tbuckley/cabot-search huggingface dataset:
First- or second-line gefitinib therapy in unknown epidermal growth factor receptor mutants of non-small cell lung cancer patients.
Authors: C. Lie, M. Lin, T. Chao, J. Wang, H. Chang
Journal: Journal of Clinical Oncology (2010)

7577 Background: Gefitinib is effective in treating patients of non-small cell lug cancer (NSCLC). The response rate and the improvement of survival are related to several aspects, including race, sex, smoking status and histology. However, several recent reports in the literature have attributed the response to mutations of epidermal growth factor receptor (EGFR). Little is known about the survival in the different time-line of gefitinib treatment. Methods: Patients with inoperable NSCLC who received gefitinib therapy from March 2003 to December 2006 were analyzed in a tertiary-referral teaching hospital in southern Taiwan. The tumor response, survival time, timing of treatment and several possible predictors were collected to analyze the relationships. Results: One hundred and forty-nine patients who had gefitinib as first or second line therapy were included in the study. The overall survival of first and second line gefitinib therapy was 12.8 months and 20.7 months, respectively (p = 0.110). There was also no significant difference in progression free survival (6.8 months vs. 4.9 months; p = 0.415). The objective tumor response and disease control rate were similar between these two settings. Female gender, adenocarcinoma, nonsmoker, and good performance status were associated with better prognosis and tumor response. The overall survival of patients with second-line treatment compared to first time treatment preceding chemotherapy was longer with significance (p = 0.041). Conclusions: The overall survival, progression free survival and tumor response rate were similar in the patients who received gefitinib as initial therapy or after conventional chemotherapy. The overall survival in patients who received first-line gefitinib therapy and sequential chemotherapy was shorter than in those with second-line treatment. No significant financial relationships to disclose.
Both VEGF and bFGF play an important role in distinctive angiogenic feature of microenvirnment surrounding EBV positive gastric cancer
Authors: J. Kang, Y. Ko, S. Roh, S. Hong, M. Lee, H. Chae
Journal: Journal of Clinical Oncology (2008)

15551 Background: EBV (Epstein-Barr virus)-positive gastric carcinoma accounts for 6–16% of all gastric carcinomas. Vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) are important angiogenic molecules for tumor growth and metastasis. The pathology in EBV-positive gastric carcinoma is characterized by distinctive stromal change known as lymphoepitheloid reaction containing abundant fibroblast and microvessels. We investigated the expression of VEGF and bFGF in the EBV-positive gastric carcinomas and also evaluated the relationship between these angiogenic molecules and the clinicopathologic parameters. Methods: EBV in situ hybridization was carried out in 621 gastric cancer patients who received surgical resection in Kangnam St. Mary's Hospital. In paraffin embedded tumor tissues of 31 EBV-positive gastric carcinomas and randomly selected 69 EBV-negative gastric carcinomas, immunohistochemistry with VEGF and bFGF antibody was executed. Median follow-up duration was 42 months. Results: Male gender, upper location, tubular adenocarcinoma, early stage, VEGF and bFGF expression were significantly correlated with EBV-positive gastric carcinomas (p <0.05). Positive EBV, upper location, lymphatic invasion, and advanced stage were more common in bFGF-positive gastric carcinomas (p <0.05). In addition, positive EBV, lymphatic invasion, upper location, tubular adenocarcinoma and lymph node invasion were statistically correlated with VEGF-positive gastric carcinomas (p <0.05). However, neither EBV nor VEGF had an influence on survival time of the gastric carcinomas. The patients with bFGF-positive gastric carcinoma had shorter survival time than that of bFGF-negative carcinomas with no statistical significance (p=0.128). Interestingly, the survival time of bFGF-positive gastric carcinoma patients was significantly lower than that of bFGF-negative carcinomas accompanying with lymph node invasion (p=0.036). Conclusions: Both bFGF and VEGF expression were found more frequently in EBV-positive gastric carcinomas. It seems tha bFGF be one of the possible prognostic markers in the patients with gastric carcinoma, particularly in the case of lymph node invasion. No significant financial relationships to disclose.
Is prophylactic cranial irradiation indicated in small-cell lung cancer?
Authors: J F Fleck, L H Einhorn, R C Lauer, S M Schultz, M E Miller
Journal: Journal of Clinical Oncology (1990)

Although prophylactic cranial irradiation (PCI) is frequently used in the treatment of patients with limited-extent small-cell lung cancer (SCLC), its role remains controversial. One hundred fourteen SCLC patients with limited disease treated at Indiana University were retrospectively reviewed. Fifty-eight of 114 (51%) patients achieved a complete remission (CR) and were analyzed. Thirty-eight of these 58 CR patients received PCI (+PCI) and 20 of 58 CR patients did not receive PCI (-PCI). Twenty-six of 38 patients who received PCI subsequently relapsed. No patient initially relapsed in the CNS, although one patient had a brain metastasis following recurrence in the chest. Eleven of 38 patients who were treated with PCI survived for longer than 30 months and were considered long-term survivors. Seven of these 11 patients (63%) developed clinically significant neurological toxicity. Sixteen of 20 patients who did not receive PCI relapsed, but there was only one initial relapse in the CNS. Three additional patients who relapsed in the chest subsequently developed CNS metastasis. All responded to palliative radiation with improvement in their symptoms. The high incidence of CNS toxicity in the long-term survivors and the relatively infrequent incidence of isolated CNS recurrent in patients not subjected to PCI raise serious questions concerning the role, if any, of PCI in limited SCLC.
Estimating direct costs of care for patients with relapsed or refractory multiple myeloma in french hospitals
Authors: X. Armoiry, F. Fagnani, L. Benboubker, T. Facon, J. Fermand, C. Hulin, P. Moreau, G. Aulagner
Journal: Journal of Clinical Oncology (2008)

8596 Background: Costly new drugs (bortezomib, lenalidomide) have been marketed in the treatment of multiple myeloma (MM) since 2004. This study aimed to describe the pattern of usual care of relapsed or refractory MM (RRMM) in specialized haematological units during this period and to evaluate the fraction of total treatment cost attributable to those drugs. Methods: A chart review study was conducted in 5 French University hospitals on a representative sample of patients treated for a RRMM during the period 2004–2007 (at exclusion of patients enrolled in a clinical trial) and with at least 18 months of follow-up in the centre. Medical resources were recorded (visits, drugs, hospital stays, treatments for grade 3–4 adverse events or complications) and the corresponding costs were estimated in the perspective of the French Sickness Insurance (these patients are fully reimbursed in France for all their medical expenses). Results: The study included 102 patients with RRMM. Mean age at diagnosis was 58.6 years and 52% were men. The average follow-up from diagnosis or the date of first relapse to death or to the latest news was respectively 56.25 and 23.53 months. From first relapse, the average number of lines per patient was 2.75 (1–7) with a significant difference according to age (2.94 for pts<65ys, 2.17 for pts>65; p<0.05). Novel agents were widely used (73 % of 281 lines) and consisted of thalidomide combinations (28%), bortezomib’s based regimens (22%), lenalidomide (13%) and bortezomib+thalidomide (10%). The average duration per line was 8.5 months of which 5.9 months on treatment. The average cost per line was 26,510 euros including 17,525 euros for drugs. The total direct costs were estimated at 73,000 euros per patient from the first relapse until death or last follow-up. Considering the third line in terms of duration and costs, lenalidomide-based treatment was similar to bortezomib (7.4months and 46,724 euros versus 6.93 months and 46,321 euros respectively). Conclusion: The actual medical cost of RRMM is substantial (73,000 euros per patient) mainly due the cost of novel agents but those drugs have contributed to prolong survival. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Cemka Eval Moreau P
Pharmacogenomic analysis of a randomized phase II trial (BOND 2) of cetuximab/bevacizumab/irinotecan (CBI) versus cetuximab/bevacizumab (CB) in irinotecan-refractory colorectal cancer
Authors: W. Zhang, D. Yang, M. Capanu, E. Hollywood, M. Lue-Yat, E. Borucka, M. Azuma, M. Gordon, L. Saltz, H. Lenz
Journal: Journal of Clinical Oncology (2007)

4128 Background: Phase II CBI VS CB trial has shown that bevacizumab added the efficacy of cetuximab and cetuximab/irinotecan in irinotecan-refractory bevacizumab-naïve CRC patients. We tested the germline polymorphisms involved in angiogenesis pathway(VEGF, IL-8, TGF-β), EGFR pathway (EGFR, COX-2, CyclinD1,E-cadherin,FCGR2A,3A), DNA repair pathway(ERCC1, XRCC1, XPD) and drug metabolism pathway (GSTP1, UGT1A1) to evaluate their association with clinical outcome. Here we expand our gene polymorphisms data involving EGFR pathway (EGF, FCGR2B, Survivin, ADAMS10/17), Angiogenesis pathway (Neuropilin-1, HIF-1, Tissue factor) and irinotecan metabolism pathway(ABCB1,OATPC). Methods: Genomic DNA was extracted from blood samples. 65 out of 81 patients enrolled in the BOND 2 trial were available for molecular correlates study. these 65 patients include 44 men, 21 women, median age 58 years (range 24–86). Patients received either with CBI (n=31) (Arm A) or with CB (n=34) (Arm B). In Arm A, 12 pts (43%) had PR, the median TTP was 7.1 months, and the median survival was 18.0 months. In Arm B, 9 pts (27%) had PR, the median TTP was 4.6 months, and the median survival was 10.3 months. PCR-RFLP based technique was used to determine polymorphisms. Univariate analysis (Fisher’s exact test for response; log-rank test for TTP and OS) was performed to examine associations between polymorphisms and clinical outcome. Results: For Arm B, we found significant associations between HIF-1 polymorphism and tumor response (P=0.017), between HIF-1, FCGR2B polymorphisms and TTP, and between OATPC polymorphism and OS (P values &lt; 0.05). For Arm A, we found a trend in association between EGF polymorphism and tumor response (P=0.08). Conclusions: These data suggest that germline polymorphisms may be potential molecular markers for clinical outcome for patients with mCRC treated with CBI or CB. Prospective studies are needed to confirm these preliminary findings. [Table: see text]
Analysis of magnetic resonance imaging (MRI) in the detection of mammographically occult breast carcinoma
Authors: L. Vallow, S. Packianathan, D. Feigel, E. DePeri, S. Buskirk, E. A. Perez
Journal: Journal of Clinical Oncology (2007)

603 Background: Breast MRI may be useful for detecting mammographically occult ipsilateral carcinoma in newly diagnosed breast cancer. Our initial experience with breast MRI, demonstrated 16% of patients to have additional breast disease detected only by preoperative MRI. We further analyzed our findings to identify an association between patient factors and MRI detected disease. Methods: Preoperative MRI scans of 390 women with newly diagnosed breast cancer were reviewed. Using only patients with pathologic verification, the incidence of mammographically occult ipsilateral cancer was determined. Patient and tumor characteristics were further analyzed to identify factors which may predict pathologically positive MRI findings. Results: Of the 390 women undergoing preoperative MRI, 120 (31%) had ipsilateral findings requiring biopsy. Pathologically verified additional ipsilateral cancer was detected in 62 (16%). Multicentric disease was detected in 32 (52%) and multifocal or more extensive local disease in 30 (48%). The median age of all patients was 62 (27% premenopausal) whereas the median age of those with MRI detected additional carcinoma was 55 (44% premenopausal). Of those with additional disease detected by MRI, 74% had index lesions =1 cm and 63% node negative. The most common histology of the index lesion was infiltrating ductal carcinoma in 64%. In the 62 patients found to have additional disease by MRI the most common histology included infiltrating ductal carcinoma (58%), ductal carcinoma-in-situ (34%) and infiltrating lobular (8%). The histology of the MRI detected additional disease was identical to the index lesion in 71%. Conclusions: In women with newly diagnosed breast cancer, there was a 16% incidence of pathologically proven, mammographically occult ipsilateral disease detected by MRI. Patients found to have additional disease tended to be younger, premenopausal or have index tumors =1cm. The contribution of preoperative MRI in breast cancer management continues to evolve. A lower threshold for obtaining breast MRI may be appropriate in selected subsets of breast cancer patients. No significant financial relationships to disclose.
The profession must work to improve standards Peers defeat government over student grants College introduces evaluation programme Views sought on public health function
Authors: Linda Beecham
Journal: BMJ (1998)

# The profession must work to improve standards {#article-title-2}

The BMA has joined with medical royal colleges and deans of medical schools to show that the profession is working to maintain and improve standards. The association has already produced the first draft of a paper, which sets out what actions are already being taken locally and regionally and suggests ways to strengthen the system.

The chairman of the BMA council, Dr Sandy Macara, told the council that it was important to demonstrate that self regulation was working and that the profession could offer guidance and support to doctors who were concerned about their own or a colleague's performance. There could be concerns about a doctor's work, health, or conduct. The ideal position, according to Dr Macara, would be that problems were resolved locally before they reached the General Medical Council's conduct or performance procedures.

One of the triggers for the work is the proposal in The New NHS for a Commission for Health Improvement, which would offer “an independent guarantee that local systems to monitor, assure, and improve clinical quality are in place.” Where local …
Prognostic factors of contralateral breast cancer (CBC) in 3,653 early breast cancer (EBC) patients (pts): 9-year follow-up results of French Adjuvant Study Group (FASG) trials
Authors: H. Simon, A. Monnier, M. Namer, H. Roche, P. Fumoleau, P. Kerbrat, J. Bonneterre, P. Clavere, E. Luporsi
Journal: Journal of Clinical Oncology (2004)

551 Objective: We analyzed retrospectively the incidence and tumor characteristics of CBC, and determine prognostic factors of their occurrence, and contribution of adjuvant treatments. Methods: Among the 8 FASG trials, 3,653 pts were assessable: 1,667 received adjuvant chemotherapy (CT), 936 CT plus tamoxifen (Tam), 682 hormonotherapy alone, and 368 no systemic treatment. In 2,603 pts receiving CT, it was FEC regimens (epirubicin [E] 50,75, or 100 mg/m2) in 85%, and other E-based CT in the others. The median follow-up was 9 years. The event-free survival (EFS) was computed in a multivariate model: the first step determined separately prognostic factors and adjuvant treatment effects, the second step combined both. Results: 152 pts (4.2%) developed a CBC with a 9-year EFS of 94.9%. The median time to develop a CBC was 52 months: the onset periods were mainly during the second and the seventh years after the primary diagnosis. The comparison with primary tumor showed that CBC presented with the same histology in 56% of cases, and with the same hormone receptors status in 36%. On the whole population, the multivariate analysis showed that independent prognostic factors of CBC occurrence were: negative progesterone-receptor (PR-) with a relative risk (RR) of 2.92 (P < 10-3) and premenopausal status (RR = 1.56, P = .03). As regards treatment effects, the multivariate analysis showed a favorable role of hormonal treatment (P = .04), whereas CT, number of CT cycles, and E dose-intensity had no significant effect. When prognostic factors and treatment effects were combined in the model, the only independent prognostic factor to develop a CBC was PR- with RR = 2.61 (P < 10-3). Conclusion: The incidence of CBC observed in our EBC adjuvant trials was classical of those previously described in the literature. Of interest, when we combined baseline prognostic factors and treatment modalities, the only independent factor of CBC was PR status. Probably, PR negative pts must be carefully monitor, increasing the frequency of contralateral mammography during their follow-up. No significant financial relationships to disclose.
Abstract 14710: Myocardial Bridging: Novel Insights from Exercise Echocardiographic Correlations with Hemodynamic Measurements - The Venturi Effect
Authors: Shin Lin, Jennifer Tremmel, Ryotaro Yamada, Celina M Yong, Ian S. Rogers, Michael V. McConnell, Rajesh Dash, Ingela Schnittger
Journal: Circulation (2012)

Shin Lin, 2012 Finalist and Presenting Author
Peter Leo Frank
Authors: Mark B Gabbay
Journal: BMJ (2015)

Peter Leo Frank was born in Prague. His education was interrupted by spending the war years in a series of concentration and slave labour camps. He put his survival down to the care and protection of a French doctor, for whom he was able to translate (owing to his fluency in French and German) and resolved to practise medicine in his honour. Having “flown to England in the belly of a Lancaster” at the end of the war to join his father in Macclesfield, he rapidly caught up on his education before attending Manchester Medical School. He trained in orthopaedic and trauma surgery …
Targeting PI3K in alveolar rhabdomyosarcoma (aRMS)
Authors: H. E. Crosswell, Q. Peng, C. Prince, P. De, D. L. Durden
Journal: Journal of Clinical Oncology (2006)

10025 Background: aRMS is a pediatric solid tumor with a poor prognosis despite aggressive therapy. HGF/c-Met &amp; PTEN-PI3K-AKT pathways are aberrant, leading to aRMS growth &amp; metastasis. We hypothesize that recapitulating the tumor suppressor (TS) function of PTEN with small molecular inhibitors (SMIs) may control aRMS. SMIs of HGF/c-Met &amp; PI3K pathways were examined for their control of aRMS growth &amp; migration. Design/Methods: Pax3/fkhr-associated aRMS cells, RH30, were infected with MIEG3/PTEN (RH30MP1), MIEG3 retroviral vector (RH30MV1) or CMV-driven luciferase (RH30Luc). Migration was assessed by a transwell migration chamber; proliferation with a MTT assay; biochemical analysis by Western blot. Tumor growth and spontaneous lung metastasis in IACUC-approved animal experiments, in which cell lines were injected s.c. in nude mice, were analysed by bioluminescent imaging (BLI) or by direct measurements. Students t-test (p&lt;.05) determined significance. Results: Western analysis revealed RH30 cells have low PTEN, high levels of c-Met &amp; p-AKT. HGF stimulation of RH30 cells results in increased p-Met, p-Akt &amp; p-Erk1/2 levels, correlating with enhanced migration and proliferation (&lt;.001). SMI of PI3K (LY294002) controls RH30 proliferation (p&lt;.01), not migration; c-Met (PHA665752) &amp; MAPK (PD98059) SMIs stop HGF-directed migration through control of p-Erk levels (p&lt;.01). PTEN induction in RH30 cells via PPAR-gamma agonist, rosiglitazone, results in decreased basal p-Akt levels. RH30 cells with stable, retroviral-infected PTEN have significantly reduced migration&amp; proliferation as compared to cells with vector alone (p&lt;.001). In nude mice xenograft models, PTEN &amp; novel PI3K SMI, SF1126 at 50mg/kg, control RH30 tumoriginesis. SF1126 also controls spontaneous RH30Luc metastasis to the lungs. Conclusions: High c-Met-expressing RH30 cells are sensitive to HGF-stimulated migration through MAPK &amp; proliferation via PI3K. PTEN’s control of aRMS migration, proliferation &amp; tumorigenesis suggests that PTEN controls both PI3K &amp; MAPK. Novel PI3K inhibitor, SF1126, controls tumor growth in vivo &amp; prevents spontaneous lung metastasis. Recapitulating PTEN TS function with SF1126 alone or in combination with SMIs of the HGF/c-Met or MAPK may benefit patients with aRMS &amp; deserves further pre-clinical study. [Table: see text]
Docetaxel versus mitoxantrone as first-line chemotherapy for hormone-refractory prostate cancer (HRPC) patients. A meta-analysis of 3-year overall survival results
Authors: S. Oudard, E. Banu, A. Banu, F. Scotte, E. Levy, J. Medioni, E. Fabre Guillevin, J. Ayllon, N. Arakelyan, J. M. Andrieu
Journal: Journal of Clinical Oncology (2005)

4634 Background: Docetaxel (DTX) based chemotherapy is considered the standard treatment for metastatic HRPC patients (pts), with a median survival advantage of 2 months, compared to mitoxantrone (MT). DTX advantage at long term is not defined and further evaluations are needed. Methods: We conducted a meta-analysis to assess the effect of DTX chemotherapy (CT) on overall survival (OS) compared to MT for metastatic HRPC pts. OS probabilities at 12, 18, 24, 30 and 36 months, were considered as the endpoints of interest. Subgroups analysis were performed to evaluate the impact on OS of DTX dose intensity (DI), between dose-dense (q1w) and dose-intense (q3w) schedules. Estimates of the effectiveness of CT were expressed as relative risk reduction (RRR), using a fixed effects model. Associated statistics with 95% confidence interval (CI) were calculated based on adjusted number of pts at risk and events (according to the extent of follow-up) using EasyMA software. Results: Three randomized controlled trials comparing DTX with MT-based CT in HRPC pts were selected (Tannock, Petrylak, NEJM 2004; Oudard, JCO 2005). A total of 1807 pts were included, 1092 allocated to DTX and 715 allocated to MT. The follow-up range was 13.9–58.5 months. No differences were found according to Gleason score, performance status and sites of metastasis. Overall analysis demonstrates a significant OS benefit for DTX at any time points, without any significant heterogeneity (Table). There was a significant difference in OS in favor of DTX dose-intense arm comparing to MT, with no OS benefit for DTX dose-dense schedule. The rank test for publication bias were not significant. Conclusions: This meta-analysis shows on a large data set that DTX-based CT significantly reduced the risk of death by 8–21%, a benefit persisting 3 years later after the start of CT. The benefit of DTX over MT was related to DTX schedule and dose-intense model. No significant financial relationships to disclose.