tbuckley/cabot-search huggingface dataset:
Right (R) or left (L) primary site of colorectal cancer and outcomes for metastatic colorectal cancer (mCRC): Results from the south Australian registry of mCRC.
Authors: Timothy Jay Price, Carol Beeke, Robert Padbury, Guy Maddern, David Roder, James Moore, Amanda Rose Townsend, Amitesh Roy, Christopher Hocking, Christos Stelios Karapetis
Journal: Journal of Clinical Oncology (2014)

596 Background: Previous reports have described differences in biology and outcome based on whether the primary is R or L sided. Possible differences in response to biological agents have also been reported based on side of primary lesion (SY Brule et al., JCO31, 2013 (supp #3528). Methods: We explored the SA mCRC registry to assess if there were any differences in patient characteristics, treatment received and outcomes based on whether the primary was R (caecum to transverse colon) or L (splenic flexure to rectum) sided (JA Bufill, Ann Int Med. 113, 1990, 779-788). KM was used for survival outcomes and Cox proportional hazards regression modeling was used to assess defined prognostic markers. Results: 2,877 patients were analysed. 33% had R sided primary. Major differences between R and L respectively are as follows; Female 51.3% vs. 37.9% (p = &lt;0.0001), Med age 75.8 yrs vs. 70.5yrs (p = &lt;0.0001), poorly differentiated pathology 34.3% vs. 20.8% (p = &lt;0.0001), KRAS mutation 48% vs. 37% (p = 0.023), and liver surgery 10.5% vs. 16.3% (p = &lt;0.0001). Analysis of chemotherapy (defined as either cytotoxic and/or molecular-targeted) revealed similar rates of first-line therapy, but differences in rates of therapy beyond first-line R vs. L respectively; second-line 46% vs. 60.4%, third-line 17% vs. 30%, fourth-line 7% vs. 13%. There was however no difference in single agent vs. combination first-line therapy. The median overall survival (mOS) for the entire group R vs. L was 9.6 vs. 20.3 months (p &lt;0.0001). For the group who had active therapy defined as chemotherapy (+/- metastasis resection), mOS was R 18.2 months vs. L 29.4 months (p &lt;0.0001). For those (n = 123) who underwent liver resection (+/- chemotherapy) mOS was 6.2 years for both R and L (p = 0.32). Patients who were treated with only chemotherapy, the mOS was 10.7 mths vs. 15.3 mths for R v L (p = 0.0005). Conclusions: Patients with R sided primary have more negative prognostic factors and indeed have inferior outcomes when compared with those with a L sided primary. This did not appear to be the case for patients who were suitable for hepatic surgery.
Thalidomide + Dexamethasone as Maintenance after Single Autologous Stem Cell Transplantation Improves Progression-Free Survival (PFS) in Advanced Multiple Myeloma. A Prospective Brazilian Randomized Trial
Authors: Angelo Maiolino, Vania T. Hungria, G. Oliveira-Duarte, LC Oliveira, DR Mercante, Ecm Miranda, A. Quero, AL Miguel Peres, Jc Barros, P. Tanaka, RP Magalhães, Eduardo M. Rego, M. Nucci, Irene Lorand-Metze, CSP Lima, I. Zalcberg, E. Braggio, Carmino De Souza
Journal: Blood (2008)
Leveraging molecular datasets for biomarker-based clinical trial design in glioblastoma
Authors: Shyam K. Tanguturi, Lorenzo Trippa, Shakti H. Ramkissoon, Kristine Pelton, David Knoff, David Sandak, Neal I. Lindeman, Azra H. Ligon, Rameen Beroukhim, Giovanni Parmigiani, Patrick Y. Wen, Keith L. Ligon, Brian M. Alexander
Journal: Neuro-Oncology (2017)

Biomarkers can improve clinical trial efficiency, but designing and interpreting biomarker-driven trials require knowledge of relationships among biomarkers, clinical covariates, and endpoints. We investigated these relationships across genomic subgroups of glioblastoma (GBM) within our institution (DF/BWCC), validated results in The Cancer Genome Atlas (TCGA), and demonstrated potential impacts on clinical trial design and interpretation.We identified genotyped patients at DF/BWCC, and clinical associations across 4 common GBM genomic biomarker groups were compared along with overall survival (OS), progression-free survival (PFS), and survival post-progression (SPP). Significant associations were validated in TCGA. Biomarker-based clinical trials were simulated using various assumptions.Epidermal growth factor receptor (EGFR)(+) and p53(-) subgroups were more likely isocitrate dehydrogenase (IDH) wild-type. Phosphatidylinositol-3 kinase (PI3K)(+) patients were older, and patients with O6-DNA methylguanine-methyltransferase (MGMT)-promoter methylation were more often female. OS, PFS, and SPP were all longer for IDH mutant and MGMT methylated patients, but there was no independent prognostic value for other genomic subgroups. PI3K(+) patients had shorter PFS among IDH wild-type tumors, however, and no DF/BWCC long-term survivors were either EGFR(+) (0% vs 7%, P = .014) or p53(-) (0% vs 10%, P = .005). The degree of biomarker overlap impacted the efficiency of Bayesian-adaptive clinical trials, while PFS and OS distribution variation had less impact. Biomarker frequency was proportionally associated with sample size in all designs.We identified several associations between GBM genomic subgroups and clinical or molecular prognostic covariates and validated known prognostic factors in all survival periods. These results are important for biomarker-based trial design and interpretation of biomarker-only and nonrandomized trials.
Interim PK analysis results of a phase IIa, open-label, randomized, pharmacokinetic comparative, cross-over study of melphalan HCl for injection (propylene glycol-free) and alkeran for injection for myeloablative conditioning in multiple myeloma patients undergoing autologous transplantation.
Authors: O. S. Aljitawi, S. Ganguly, S. H. Abhyankar, D. Robinson, R. Marks, J. Pipkin, J. McGuirk
Journal: Journal of Clinical Oncology (2011)

6571 Background: High dose melphalan and autologous transplantation is a standard procedure in transplant eligible multiple myeloma patients. The marketed formulation of melphalan, Alkeran, has marginal solubility and limited chemical stability upon reconstitution. Alkeran uses propylene glycol as a co-solvent, which has been reported to cause some complications. On the other hand, Melphalan HCl for Injection (Propylene Glycol-Free), is a reformulation of Alkeran for Injection developed by CyDex Pharmaceuticals, Inc.. It incorporates the Captisol brand of SBECD as a co-solvent which improves stability, potentially allowing for alternative dosing such as longer infusion times. Methods: This is a planned interim pharmacokinetic (PK) analysis of a phase IIa, open-label, randomized, cross-over design study. In this study,the PK of Melphalan HCl for Injection and Alkeran for Injection are assessed in the same MM patients undergoing transplantation. This analysis was planned after 15 patients were treated on the study. The PK measures were determined using WinNorLin 6.1, and a paired difference t-test was used to determine statistical signficance. Furthermore, the safety and tolerability of high-dose melphalan HCL and rates of myeloablation and subsequent engraftment are determined in all patients. Results: All patients achieved myeloablation followed by successful engraftment. Median time to myeloablation was 6.5 days (range 4-7 days). Median time to neutrophil engraftment was day +10. Beside expected grade 2-3 toxicities related to high dose melphalan, no additional toxicities were reported. PK analysis revelaed that Cmax, and AUC were statistically significantly higher after PG-free Melphalan HCL infusion. Conclusions: Melphalan HCl for Injection, administered as half of a high-dose conditioning regimen, appears to result in statistically significant greater exposure to drug and successful myeloablation and subsequent engraftment with no additional toxicity.
Randomized sham controlled pilot trial of weekly electro-acupuncture for the prevention of taxane-induced peripheral neuropathy.
Authors: Danielle Awad, Heather Greenlee, Katherine D. Crew, Donna Buono, Jillian Capodice, Kevin Kalinsky, Matthew A. Maurer, Dawn L. Hershman
Journal: Journal of Clinical Oncology (2015)

e20738 Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a common and potentially disabling effect of taxanes. There are no effective preventive therapies. Electro-acupuncture (EA) uses acupuncture needles attached to an electro-stimulator that generate a low electrical current, and is used to treat acute and chronic pain. Methods: Women with stage I-III breast cancer undergoing 12 weekly taxane treatments were randomized to receive a standardized protocol of either 12 true (EA) or sham (SEA) weekly treatments concurrently. Subjects completed the Functional Assessment of Cancer Therapy-Neurotaxane scale (FACT-NTX), Brief Pain Inventory-Short Form (BPI-SF), Neuropathy Pain Scale (NPS), and a grooved pegboard test at baseline, weeks 6, 12, and 16. Chi square analyses and t-tests examined differences between the two groups. A clinically significant change in the FACT-NTX was defined as ≥ 5-point decrease (worse CIPN) from baseline. Results: A total of 180 subjects were screened, 63 enrolled and 46 completed (25 EA, 21 SEA). Mean age was 50; 25.4% were White, 25.4% Black, and 42.86% Hispanic; 52.4% had no prior chemotherapy. No imbalances by arm were observed. The proportion of subjects with a ≥ 5-point FACT-NTX decrease from baseline at 12 weeks was 44% with EA and 67% with SEA, p = 0.12. At 12 weeks both the SEA and EA groups had an increase in mean BPI Score, but no between group differences were found (mean 2.81 vs. 2.64, p = 0.86). However by 16 weeks (4 weeks after completion of therapy) the SEA group returned to baseline while the EA group continued to worsen (mean 1.65 vs. 3.40, p = 0.03). The NPS score did not differ between groups at 12 weeks, however at 16 weeks the EA group had higher (worse) scores compared to SEA (2.84 vs. 1.59, p = 0.05). Both quality of life and grooved pegboard scores worsened over time, but no between group differences seen. No adverse events were reported. Conclusions: We failed to find a significant difference in pain or neuropathy between groups at 12 weeks. However, of concern, subjects on EA had a slower recovery after taxane completion than SEA subjects. Future studies should focus on EA for treatment as opposed to prevention of CIPN. Clinical trial information: NCT01163682.
Potential cost-effectiveness of a diagnostic that identifies localized versus metastatic prostate cancer in men with biochemical recurrence after radical prostatectomy.
Authors: Mark Eliot Bensink, Kristin Berry, Zahra Musa, Carolyn Bodnar, Daniel Ari Barocas, Daniel W. Lin, Scott David Ramsey
Journal: Journal of Clinical Oncology (2013)

229 Background: Asymptomatic men with low but detectable PSA elevation following radical prostatectomy, often receive costly, burdensome, and potentially damaging salvage radiation therapy with uncertain benefit. A new prostate cancer specific functional imaging technology capable of identifying residual localized disease vs. small volume metastatic disease, to more accurately guide therapy decisions, could be of benefit. As a guide to diagnostic development efforts, the objective of this study was to assess the potential cost-effectiveness of using a novel diagnostic in this way. Methods: A Markov model was built to reflect the life-time natural history of prostate cancer recurrence. The model was used to estimate the incremental impact on costs (US healthcare system perspective) and quality adjusted life years (QALYs) of two alternative strategies: 1) using the new diagnostic to guide therapy vs. 2) usual care - using a combination of CT, MRI and bone scan to guide therapy. Costs were based on estimates from the literature, Medicare reimbursement and expert opinion. Prostate cancer progression, survival, and utilities plus the background risk of all-cause mortality, were obtained from the literature. Base-case diagnostic sensitivity, specificity, and cost were 75%, 90%, and $2,500. Results: The new diagnostic strategy provided an average per patient gain of 1.83 (95% UI: 1.41 - 2.5) QALYs and added cost of $15,600 (95% UI: -$7,000 - 48,800) with an incremental cost-effectiveness ratio of $8,500/QALY (95% UI: -$4,100 - 22,900). Results were most influenced by utility parameters and test performance characteristics however; the new diagnostic provided clinical benefits over a wide range of specificity and sensitivity. Conclusions: This analysis suggests that a diagnostic technology capable of identifying whether men with biochemical recurrence after radical prostatectomy have localized vs. metastatic disease would be cost-effective by reducing the costs and quality-of-life burden associated with non-beneficial radiation therapy. These results support additional investment in the development and validation of such a diagnostic.
Influence of underlying liver disease on response to sorafenib in patients with advanced hepatocellular carcinoma (HCC).
Authors: M. Bouattour, S. J. Faivre, C. Dreyer, V. Paradis, E. Raymond
Journal: Journal of Clinical Oncology (2011)

172 Background: Based on SHARP and Asia-Pacific trials, sorafenib is the first active therapy registered in advanced-stage HCC. The clinical benefit of sorafanib was not evaluated according to underlying liver disease. We aim to evalute results of sorafenib in specific subgroups of patients with various etiology of underlying liver disease. Methods: Between Jan 2006 and Sep 2009, patients with advanced HCC treated with sorafenib in our institution were analyzed. Response evaluated by RECIST criteria, overall survival (OS) and time to progression (TTP) were assessed in each subgroup according to the etiology of liver disease. Results: At the time of analysis, 134 patients were registered. Median age was 63.4 years (range 34–85) and a majority of patients were male (80%). Diagnosis of HCC was pathologically proven in 81% of cases. Patients were classified BCLC stage B and C in 25% and 75%, respectively. Etiology of underlying liver disease was hepatitis B, hepatitis C, alcohol consumption, and NASH in 17%, 25%, 32%, and 13%, respectively (others etiologies in 13% of cases). Demographic characteristics, Child-Pugh class and BCLC tumor stage, and prior therapy were similar for each subgroup. Overall duration of sorafenib treatment was comparable in all subgroups. Among 101 patients evaluable, only two had a partial response (2 %), and median OS was 9.5 months (95% CI: 7.35-11.67). Median TTP was significantly shorter in patient with hepatitis B compared with those with hepatitis C infection (4.4 and 7.3 months respectively; p: 0.036). This difference was not observed in patients with alcohol consumption compared to those with NASH (6.4 vs. 5.2 months; p=0.7). Median OS in patients with hepatitis C infection was 8.4 months and 6.1 months in those with hepatitis B infection (p value: 0.7). No significant difference was observed in patients with alcohol abuse compared with those with NASH (14.2 and 9.9 months respectively; p: 0.72). Conclusions: Overall, clinical benefit of sorafenib does not appear to be influenced by liver disease etiology. However, in patients infected with hepatitis B, progression under sorafenib seems to occur earlier, suggesting a possible role of hepatitis B chronic disease on the outcome. No significant financial relationships to disclose.
End-of-life care for glioblastoma multiforme (GBM) patients at a large academic center.
Authors: Kamini Kuchinad, Xiao Wang, Jiangxia Wang, Anne Evans, W. Anthony Riley, Thomas J. Smith
Journal: Journal of Clinical Oncology (2016)

56 Background: GBM is a uniformly fatal disease with average survival of &lt; 3 years and universal cognitive problems, making advance care planning paramount. End of life (EOL) patterns of GBM care in the US have not been studied. We examined care in a cohort of GBM and brain tumor (BT) patients as part of a program to provide individual provider feedback about EOL care. Methods: We reviewed the care of all GBM patients over 3 years with a random sample of 100, and a 5-yr subset of 45 who received their care at Gilchrist Hospice (GH), our largest provider. We queried EPIC EMR for markers of quality. We also reviewed all 452 advanced cancer pts of the Sidney Kimmel Comprehensive Cancer Center (SKCCC) referred to GH from 7/1/13 to 3/31/15 to find the median length of stay (LOS) and %LOS &lt; 7 days for each division and each physician; 29 BT patients (most GBM) are included. Results: Few patients had documented Advance Directives or code status. Of the 100 pts, 37% were hospitalized in the last 4 weeks of life, and 17% received chemotherapy. Hospice referral and use was 76%. Of those in GH, 64% died at home with hospice and 20% died in inpatient hospice. Variability among physicians in hospice LOS was high (c v = 124.30%) ranging from 6 to 158 days with a median of 33.5 days, exceeding national averages, and 3 of 6 practitioners were below average LOS. Conclusions: In this snapshot of GBM EOL care in the US, improvements can be made in the use of advance care planning, code status, chemotherapy near death, and hospitalization rates. Hospice LOS is above national averages but varies by physician. [Table: see text]
A phase I dose-escalation study of NKP-1339 in patients with advanced solid tumors refractory to treatment.
Authors: N. R. Dickson, S. F. Jones, H. A. Burris, R. K. Ramanathan, G. J. Weiss, J. R. Infante, J. C. Bendell, W. McCulloch, D. D. Von Hoff
Journal: Journal of Clinical Oncology (2011)

2607 Background: NKP-1339 is a novel transferrin targeted ruthenium based anti-cancer compound which is intravenously administered. Its intracellular targets include GRP78, a key regulator of misfolded protein processing. In nonclinical anti-tumor studies, NKP-1339 showed activity against different tumor types, including those resistant to platinum and other standard anti-cancer agents. This Phase I trial evaluates the safety, tolerability, maximum tolerated dose, pharmacokinetics, and pharmacodynamics of NKP-1339. Methods: NKP-1339 is administered as a 30-90 minute infusion (based on volume to be infused) on days 1, 8, and 15 of a 28 day cycle. Full PK sampling in blood and urine is performed on Day 1; trough plasma and urine samples are obtained predose on Cycle 1 Day 8 and Cycle 2 Day 1. PD samples, including transferrin, transferrin receptor, ferritin, serum iron, and TIBC are also collected. Results: A total of 16 patients with various solid tumors have been treated at 6 different dose levels (20, 40, 80, 160, 320, and 420 mg/m2). Tumor types represented in this population include: lung (5); neuroendocrine (3); colon (4) and 1 each of ovarian, cervical, pancreatic, and head and neck cancer. All patients have a performance score of 0 or 1. Demographics: 7 female /9 male; 14 white /2 black; median age 63.5 years (range 51 to 75). At 420 mg/m2 an unusual finding of a transient green discoloration to the plasma in the absence of clinical jaundice or other signs/symptoms has been noted. This is probably due to the complex chemical state of ruthenium in plasma. Unrelated to the plasma discoloration, Grade 1-2 pyrexia and/or rigors has been observed in 2 of 5 patients at the 420 mg/m2 dose level, but has been prevented in subsequent infusions with steroid-based premedications. Preliminary PK results on the first 16 patients show dose proportionality of Cmax and AUC 0-192 (AUC of first dosing interval). Two patients with Stage IV neuroendocrine tumors have experienced stable disease for up to 9 cycles. Conclusions: Promising anti-cancer activity in neuroendocrine tumors has been observed with this novel ruthenium based compound. The toxicity profile is manageable and the PK profile is consistent with preclinical predictions.
Gastric cancer prevalence: A preliminary study according to the cancer registry data at the Jigme Dorji Wangchuck National Referral Hospital, Rhimphu, Bhutan.
Authors: T. D. Wangdi
Journal: Journal of Clinical Oncology (2011)

e12003 Background: Gastric cancer is a common and lethal disease worldwide.Gastric cancers have been reported to be the most common cancer in Bhutan. The JDWNR hospital serves as an apex referral center for cancer referral in Bhutan. Cancer registration was established in Bhutan on June 2008. Methods: Prevalence of gastric cancers among patients attending surgical and oncology services were determined from the cancer registry unit. Results: Data showed that during a two year period from 1’st July 2008 to 31’st December 2010 a total of 352 cases of solid organ malignancies were registered with the cancer registry unit. Among them, 249 (70.7%) were gastrointestinal cancers. Out of which 158 (63%) were gastric cancers, 38 (15%), 34 (14%) and 18 (7%) were cancers of the esophagus, anorectal and colon respectively. Out of 158 gastric cancers, 67 (42.2%) reported at stage IV among which 37 (55%) and 23 (34%) were dead and alive, respectively at the time of reporting. Conclusions: Gastric cancer is the most common cancer of the GIT in Bhutan. Cure rates for this cancer was very low especially in a setting of advanced presentation. The noncommunicable disease programme of the public health division under the ministry of health in the country needs to emphasize more on prevention and early detection in order to reduce the significant mortality resulting due to this disease.
Impact of chemotherapy induced haematotoxicity on blood component use and associated costs in NSCLC and lymphoma patients in Germany
Authors: B. J. Paessens, A. Ihbe-Heffinger, C. von Schilling, R. Bernard, C. Peschel, W. Schramm, K. Berger
Journal: Journal of Clinical Oncology (2008)

20715 Background: Myelosuppression is one of the most relevant side effects of cancer chemotherapy (CT). To date its impact on blood component (BC) use and cost is not well characterised. Methods: Prospective, observational study to determine BC use and associated costs in NSCLC and lymphoma patients (pts). Pts were enrolled consecutively at the start of 1st or 2nd line (immuno-)CT at an academic cancer center in Germany (01/05–06/06). Pts receiving myeloablative CT with peripheral blood stem cell support were excluded. Clinical data and consumption of BC were collected from medical charts. Costs of BC are presented from provider perspective. Results: 180 pts undergoing 633 CT cycles were evaluable (Mean age 59 yrs, 47% NSCLC, 53% lymphoma, 68% stage III/IV, 86% ECOG ≤1). During 11% of CT cycles BC were transfused to 27% of pts (n=49; lymphoma n=22; NSCLC n=27). Fourty six pts (26%) were substituted with red blood cells (RBC), 8 (4%) and 3 (2%) with platelets (PLT) and fresh frozen plasma (FFP). In total, 310 units of blood were consumed (210 RBC, 49 PLT and 51 FFP). Mean number of transfused units (TU) per patient with transfusion amounted to 6.3±5.2 and varied between 4.3±4.9 for NSCLC and 8.9±16.0 for lymphoma pts. The table shows mean BC costs per patient with transfusion stratified by tumour type. Conclusions: Haematotoxicity has significant impact on BC use and associated costs in NSCLC and lymphoma pts. In lymphoma pts BC costs are higher than in pts with NSCLC. Number of TU is highest for RBC. BC costs are highest for pts with PLT transfusion. All (n=49) Lymphoma (n=22) NSCLC (n=27) Total 626.0 (1,484.0) 1,009.7 (2,136.6) 314.0 (391.4) RBC 309.7 (266.9) 389.5 (353.7) 248.4 (155.5) PLT 1,831.5 (2,465.6) 2,193.7 (2,793.1) 745.0 (632.2) FFP 596.3 (462.3) 630.5 (648.4) 548.0 Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Amgen Amgen, Eli Lilly