tbuckley/cabot-search huggingface dataset:
Effect of TP53 mutation status on survival in the MAGIC trial.
Authors: Elizabeth Catherine Smyth, Sanna Hulkki Wilson, Matthew Guy Nankivell, David Gonzalez de Castro, Andrew Wotherspoon, Alicia Frances Clare Okines, Ruth E Langley, Sally Patricia Stenning, David Cunningham
Journal: Journal of Clinical Oncology (2015)

71 Background: In oesophagogastric cancer TP53 mutation may be prognostic and/or predict for chemoresistance, however available data are conflicting. We hypothesised that TP53 status would impact on survival for patients (pts) randomised to surgery alone or perioperative ECF chemotherapy in the MRC MAGIC trial. Methods: Genomic DNA FFPE tissue sections were extracted with QIAmp DNA FFPE Tissue Kit (Qiagen, Hilden, Germany). Mutations in exons 4-9 were screened for by fluorescent PCR -amplification of genomic DNA, followed by Capillary Electrophoresis-Single Strand Conformational Analysis (CE-SSCA). Mutations were characterised by bi -directional Sanger sequencing analysis performed on an independent PCR -reaction and the sequencing results were compared to the reference sequences in the COSMIC database. TP53 status was correlated with demographics and survival. Results: TP53 results were available on 154 pts (50% of pts with available DNA). The remainder failed CE-SSCA due to degraded DNA. Pts with/without TP53 data had similar demographics and survival. TP53 mutation was detected in 51/154 (33%) samples. Exon 4, 5, 6, 7 and 8 mutations occurred in 4%, 42%, 8%, 36% and 10% of specimens with a TP53 result. Pts with TP53 mutations were more likely to have an oesophageal or junctional tumor (vs. gastric) than TP53 wild type (WT) pts (38% vs. 17% respectively p = 0.016). Survival from surgery was comparable for pts with mutant and WT TP53 tumors in both arms of the trial (See Table). P-value for interaction between treatment group and TP53 status was 0.776, indicating no interaction was present. Conclusions: In the MAGIC trial, TP53 mutation status was not prognostic, and did not predict for lack of benefit from chemotherapy. Further study is required in order to evaluate the effect of differing TP53 mutations on treatment and survival. [Table: see text]
Primary Glioblastoma Treated With Boron Neutron Capture Therapy-Evaluation Of A Prolonged High Dose Of Boronophenylalanine (Bpa)
Authors: R. Henriksson, J. Capala, A. Michanek, S. Lindahl, Leif Salford, L. Franzen, E. Blomquist, J. Westlin, T. A. Bergenheim
Journal: Neuro-Oncology (2008)
Co-stimulated autologous T-cell infusion after autologous stem cell transplantation (SCT) for myeloma accelerates lymphocyte recovery and augments response to pneumoccal vaccine: Results of a randomized trial
Authors: E. A. Stadtmauer, A. P. Rapoport, B. L. Levine, A. Badros, D. L. Porter, S. M. Luger, D. Mann, A. Cross, C. H. June
Journal: Journal of Clinical Oncology (2005)

6534 Background: Autologous (auto) SCT can lead to CR and prolonged survival in myeloma patients (pts) but cure is rare. Post-SCT infusion of auto T-cells may improve outcome and accelerate lymphocyte recovery, reduce immune suppression, and allow for improved immune response. Ex-vivo stimulation of auto T-cells using anti-CD3/CD28 laden magnetic beads may augment an auto graft-vs-myeloma effect. We treated 54 pts with high-dose melphalan and SCT followed by co-stimulated T-cell infusion and pneumococcal conjugate vaccine (PCV, Prevnar) randomly assigned to 4 different groups Methods: After lymphocyte pheresis, pts underwent cytoxan (4g/m2) + GCSF and stem cell collection, then melphalan 140–200mg/m2 followed by stem cell infusion. T-cells were cultured for ∼12 days with anti-CD3/anti-CD28-immunomagnetic beads + IL-2 (100 units/ml). 12 patients received stimulated T-cells day(d) +12 alone. The other 42 pts participated in a 2 x 2 randomization of early vs late T-cell infusion (d+12 vs d+100) and early vs late PCV immunization (both groups receiving two doses d+30 and d+90 but the early group receiving a third dose prior to the stem cell infusion) Results: Median age was 56 (38–71), 67% male, 19% non-caucasion, 22% IgA, 20% Bence Jones, 15% abnormal karyotype, median β2M 3.3. Maximal response was 12 CR, 21 nCR, 20 PR 1 unevaluable (98% RR, 61% CR+nCR). 1.5 year survival was 78%. T-cell infusion events were most commonly chills. fever,and nausea generally less than grade 2. 12% developed facial or upper body rash. 52 pts received a mean 8 x 109 CD3+ cells. Day + 42 CD4 and CD8 counts were greater in the early vs late T-cell infusion group (p<0.04). Pneumococcal antibody response to PCV was greatest in the group immunized pre-transplant and receiving early T-cells and cellular PCV response was augmented in those receiving early T-cell infusion. Conclusions: Infusion of co-stimulated auto T-cells early after SCT for myeloma accelerates T-cell recovery and augments antibody and cellular immune response to PCV vaccine with low additional toxicity. This approach holds promise for other anti-microbial and tumor vaccines. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration excite
Optic pathway gliomas in children: A single institution study
Authors: R. Kebudi, O. Ayrancı, S. Tuncer, I. Ayan, G. Peksayar, O. Gorgun, E. Darendeliler
Journal: Journal of Clinical Oncology (2007)

20024 Background: Optic pathway gliomas (OPG) constitute 1–5% of childhood brain tumors, they can occur in patients with NF1. The aim of this study is to evaluate our patients with OPG through a 16 year period. Methods: We reviewed the medical records of 22 patiens treated between Dec. 1990- Dec. 2006. Results: 12 girls and 10 boys (6 mo-19 yrs, median 5yrs) were diagnosed with OPG. 13 patients had NF1.Two had diencephalic syndrome. In 10 the tumor extended to the hypothalamus.Two had leptomeningeal disease, both died despite therapy.Median follow up was 56 months (6–147 mo). 3 patients had stable disease and were followed without treatment, 6 underwent surgery (4 total tumor resection, 2 ventriculoperitoneal shunt; 5 had no additional therapy). 2 patients (14 and 19 years old ) were treated with radiotherapy and 12 (6 mo-9 yrs) received chemotherapy. 3 patients, with stable disease, remained stable. 4 patients, who had total tumor resection, an one with VPS were followed more than 26 months. In two patients , treated with radiotherapy because of progressive disease, clinical response was attained and remained stable. 12 patients recieved chemotherapy, 11 had vincristine 1.5 mg/m 2 and carboplatinum 560 mg/m 2 in one day every 28 days. Of these 11 patients, 10 patients had clinical response/stable disease after chemotherapy, 1 died of progressive disease. Two patients had hypersensitivity to carboplatinum after 8 courses. There were no other major side effects of treatment. In a patient who had vincristine, CCNU,CTX and PCZ, 7 months after achievement of stable disease with chemotherapy, progressive disease occured, and died. Conclusion: OPG are rare childhood central nervous system tumors. The rarity ot these tumors and their variable course make assesment and standardization of treatment methods difficult. Conservative management can be suggested for asymptomatic or stable cases. Based on the primary location of the tumor and age of the patient; surgery, radiotherapy and chemotherapy can be used as a single treatment modality or in combination. Treatment should be planned on an individual basis. In young children with progressive disease chemotherapy with vincristine, carboplatinum once a month seems to be effective and provides a good quality of life during treatment. No significant financial relationships to disclose.
Cancer prevention in Primary care Cancer prevention: setting the scene
Authors: J Austoker
Journal: BMJ (1994)

Each year in the United Kingdom there are over 300,000 new cases of cancer and nearly 165,000 deaths from cancer. It is widely believed that as many as four fifths of all cancers are preventable by means that are already available. The Health of the Nation and the Europe Against Cancer programme have set targets and strategies for reducing the risk of cancer. An approach based on the whole population will achieve the greatest reductions in morbidity and mortality. Complementary to this is the individual approach, which can be based in primary care and targeted at high risk subjects. Health promotion and screening in primary care are not in themselves self evidently valuable. Their effectiveness must be tested rigorously and scientifically. Furthermore, because of limited time and resources, health education in primary care should be focused on interventions that are likely to achieve the greatest benefit, such as helping people to stop smoking.
Phylogenetic relationships among Taphrina, Saitoella, and other higher fungi.
Authors: H Nishida, J Sugiyama
Journal: Molecular Biology and Evolution (1993)

To determine the phylogenetic placement of the major groups of higher fungi, we sequenced the DNA sequences from the small-subunit ribosomal RNA (18S rRNA) coding regions from Taphrina wiesneri (synonym: T. cerasi) and Saitoella complicata and compared them to 18S rRNA sequences from the oomycetes, chytridiomycetes, zygomycetes, ascomycetes, and basidiomycetes. Here we demonstrate that the ascomycetes have at least two major evolutionary lineages. Taphrina wiesneri and Saitoella complicata form a monophyletic branch that diverged prior to the separation of other ascomycetes. The same treatment could be accorded to Schizosaccharomyces pombe.
Gastric cancer risk predisposition and prognostic significance of vascular endothelial growth factor (VEGF) gene polymorphisms in an Omani population
Authors: M. S. Al-Moundhri, M. Al-Nabhani, I. Burney, A. Rizvi, A. Al-Farsi, B. Al-Bahrani
Journal: Journal of Clinical Oncology (2009)

4568 Background: VEGF plays a central role in the angiogenesis, tumor growth and metastasis. VEGF gene polymorphisms at various loci and gastric cancer (GC) risk predisposition and their prognostic significance were studied previously with controversial results Methods: We analyzed three VEGF polymorphisms (+405 G&gt;C, -460T&gt;C, and +936C&gt;T) by extraction of genomic DNA from peripheral blood of 130 GC patients and 130 control subjects followed by VEGF genotyping using PCR-RFLP analysis and the determination of the polymorphisms GC risk predisposition and their prognostic significance Results: There was no significant association between the VEGF polymorphisms and gastric cancer risk. There was a significant correlation between +405 C/C genotype and poor tumor differentiation (p=0.007) and lymph node metastasis (p=0.03) and 460T/T genotype and poor differentiation (p=0.03) with statistical trend for lymph node involvement (p=0.05). VEGF gene polymorphisms had no significant effect on survival, but VEGF +405 G/G genotype had lower survival with hazard ratio 1.6 [95% CI, 0.9–2.9] compared to VEGF +405 CC/GC combined genotype (p=0.04). Multivariate analysis showed that disease stage at diagnosis, and +405 G/G genotype were independent variables of adverse prognostic significance. There were no associations between the common six haplotypes identified and GC risk predisposition and survival. Conclusions: The current study suggests that VEGF polymorphisms in GC patients may have predictive and prognostic significance. No significant financial relationships to disclose.
Palliative treatment in neuroblastoma: Etoposide (VP16), an effective drug
Authors: D. Valteau-Couanet, D. De Pasquale, J. Chevalier, M. Dubrel, C. Dufour, G. Goma, O. Hartmann
Journal: Journal of Clinical Oncology (2008)

10037 Background: No further treatment of relapse after high-dose chemotherapy (HDC) and stem cell transplantation (SCT) has been described yet. Patients treated at our centre can undergo phase I-II studies or palliative treatments. We present herewith our experience on VP16 in relapsing or progressing patients after HDC and SCT. Methods: VP16 was administered orally at the dose of 100 mg/m2/day for 3 consecutive days for 3 consecutive weeks with a stop of one week between the courses. It continued until evidence of clinical progression. Patients who received 1 to 2 courses were considered non-responders, those who received 2–4 courses poor- responders and those who received more than 4 courses good-responders. Results: From 1985 to 2006, 69 patients were treated with oral VP16 which was first-line relapse chemotherapy in 46 patients, second-line in 19, and third-line in 4. They received a total of 342 courses with a median of 3 (1–21) courses. 28 patients (40.5%) were non-responders, 17 (24.7%) poor responders and 24 (34.8%) were good responders and received a median of 8.5 (7–21) courses. No significant toxicity were observed and this treatment allowed a good quality of life. The only factor displayed to have a significant impact on response and survival was the time to relapse. Number and percentages of good-responders were 0 (0%), 4 (23%), and 20 (50%) (P= .006) and median time from relapse to death was 2.4 mos, 5.1 mos, and 12.3 mos in patients who relapsed between 0–6 mos, 7–12 mos, and > 12 mos, respectively. Conclusions: Low-dose oral VP16 schedule should be considered as an effective palliative treatment. As time to relapse has been demonstrated to impact on response and survival, this should be taken into account for further studies evaluating new drugs. No significant financial relationships to disclose.
Preclinical study of lithium sensitivity in human breast <i>PTEN</i> knock out cell lines
Authors: M. J. Higgins, A. M. Abukhdeir, J. Gustin, M. I. Vitolo, K. E. Bachman, B. H. Park
Journal: Journal of Clinical Oncology (2009)

e14641 Background: Mutations of PIK3CA, the catalytic subunit of phosphatidylinositol 3-kinase (PI3K), are found in ∼25% of breast cancers. The tumor suppressor PTEN reverses the effects of PI3K and genetic alterations leading to loss or reduced function of PTEN also occur at high frequency in breast cancers. We have used somatic cell gene targeting to create paired isogenic cell lines with critical genetic alterations as their only differentiating factor. Our lab has introduced two “hotspot” oncogenic PIK3CA mutations into the MCF-10A human breast epithelial cell line. This study led to the discovery that lithium, an FDA approved therapy for bipolar disorders, has selective anti-neoplastic properties against human breast cancer cell lines containing oncogenic PIK3CA mutations. Due to the opposing interactions between PI3K and PTEN, we are now studying whether loss of PTEN also confers sensitivity to lithium using human somatic cell knock outs. Methods: Targeting vectors were created and used to knock out the PTEN gene in MCF-10A. Biochemical and phenotypical characterizations were performed. Paired isogenic cell lines were exposed to lithium to evaluate heterozygous and homozygous loss of PTEN as a predictive biomarker of response. Proteomic and phenotypic changes were measured and assessed. Results: Homozygous loss of PTEN (PTEN-/-) resulted in a transformed phenotype enabling growth in the absence of exogenous growth factors, a hallmark of malignant potential. Preliminary results suggest that treatment of PTEN-/- cells with lithium leads to a decrease in cell proliferation with selectivity for mutant PTEN knock out cell lines, although the effects are not as pronounced as that seen with mutant PIK3CA knock in cells. Conclusions: Our preliminary results suggest that loss of PTEN predicts for sensitivity to lithium in breast cell lines in a manner similar to that seen with oncogenic PIK3CA. We hypothesize that differences in the magnitude of response to lithium may be the result of varied levels of non-PI3K-AKT-mTOR activation between the PIK3CA knock in cell lines and the PTEN knock out cells. No significant financial relationships to disclose.
A retrospective analysis of second-line chemotherapy for malignant pleural mesothelioma (MPM).
Authors: N. M. La Verde, A. Bramati, M. Cinquini, M. Tiseo, E. Collovà, G. Michetti, M. Lo Dico, A. Follador, M. C. Garassino, P. Zucali
Journal: Journal of Clinical Oncology (2010)

7040 Background: Chemotherapy is the only option for MPM. Cisplatin + pemetrexed became the standard in the first-line (FL), while the role of a second-line (SL) remains controversial. Methods: We retrospectively collected data of all consecutive MPM patients (pts), from 8 italian institutions, receiving SL chemotherapy after a platinum based FL treatment from 1996 to 2008. The primary endpoint was overall survival (OS). Secondary endpoints were progression-free survival (PFS), best overall response rate (ORR) and prognostic factors. Kaplan Meier curves and Log Rank were used for statistical analysis. Results: Of 414 MPM pts treated in FL setting, 161 underwent a SL chemotherapy (63% male; median age 62.5 years). Main regimens were: platinum rechallenge (21 pts, 13.1%), pemetrexed rechallenge: (23 pts - 14.4%), pemetrexed + platinum rechallenge (32 pts-20%), biological agents (23 pts-14.3%) and others (62 pts-38.2%). 89 pts achieved disease control (partial remission + stable disease) with a SL regimen (55,6%) (median OS 10,23 months (mths), median PFS 5.72 mths). OS was statistically significantly higher in pts rechallenged with platinum + pemetrexed (20.56 vs 8.49 mths – HR 0.39 95%IC 0.21-0.71; p = 0.0015), while PFS wasn't (9.77 vs 5.39 mths – HR 0.71 95%IC 0.47-1.08; p = 0.111). PFS (p < 0.0001) and OS (p < 0.0001) were statistically significant in pts responding to FL and with an epithelial histology (p = 0.0008). Univariate and multivariate logistic analysis showed that the only factors for the choice of SL regimen were response after FL and smokers. Conclusions: The benefit of SL is strictly dependent on histology and response to FL. According to our data, rechallenge with platinum-based regimens seems the best option. No benefit has been proven in favour of polichemotherapy regimens in respect to single agents. The superiority of cisplatin + pemetrexed rechallenge has been demonstrated also at the multivariate analysis adjusted for time to SL and histology. The role of platinum-based rechallenge in SL should be further investigated, considering also that a SL has palliative intent on the basis of histology and of the extent of response to FL treatment. No significant financial relationships to disclose.
Neoadjuvant chemotherapy (CT) and postoperative chemoradiation (PCRT) in locally advanced, resectable, gastric cancer (LAGC). Preliminary results of a pilot study
Authors: A. Buonadonna, A. De Paoli, R. Sigon, R. Cannizzaro, V. Canzonieri, G. Boz, R. Innocente, C. Rossi, F. De Marchi, S. Frustaci
Journal: Journal of Clinical Oncology (2007)

15078 Background: Curative surgery is achieved in fewer than 50% of patients (pts) in LAGC. PCRT has shown significant improvement in disease control and survival but a limited impact on metastatic disease. To improve this results, a combined modality approach, including IORT, was planned. Methods: Pts with resectable LAGC (stage T3–4 and/or N+) were eligible. EGDS, EUS, abdomen CT were used for staging. 3 cycles of ECF (Epirubicin 50mg/mq, q 3wks; Cisplatin 60mg/mq, q 3wks and 21-day c.i. 5-FU 200mg/mq/day) were planned before radical surgery. IORT (10–15 Gy) included the high risk area defined at surgery. Postop RT included gastric area, anastomosis, duodenal stump and draining lymph node stations. RT (41.4–45 Gy in 23–25 fractions) and concurrent c.i. 5-FU (200 mg/mq/day) were administered. An oral caloric intake &gt;= 1500 Kcal was provided. Results: From June 2001 to December 2006, 22 pts (13 M and 9 F), median age 64 yrs (41–74), with uT3N1 (21pts) and uT2N1 (1pt), entered the study. Tumor location was proximal in 10, lower in 8 and middle in 4 pts, respectively. All pts underwent the planned neoadjuvant ECF with a median of 3 cycles (range 3–5). Toxicity was moderate (&lt;= grade 3) without toxic deaths: nausea and vomiting in 3%, mucositis in 3%, hematological in 7%. Twenty/22 pts underwent surgery (in progress in 2 pts) and 15 (75%) had R0 resection. Tumor downstaging was reported in 9/20 (45%) pts (8 pT2, 1pT1). IORT with 12.5 Gy (10–15 Gy) was given to 12 pts and 12 pts had PCRT. Eight pts were excluded from PCRT for postop complications (2 pts), disease progression (3 pts) or pN3 (3 pts). All 12 pts completed RT with a median dose of 41.4 Gy (41.4–56Gy), but 3 (25%) required RT interruption and 5 pts (40%) also definitive 5-FU interruption (overall PCRT compliance of 60%). Major toxicity from PCRT consisted of G3 asthenia and anorexia, requiring parenteral nutrition. Conclusions: Neoadjuvant CT confirmed feasible in LAGC and resulted in a substantial downstaging with a favourable R0 resection rate. Combined modality approach with IORT and PCRT appears attractive, but limited compliance to PCRT was observed. A definitive evaluation and data on disease control and survival will be reported. No significant financial relationships to disclose.
Phase I study of nimotuzumab, a humanized anti-epidermal growth factor receptor (EGFR) IgG1 monoclonal antibody in patients with solid tumors in Japan
Authors: N. Boku, K. Yamazaki, N. Yamamoto, T. Takahashi, A. Fukutomi, M. Miyazaki, T. Satoh, I. Okamoto, K. Nakagawa, M. Fukuoka
Journal: Journal of Clinical Oncology (2009)

e14574 Background: Nimotuzumab, a humanized IgG1 monoclonal antibody targeting EGFR, has been used in head &amp; neck cancer or malignant glioma outside Japan, and MTD including severe skin rash were not observed up to 800mg/body. This phase I study of nimotuzumab was conducted to investigate the safety profile, MTD, DLT, PK, human antibody against nimotuzumab (HAHA) in Japanese patients (pts), and PD analysis (activation of EGFR, Akt, MAPK, Ki67) was done. Methods: Pts with advanced solid tumors having no available standard therapy were enrolled. Nimotuzumab was given intravenously at dose levels of nimotumumab 100, 200 and 400mg/body, weekly. Blood, skin samples before treatment and after 4th infusion and pre-treatment tumor were collected for PD analysis. Results: 4 pts were enrolled in each level (total 12 pts). Pt characteristics were M/F 5/7, median age 57 years, ECOG PS 0/1 7/5. No grade 3 or 4 toxicities and no DLT were observed, and MTD was not determined. The major adverse event was grade 1 or 2 skin rash (58%, 7/12). Neither infusion reaction nor HAHA was observed. AUC 0-inf , C max and t 1/2 increased and CL deceased by dose dependent manner, indicating nonlinear PK characteristic. SD and PD were observed in 8 patients (67%) and4 patients (33%), without objective responses. Median time to progression was 4 months. Time to progression seemed to be longer in the pts with amplified gene copy number of EGFR though the number of pts was limited. Conclusions: Weekly infusion of nimotuzumab was well tolerated up to 400 mg/body in Japanese pts. A correlation between anti-tumor activity and EGFR amplification was speculated. Additional PD analysis is currently ongoing. No significant financial relationships to disclose.