572016, gemcitabine and GW572016, gemcitabine, oxaliplatin, a two-stage, phase I study for advanced pancreaticobiliary cancer
Authors: H. Safran, D. Iannitti, T. Miner, K. Demel, D. Yoo, P. Joseph, C. Maia-Acuna, L. Lockridge, D. Evans, K. Teresa
Journal: Journal of Clinical Oncology (2006)

4002 Background: GW572016 is an orally active small molecule that reversibly inhibits ErbB1 and ErbB2 tyrosine kinases. ErbB1 is commonly expressed in pancreaticobiliary cancers. ErbB2 is the preferred heterodimer partner for other ErbB receptors. Baerman et al demonstrated that GW572016 was active against pancreatic cancer cell lines (ASCO GI 2005). We have completed a two-stage, phase I evaluation of GW572016 and gemcitabine (gem), and GW572016 with the combination of gemcitabine and oxaliplatin (GEMOX). Methods: Patients with advanced adenocarcinoma of the pancreas or bile ducts were treated with GW572016 and either weekly gemcitabine (1gm/m 2 /week, 3 weeks on, 1 week off) or GEMOX (gemcitabine 1g/m 2 over 100 minutes and oxaliplatin 100 mg/m 2 , every 14 days). Cohort 1: Weekly gem + GW572016, 1000mg/day. Cohort 2: Weekly gem + GW572016, 1500 mg/day. Cohort 3: GEMOX + GW572016 1000 mg/day. Cohort 4: GEMOX + GW572016 1500 mg/day. Results: Twenty-one patients have been treated; pancreatic cancer (n=15), biliary cancer (n=6). The median age was 64 (41–78). One of six patients in cohort 2 had grade 3 diarrhea. Dose limiting grade 3 nausea occurred in 2 of 5 patients in cohort 4. Two patients had a temporary decrease in cardiac ejection fraction. Five of 20 evaluable patients (25%) responded. Conclusions: GW572016 1500 mg/day can be administered will full dosage gem. The MTD of GW572016 is 1000mg/day with GEMOX. Dramatic responses have been demonstrated in patients with diffuse liver and peritoneal metastases suggesting that erbB1/erbB2 signaling is important in pancreaticobiliary cancers. Further evaluation of GW572016 in pancreaticobiliary cancer is indicated. [Table: see text]
Development of prognostic models in non-small cell lung cancer based on 60 serum markers and clinical variables
Authors: S. Holdenrieder, D. Nagel, V. Heinemann, J. von Pawel, H. Raith, K. Feldmann, U. Stenman
Journal: Journal of Clinical Oncology (2007)

18079 Background: Currently available data concerning the prognostic relevance of biochemical markers in NSCLC are conflicting. Methods: In a prospective study, 60 pretherapeutic parameters including 23 clinical factors, 22 “classical” laboratory markers, and 15 oncological biomarkers were investigated in 300 patients with newly diagnosed advanced NSCLC undergoing first-line chemotherapy. After selection of prognostically independent, clinical parameters by Cox regression analysis, biochemical markers were separately tested together with these clinical factors, and if independently prognostically relevant, simultaneously analyzed by Cox regression using both forward and backward selection. Dependent on clinical preconditions, multivariate analyses were performed on A) clinical, laboratory and oncological lung parameters and B) clinical, laboratory and all oncological parameters. Results: Concerning clinical factors, performance score (PS), weight loss, metastases other than lung (MOL), and chemotherapy showed independent prognostic relevance. Testing biochemical variables with these clinical factors revealed a plentitude of them remaining prognostically significant. When analyzing all prognostically relevant clinical and biochemical variables simultaneously, multivariate models of independently prognostic parameters included for panel A) PS, MOL, CRP, CYFRA 21–1 and chemotherapy. In panel B) CYFRA 21–1 was replaced by the combination of HCG-beta, CA72–4, CA19–9 and S100. Both models improved the prognostic information within the various PS categories significantly. Conclusion: Depending on the availability of pretherapeutic clinical and laboratory variables, various prognostic models for NSCLC patients undergoing first-line chemotherapy can be established. The resulting multivariate models improve the prognostic power over the currently used performance score and provide a more precise pretherapeutic, prognostic stratification of these patients. No significant financial relationships to disclose.
Retrospective analisys of novel therapy for non-small cell lung cancer
Authors: Baofa Yu, Zhenlu Ma, Changjiang guan
Journal: Cancer Research (2008)

AACR Annual Meeting-- Apr 12-16, 2008; San Diego, CA

5719 

Objective: Novel Therapy: Drug Slow Release Depot Therapy (DSRDT) was developed by Dr. Baofa Yu, M.D.. Novel therapy is applied by injection of drug cocktail into the tumor, matrix of tumor self is played as the carrier of the anti-cancer drug after the drug is in laying directly into the tumor slowly. During Drug Slow Release Depot Therapy the drug does not join the circulation of blood and it can kill more than 95% of the cancer cells without damaging the healthy ones and burst the immuno-therapy as vaacines, which is the advantages of this therapy in comparison with the traditional ones. Besides, this therapy can be used as an alternative to surgery, chemotherapy and radiotherapy, thus saving the patient much pain and suffering while extending their life. We evaluated the median survival time and the benefit rate of advanced non-small cell lung cancer patients received DSRDT and radiotherapy.    Methods: Median survival time and benefit rate of 156 advanced non-small cell lung cancer patients (stage III,106 patients; stage IV,50 patients) from January 1999 through October 2006 were retrospectively reviewed. The median follow up period was 36.7months.    Results: 112 patients of all can be evaluated effect. The clinical benefit rate 88.39%,including 3 CR,22 PR and 74 SD patients, which was better than stage III clinical study of patients treated with Endostar and NP(Clinical benefit rate was 76.5%). 90 patients of all can be evaluated survival time. The median survival time was 12.31 months, which was better than patients treated with NP (8.7 months) or radiotherapy alone (9 months), the one year survival rate was 47.78%,which was better than patients treated with NP (23%) or radiotherapy alone (30.1%).    Conclusion: DSRDT improves the median survival time and clinical benefit rate of patients with non-small cell lung caner, which is a new methods of treating non-small cell lung cancer and worthy of using in clinic.    [Key words]Non-small Cell Lung Cancer; Novel therapy: DSRDT; Radiotherapy
Potential biologic causes of the racial survival disparity in adjuvant trials of ER-positive breast cancer.
Authors: K. S. Albain, W. E. Barlow, S. Shak, G. N. Hortobagyi, D. F. Hayes
Journal: Journal of Clinical Oncology (2010)

511 Background: An analysis of SWOG adjuvant breast cancer clinical trials (n = 6,676) found African American (AA) patients (pts, n = 662) had significantly worse survival than others (adjusting for treatment, tumor factors, BMI and SES) overall and in ER-positive (ER+) and ER-negative cohorts separately (JNCI 2009; 101:984). As triple negativity could not fully explain the disparity, we analyzed the ER+ S8814 phase III study to assess if level of ER-positivity or expression of single genes within the 21-gene Recurrence Score (RS) assay might inform this critical issue. Methods: S8814 (ER+, node+, postmenopausal: tamoxifen vs. CAF plus tam; Lancet 2009; 374:2055) was analyzed for disease-free survival (DFS) and overall survival (OS) for AA vs. others, adjusting for other factors. Within the subset available for RS analysis of prognosis/prediction of CAF benefit (Lancet Oncol 2010; 11:55), outcome of AA vs. others was assessed overall; and by ER level, the composite RS, and each of the genes analyzed by RT-PCR. Results: Of 1,477 pts, 139 (9%) were AA, who derived similar benefit from CAF as did others. However, outcomes were worse for AA after adjusting for treatment and other prognostic factors: DFS AA vs. others HR = 1.44 and for OS = 1.70. 27 of 367 pts in the RS sample were AA, for whom DFS was also worse (logrank p = 0.073; adjusted HR 1.65; 5-year DFS 67% AA, 79% others). There was no significant difference in RS by race, although fewer AA had low RS (33% vs. 40%) and more had high RS (41% vs. 32%). There was no significant difference by race in ER level by Allred IHC score or by RT-PCR for each of the 4 ER genes. However, all 5 genes in the proliferation group by RT-PCR had higher quantitative gene expression in AA vs others (p < 0.05 for CCNB1, MKI17, MYBL2, BIRC5; p = 0.051 for AURKA). While Cox regression models that adjusted for nodes, CAF and RS made a marginal impact on the DFS HR by race (1.60), the HR decreased substantially to 1.23 upon adjustment for proliferation. Conclusions: AA on ER+ early breast cancer trials have worse survival than others, due in large part to tumors with higher proliferation and not to differences in degree of endocrine responsiveness. If confirmed in other studies, this finding might impact choice of adjuvant therapy. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genomic Health Genomic Health Agendia, Genomic Health