tbuckley/cabot-search huggingface dataset:
Prognostic value of MGMT promoter status and EGFRvIII expression in glioblastoma patients.
Authors: N. Montano, G. L. Banna, M. Martini, G. D'Alessandris, T. Cenci, D. Giuffrida, G. Maira, R. De Maria, L. Larocca, R. Pallini
Journal: Journal of Clinical Oncology (2010)

e12518 Background: Methylation of MGMT promoter, an enzyme involved in DNA repair, has been associated with longer survival and efficacy of alkylating agents in patients with glioblastoma (GBM). The prognostic value of GBM-associated alterations of signal transduction pathways, such as the epidermal growth factor receptor (EGFR)/phosphoinisitide-3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway, that is inhibited by the negative regulator phosphatase and tensin homology (PTEN), has not yet been established. Methods: We prospectively evaluated 34 adult patients with GBM who underwent gross total resection followed by standard radiotherapy and temozolomide. Clinical variables included age, sex, and KPS. Tumor samples from these patients were analyzed for MGMT promoter status and expression of EGFRvIII (the mutant variant III of the EGFR) by RT-PCR, and for expression of PTEN and vascular endotelial growth factor (VEGF) by immunohistochemistry. Overall survival curves were estimated by the Kaplan-Meier method and compared with use of the two-sided logrank test. Results: Preoperative KPS more than 70 and expression of EGFRvIII were significantly associated with longer overall survival of patients (p = 0.0014 and p = 0.0336, respectively). Patients with GBM harboring methylation of the MGMT promoter and expression of EGFRvIII showed a trend toward a better survival, albeit it did not reach the statistical significance (p = 0.0763). Conclusions: Our study suggests a prognostic role for the EGFRvIII expression. The evaluation of this factor may be useful in adjunct of the determination of MGMT promoter status for the stratification of patients with GBM into distinct prognostic and therapeutic subgroups. No significant financial relationships to disclose.
Association of PDCD1 and CTLA-4 Gene Expression with Clinicopathological Factors and Survival in Non–Small-Cell Lung Cancer: Results from a Large and Pooled Microarray Database
Authors: Lei Deng, Balazs Gyorffy, Feifei Na, Baoqing Chen, Jie Lan, Jianxin Xue, Lin Zhou, You Lu
Journal: Journal of Thoracic Oncology (2015)
Treatment of acute myelogenous leukemia in children: results of the Italian Cooperative Study AIEOP/LAM 8204.
Authors: S Amadori, A Ceci, A Comelli, E Madon, G Masera, L Nespoli, G Paolucci, L Zanesco, A Covelli, F Mandelli
Journal: Journal of Clinical Oncology (1987)

One hundred thirty-three children with acute myelogenous leukemia (AML) entered the multicenter Pediatric Branch of the Italian Association Against Leukemia trial AIEOP/LAM 8204 between July 1982 and May 1986. Induction therapy consisted of two courses of daunomycin (DNM) plus cytosine arabinoside (Ara-C). Those patients who achieved remission were given four courses of consolidation with DNM, 6-thioguanine (6-TG) and escalated doses of Ara-C followed by six courses of sequential continuation therapy using monthly pairs: etoposide (VP-16)/Ara-C, Ara-C/6-TG, and DNM/Ara-C. Periodic intrathecal Ara-C was used for CNS prophylaxis. One hundred seven (80%) children achieved complete remission (CR). Kaplan-Meier estimates of 3-year disease-free survival (DFS) and event-free survival (EFS) are 41% and 33%, respectively. Relapses occurred in 34 patients after 5 to 97 weeks (32 marrow; 2 marrow plus CNS). Overall, 14 patients died of complications during treatment (nine during induction; five during the postremission phase), mostly from infection. Risk factor analysis showed that induction failures occurred predominantly in children with French-American-British (FAB) M5 and in those with elevated leukocyte counts; by step-up Cox analysis, only FAB subtype was predictive of remission success. None of the variables examined was significant for predicting the duration of remission. Hyperleukocytosis was predictive of a significantly worse EFS rate. These results are encouraging and further support the use of intensive chemotherapy programs for childhood AML.
Fibromodulin reprogrammed cells: A novel cell source for bone regeneration
Authors: Chen-Shuang Li, Pu Yang, Kang Ting, Tara Aghaloo, Soonchul Lee, Yulong Zhang, Kambiz Khalilinejad, Maxwell C. Murphy, Hsin Chuan Pan, Xinli Zhang, Benjamin Wu, Yan-Heng Zhou, Zhihe Zhao, Zhong Zheng, Chia Soo
Journal: Biomaterials (2016)
Paclitaxel and recombinant human granulocyte colony-stimulating factor as initial chemotherapy for metastatic breast cancer.
Authors: B S Reichman, A D Seidman, J P Crown, R Heelan, T B Hakes, D E Lebwohl, T A Gilewski, A Surbone, V Currie, C A Hudis
Journal: Journal of Clinical Oncology (1993)

PURPOSE A phase II study of Taxol (paclitaxel; Bristol-Myers Squibb Co, Princeton, NJ) as initial chemotherapy for metastatic breast cancer was conducted. Recombinant human granulocyte colony-stimulating factor (rhG-CSF) was used to ameliorate myelosuppression, the anticipated dose-limiting toxicity. PATIENTS AND METHODS Twenty-eight patients with bidimensionally measurable breast cancer who had not received prior chemotherapy for metastatic disease were treated. Taxol was administered at 250 mg/m2 as a continuous 24-hour intravenous (i.v.) infusion every 21 days. rhG-CSF was administered at 5 micrograms/kg/d subcutaneously on days 3 through 10. RESULTS Objective responses were observed in 16 of 26 assessable patients (62%; 95% confidence interval, 41% to 80%). There were three (12%) complete responses (CRs) and 13 (50%) partial responses (PRs). Ten of 16 patients (63%) who had received prior adjuvant chemotherapy responded, which included one CR and four PRs among eight patients who had received prior doxorubicin-containing therapy. Responses were observed in all sites of metastatic disease. The median time to first objective response was 5 weeks (range, 1 to 14). Administration of rhG-CSF was associated with a short duration of neutropenia (median, 2 days with absolute neutrophil count &lt; 500 cells/microL). Eight of 26 patients (31%) who received more than one course received subsequent therapy without dose reduction. One hundred seventy-eight cycles of treatment were administered, with a median of six cycles per patient (range, one to 19). Eight courses (4.5%) were associated with admissions for neutropenic fever. Twenty-two patients (79%) did not require admission for neutropenic fever. Treatment was well tolerated. Adverse effects included generalized alopecia in all patients. Myalgias, arthralgias, and peripheral neuropathy were mild. No hypersensitivity reactions and no cardiac toxicity were observed. CONCLUSION Taxol is highly active as initial chemotherapy for metastatic breast cancer. Administration of rhG-CSF reduced the incidence, depth, and duration of neutropenia, compared with published prior experience. Further studies of Taxol in breast cancer, including combinations with other active agents, are clearly warranted.
Prevalence of BRCA1 mutations in triple negative breast cancer (BC)
Authors: M. J. Kandel, Z. Stadler, S. Masciari, L. Collins, S. Schnitt, L. Harris, A. Miron, A. Richardson, J. E. Garber
Journal: Journal of Clinical Oncology (2006)

508 Background: 90% of BCs in women with germline BRCA1 mutations are ER, PR and HER2 negative (so-called “Triple Negatives”), and 80–90% of triple negative BCs are “basal-like” by DNA microarray and IHC analysis. Prevalence of germline BRCA1 mutations among women with triple negative BC may therefore, be elevated, and underestimated by available calculation models, which do not take tumor features into account. Methods: We randomly identified 200 women from the Dana-Farber/Harvard Cancer Center SPORE annotated specimen bank with histologically confirmed primary invasive, ER, PR and HER2 negative BC. Myriad prevalence tables for BRCA1 were used to estimate the probability that each subject carried a BRCA1 mutation according to age at BC diagnosis, family and personal history of breast and/or ovarian cancer, and Ashkenazi Jewish ancestry. Full sequencing analysis for BRCA1 germline mutations is in progress. Results: The median age at diagnosis of triple negative BC was 49 years (range 26–79). The majority of tumors were high grade (89%) ductal (95%) carcinomas; median tumor size was 2 cm, 50% had positive nodes. 3 patients had a personal history of ovarian cancer and 13 reported Ashkenazi Jewish ancestry. 44% had at least one first or second degree relative with BC; 12% had at least one relative with ovarian cancer. The estimated probability of detecting a BRCA1 mutation according to the Myriad tables ranged from 0.019 to 0.386 (median 0.039): the total expected number of BRCA1 mutations was 11. In a subgroup of 23 patients (12%), who had undergone clinical testing, 2.7 BRCA1 and 1.4 BRCA2 mutations were expected according to the Myriad tables. However, 9 deleterious BRCA1 mutations (39.1%) were found; 2 patients had a BRCA2 mutation (8.7%). Conclusions: The relative excess of BRCA1 mutations in a small group of patients with triple negative BC suggests that established risk factors alone may underestimate the prevalence of BRCA1 mutations among women with this BC subtype. We anticipate that complete BRCA1 analysis of our entire group will more definitively estimate the prevalence BRCA1 mutations among women with triple negative BC. No significant financial relationships to disclose.
Preliminary experience with the use of chemotherapy (CT) following treatment with olaparib, a poly(ADP-ribose) polymerase inhibitor (PARPi), in patients with <i>BRCA1/2</i>-deficient ovarian cancer (BDOC).
Authors: J. Ang, T. A. Yap, P. Fong, C. P. Carden, D. S. Tan, J. Hanwell, J. Carmichael, J. S. De Bono, M. E. Gore, S. B. Kaye
Journal: Journal of Clinical Oncology (2010)

5041 Background: A synthetic lethal approach by PARP inhibition has clinical activity in BDOC (NEJM 2009; 361: 123-34). Proposed mechanisms of PARPi resistance include the restoration of BRCA1/2 function, with theoretical impact both on platinum (PL) and taxane (TX) sensitivities (Nature 2008; 451: 1111-5, CCR 2007; 13: 7413-20). The aim of this study was to provide clinical data on the use of CT following olaparib therapy. Methods: Patients (p) with advanced BDOC who received CT following disease progression on olaparib (Apr 06-Nov 09; doses ≥200mg bd) were included. Demographic and clinicopathologic factors, treatment details, and responses were documented. Results: Twenty-six p (confirmed BRCA1/2 mutations [n=22]; strong family history of BRCA1/2-associated cancers [n=4]) were treated with CT following progression on olaparib. These p previously received a median of 3 lines of CT (range 1-10), a median of 2 with PL (range 1-7) and 1 with TX (range 1-2); 58% and 38% of these p had previous progression-free survival (PFS) of <6 months (m) following PL and TX-based CT, respectively. Response rate (RR) by RECIST/GCIG criteria to olaparib was 54% (95% CI 35-73). Following olaparib, most p received carboplatin (Cb) and/or TX-based CT. The median interval between the start of olaparib and CT was 8.7 m (range 1.2-26.6). Of 23 evaluable p (Table), overall RR was 43% (95% CI 23-64); these responses occurred independently of responses to olaparib. Overall median PFS and overall survival were 3.8 m (95% CI 2.1-5.6) and 7.6 m (95% CI 6.2-8.9). RRs to Cb and TX-based CT were 64% (95% CI 35–92) and 70% (95% CI 42-98), respectively. Seven p who received other regimens had no response. Conclusions: This study provides preliminary evidence that chemoresponsiveness is maintained, particularly with Cb and TX, in this group of heavily pretreated p following treatment with olaparib. Further correlative work with additional follow-up will be conducted. Regimen n (evaluable p) n (responses) Cb/liposomal doxorubicin (LD) 3 2 Cb/gemcitabine 3 1 Weekly Cb/paclitaxel (P) 5 4 Weekly P 4 3 Docetaxel 1 0 LD 4 0 Topotecan 2 0 5-FU/doxorubicin 1 0 Total 23 10 Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca AstraZeneca AstraZeneca AstraZeneca AstraZeneca
The role of reprimo-like gene methylation in radiation responsiveness and prognosis in pancreatic cancer.
Authors: S. H. Lin
Journal: Journal of Clinical Oncology (2010)

e14593 Background: REPRIMO is a radiation-inducible, p53 dependent gene that is commonly hypermethylated and silenced in various GI malignancies and confers a poorer prognosis. We have identified a second gene called Reprimo-like (RPRML) that is highly homologous to REPRIMO and conserved from Xenopus to mammals. We determined the methylation status of this gene in GI malignancies, and whether it has a functional and prognostic role in pancreatic cancers. Methods: DNA methylation was assessed by Methylation-Specific PCR (MSP). Gene expression knock down was performed using siRNA transfection in cells with or without RPRML methylation. Under these experimental conditions, cell cycle analysis, apoptosis using Annexin staining and radiation responsiveness using clonogenic assays were evaluated. DNA methylation status in patient samples was performed using MSP from DNA extracted from paraffin-embedded tumor samples. Survival analysis was performed using Kaplan-Meir statistics. Results: We found RPRML to be methylated in various tumors and cell lines of GI origin, albeit at lower frequency (25%-50%) in comparison to REPRIMO (60%-80%). Treatment using 5-azacytidine reverses promoter methylation and causes gene re-expression. This gene is inducible with gamma-irradiation, and like REPRIMO, is also p53 dependent. Unlike Reprimo, RPRML does not have effects on the cell cycle dynamics. However siRNA knockdown of RPRML induced apoptosis and radiation sensitization. We therefore hypothesized that RPRML methylation in tumors may predict for treatment responsiveness. Indeed, we found RPRML methylation status predicts for a better survival compared to patients without RPRML methylation in 52 non-metastatic pancreatic cancer patients treated with surgery and adjuvant chemoradiation (median survival of 28 months versus 15 months, p=0.05, log-rank test). Methylation status of 4 other genes (Chfr, DYPD, CXCL14, and Reprimo) was not predictive of outcome. Conclusions: These results suggest that RPRML gene silencing by promoter hypermethylation may confer tumor sensitivity to radiation treatment. RPRML methylation may be a useful marker to determine radiation sensitivity in pancreatic cancer patients. No significant financial relationships to disclose.
Use of radioimmunotherapy for consolidation for chemosensitive mantle cell lymphoma (MCL): Summary of International Radioimmunotherapy Registry data.
Authors: W. Jurczak, A. Giza, A. B. Skotnicki, A. Deptala, C. Windemuth-Kiesselbach, M. Lorsbach, C. Suh, P. L. Zinzani, W. M. Linkesch, L. H. Trumper
Journal: Journal of Clinical Oncology (2010)

e18519 Background: Mantle cell lymphoma (MCL) is a rare subtype (3-9%) of non-Hodgkin lymphoma (NHL) with a relatively poor prognosis (5-year survival < 40%). Consolidation with autologous stem cell transplantation (ASCT) but only less than one-fourth of the patients may be subjected to this intensive treatment due to advanced age and co- morbidities. Standard-dose non-myeloablative radioimmunotherapy (RIT) was proved to be an efficient approach for treatment of certain NHL, however, there are almost no data available on the efficacy and safety of RIT in MCL. Methods: In the RIT-Network, a web-based international registry collecting real observational data from RIT-treated patients, 115 MCL patients treated with ibritumomab tiuxetan were recorded. Most of the patients were elderly males with advanced stage of the disease: median age – 61 (range 31-78); males – 70.4%, stage III/IV – 91%. RIT was a part of the first line therapy in 53 pts. (46%). Further 27 pts. (24%) received ibritumomab tiuxetan after two previous chemotherapy regimens, and 35 pts. (30%) after completing 3-6 lines. In 75 cases RIT was applied as a consolidation of chemotherapy induced response. Results: After RIT the patients achieved high response rate: CR 64.2%, PR 22.1%, and SD 2,1%. Only 11,5% of the patients progressed. The projected 3-year overall survival after radioimmunotherapy was 72% (41% for progression free survival). In 75 patients RIT was a consolidation of chemosensitive patients (49 pts – after the first and 26 after previous 2-6 lines of chemotherapy). The 3 year OS is 79 and 60% respectively. RIT was feasible for almost all patients; only 3 procedure-related deaths were reported in the whole group. The main adverse event was hematological toxicity (grade III/ IV cytopenias) showing a median time of recovery of Hb, WBC and Plt of 65, 52 and 60 days respectively. Conclusions: Standard-dose non-myeloablative RIT is a feasible and safe treatment modality, even for elderly MCL pts. Consolidation radioimmunotherapy with ibritumomab tiuxetan may pro-long survival of patients who achieved clinical response after chemotherapy. No significant financial relationships to disclose.
Folfiri (CPT11/LV5FU2) and folfox4 (oxaliplatin/LV5FU2): Two safety regimens in elderly fit patients with metastatic colorectal cancer (MCRC)
Authors: M. Nardi, M. Mare, M. Zavettieri, M. Raffaele, V. Panuccio, D. Azzarello, C. Cortese, P. Del Medico, A. Falzea
Journal: Journal of Clinical Oncology (2004)

3711 Background: Although CRC is considered to be a common age related cancer, there is a paucity of data on age-appropriate chemotherapy treatment because of frequent exclusion of older patients from clinical trials. These pts are commonly considered frail and so not amenable to receive standard chemotherapy regimens. FOLFIRI and FOLFOX4 are both considered the regimens of choice in the treatment of MCRC due to their demonstrated tolerability and efficacy. Objective: In order to assess the safety of these regimens in the clinical practice in elderly pts, we retrospectively collected the data on toxicity among 42 MCRC fit pts(PS0–1)with median age of 71 years(range70–80) treated with these regimens as first or second line chemotherapy. Results: 29 pts received 219 cycles of FOLFIRI(median 6cycles range 2–18)and 13 pts 109 cycles of FOLFOX4 regimen(median 8cycles range 4–12)as first line chemotherapy .The severe toxicities(NCI grade 3/4)are listed in table.We also recorded the toxicities among the pts who crossed chemotherapy regimen due to progression of disease. 14 pts received 68 cycles of FOLFOX4 median 3cycles range 1–12)and 4 pts 18 cycles of FOLFIRI median 4.5 cycles range 1–8)with no severe toxicity except for one episode of febrile neutropenia(7%)in one pt who received FOLFOX4 as second line. Conclusion: Both regimens were sufficiently tolerated; in fact the resolution of the toxicities was possible in all cases without sequelae and there were no treatment-related death. The main cause of chemotherapy delays and/or dose reductions in both regimens was neutropeniaG3/4. In order to improve the tolerability of these regimens, we think that in this cancer population the treatment should be tailored to individual patient's status on the basis of clinical/diagnostic examination and comprehensive geriatric assessment. Moreover the management of treatment-related toxicities requires particular attention to supportive care above all in the prevention of neutropenia by G-CSF. No significant financial relationships to disclose.
L-carnitine supplementation improves fatigue, mood and sleep in cancer patients with fatigue and carnitine deficiency
Authors: R. A. Cruciani, E. Dvorkin, P. Homel, B. Culliney, S. Malamud, L. Shaiova, J. Lapin, R. H. Blum, P. Lesage, R. K. Portenoy, N. V. Esteban-Cruciani
Journal: Journal of Clinical Oncology (2006)

8588 Background: Carnitine is a natural aminoacid derivative that plays a crucial role in cellular energy metabolism. To determine the dose and tolerability we conducted a phase II study with increasing doses of L-carnitine supplementation. In a preliminary analysis, we reported that L-carnitine could improve fatigue, mood and sleep. (Cruciani et al., 2004). Analysis of the full dataset has confirmed and extended these findings. Methods: Patients had active cancer, fatigue and a Karnofsky ≥50. Carnitine deficiency was defined as free carnitine &lt;35 μm]/L for males and &lt;25 for females (normal range 35–67 and 25–55 respectively), or a ratio of acyl/free carnitine &gt;0.4. We utilized a standard maximum tolerated dose (MTD) design, with 3 patients assigned to each successive dose group, starting at 250 mg/day and increasing in each group by 500 mg/day to a maximum dose target of 3000 mg/day. Fatigue (measured by the BFI), depressed mood (CES-D), quality of sleep (ESS), and performance status (Karnofsky), as well as carnitine serum levels were assessed at baseline and after one week of L-carnitine supplementation. Results: Seven groups of three patients each received L-carnitine supplementation for a week with 250, 750, 1,250, 1,750, 2,250, 2,750 or 3,000 mg/day. Of the 27 patients accrued 21 completed the study. Of these, 17 (mean (SD) age = 63.0 (18), females=8) showed an increase in serum L-carnitine levels. The median (min, max) total carnitine increased from 31 (21, 68) to 51 (29, 111) (p &lt; 0.001) and the free carnitine increased from 25.0 (17, 48) to 39 (25, 82) (p &lt; 0.001). The median (min, max) BFI score at baseline was 63 (36, 81) versus 39 (8, 82) after one week (p&lt;0.001). There was also a significant dose response for BFI (r = -0.61, p = 0.01). Median (min, max) CES-D at baseline was 31. (4, 48) and 18.0 (0, 40) after one-week (p = 0.001). Median (min, max) ESS at baseline was 13.7 (2, 22) and 10.3 (1, 18) after one week (p=0.003). Median Karnofsky score did not change (pre and post = 70). Side effects were not observed in any of the groups. Conclusions: This study suggests that L-carnitine is safe up to 3,000 mg/day. Supplementation was associated with improvements in fatigue and depression scores. Fatigue improved in a dose dependent manner. [Table: see text]
Jon Patricios
Authors: Johann Windt
Journal: British Journal of Sports Medicine (2016)

“Make a diagnosis, treat the condition and address the cause.”

This simple approach, which applies to every clinical scenario, was taught to me by Dr. Clive Noble, an orthopaedic surgeon, the first President of the South African Sports Medicine Association, and one of my mentors.



The “438” cricket game at The Wanderers Stadium, Johannesburg between South Africa and Australia. Australia set a world record target of 434 with Ricky Ponting tearing the South African bowling apart in scoring 164 of 105 balls. Miraculously, South Africa chased down the score eventually scoring 438 thanks to 175 off 111 by Herschelle Gibbs – allegedly batting with a hangover!

I was the neutral match doctor and witnessed the ebb-and-flow of emotions in both teams as I moved between the change rooms as well as the ecstasy of the crowd.

I hate “blow-your-own-trumpet” questions! Probably the translation of international consensus guidelines into an accessible programme for …