tbuckley/cabot-search huggingface dataset:
Association of clinical parameters and overall survival (OS) in patients (pts) with metastatic renal cell carcinoma (mRCC) treated with high-dose interleukin-2 (HD IL-2).
Authors: David D. Stenehjem, Kinjal Parikh, Julia Anne Batten, Joan Van Atta, Hilda Crispin, Daniel S. Sageser, Kenneth F. Grossmann, Junfeng Wang, Srinivas Kiran Tantravahi, Wolfram E. Samlowski, Neeraj Agarwal
Journal: Journal of Clinical Oncology (2014)

476 Background: HD IL-2 immunotherapy can provide durable responses in mRCC, but has a high incidence of severe adverse events (AEs). Therefore, determining pts most likely to achieve response before and during HD-IL2 treatment will help clinicians and pts best utilize HD IL-2 for the treatment of mRCC. Methods: Sequential clear cell mRCC pts treated with HD IL-2 at the University of Utah Huntsman Cancer Institute from 2000 to 2012 were included. The following clinical parameters were assessed: AE incidence, type and severity; total dose of IL-2 received and use of a 40 MIU dose cap; baseline weight, age, gender and MSKCC prognostic risk; and systemic therapy pre- or post-HD IL-2. Univariate and multivariate analyses were constructed using COX Proportional Hazard model. Results: 85 pts with clear cell mRCC treated with HD IL-2 were included with a median age of 56 years (range 32-76). Pts belonged to the following MSKCC categories: 11 (13%) good, 70 (82%) intermediate, and 4 (5%) poor risk. The median OS was 817 days. Multivariate analysis identified 6 factors associated with OS including: MSKCC prognostic group (intermediate vs good HR = 4.31, CI 1.41-16.04), grade 3 rigors (no vs yes HR = 3.07, CI 1.49-6.47), baseline weight (&lt;80 vs &gt;80 kg HR = 2.18, CI 1.08-4.39), total dose of IL-2 administered (quartile 1 vs 2 HR 2.90, CI 1.06-8.57; quartile 1 vs 3 HR 7.37, CI 2.63-21.54; quartile 1 vs 4 HR 25.17, CI 7.34-102.01), composite of the number and severity of AEs (continuous, HR 5.11, CI 1.01-27.56), and gender (female vs male HR 2.84, CI 1.06-7.20). Factors not associated with an OS benefit in this model include age at metastatic disease, use of a 40 MIU IL-2 dose cap and systemic therapy pre- or post-HD IL2. Conclusions: The following parameters predicted an OS benefit with HD IL-2 when controlled for MSKCC prognostic risk and systemic therapy pre or post HD IL-2: fewer and less severe AEs; higher baseline weight; male gender; and the ability to tolerate a higher cumulative dose of IL-2. Notably increased age did not portend poor outcome, and should not be considered a contraindication to treatment with HD IL-2 in otherwise eligible patients.
A novel and simple <i>KRAS</i> mutation detection method, FRET-Based Preferential Homoduplex Formation Assay (f-PHFA): Results from a multicenter, clinical evaluation trial.
Authors: Kensei Yamaguchi, Kiwamu Akagi, Miho Kakuta, Masafumi Kurosumi, Yoji Nishimura, Norio Saito, Motohiro Kojima, Atsushi Ochiai, Atsushi Ohtsu, Takayuki Yoshino
Journal: Journal of Clinical Oncology (2012)

476 Background: KRAS gene mutation in colorectal tumors is predictive of nonresponse to anti-epidermal growth factor receptor (EGFR) antibodies in patients with metastatic colorectal cancer (CRC). The F-PHFA has been developed as a simple and accurate mutation detection assay especially for somatic mutations. In this study, we evaluated KRAS mutation detection by F-PHFA which detects 7 common mutations in codon 12 and 13. This study was a multicenter, clinical evaluation trial designed to evaluate the efficacy of the F-PHFA method forKRAS testing in patients with CRC. Primary endpoint was the concordance rate of KRAS mutation between F-PHFA and direct sequencing with manual micro-dissection (MMD) to enrich the tumor concentration. Secondary endpoints included the concordance rate between F-PHFA and direct sequencing without MMD. Methods: The key eligibility criteria included histologically confirmed colorectal adenocarcinoma with adequate tumor samples. The materials were formalin-fixed paraffin-embedded (FFPE) 8 unstained slides at 10 um and 2 matching hematoxylin-eosin (HE)-stained slide, which were sent to the central pathology review to confirm the tumor content and to mark the tumor area. Genomic DNA was extracted using QIAamp DNA FFPE Tissue from both whole tissue of slide and tissue with MMD. F-PHFA and direct sequencing were conducted independently in two laboratories. Results: FFPE specimens from 165 patients with colorectal adenocaricinoma were registered. Success rates on KRAS tests of F-PHFA both of with or without MMD were 100% (165/165). However, those of direct sequencing were 99.4% (164/165). The concordance rate between F-PHFA and direct sequencing were 99.4% (163/164) for both of with MMD and without MMD. Only one discordant sample had a rare mutation other than the 7 common mutations. Total assay time was about 3.5 hrs. Also 20 ng of DNA was enough to examine 7 types of KRAS mutations. Conclusions: We confirmed that F-PHFA and direct sequencing shows high concordance rate regardless of MMD. F-PHFA for KRAS mutation detection method is very suitable for clinical use in terms of easiness and accuracy.
Efficacy and safety of valrubicin in non–muscle-invasive bladder cancer in older and younger patients.
Authors: Michael S. Cookson, Christine Francis Lihou, Samira Q. Harper, Thomas Li, Surya Chitra, Ronald Tutrone
Journal: Journal of Clinical Oncology (2013)

309 Background: Valrubicin was approved in the United States in 1998, removed from the market in 2002 because of manufacturing issues, and reintroduced in 2009. We report the effectiveness and safety of valrubicin, stratified by patient age, from a US multicenter, observational, retrospective study. Methods: Medical records of adults with non–muscle-invasive bladder cancer (NMIBC) who used valrubicin were abstracted between March and September 2011. The median age (75 [range 42–95] years) was the stratification cutoff. Kaplan-Meier analyses were performed for event-free survival (EFS), worsening-free survival (WFS), and progression-free survival (PFS). Results: 113 patients (mean age, 73.7 years) received intravesical valrubicin (median, 6 [range, 2–18] instillations). Median EFS, WFS, and PFS were similar in patients ≤75 vs &gt;75 years old (see Table); 1-year rates were 17.8% vs 15.4%, respectively, for EFS; 16.1% vs 14.3% for WFS; and 80.2% vs 81.4% for PFS. 11 (19%) patients aged ≤75 years vs 4 (7%) aged &gt;75 years underwent radical cystectomy; 28 (48%) vs 28 (51%), respectively, experienced ≥1 local adverse reaction; 3 (5%) vs 4 (7%) experienced ≥1 serious adverse event; and 4 (7%) vs 1 (2%) discontinued as a result. Conclusions: In patients with NMIBC treated with intravesical valrubicin, effectiveness and safety are similar in patients aged ≤75 and &gt;75 years. Funding: Research and abstract were supported by Endo Pharmaceuticals Inc. [Table: see text]
The Predictive Significance of Early Metabolic Remission Post Autologous Hematopoietic Transplantation in Lymphomas Conditioned with Either BEAM or a Busulfan-Based Regimen
Authors: Ioanna Sakellari, Despina Mallouri, Varnavas C Constantinou, Michail Iskas, Ioannis Batsis, Stergios Papadimitriou, Kira Panteliadou, Panayiotis Palladas, Ioannis Datseris, Achilles Anagnostopoulos
Journal: Blood (2015)
Incidence and Characteristics of Therapy-Related Myeloid Neoplasms in Patients with Non-Hodgkins Lymphoma Treated with Radioimmunotherapy
Authors: Salman Waheed, Iva Ferreira, Deborah A. Katz, Reem Karmali, Stephanie A. Gregory, Parameswaran Venugopal, Jamile M. Shammo
Journal: Blood (2012)
Prognostic significance of tumor infiltrating natural killer cells in periampullary adenocarcinoma.
Authors: Sebastian Lundgren, Jacob Elebro, Margareta Heby, Bjorn Nodin, Jakob Eberhard, Karin Jirstrom
Journal: Journal of Clinical Oncology (2016)

267 Background: Adenocarcinomas in in the pancreas and the periampullary region are heterogenous with the shared trait of having dismal prognosis. Despite recent progress in cancer therapy this has not been reflected in better prognosis for this patient group. Research has thus begun to explore the role of the immune system in pancreatic cancer. The aim of this study was to analyze the prognostic value of CD56+ natural killer (NK) cells in periampullary cancer, with particular reference to morphological type. Methods: Immunohistochemical expression of CD56 in lymphocytes and tumor cells was analyzed in tissue microarrays with tumors from 175 consecutive cases of operated periampullary adenocarcinoma, 110 of pancreatobiliary-type (PB type) and 65 of intestinal-type (I type) morphology. Kaplan-Meier and Cox regression analysis, unadjusted and adjusted for sex, age, stage, grade, size, growth in peripancreatic fat, perineural tissue and blood vessels, adjuvant chemotherapy and resection margins, were applied to determine the impact of CD56 expression on 5-year overall survival (OS). Results: A high density of CD56+ NK cells correlated significantly with low T- and N-stage (p = 0.003; p = 0.009), absent lymphatic, vascular and perineural infiltration (p = 0.007; p = 0.006; p = 0.023) and growth in peripancreatic fat (p = 0.016). High density of CD56+ NK cells was associated with a prolonged OS in univariable, but not multivariable, analysis in PB type, but not in I type, tumors (HR = 0.60; 95% CI 0.37-0.98). Interestingly, high density of CD56+ NK cells was a negative predictor of response to adjuvant chemotherapy in patients with PB-type tumors (p for interaction = 0.020). Tumor specific CD56 expression was significantly associated with reduced OS in univariable, but not in multivariable analysis, in patients with PB type but not in I type tumors (HR = 1.65; 95% CI 1.09-2.49). Conclusions: These results demonstrate that stromal CD56+ NK cell infiltration has a significant favorable impact on prognosis in PB type, but not in I type, periampullary cancer. Of note, this beneficial effect was only seen in patients not receiving chemotherapy, indicating that chemotherapy may modulate the beneficial prognostic effect of NK cells.
Rare respiratory diseases are ready for primetime: from Rare Disease Day to the European Reference Networks
Authors: Marc Humbert, Thomas O. Wagner
Journal: European Respiratory Journal (2017)

Rare diseases are life-threatening or chronically debilitating conditions which are of such low prevalence (fewer than 1 in 2000 people) that special combined efforts are needed to address them [1]. Launched in 2008 by Rare Diseases Europe (EURORDIS), a non-governmental patient-driven alliance representing 733 rare disease patient organisations in 64 countries, Rare Disease Day (figure 1) takes place on the last day of February each year. The main objective of Rare Disease Day is to raise awareness amongst the general public and decision-makers about rare diseases and their impact on patients' lives [2]. In 2017, Rare Disease Day will emphasise that research brings hope to people living with a rare disease [2]. Indeed, due to the rarity and diversity of rare diseases, research needs to be international to ensure that experts, researchers and clinicians are connected, that clinical trials are multinational, and that patients can benefit from the pooling of resources across borders [2]. The ERN-LUNG network is currently made up of 60 centres in 12 countries and is focused on rare respiratory diseases <http://ow.ly/CG0d3089xDC>
Ifosfamide based chemotherapy in nasopharyngeal cancer: Evaluation of its role as neo-adjuvant chemotherapy
Authors: P. Mohindra, S. G. Laskar, J. P. Agarwal, M. Sengar, S. Vyas, V. R. Pai, A. Budrukkar, P. Pai, A. D’Cruz, K. A. Dinshaw
Journal: Journal of Clinical Oncology (2008)

17043 Background: Ifosfamide based chemotherapy (CT) has been used in non-nasopharyngeal Head-Neck cancers and recurrent/ metastatic nasopharyngeal carcinomas (NPC). It’s use as Neo-adjuvant chemotherapy (NACT), in primary NPC isn’t sufficiently evaluated. Materials and Methods: From 1997 to 2004, treatment results of 78 patients of untreated, NPC who received Ifosfamide-Cisplatin based NACT at our institute were retrospectively analysed. A third drug; paclitaxel, 5-Fluoruracil or Doxorubicin was used in 45% patients. About 80% patients had stage III/IV disease. Definitive treatment comprised of radical radiotherapy (RT) or concurrent chemoradiotherapy (CTRT), which was given in 55% patients using weekly Cisplatin. The median follow up of all patients was 29 months while that for surviving patients was 38 months. Results: Post NACT, 92% patients had a partial response (PR) while 3% had a complete loco-regional response (CR). The rates of CR increased to 89% after completion of definitive treatment, with overall response rates of 99%. With follow up, 29.5% patients developed recurrent/ persistent disease. At the end of follow up, 60 patients were alive amongst which 77% patients were disease-free. The local and loco-regional control rates at 2 years were 81% and 77%, respectively. The 2-year overall survival (OAS) was 90% and disease-free survival was 70%. 15.7% developed Grade III or more neutropenia. Ifosfamide dose of more than 25gm showed a trend towards increased grade III/IV neutropenia. Early presentation, Undifferentiated histology, RT dose more than 66 Gy, six or more cycles of CCRT and CR at treatment conclusion were the significant factors affecting OAS. An increased probability towards a complete response was seen with symptom duration less than 4 months, early nodal stage and use of a 3-day regime in NACT. No case of febrile neutropenia was reported with no treatment related mortality. Conclusion: Results from this retrospective analysis of use of Ifosfamide and Cisplatin combination as a NACT in advanced NPC have been quite encouraging with prospects to be incorporated in prospective trials. No significant financial relationships to disclose.
18F-FDG PET as a predictor of resectability and clinical outcomes in locally advanced pancreatic cancer patients treated with radiotherapy.
Authors: Richard Tuli, Wensha Yang, Mourad Tighiouart, Yong Yue, Benedick Fraass, Howard Mark Sandler, Andrew Eugene Hendifar, Nicholas N. Nissen
Journal: Journal of Clinical Oncology (2014)

378 Background: Surgical resection is the preferred approach for localized pancreatic adenocarcinoma, yet likelihood of margin positive resection precludes its use in patients with locally advanced (LAPA) disease. Whereas CT imaging is the standard for defining resectability, studies suggest reduced accuracy following radiotherapy (RT). Given the potential clinical implications, improved methods to define resectability are needed. We investigate whether PET and other clinical factors can be used to predict likelihood of margin negative resection in LAPA patients. Methods: We reviewed LAPA patients treated with RT from 2011-2013 who also underwent pre- and 6-week post-RT PET/CT. Mann-Whitney test and Cox modeling were used to identify predictors of margin negative resection and progression-free survival (PFS), respectively. Variables assessed included: pre- and post-RT SUV max, mean, coefficient of variation (CV), total lesion glycolysis, CA19-9 and tumor size. Results: Eighteen LAPA patients treated with RT were identified. Median age was 66 years. Seven were considered resectable following RT. 6 patients underwent margin negative resection, while the 7 th patient refused surgery. An additional 2 patients were technically resectable, but developed metastatic disease. Mean value for post-RT SUV max was 3.5 in resected patients versus 4.9 in unresected patients. This difference was borderline significant (p=.08) for predicting resectability. Similarly, pre- to post-RT change in SUV max was -4.37 in resected patients and -1.26 in unresected patients, which was also not significant (p=.17). Median PFS was 13 months for resected patients and 8.5 months for unresected patients (p=.06). Predictors of PFS included post-RT SUV CV (p=.05) and pre-RT CA19-9 (p=.03). Conclusions: Mean post-RT SUV max was borderline significant for predicting which LAPA patients may undergo successful margin negative resection. Post-RT metabolic response was also predictive of improved PFS, further validating PET/CT as an important prognostic imaging tool. Studies are ongoing to further validate these predictors of resectability given the potential clinical significance.
Attrition rates, reasons, and predictive factors in supportive/palliative oncology clinical trials at a comprehensive cancer center.
Authors: Isabella Claudia Glitza, David Hui, Gary B. Chisholm, Eduardo Bruera
Journal: Journal of Clinical Oncology (2012)

9069 Background: Attrition is common among supportive/palliative oncology clinical trials. Few studies have documented the reasons and predictors for dropout. We aimed to determine the rate, reasons and factors associated with attrition both before reaching the primary endpoint (PE) and the end of study (EOS). Methods: We conducted a review of all prospective interventional supportive/palliative oncology trials by our department between 1999-2010. Patient and study characteristics and attrition data were extracted. We determined factors associated with attrition using multivariate logistic regression analysis. Results: 15 blinded randomized trials and 3 single arm trials were included. 16 of 18 studies did not reach accrual target. Baseline demographics for the 1214 patients were: median age 60 (range 23-93 years), female 56%, Caucasians 69%, ECOG performance status ≥3 41%, gastrointestinal malignancies (23%), median fatigue 7/10, appetite 5/10 and pain 4/10. Attrition rate was 26% (N=311) for PE and 44% (N=535) for EOS. Common reasons for EOS dropout were patient preference (N=93, 17%), symptom burden (N=87, 16%), death (N=45, 8%) and hospital admission (N=43, 8%), and were similar for PE dropouts. No predictors were identified for PE attrition. The Table shows poor performance status, anorexia and dyspnea are associated with EOS attrition in multivariate analysis. Conclusions: We found that attrition rate was high amongsupportive/palliative oncology clinical trials, and was associated with poor function and high baseline symptom burden. These findings have implications for future study designs including eligibility criteria and sample size calculation. [Table: see text]
The value of research for ERCC1 testing in stage I non-small cell lung cancer (NSCLC).
Authors: J. A. Roth, J. J. Carlson, L. Steuten, S. D. Ramsey, D. L. Veenstra
Journal: Journal of Clinical Oncology (2011)

e16544 Background: Value of research analysis can be used to assess the value of clinical trials and prioritize research funding. We used this approach to assess the value of additional trials to investigate ERCC1 expression testing to guide adjuvant chemotherapy decisions in fully resected Stage I NSCLC. Methods: We developed a decision-analytic model and used value of information methodology to assess the value of research (VOR) for two treatment strategies: 1) ERCC1 testing to inform adjuvant chemotherapy decisions, with ERCC1+ patients receiving no chemotherapy and ERCC1- patients receiving cisplatin+vinorelbine chemotherapy; 2) standard care, with all patients receiving no chemotherapy. Model parameters and uncertainty ranges were derived from a retrospective analysis of the International Adjuvant Lung Cancer Trial and published literature. The affected population was derived from SEER incidence estimates, and examined over a discounted 10-year time horizon. A variety of willingness to pay (WTP) thresholds were examined. Results: At a WTP of $100,000 per quality-adjusted life year, the ERCC1 testing strategy produced greater net-benefit in 61% of simulations. The average consequence of selecting the wrong strategy was $10,000. With an affected population of 233,825, the VOR for a trial large enough to reduce all uncertainty was $910 million, with $470 million due to uncertainty about the overall survival hazard ratio for treated and untreated ERCC1- patients. Preliminary estimates suggest a VOR of $650 to $870 million for a trial comparing ERCC1 and standard care strategies in samples of 100 to 1,000 per arm, respectively. Conclusions: Considerable value could be created through additional clinical trials to reduce uncertainty about the comparative health outcomes of ERCC1 testing and standard care strategies in stage I NSCLC. The large VOR for clinical trials with plausible sample sizes demonstrates that there is great potential to realize this value. Forthcoming expected net-benefit of research results will compare the VOR of various trial designs and sample sizes to the cost of such trials. These findings can assist stakeholders in prioritizing funding for ERCC1 research relative to alternative research investments.
Older patients with germ cell cancer of the ovary
Authors: R. Urban, J. M. Hu, J. Y. Shin, D. S. Kapp, C. B. Powell, L. Chen, K. Osann, J. K. Chan
Journal: Journal of Clinical Oncology (2008)

16588 Background: To determine prognostic factors and survival of older (>40 years) patients with germ cell ovarian cancer. Methods: Demographic, clinico-pathologic, treatment and surgery information were obtained on all patients with invasive ovarian carcinoma registered in the Surveillance, Epidemiology and End Results (SEER) Program of the National Cancer Institute between 1988 and 2001. Patients were divided into two groups: those diagnosed at age 40 years or less and >40 years old. Survival data were analyzed using Kaplan-Meier estimates. Results: Of 778 women diagnosed with germ cell cancer of the ovary, 77 were older than 40 years with a median age of 50 years. 701 women 40 years or less were used as controls; with a median age was 22 years. Older patients, greater than 40 years, had significantly more advanced stage cancers (stage III-IV) compared to the younger cohort (44.2% vs. 21.6%; p<0.001). Furthermore, the proportion of grade 3 tumors was significantly higher in the older cohort (28.6% vs. 17.8%; p=0.004), while the proportion of dysgerminomas in the older cohort was significantly lower (20.0% vs. 32.0%; p40 years with grade 1, 2, and 3 cancers have a worse survival compared to the younger patients (50.0% vs. 98.5% for grade 1; 75% vs. 99.1% for grade 2; 53.2% vs. 94.7% for grade 3; p<0.001). On multivariate analysis, age, stage and histology were significant predictors of survival. Conclusions: Germ cell ovarian cancer in women greater than 40 years have a significantly poorer prognosis compared to younger women after adjusting for stage and histologic cell type. Older patients were more likely to present with advanced stage, non-dysgerminomas, and grade 3 cancers. No significant financial relationships to disclose.