tbuckley/cabot-search huggingface dataset:
Funding of biomarker, imaging, quality-of-life (QOL), and cost-effectiveness analysis (CEA) studies by NCI.
Authors: Ray A. Petryshyn, Geoffrey David Seidel, Sheila Ann Prindiville
Journal: Journal of Clinical Oncology (2012)

104 Background: NCI’s purpose for the Biomarker, Imaging, and QOL Studies Funding Program (BIQSFP) is to ensure that the most important, scientifically meritorious biomarker, imaging, QOL, and/or CEA studies can be initiated in a timely manner in association with NCI clinical trials. BIQSFP studies are embedded in selected large, randomized phase II treatment trial concepts with a control arm and an integral study(ies), along with integral and/or integrated studies associated with phase III treatment trials, cancer prevention trials, and primary symptom management trials. Methods: BIQSFP provides opportunities to enhance clinical outcomes by validating targets, reducing morbidity, predicting treatment effectiveness, identifying populations that may better benefit from treatment, improving clinical trial accrual and retention, and modifying standards of care. BIQSFP applications are accepted from NCI Cooperative Groups and Community Clinical Oncology Programs. Integral components must be performed in order for the trial to proceed. Integral studies have the highest funding priority. Integrated components are clearly identified as part of the clinical trial from the beginning, are intended to identify or validate (in the patient population of interest) assays/tests/QOL tools that are planned for use in future trials, are performed in real time, and include complete plans for specimen collection, laboratory measurements, and statistical analysis. Integrated studies in general should not be exploratory but rather should be designed to test a hypothesis, not simply to generate hypotheses. Results: Since 2009, 36 BIQSFP funding applications have been reviewed with most evaluations via NCI’s Scientific Steering Committees (http://ccct.cancer.gov/). Twenty studies have been approved for BIQSFP funding. Conclusions: BIQSFP information presented in the poster includes scope of activity, process for application and evaluation, and funded projects (http://biqsfp.cancer.gov/). Funded by NCI Contract No. HHSN261200800001E.
A phase I dose escalation trial of pulsatile high dose gefitinib and docetaxel in patients with an advanced solid tumor
Authors: M. G. Fury, M. Kris, D. Solit, D. G. Pfister, C. G. Azzoli, R. Henry, Y. B. Su, N. Rizvi
Journal: Journal of Clinical Oncology (2005)

3132 Background: Gefitinib has known anti-tumor activity with partial response, durable stable disease and symptom improvement in NSCLC. Concurrent gefitinib and other EGFR-TKI with chemotherapy failed to demonstrate an advantage over chemotherapy alone in phase 3 studies. We have shown that pulsatile administration of gefitinib and taxane therapy in mice xenograft studies allowed for gefitinib dose-escalation and was significantly more effective than continuous therapy. Methods: We initiated a phase 1 study in patients with a solid tumor to study gefitinib preceding docetaxel to determine the MTD and toxicity of pulsatile gefitinib (days 1 and 2) + docetaxel (75 mg/m2 day 3). The starting dose of gefitinib is 1000 mg/day with 6 dose escalation levels planned: 50%→50%→33%→33%→25%. Gefitinib PK was obtained Cycles 1 and 2 of each dose level. Results: We have completed the first two dose levels (n=9 patients). Patient characteristics: 2 F, 7 M; KPS median 80% (70–90%); age median 62 years; prior chemotherapy median 1 regimen (0–2); 4 patients with NSCLC, 3 patients with H/N, 1 patient with NPC, and 1 patient with thyroid cancer. Median cycles = 4 (2–7). No DLTs were observed for the 1st dose level of 1000 mg/day of gefitinib. Toxicities during cycle 1 at dose level 1 (n=3): G1–2 rash (n=3), G3 neutropenia (n=1), G1 diarrhea (n=1). At the 2nd level, 1 patient experienced neutropenic fever and grade 3 hyperbilirubinemia. The dose level was expanded to 6 patients and no further DLT was observed. Toxicities during cycle 1 of dose level 2 (1500 mg/day) (n=6): G1–2 rash (n=3), G1–2 fatigue (n=2), G2 neutropenia (n=1), G4 neutropenia (n=1), G3 hyperbilirubinemia (n=1), G1 diarrhea (n=2). 1 patient with anaplastic thyroid carcinoma with dermal metastases experienced a partial response. 2/3 pretreated H/N patients had symptom improvement and disease stabilization (>7 cycles). Conclusions: Preliminary results suggest that pulsatile high dose gefitinib preceding docetaxel is well tolerated without dose limiting diarrhea or rash to date. We are currently accruing to dose level 3 (gefitinib 2250 mg/day). Supported in part by AstraZeneca. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca
The impact of new strategies on liver metastases from colorectal cancer-a comparison between four time cohorts
Authors: M. Rizell
Journal: Journal of Clinical Oncology (2005)

3745 Background: There have been significant changes in the strategy for treatment of liver metastases from colorectal cancer during the last ten to fifteen years, but the 5-year survival is still reported between 30 and 40%. The changes include portal embolization, neoadjuvant chemotherapy, postoperative adjuvant chemotherapy and radiofrequency ablation. If these strategies have affected outcome, survival and complications of standard anatomical liver procedures; right lobe(RL), extended right lobe(ERL) and left lobe(LL) is reported in this retrospective analysis. Methods: In the year 1983–2003,147 standard liver resections (78 RL, 32 ERL and 36 LL) were performed. Further 60 atypical non-anatomical or segmental resections were done but not included in this analysis. The material is divided in four time cohorts; 83–93, 94–99, 00–04 with 55,40,52 patients in the cohort. The tumors were larger in the first cohort and there were fewer patients with 4 or more tumors in the second cohort. Results: Radical surgery(RO) was reported 50, 75, 60% in the three cohorts. There was no significant difference in 5-year survival in these groups. No impact on survival has been registered of pre- and postop. chemotherapy in R0 as well as in R1 and R2 resections. Postop mortality in 1983–93 was 4%, in 94–99 (5 and no mortality after that. Major postop complications were registered in 14%, 18% and 11%. ERL resection was preceeded in 16 cases with portal embolization of right liver lobe. There were seven major complications with three postop. death without and three major complications and no postop death with embolization. There is a trend to better long time survival after embolization (p=0.09) Conclusions: Although the mortality are less, the 5 year prognosis after liver sugery has been unchanged in our department, despite of new treatments since 1983, although more patients with 4 or more tumors are operated. No significant financial relationships to disclose.
HPV16 infection and p53 codon 72 polymorphism in cervical cancer and precursor lesions in Hubei, China.
Authors: H. Cai, C. Chen, X. Ding
Journal: Journal of Clinical Oncology (2011)

e15582 Background: The aim of this study was to investigate the prevalence of HPV16 infection and distribution of p53 codon72 polymorphism with cervical cancer and precursor lesions and to correlate these to cervical cancer risk in Chinese population in Hubei, China. Methods: A total of 104 patients with cervical squamous-cell carcinoma (SCC) and 52 patients with cervical intraepithelial neoplasia (CIN) II-III and 88 Patients with CIN I were obtained from women undergoing biopsy or surgery. HPV16 and p53 codon72 polymorphism were examined by PCR. Results: The prevalence of HPV16 was 78.5% in the SCC group, 44.2% in the CINII- III group and 16.7% in the CIN I group. There was significantly association between HPV16 positivity and cervical neoplasia progression (Spearman R=0.550, P=0.001). The percentages of Arg/Arg, Pro/Arg and Pro/Pro genotypes in the SCC group were 38.5%, 44.2%, 17.3%, and in CIN I group were 52.4%, 40.5%, 7.1%, respectively. The RR (risk ratio) of Pro/Pro genotype was 3.300 (95% CI=1.192-9.136) compared with Arg/Arg genotype. The frequencies of p53 Arg/Arg genotype in SCC group were not statistically different from those in the CIN I and CINII- III group. The distributions of p53 codon72 genotype Arg/Arg, Arg/Pro, Pro/Pro were 32.8%, 57.1%, 14.2% in the HPV16 infected SCC group; 27.1%, 47.8%, 30.4% in the HPV16 infected CINII- III group; and 28.6%, 57.1%, 17.3% in the HPV16 infected CIN I group respectively. The distribution of p53 genotypes was not significantly different from each other in the three groups (P=0.517). The frequency of p53 Arg/Arg genotype in HPV16 negative SCC group (50%) was not statistically different from that in the HPV16 positive SCC group (P=0.210). Conclusions: The p53 codon72 Pro/Pro genotype was one of the highest risk factors of precancerous cervical lesion in Chinese population in Hubei areas.
Data accuracy and financial cost of conducting retrospective ontological clinical trials using ICD-9-CM in the age of ICD-10-CM.
Authors: Ardaman Shergill, Parvaneh Dorestani, Andrew D. Boyd, Neeta K. Venepalli
Journal: Journal of Clinical Oncology (2014)

229 Background: Estimates of the 1 year implementation delay of ICD-10-CM (I10) range upto $6.6 billion with the majority of cost attributable to I10 implementation. Little attention has been paid to post implementation costs and management strategies for data accuracy within longitudinal cancer related databases spanning both ICD-9-CM (I9) and I10. The objective of our study was to quantify financial impact and compare data quality of I10 transition in cancer clinical trials through backward I10 to I9 mapping via two tools. Methods: Cancer related original research articles published in NEJM, Blood and JCO between Jan 1 st 2013 and Dec 31 st 2013 were reviewed for I9 utilization. Each I9 code was mapped forward to I10 via the Motif web portal tool. The I10 codes were manually reviewed with additional clinically relevant I10 codes added. The final I10 code list was mapped backward to I9 using two tools, the Motif web portal and CMS GEMs. Generated I9 codes were compared to the original I9 list to identify ‘lost’ codes. To assess financial implications of lost data, lost I9 codes were assessed in 2010 Illinois Medicaid data. Results: Of 1,567 original articles reviewed, 7 articles were included and yielded 412 I9 codes which mapped to 1437 I10 codes. Upon manual review, 416 I10 codes were added. Backward mapping by Motif web and CMS GEMs respectively yielded 652 and 551 I9 codes; 16 of the original I9codes were absent from the CMS GEMs list while Motif tool yielded 100% of original codes. Of these 16, 12 codes were present in 2010 Illinois Medicaid data, and accounted for 7,490 patient encounters (0.52%) and $1.1 million (0.35%) of total Medicaid reimbursements. Conclusions: We report significant differences in data quality of I9 generated by backward coding via CMS GEMs and the Motif web tool, with major financial impact. Longitudinal data analyses upto 5 years post ICD-10-CM transition will require backward coding, and comparison of ICD-9-CM codes for accuracy. The bridging methodology and analytic tools presented can be replicated by organizations and clinical researchers to increase data fidelity spanning the upcoming transition.
High sensitivity detection and robust enrichment for PIK3CA somatic mutations using ice COLD-PCR technology.
Authors: R. Lin, T. Woodford, G. Wu, P. Eastlake, R. Candau, B. J. Legendre, K. Richardson
Journal: Journal of Clinical Oncology (2011)

e13546 Background: High sensitivity detection of cancer biomarkers facilitates early diagnosis and provides insight for intervention including stratification for drug treatment and monitoring changes in tumor mutation profiles by analyzing DNA isolated from serum/plasma or circulating tumor cells. PIK3CA, encoding the PI3K p110α catalytic subunit, is mutated frequently in common cancers, including breast and colon carcinomas. 80% of these mutations are represented by three amino acid substitutions in the enzyme’s helical (E542K and E545K) or kinase (H1047R) domains. Methods: In this study, we have applied improved and complete enrichment CO-amplification at lower denaturation temperature PCR (Ice COLD-PCR) technology for high sensitivity detection and robust enrichment of any mutations present in a DNA sample. Ice-COLD-PCR preferentially amplifies low levels of any mutant DNA in a sample containing a vast excess of wild-type DNA. The use of a reference sequence oligonucleotide complimentary to one of the wild-type DNA strands results in linear amplification of one of the wild type strands while both mutant strands amplify exponentially during ice COLD- PCR. After Ice COLD-PCR, there is sufficient mutant allele enrichment to allow Sanger sequencing confirmation of the mutation. Results: The use of Ice COLD-PCR allows for the enrichment of mutations any of the key mutations in the PIK3CA gene that cannot be detected by standard PCR followed by Sanger sequencing methods. Initial limit of detection experiments indicate that the detection and sequence confirmation of mutations in PIK3CA more sensitive than standard PCR amplification or allele specific probe methodologies. Conclusions: After Ice COLD-PCR, low level PIK3CA mutant alleles are enriched over the wild-type allele such that simple sequence confirmation on multiple downstream systems such as Sanger Sequencing or allele-specific probe platforms is possible. Ice COLD-PCR amplification of PIK3CA and other genes requires only a standard thermocycler coupled to any downstream sequence analysis platform and therefore can be developed as a powerful, highly sensitive diagnostic assay.
Comparing the cost-effectiveness of linezolid to trimethoprim/sulfamethoxazole plus rifampicin for the treatment of methicillin-resistant Staphylococcus aureus infection: a healthcare system perspective
Authors: E. von Dach, C.M. Morel, A. Murthy, L. Pagani, M. Macedo-Vinas, F. Olearo, S. Harbarth
Journal: Clinical Microbiology and Infection (2017)

Few industry-independent studies have been conducted to compare the relative costs and benefits of drugs to treat methicillin-resistant Staphylococcus aureus (MRSA) infection. We performed a stochastic cost-effectiveness analysis comparing two treatment strategies-linezolid versus trimethoprim-sulfamethoxazole plus rifampicin-for the treatment of MRSA infection.We used cost and effectiveness data from a previously conducted clinical trial, complementing with other data from published literature, to compare the two regimens from a healthcare system perspective. Effectiveness was expressed in terms of quality-adjusted life-years (QALYs). Several sensitivity analyses were performed using Monte Carlo simulation, to measure the effect of potential parameter changes on the base-case model results, including potential differences related to type of infection and drug toxicity.Treatment of MRSA infection with trimethoprim-sulfamethoxazole plus rifampicin and linezolid were found to cost on average €146 and €2536, and lead to a gain of 0.916 and 0.881 QALYs, respectively. Treatment with trimethoprim-sulfamethoxazole plus rifampicin was found to be more cost-effective than linezolid in the base case and remained dominant over linezolid in most alternative scenarios, including different types of MRSA infection and potential disadvantages in terms of toxicity. With a willingness-to-pay threshold of €0, €50 000 and €200 000 per QALY gained, trimethoprim-sulfamethoxazole plus rifampicin was dominant in 100%, 96% and 85% of model iterations. A 95% discount on the current purchasing price of linezolid would be needed when it goes off-patent for it to represent better value for money compared with trimethoprim-sulfamethoxazole plus rifampicin.Combined treatment of trimethoprim-sulfamethoxazole plus rifampicin is more cost-effective than linezolid in the treatment of MRSA infection.
Efficacy of palonosetron for prevention of chemotherapy-induced nausea and vomiting in patients with stomach cancer receiving FOLFOX4 regimen.
Authors: S. K. Kim, Y. J. Choi, Y. M. Seol, M. G. Song, H. J. Shin, J. Chung, G. J. Cho
Journal: Journal of Clinical Oncology (2011)

e19580 Background: Palonosetron, a unique second generation 5-HT3RA, has demonstrated superiority in preventing both acute and delayed emesis when compared with the first-generation 5-HT3RAs. The aim of this study was to assess the efficacy and safety of a single dose palonosetron in patients with stomach cancer receiving moderately emetogenic chemotherapy, FOLFOX4 regimen. Methods: Patients received a single intravenous bolus of palonosetron (0.25mg) before administration of oxaliplatin. Nausea and vomiting were evaluated over 7-day period. Also the adverse effects were reported. Complete response (CR) was defined as no vomiting without use of rescue medication during overall phase (0-168h) and complete control (CC) was defined as CR and only mild nausea. The primary endpoint was CR during overall study period. Efficacy and toxicity was compared to our immediate historical cohort or 108 patients treated with ondansetron. Results: Between March and September 2010, we enrolled 48 patients with histologically confirmed stomach cancer scheduled to receive FOLFOX4 regimen. More than half of the patients had not received any previous chemotherapy (66.7%) and all of patients had stage IV disease. Complete response rate during overall phase was 54.2% (palonosetron, ITT cohort) and 38.9% (ondansetron, historical cohort). The proportion of patient with a CC during the acute phase (0-24h) was significantly higher in the ITT cohort [44 of 48 patients (91.6%)] than in the historical cohort [81 of 108 patients (75.0%)]. All adverse events induced by palonosetron were mild, suggesting no safety-related problem. Conclusions: Palonosetron is a very effective and safe antiemetic drug for the prevention of nausea and vomiting in patients with stomach cancer receiving FOLFOX4 chemotherapy.
Treatment breaks due to mucositis in patients with head and neck (H&amp;N) cancer
Authors: S. Patel, M. Abboud-Finch, J. A. Petersen, J. T. Marron, V. K. Mehta
Journal: Journal of Clinical Oncology (2008)

17024 Background: Mucositis is a primary factor limiting the dose intensity of radiation therapy (RT) in H&N cancer. Because reduced dose intensity can affect survival, we studied whether mucositis affected dose intensity in patients treated for H&N cancer. Methods: Patients with H&N cancer (or family members) who had registered to use NexCura’s online NexProfiler Treatment Option Tool for H&N Cancer between Aug 2001 & Oct 2006 and previously opted to participate in surveys were invited to complete an online survey about their treatment experience. Of the 5246 individuals invited, 233 completed the survey of 84 questions during a 4 week period in Jan-Feb 2007. All eligible patients had received RT as part of their treatment. Results: 74% of respondents were male. 86% had completed treatment in 2001–2006. 15% received RT alone, 85% received RT + chemotherapy. 77% of all patients rated mucositis as the most severe treatment side effect. 30% of patients had an RT break to recover from a side effect. Of these, 38% said RT was stopped ≥2 times and 43% said RT was stopped for ≥5 days (4% for ≥10 days). The top 3 reasons for RT breaks were mouth pain, skin burn, and dehydration. 46% of patients cited some form of mucositis (difficulty/pain on swallowing; mouth soreness; mouth sores/ulcers; pain and/or burning; throat soreness; inability to swallow food/solids, liquids, or own saliva) as the primary or secondary reason for RT breaks. 33% of 199 patients had delays or early termination of chemotherapy due to side effects; the top 3 reasons were neutropenia, dehydration, and anemia. 13% reported mouth sores/ulcers, mouth pain, or swallowing difficulty as a primary or secondary reason for interruption of chemotherapy. Conclusions: In a large survey of patients who had undergone treatment for H&N cancer, the patients felt that mucositis was the most common reason for interruption of RT. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Amgen, Medimmune Amgen Amgen, Medimmune
Human papillomavirus in non-small cell lung cancer in never smokers in east Asia: A systematic review of the literature.
Authors: Yoshikazu Hasegawa, Masahiko Ando, Akihito Kubo, Shunichi Isa, Satomi Yamamoto, Kazuyuki Tsujino, Takayasu Kurata, Sai-Hong Ignatius Ou, Minoru Takada, Jill Koshiol, Tomoya Kawaguchi
Journal: Journal of Clinical Oncology (2012)

e18128 Background: Non-small cell lung cancer (NSCLC) in never-smokers has emerged as a global health concern, but its cause is undetermined. Epidemiological studies have shown that the disease is frequently observed in East Asia. Human papillomavirus (HPV) infection has been widely investigated in NSCLC, particularly in Asia. However, few studies have focused on regional differences in the prevalence of HPV in NSCLC tissue from never smokers. Methods: We performed a systematic search of PubMed for articles of HPV infection in human subjects with NSCLC between Jan. 1993 and Dec. 2011. We included studies that used polymerase chain reaction (PCR) as the primary HPV detection method. Because smoking status was not fully reported in all studies, we contacted the authors by e-mail to supplement this information. Differences in the distribution of patients with and without HPV infection were tested with the Chi squared test. Results: We identified 42 eligible articles, including 21 from Asian countries (N=2095 NSCLC cases), 17 from European countries (N=1430) and 4 from North and South America (N=160). The HPV prevalence was 28.0% (95% confidence interval (CI): 26.1-30.0%), 8.7% (95% CI: 7.3-10.3%) and 21.2% (95% CI: 15.2-28.4%), respectively. Seven studies from East Asia (N=939) and 4 from Europe (N=569) provided information on smoking status. The number of never smoker was 314 patients (33.4%) in East Asia and 54 patients (9.5%) in Europe. The HPV prevalence in East Asian countries was similar between never and ever smokers (38.2% vs 39.5%, P=0.94) and was significantly higher compared with European countries, where the prevalence was14.8% in never smokers (P&lt;0.001) and 2.9% in ever smokers (P&lt;0.001). In East Asia, the HPV prevalence was particularly high in Taiwan, the central part of China and Okinawa, south of mainland Japan. Conclusions: The prevalence of HPV is high in NSCLC tumor tissues from East Asia. Although the numbers of never smokers from European studies are very small, the different patterns of HPV prevalence from Asian and European countries is intriguing and deserves further study.