tbuckley/cabot-search huggingface dataset:
Silencing of SLC35F2 gene influences the biologic behavior of human lung cancer cell line H1299.
Authors: X. Li, G. Jiang, J. Wang
Journal: Journal of Clinical Oncology (2011)

e13512 Background: SLC35F2 is a member of solute carrier family 35 which encode nucleotide sugar transporters localizing in the Golgi apparatus and/or the endoplasmic reticulum, and transport nucleotide sugars that have pooled in the cytosol into the lumen of this organelle, where most of the glycoconjugate synthesis occurs. However, the SLC35F2 subfamily has not been completely characterized with regard to its biological activity. In this study, we tested the hypothesis that SLC35F2 influences the biological behavior of lung cancer cell line. We examined the effect of the inhibition of SLC35F2 expression on proliferation and invasion by establishing the SLC35F2 knockdown lung cancer cell line using lentivirus-mediated RNA interference (RNAi). Methods: The lentiviral vector of small interfering RNA targeting SLC35F2 was introduced into H1299 cells by liposome-mediated transfection. The expression of SLC35F2 protein was measured by Western blot. The proliferation of H1299 cells was determined by cell counting kit-8 (CCK-8) assay. The migration and invasion ability of H1299 cells was evaluated by Transwell migration and invasion assay. Cell cycle analysis was also performed by fluorescence-activated cell sorting (FACS). Results: SLC35F2 expression was markedly down-regulated in H1299 cell clone transfected with the lentiviral vector harboring small interfering RNA targeting SLC35F2. The proliferation of H1299 cells decreased significantly compared with untransfected H1299 cells. Transwell migration assay showed that less H1299 cells could move through the artificial basement membrane when compared with untransfected H1299 cells (38.3±5.7 vs 113.5±8.5, P <0.05). The cell cycle of H1299 cells was changed. Compared with untransfected H1299 cells, the percentage of H1299 cells in S and G2/M phase decreased significantly (S phase: F15.31%±3.04% vs 27.00%±5.41%, P >0.05; GG2/M phase: F3.02%±1.10% vs 10.47%±1.72%, P <0.05), whereas the percentage of H1299 cells in G0/G1 phase increased remarkably (81.67%±3.98% vs 62.53%±1.89%, P <0.05). Conclusions: RNA interference-mediated down-regulation of SLC35F2 by lentiviral vector can attenuate the proliferation and migration of H1299 cells.
Clinical benefit and quality of life in patients with advanced biliary tract cancer receiving gemcitabine plus capecitabine (GemCap): Results from a multicenter phase II trial (SAKK 44/02)
Authors: D. Gerber, D. Dietrich, D. Koeberle, P. Saletti, M. Borner, C. B. Caspar, W. Mingrone, K. Beretta, R. Herrmann
Journal: Journal of Clinical Oncology (2008)

15531 Background: In patients (pts) with advanced biliary tract cancer receiving palliative chemotherapy, no information is available on clinical benefit response (CBR) and quality of life (QL). Methods: Pts with pathologically confirmed, untreated, locally advanced, unresectable or metastatic biliary tract cancer with Karnofsky Performance Status (KPS) 60–80, and/or daily analgesic consumption ≥10 mg morphine equivalents, and/or pain intensity ≥20 (range 0–100) received gemcitabine 1 g/m2 IV on days 1 & 8 and capecitabine 650 mg/m2 orally twice daily on days 1–14 of a 3-week cycle for up to 8 cycles. CBR criteria were rated prior to randomization and on treatment: pts rated pain intensity (0–100) and analgesic consumption daily; physicians rated KPS and weight weekly. CBR was defined as improvement from baseline for ≥4 consecutive weeks either in pain and KPS, or stability in one but improvement in the other, or stability in pain and KPS but improvement in weight. Stable CBR (SCBR) was defined as stability in all 4 criteria. Pts rated QL indicators at baseline, weekly during cycles 1–3, and then twice per cycle. The primary endpoint was the proportion of pts with CBR or SCBR within the first 3 cycles. Associations between QL and CBR, objective response (OR), time to progression (TTP) and overall survival (OS) were described. Results: All 44 pts (median age: 65 years) enrolled from 6 Swiss centers between 2003 and 2006 completed baseline CBR and QL assessments. On treatment, 95% (771/812) of CBR and 92% (560/607) of QL assessments were completed. In the first 3 cycles, 16 pts (36%) had a CBR and 15 pts (34%) a SCBR. Baseline QL scores were moderate to good. Most QL indicators improved from cycle 3 onward. There was no QL difference between CBR and SCBR. Up to cycle 3, pts with no CBR (NCBR) reported worse scores than responders (CBR & SCBR) in several QL indicators. Pts with no OR, TTP<4 months, or OS ≤9 months had worse baseline scores in most QL indicators. Conclusions: GemCap is associated with high CBR and SCBR rates. The observation that poorer QL scores at baseline may be associated with a NCBR or unfavorable OR, TTP or OS outcomes needs further investigation. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Roche Roche Roche
Comparison of prognostic factors and survival outcome between gastrointestinal tract and cutaneous invasive malignant melanoma.
Authors: Chi Lin, Christopher K Brown, Charles Arthur Enke, Fausto R. Loberiza
Journal: Journal of Clinical Oncology (2012)

618 Background: Gastrointestinal melanoma (GIM) is a rare disease. The objective of this study is to compare the overall survival (OS), cancer specific survival (CSS) and prognostic factors of GIM to those of skin melanoma (SKM) using the Surveillance, Epidemiology, and End Results (SEER) registry. Methods: Patients diagnosed with invasive GIM (406) and SKM (173,622) between 1973 and 2008 were identified from the SEER database. Factors analyzed included age (18-40/41-60/61-100), gender, race (White/nonwhite), marital status, stage (localized/regional/distant), year of diagnosis (1973-87/1988-97/1998-2008), and type of treatment (radiotherapy (RT)/surgery). OS and CSS were evaluated using the Kaplan-Meier method. Cox proportional hazards regression analysis examined what factors were prognostic of survival. Results: The median age was 69 and 57 for patients with GIM and SKM, respectively. The GIM group was older with more advanced-stage cancer than the SKM group. Surgery was performed on 85% and 95%, while RT was received by 18% and 2% of GIM and SKM patients, respectively. The GIM group had a median OS and CSS of 15 and 16 months, respectively, while the SKM group had a median OS of 283 months and did not reach a median CSS. Cox analysis showed that SKM had significantly lower risk of total and cancer-specific mortality compared to GIM (Hazard Ratio (HR) 0.40, p&lt;0.0001) and (HR 0.34, p&lt;0.0001). Factors associated with improved OS and CSS in SKM included: age ≤60, female gender, non-white race, early stage, being married, more recent diagnosis, undergoing surgery and not receiving RT. Factors associated with improved OS and CSS in GIM included: age ≤60, early stage, non-white race and undergoing surgery. Subgroup analysis on patients who underwent surgery showed that lymph node status was the only prognostic factor for GIM, while all of the previously identified prognostic factors except for race were associated with OS and CSS for SKM. Conclusions: Outcomes of patients with GIM are inferior to those with SKM. The melanomas in these two sites also have different prognostic factors. Future studies should explore the reasons behind these differences to improve treatment outcomes.
Expression of p16 as a prognostic marker in head and neck squamous cell carcinomas (HNSCC)
Authors: Q.-T. Le, A. C. Koong, H. A. Pinto, A. J. Giaccia, C. Kong
Journal: Journal of Clinical Oncology (2005)

5520 Background: Silencing of p16 expression has been implicated in the formation and progression of HNSCC. Here, we evaluate p16 protein expression in a cohort of HNSCC patients and correlate its expression to tumor location and prognosis. Methods: We constructed duplicate HNSCC tissue arrays from patients treated with either chemoradiotherapy (CRT) or surgery followed by radiotherapy at Stanford University. We performed immunohistochemical staining of the tissue arrays for p16 using p16INK4A antibody (clone E6H4, DakoCytomation, Glostrup, Denmark). The cores were interpreted by an independent pathologist (CK), who was blinded to the clinical data, and scored 0 for negative, 1 for uninterpretable, 2 for weakly positive and 3 for strongly positive staining. χ2 and Fisher exact tests were used to correlate p16 staining to clinical parameters. Cox proportional hazard model and log rank tests were used to determine the relationship between p16 expression and prognosis. Results: 101 patients formed the cohort of this study, of which 11 had equivocal, 46 negative, 8 weakly positive and 36 strongly positive p16 staining. Positive p16 expression strongly correlated with oropharyngeal tumor location (38 of 44 for p16 positive versus 17 of 46 for p16 negative, p = 0.000001). In addition, patients with positive tumoral p16 expression had significantly higher freedom-from relapse (FFR, p = 0.001), cause-specific survival (CSS, p = 0.006) and overall survival (OS, p<0.0001) than those with negative expression. At a median follow up of 53 months, the 5-year FFR, CSS and OS were 77%, 83% and 75%, respectively for the p16 positive group and 40%, 45%, and 30%, respectively, for the p16 negative group. On multivariate analysis, p16 expression (favoring positive) and treatment (favoring CRT) were independent prognostic factors for FFR, CCS and OS. Conclusions: P16 protein expression was more commonly detected in tumors arising from the oropharynx than those from other head and neck sites. Lack of p16 expression was associated with poor prognosis, consistent with its role as a tumor suppressor gene in HNSCC. No significant financial relationships to disclose.
Phase III results of adjuvant radiotherapy (RT) versus wait-and-see (WS) in patients with pT3 prostate cancer following radical prostatectomy (RP)(ARO 96–02/AUO AP 09/95)
Authors: T. Wiegel, D. Bottke, N. Willich, H. Piechota, A. Siegmann, M. Stoeckle, C. Ruebe, A. Hinke, W. Hinkelbein, K. Miller
Journal: Journal of Clinical Oncology (2007)

5060 Background: Adjuvant RT for pT3 R1 or R0 patients (pts.) after RP remains controversial. Results of an EORTC-phase-III- study (with unknown PSA-status after RP) suggested a 20% better biochemical control (bNED) after 5 years for RT. Methods: 385 men with prostate cancer were randomized to either 60 Gy RT (arm A; n=193) or WS (arm B; n=192) before achieving an undetectable PSA. Pts. were stratified for Gleason-score, margin status, neoadjuvant hormonal treatment and stage (pT3A+B vs. C). When the undetectable PSA-level after RP was not achieved, the pts. were stated as progressive disease and left arm A/B and were irradiated. PSA-progression for pts. with undetectable PSA was stated after two consecutive increasing PSA out of the undetectable range. Primary endpoint was bNED. Study was powered to demonstrate a 15% increase in bNED for RT. Results: 78 pts. (20%) did not achieve an undetectable PSA and were stated as progressive disease (arm A: 45 pts., arm B: 33 pts.). Additionally, 34 pts. (23%) from the RT-arm did not receive RT. Therefore, 114 pts. had RT (arm A) and 159 pts. WS (arm B). Median follow up was 53.6 months for arm A and 53.7 months for arm B. BNED at 5 years increased to 72% for arm A (RT) compared with 54% for arm B (WS) (p=0.0015, hazard ratio 0.53). Pts. with a preop. PSA &gt; 10 ng/ml, tumor stage =pT3b, Gleason score =8 as well as positive margins profited significantly from adjuvant RT. The rate of late grade II side effects for the rectum was 1%. Conclusions: Adjuvant radiotherapy for pT3 prostate cancer significantly reduces the risk of biochemical progression after radical prostatectomy. The rate of side effects is very low. No significant financial relationships to disclose.
A rapid method to estimate the value of genetic analysis of excised cancers: A comparison in the phase I setting.
Authors: Henry Jacob Conter, Razelle Kurzrock, Vancheswaran Gopalakrishnan, Leonard A. Zwelling
Journal: Journal of Clinical Oncology (2013)

264 Background: There is great interest in delivering personalized phase I clinical trials for patients. The value of this strategy will be determined by the increased benefit of the testing against the testing’s associated increased costs. We developed and employed a rapid method for determining this value in a cohort of metastatic melanoma patients who participated in phase I clinical trials at M.D. Anderson Cancer Center. Methods: The clinical parameter of benefit used was time to treatment failure (TTF) and the charges were those accrued by patients during their participation on the trial. Charge data were extracted from the MD Anderson business database. Clinical and charge data were employed in a simulation to compare two strategies: testing all patients' tumor for genetic aberrations or not. Results: In the subcohort of patients (N = 103) that were reviewed for this analysis, patients who underwent molecular testing experienced an increase in TTF of 2 months (4.2 versus 2, p=0.1) compared to those not tested, but this was not the primary concern of this study. Rather, the charges and clinical data allowed for a calculation of the value of the testing. The incremental cost-effectiveness ratio (ICER) of genetic sequencing was $49,103 per failure-free month. Ninety-four percent of the this incremental cost was due to the cost of staying on the phase I trial, with only 6% due to the cost of the genetic testing. If the cost of the genetic test was zero, the incremental ICER would still over $46,000 per failure-free month. Probabilistic sensitivity analysis demonstrated that the untested strategy was predicted to be the most cost-effective strategy with a willingness-to-pay (WTP) under $52,000 per failure-free month. The sequencing of tumors becomes 85% likely to be the most acceptable strategy by a WTP threshold of $360,000 per failure free month. Conclusions: These data suggest that making molecular testing cost effective requires reducing the costs of clinical research. This methodology is a way to make a determination of value, as well as attributable costs, which we believe will have to be made for each individual clinical setting.
Improvements in Patient Outcomes with Autologous Stem Cell Transplantation for Multiple Myeloma over 25 Years at a Single Center
Authors: Sandy W. Wong, Melissa Warner, Alejandro Moreno-Koehler, Athena Kritharis, Michael E Coyle, Deborah Black, Valerie Relias, Terry Fogaren, Nancy Cody Lyons, Francois Toka, Denise Larivee, Hedy Smith, Andrew M. Evens, Grace Kao, Kellie Sprague, Andreas K. Klein, Kenneth B. Miller, Raymond L. Comenzo
Journal: Blood (2015)
Economic evaluation of two adjuvant chemotherapy regimens in lung cancer: Vinorelbine and cisplatin versus paclitaxel and carboplatin
Authors: T. Younis, C. Skedgel, M. Sellon, L. Wood, M. Davis, W. Morzycki, K. Virik
Journal: Journal of Clinical Oncology (2005)

6076 Background: Adjuvant chemotherapy in lung cancer has become the new standard of care. Assuming comparable survival and quality of life among acceptable chemotherapy options, an economic evaluation becomes pivotal in choosing the preferred regimen. Methods: A cost minimization analysis was performed in Canadian dollars of the adjuvant chemotherapy regimens used in the NCIC BR10 and CALGB 9633 trials; VP (Vinorelbine and Cisplatin) and PC (Paclitaxel and Carboplatin), respectively. We examined the direct costs of chemotherapy drug acquisition, supportive medications, laboratory investigations, and health resources utilization based at the Nova Scotia Cancer Center. We also estimated the indirect costs incurred by patients, including the potential loss of income based on the average provincial wages and participation rates. The primary analysis assumes uncomplicated cycles and complete drug delivery. Sensitivity analyses to different factors were performed. Results: Compared to the VP regimen, the PC regimen is associated with a higher direct cost, principally reflecting a higher chemotherapy drug acquisition cost (difference: $3749 / patient) but a less resources utilization cost (difference: $1091/patient). This was offset by a higher indirect cost in the VP regimen, which mounted up to an additional $2629/patient with 100% participation rate, reflecting a higher opportunity cost with this longer chemotherapy schedule. Conclusions: The PC regimen is associated with a higher direct cost compared to the VP regimen; principally reflecting a higher drug acquisition cost. However, the total costs were offset by other factors such as indirect patient costs. When making a decision about adjuvant chemotherapy choices in lung cancer, both the direct and indirect costs incurred should be considered. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bristol-Myers Squibb
An exploratory phase I trial of immunochemoradiotherapy in locally advanced and borderline resectable (LA/BR) pancreatic adenocarcinoma (PC).
Authors: Todd S. Crocenzi, Marka Crittenden, Ronald Wolf, Chet Hammill, Pippa Newell, Alan Savoy, Lehel Somogyi, Michael Phillips, James Regan, Michael Owens, Matthew C. Solhjem, Steven Seung, Anupama Kurup, Shane Orion Rogosin, Walter John Urba, Carlo Bruno Bifulco, Xiaohong Cai, Alexandru Bageac, Michael Gough
Journal: Journal of Clinical Oncology (2013)

174 Background: The primary aim of this exploratory trial was to determine the feasibility and safety of chemoradiotherapy (CRT) with combinatorial immunotherapy in LA or BR PC. Methods: 10 patients (pts) with untreated, LA (n=6) or BR (n=4) biopsy-proven PC received gemcitabine (GEM) in combination with telomerase peptide vaccine (GV1001) and sargramostim (GM-CSF) both by intradermal injection. Tadalafil was taken once daily throughout the course of therapy for myeloid derived suppressor cell inhibition. The 2 nd month of treatment included external beam radiation therapy (50.4 Gy, 28 fractions) and concurrent twice-weekly GEM 50 mg/m2. Disease response was assessed at 12 weeks. Following recovery from either concurrent CRT or resection, 8 weeks of GV1001 + GM-CSF, tadalafil and GEM completed treatment. Peripheral blood was analyzed by quantitative multiparameter whole blood flow cytometry of immune cell subtypes. Samples were also cryo-preserved for future analysis of peripheral blood mononuclear cell (PBMC) populations and ELISPOT analysis of antigen-specific T cell numbers. Tumor resection specimens were sectioned for immunohistological analysis of macrophage and T cell infiltration. Results: 9 of 10 pts completed therapy to assess response. Grade (Gr) 3-4 hematologic adverse events (AE) were observed during CRT. Immune-related AE were infrequent and mild. 3 of 4 pts with BR disease and 1 with initial LA (unresectable) disease achieved R0 resection. No unanticipated surgical complications were observed. Changes in monocytes and granulocytes occurred throughout treatment and may correlate with clinical benefit. At least 50% reduction in serum CA19-9 was observed in 8 pts. Partial response (n=2) or stable disease (n=7) was achieved in 9 pts. Conclusions: Combinatorial immunotherapy concurrent with GEM-based CRT is feasible and appears safe in LA or BR PC. Initial biochemical responses as well as disease control were observed in the majority of pts. Preliminary immune correlative data suggest a relationship between hematopoietic populations and clinical response.
Observation vs ESHAP as consolidation therapy in stages III-IV non-Hodgkin’s lymphoma in patients with complete remission with CHOP: Non-randomized comparative study
Authors: L. Casanova, D. Venegas, M. Paola, J. León, C. Flores
Journal: Journal of Clinical Oncology (2005)

6690 Background: Patients with stage III-IV non-Hodgkin’s Lymphoma (NHL) have poor prognosis in disease-free survival (DFS) at treatment with conventional chemotherapy, usually CHOP regimen. In patients who reached complete remission (CR), the consolidation treatment is still in discussion. ESHAP regimen, has been shown to be active against refractory or relapsed NHL in clinical trials. The aim was to determine if consolidation treatment with ESHAP would improve the DFS and overall survival (OS) of patients with stage III-IV NHL in CR after treatment with CHOP. Methods: We compared in a retrospective non-randomized study the DFS and OS in patients with NHL stage III-IV (according Ann Arbor) in CR to CHOP (x6cycles) standard dose continued by ESHAP (x4cycles) vs observation, in patients treated in our institution between 1995–2000. We revised the clinical records of 186 patients older than 13 years old in CR at treatment with CHOP regimen. Of this group, 91 patients continued with ESHAP (CHOP+ESHAP) and 67 patients were observed (CHOP). Patient characteristics were compared between both groups by Chi-square test. Survival probability was estimated by Kaplan-Meier and survival curves was compared by log-rank test. Results: Median age was 62 and 52 years; and 49% and 40% of the patients were stages IV in CHOP and CHOP+ESHAP, respectively. The patients characteristics between both groups don’t differ significantly. The disease was recurrent in 44% and 42% of the patients, these were similar in both groups. However, the DFS and OS in patients that received CHOP concurrently with ESHAP as consolidation treatment have an DFS (p <0.001) and OS (p = 0.002) significantly better than the treated with CHOP only (p = 0.002). Conclusions: Our data suggest that DFS and OS in patients with CR after CHOP followed by consolidation ESHAP have a better outcome that at treatment with only CHOP in NHL stage III-IV. No significant financial relationships to disclose.