tbuckley/cabot-search huggingface dataset:
Role of bevacizumab as post-progression maintenance therapy in metastatic colon cancer
Authors: K. M. Galal, M. Abdel-salam, E. F. Esmat, S. Mansour, K. D. Zaghlol, E. Mostafa
Journal: Journal of Clinical Oncology (2008)

14675 Background: Colon cancer is one of the most commonly occurring cancers worldwide, with approximately 50–60% of these patients of metastatic disease and requiring systemic chemotherapy (CTh). Bevacizumab (BVC), a monoclonal antibody directed against vascular endothelial growth factor, provides a significant survival advantage when added to first-line chemotherapy for metastatic colon cancer. The question of whether to continue BVC with the next therapy regimen, and the timing of bevacizumab in the overall treatment strategy of advanced metastatic colon cancer-early use (first-line) or later use? awaits further study. Patients and Methods: Thirty three patients with progressive metastatic colon cancer after first-line therapy were included. Patients were randomized to receive either chemotherapy or combined chemotherapy with bevacizumab. The primary end point was objective response. Secondary end points were median survival, time to tumor progression, toxicity. Results: Median age was 59.7 years (range, 39–70 years), with male/female ratio of 17/16. Partial response with second-line BVC group constituted (25% and 18.8%) in patients with first-line chemotherapy and BVC-based regimen respectively, compared to (11.8% and 5.9%) with second-line chemotherapy (P = 1.01). Median time to progression was (2.3 vs. 4.3 months) for cases with second-line chemotherapy and BVC-based regimens respectively (P=0.12). Median survival was (4 vs. 6.7 months) in both groups respectively (P=0.22). Grade III/IV of neutropenia occurred in 40%, 14.3% and 31.3% in FOLFOX, FOLFIRI and combined BVC-CTh respectively (P=0.66). Conclusion: Bevacizumab is recommended to be maintained in the second- and third-line settings. Post-progression addition of BVC showed statistically significant effect on median survival. Second-line combined bevacizumab with chemotherapy had higher disease control, median time to progression and median survival in bevacizumab- naïve patients compared to patients with first-line BVC-based therapy. Selection of patients for bevacizumab was recommended with taking into consideration the cost-benefit value and that discontinuation of BVC would increase tumor progression. No significant financial relationships to disclose.
Oncolytic poliovirus directs tumor antigen presentation and T cell activation in vitro
Authors: Michael C Brown, Eda Holl, David Boczkowski, Ross Walton, Darell D Bigner, Matthias Gromeier, Smita K Nair
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts Our group has developed an oncolytic poliovirus, PVSRIPO, capable of lysing malignant cells while generating inflammation at the site of the tumor. PVSRIPO is a recombinant polio:rhinovirus chimera, engineered to eliminate neuropathogenicity, that has cancer tropism due to ectopic
Ductal lavage of non-fluid yielding ducts in BRCA1 and BRCA2 mutation carriers and other women at high genetic risk for breast cancer
Authors: A. W. Kurian, M. A. Mills, K. W. Nowels, S. K. Plevritis, B. M. Sigal, N. M. Chun, K. E. Kingham, J. M. Ford, A. R. Hartman
Journal: Journal of Clinical Oncology (2004)

9535 Background: Atypical breast duct cells in patients at increased risk of breast cancer have been predictive of subsequent breast cancer. It has been reported that women whose breasts yield no fluid on nipple suction aspiration have lower risk for breast cancer than women whose breasts yield fluid; publications on ductal lavage (DL) have reported attempt of DL only on patients with fluid-yielding ducts (FY) on initial suction aspiration. We report preliminary results of a study of DL including evaluation of non-fluid yielding ducts (NFY) in women at increased genetic risk of breast cancer. Methods: A pilot study of screening with breast MRI, mammogram, and ductal lavage was conducted in 41 women at increased genetic risk of breast cancer; 26 (63%) had BRCA mutations, and 15 (37%) were included because family history conveyed greater than 10% breast cancer risk at 10 years via the Claus model. Whether or not fluid was obtained on suction aspiration, ducts which could be identified with a dilator underwent attempted lavage. Cytologic diagnostic categories were benign, atypical, or malignant. Fisher's exact test, 2 tailed, was used for statistical analysis. Results: DL was successful in 34 of 41 patients (82.9%); 17 (50%) had NFY. Ten patients (29.4%) had atypical cells; none had malignant cells. Seven of 17 patients (41.2%, 95% confidence interval 18.4–67.1%) with NFY had atypical cells. Patients with atypical cells from NFY were more likely than those with atypical cells from FY to have a BRCA mutation (57.1 versus 0%, p 0.20). Patients with NFY were more likely than those with FY to have had breast or ovarian cancer (58.8% versus 17.6%, p 0.03), and to have received chemotherapy (47.1% versus 17.6%, p 0.14). Conclusions: Atypical cells can be found in NFY patients at high risk for breast cancer, with trends toward higher incidence of atypical cells from NFY in BRCA mutation carriers, and of NFY in cancer survivors. Larger studies are needed to confirm this finding, and to identify risk factors and outcomes associated with atypical cells and NFY. No significant financial relationships to disclose.
Allogeneic marrow transplantation for myelodysplastic syndrome with advanced disease morphology: a phase II study of busulfan, cyclophosphamide, and total-body irradiation and analysis of prognostic factors.
Authors: J E Anderson, F R Appelbaum, G Schoch, T Gooley, C Anasetti, W I Bensinger, E Bryant, C D Buckner, T Chauncey, R A Clift
Journal: Journal of Clinical Oncology (1996)

PURPOSE To determine if an intensive preparative regimen of busulfan (BU), cyclophosphamide (CY), and total-body irradiation (TBI) could improve outcome after marrow transplantation for advanced morphology myelodysplasia (refractory anemia with excess blasts [RAEB], RAEB in transformation [RAEB-T], and chronic myelomonocytic leukemia [CMML]) compared with that obtained with conventional CY/TBI and to analyze prognostic factors for transplantation for myelodysplasia. PATIENTS AND METHODS A phase II study was conducted of 31 patients (median age, 41 years) treated with BU (7 mg/kg), CY (50 mg/kg), TBI (12 Gy), and human leukocyte antigen (HLA)-matched (n = 23) or -mismatched (n = 2) related or unrelated donor (n = 6) marrow transplantation. Results were compared with 44 historical control patients treated with CY (120 mg/kg) and TBI. RESULTS The 3-year actuarial disease-free survival (DFS) rate was similar for the BU/CY/TBI group and the CY/TBI group (23% v 30%, P = .6), but there were trends toward lower relapse rates (28% v 54%, P = .27) and higher nonrelapse mortality rates (68% v 36%, P = .12) among the current patients compared with historical controls. Multivariate analysis showed that a normal karyotype pretransplant and the use of methotrexate as part of posttransplant immunosuppression were associated with improved survival and reduced nonrelapse mortality. Univariate analysis showed significant differences in relapse rates based on marrow source (57% for HLA genotypically matched marrow v 18% for all others, P = .04) and on disease morphology (66% for RAEB-T v 38% for RAEB and CMML, P = .05). CONCLUSION Patients with advanced morphology myelodysplasia tolerated the intensified BU/CY/TBI preparative regimen and reduced posttransplant immunosuppression poorly. Novel transplant procedures are needed to reduce relapse rates without increasing nonrelapse mortality rates. In addition, transplantation before progression to RAEB-T, if possible, may reduce the risk of relapse.
Drug-induced DNA damage and tumor chemosensitivity.
Authors: R J Epstein
Journal: Journal of Clinical Oncology (1990)

Cytotoxic drugs act principally by damaging tumor-cell DNA. Quantitative analysis of this interaction provides a basis for understanding the biology of therapeutic cell kill as well as a rational strategy for optimizing and predicting tumor response. Recent advances have made it possible to correlate assayed DNA lesions with cytotoxicity in tumor cell lines, in animal models, and in patients with malignant disease. In addition, many of the complex interrelationships between DNA damage, DNA repair, and alterations of gene expression in response to DNA damage have been defined. Techniques for modulating DNA damage and cytotoxicity using schedule-specific cytotoxic combinations, DNA repair inhibitors, cell-cycle manipulations, and adjunctive noncytotoxic drug therapy are being developed, and critical therapeutic targets have been identified within tumor-cell subpopulations and genomic DNA alike. Most importantly, methods for predicting clinical response to cytotoxic therapy using both in vitro markers of tumor-cell sensitivity and in vivo measurements of drug-induced DNA damage are now becoming a reality. These advances can be expected to provide a strong foundation for the development of innovative cytotoxic drug strategies over the next decade.
Phase II study of cetuximab in mucinous peritoneal carcinomatosis
Authors: E. Andreopoulou, F. Muggia, M. Safa, J. Escalon, A. Downey, E. Newman, H. Hochster, C. Wojtaszek, D. Mauro, A. Lowy
Journal: Journal of Clinical Oncology (2006)

14020 Background: Mucinous peritoneal carcinomatosis is most commonly associated with primariy tumors of the appendix and colon. Typically, spread remains confined to the abdominal cavity. Imaging assessment of these mucinous lesions is difficult, and tumor markers (CEA and CA19.9) are often used as a surrogate for extent of disease. Patients (pts) often undergo surgical debulking, sometimes coupled with intraperitoneal (IP) drug delivery, but recurrence is common. Since mucin genes are regulated by EGFR, our two institutions initiated this study. Methods: Between Sept 2004 and Dec 2005, weekly cetuximab (loading 400 mg/m 2 on first dose, followed by 250 mg/m 2 /week thereafter) was given to 20 pts (4 men, 16 women): 17 of appendiceal origin were entered a median 3 y (6 m-7 y) after diagnosis; 3 were unknown primaries 24, 23, and 2 m after diagnosis. Prior treatment included surgery (18), systemic (17), and intraoperative (4) or subsequent IP therapy (2). Results: Pts received a median of 12 doses (0–51) of cetuximab. No major objective responses were observed; transient &gt; 25% decreases in CEA and CA19.9 were noted in 4/19 pts; markers were never elevated in 1. Stable disease was best response in 3 of 15 evaluable (5 too early). The most common toxicities, as expected, were skin rash, dryness, and nail fragility. Hypersensitivity reactions in 2 patients did not preclude repeated dosing with premedications. The median time to progression from the start of treatment was 3 m. Conclusions: Brisk accrual by two institutions in this rare clinical entity is noteworthy. In this heavily pretreated population, transient decrease in tumor markers and time on study with stable disease were encouraging, prompting plans for a future study of cetuximab with the addition of systemic irinotecan. [Table: see text]
The significant influence of smoking status and gender on the clinical outcome in the patients with non-small cell lung cancer: The large cohort based study
Authors: T. Kawaguchi, T. Tamura, M. Takada, Y. Kusunoki, A. Matsumura, K. Iuchi, S. Fukai, H. Komatsu, A. Tamura, M. Kawahara
Journal: Journal of Clinical Oncology (2007)

7587 Background: To determine retrospectively whether smoking status and gender affect the treatment outcome and survival for the Japanese patients with non-small cell lung cancer. Methods: Using the database from the lung cancer registry of the National Hospital Study Group for Lung Cancer between 1987 and 2002, detailed demographic and survival information were obtained. A total of 18,346 (70%) documented smokers including the former and the current and 7,755 (30%) documented never smokers with non-small cell lung cancer were studied. A minimal follow-up period was two years. Among them, the 2,546 patients with stage IV lung adenocarcinoma were studied to examine the relationship between the smoking status or the gender and the chemotherapy effect. Multivariate analysis was performed using the Cox regression method. Results: There was an increased percentage of female subjects (72%) in the never smokers, and an increased percentage of male subjects (90%) in the smokers. The never smokers had lower performance status (PS) and lower clinical stage than the smokers (p&lt;0.001). There was an increased percentage of adenocarcinoma (83%) in the never smokers. Multivariate analysis for all the patients demonstrated that the lower clinical stage, the lower PS, younger age, female and never smoking was an independent good prognostic factor The hazard ratio (HR) and its 95% CI was 3.73 (3.58–3.88), 2.69 (2.59–2.79), 1.21 (1.17–1.25), 1.15 (1.09–1.20), and 1.08 (1.04–1.14), respectively. Multivariate analysis for the stage IV adenocarcinoma also showed that the lower PS, female and never smoking was an independent good prognostic factor. The HR and its 95% CI was 2.37 (2.15–2.61), 1.35 (1.19–1.52) and 1.17 (1.04–1.32) respectively. In the treatment of chemotherapy for the stage IV adenocarcinoma patients, the never smokers had higher disease control rates (CR+PR+SD) than the smokers (p=0.08) and the females had higher response rates (CR+PR) than the males (p=0.02). Conclusions: The never smokers and females with non-small cell lung cancer were found to have a distinct and improved clinical outcome. No significant financial relationships to disclose.
SCALOP: Results of a randomized phase II study of induction chemotherapy followed by gemcitabine (G) or capecitabine (Cap) based chemoradiation (CRT) in locally advanced pancreatic cancer (LANPC).
Authors: Somnath Mukherjee, Chris Hurt, Gareth Griffiths, John A. Bridgewater, Thomas Crosby, Stephen Falk, Sebastian J. Cummins, Rajarshi Roy, Stephen Mangar, Alec Mcdonald, John Staffurth, Ross A. Abrams, Tim Maughan
Journal: Journal of Clinical Oncology (2013)

LBA146 Background: CRT with G or 5FU (F) is used to treat LAPC. No multicenter, randomized studies have compared G-CRT vs. F-CRT or the oral fluropyrimidine, Cap-CRT. In the UK, where chemotherapy is traditionally standard of care for LAPC, a trial was conducted to assess the safety, efficacy, and deliverability of G-CRT and Cap-CRT. Methods: Eligibility: histologically proven inoperable LAPC &lt; 7 cm in diameter. Induction chemotherapy: 3 cycles of GEMCAP (G 1,000 mg/m 2 days 1, 8, 15; Cap 830 mg/m 2 days 1-21 q28 days). Patients with stable/responding disease, tumor diameter ≤ 6cm, and PS 0-1 were eligible for CRT randomisation where patients received a further cycle of GEMCAP followed by either Cap (830 mg/m 2 bd weekdays only) or G (300 mg/m 2 weekly) with radiation (50.4 Gy/28 fractions). Treatment volume = tumour plus enlarged nodes and margins of 2 cm sup-inf and 1.5 cm radially. Prospective RT quality assurance was mandated. Primary end-point was 9-month PFS (Fleming’s design). Funder: Cancer Research UK (CR UK 07/040). Results: Between July 2009 and October 2011, 114 patients from 28 UK centres were registered of whom 74 patients were randomised. Randomised patient characteristics: median age 64.6; 55.4% male; WHO PS (0:1) 41.9%:58.1%; median tumor diameter 4cm; site (head:body) 85.1%:14.9%. During CRT, more patients in the G arm experienced grade 3/4 haematological (18.4% vs 0%, p=0.007) and non-haematological (26.3% vs 11.1%, p=0.095) toxicity. Both C and G arms passed the primary endpoint with 9-month PFS of 62.9% (80% CIs: 50.6%-73.9%) and 51.4% (80% CIs: 39.4%-63.4%) respectively. OS was significantly superior in the Cap-CRT arm (median OS 15.2 vs 13.4 months, HR=0.50, log rank p=0.025). Conclusions: SCALOP is the largest RCT comparing radio-sensitizers in pancreatic cancer and demonstrates that both G-CRT and Cap-CRT can be delivered safely and effectively. Both regimens met the pre-specified PFS criteria. Compared to G-CRT, Cap-CRT demonstrated significantly better survival and toxicity and should form the template regimen for future trials investigating RT dose escalation and combination with novel radio-sensitizers. Clinical trial information: NCT01032057.
Analysis of Iron Distribution and Magnetic Characterization of Schistosoma Mansoni and Schistosoma Japonicum Eggs
Authors: Stephan Karl, Lucia Gutierrez, Rafael Lucyk-Maurer, Renata R. F. Candido, Shu Qin Toh, Roland Kerr, Martin Saunders, Alexandra Suvorova, Jeremy Shaw, Michael J. House, Robert C. Woodward, Carlos Graeff-Teixera, Malcolm K. Jones, Timothy G. St Pierre
Journal: American Journal of Hematology (2013)
Decompression surgery and intraoperative radiation therapy (IORT) for metastatic spinal tumors
Authors: K. Karasawa, N. Hanyu, T. Chang, G. Kuga, D. Yoshida, Y. Kiguchi, M. Takahashi, T. Hozumi, T. Kondo
Journal: Journal of Clinical Oncology (2007)

20515 Background: Metastatic spinal tumors often cause spinal cord compression and jeopardize the quality of life of the patients much. To decrease the local symptomatic recurrence rate, we have been adding IORT to decompression surgery. Methods: For those patients whose life expectancy was more than 6 months were eligible for this treatment. Posterior decompression by laminectomy of the involved vertebrae was performed. Following decompression, the patient was irradiated the lesions intraoperatively with electrons generated from Microtron by shielding the spinal cord with lead plate. The central aspects of the vertebrae were irradiated by scattered electrons detouring from the edge of the lead shield up to 40% of the administered dose. Following IORT, posterior instrumentation was performed. External beam radiotherapy might be added pre- and/or postoperatively when considered necessary. Results: 108 patients were treated between 1992–2005. There were 58 males and 50 females. Age ranged from 26 to 85 with a median of 62.5. By primary sites, 26 breast, 24 kidney, 18 colorectum, 17 lung 12 prostate and 11 thyroid cases were included. Irradiated spines were cervical in 6, thoracic in 76, and lumbar/sacral in 27. Overall median follow-up period was 12.7months. Median IORT dose was 20Gy (range 15–26Gy) and median electron energy was 16MeV (range 11–22MeV). There were 37 cases with preoperative RT and 41 cases with postoperative RT. Overall median survival time was 14.5months (breast 15.3, kidney 22.6, colorectum 5.7, lung 6.2, prostate 31.6, thyroid 60.6months). Neurological response rate was 73.1%. Ambulatory rates were 87.0% for success and 80.6% for rescue by Klimo's definition(2005). There were only 8 symptomatic relapses (7%). As for major complications, only one myelopathy has been observed. Conclusions: Decompression surgery and IORT for metastatic spinal tumors with impending spinal cord compression was a promising treatment modality with excellent local control and neurological response rate and with minimal toxicity especially for those patients with long-term prognosis. No significant financial relationships to disclose.
Survival among never and ever smokers with lung cancer in the Cancer Care Outcomes Research and Surveillance Consortium (CanCORS) study.
Authors: C. Clément-Duchêne, X. Xu, S. L. Gomez, E. T. Chang, D. W. West, H. A. Wakelee, M. K. Gould
Journal: Journal of Clinical Oncology (2010)

1595 Background: Clinical, treatment, and survival differences have been observed among current smokers (CS), former smokers (FS), and never smokers (NS) with lung cancer, but many studies have few NS and most studies have not been prospective. This study addresses these limitations. Methods: Clinical, treatment, and demographic characteristics and their impact on survival by smoking status for lung cancer patients were examined using data from CanCORS, a large prospective study of lung cancer care and outcomes in the US. Smoking status at diagnosis was determined by self-report and survival was determined from medical records and cancer registries. Cox proportional hazards regression analysis was used to identify predictors of overall survival among ever smokers (ES; CS and FS combined) and among NS, adjusting for socio-demographic and tumor characteristics. Results: The cohort of 3885 patients with lung cancer diagnosed between September 1, 2003 and October 14, 2005 included 324 NS (8%), 3,016 FS (78%), and 545 CS (14%). At diagnosis, the median age for NS was similar to FS but older than CS (70.5, 70.0 and 63.0 years, respectively). NS were statistically more likely than FS and CS to be female, Asian or Hispanic and to have adenocarcinoma, fewer comorbidities, private insurance, and higher income and education. Compared with CS, NS had a 13% lower adjusted hazard of death from any cause (hazard ratio [HR] 0.87, 95% confidence interval [CI] 0.73 to 1.04) and FS had a 12% higher hazard of death (HR 1.12, 95% CI 1.00 to 1.25). After stratification by smoking status, Asian NS had better overall survival than white NS (HR 0.57, 95% CI 0.34 to 0.98), but this was not found among ES. Factors predicting better overall survival for both NS and ES included adenocarcinoma or squamous histology, and as expected, receipt of surgery, chemotherapy, or radiotherapy, and no or mild comorbidity. These prognostic variables had stronger magnitudes of association with survival for NS compared to smokers. Conclusions: NS with lung cancer are more likely to be female, Asian or Hispanic, and more advantaged socioeconomically. Asian ethnicity is a favorable prognostic factor among NS but not ES. No significant financial relationships to disclose.
Phase I study of pegylated liposomal doxorubicin (PLD) and irinotecan (I) in patients with solid tumors
Authors: G. A. Pillot, J. Wildi, B. Tan, R. Suresh, P. Fracasso, R. Govindan
Journal: Journal of Clinical Oncology (2006)

12023 Background: Irinotecan (I) and doxorubicin are cytotoxic agents that interact with topoisomerase I and II respectively, and display some evidence of preclinical synergy. Pegylated liposomal doxorubicin (PLD) is a novel formulation of doxorubicin that may be more tolerable than doxorubicin. We sought to define the maximum tolerated dose (MTD) of PLD and I when given in combination. Methods: Patients (pts) with good performance status (PS 0–2) and adequate cardiac, renal, liver, and bone marrow function who had received any number of prior therapies for advanced solid tumors were eligible. Pts in the first cohort received PLD at a dose of 20 mg/m 2 IV on day 1 and I 100 mg/m 2 on days 1 and 8 of a 21 day cycle to a maximum of 6 cycles. Growth factor support was not permitted. Results: Eleven pts were enrolled, 6 male, 5 female. Median age of the pts was 63 years (range 19–73). There were 2 cases each of non-small cell lung cancer, renal cell carcinoma, and biliary carcinoma, and one case each of breast, pancreatic, ovarian, colon, and bladder carcinoma. Three pts were initially enrolled without dose-limiting toxicity (DLT) in cohort 1, and six pts were subsequently enrolled in cohort 2 (20 mg/m 2 PLD and 125 mg/m 2 I), with 2 patients experiencing DLT (neutropenia, diarrhea, and fatigue). Two additional pts have been enrolled in cohort 1 (5 pts total) without DLT, and the 6 th patient will be enrolled soon to define the MTD. Grade 3 neutropenia was noted in 1 pt and grade 4 neutropenia in 2 pts. Other non-hematologic toxicities across all cycles have included grade 3 anorexia, diarrhea, nausea, and fatigue in 2 pts each, and 1 pt each with grade 3 dehydration, emesis, pneumonitis, and DVT. No cardiac toxicity has been observed. Of 6 evaluable pts, 4 experienced stable disease (1 each of NSCLC, breast, pancreas, and renal cell carcinoma). Conclusions: The combination of pegylated liposomal doxorubicin and irinotecan is feasible and well- tolerated. The maximal tolerated dose is likely to be PLD 20 mg/m 2 d1 and I 100 mg/m 2 d1 and 8 IV q 21 days (pending enrollment of the last patient). This study was supported by Tibotec Therapeutics, Division of Ortho Biotech. [Table: see text]