tbuckley/cabot-search huggingface dataset:
Breast cancer patient functional status and comorbidities and their impact on treatment aggressiveness: A population-based study.
Authors: Kevin A. Pearlstein, Ramsankar Basak, Ronald C. Chen
Journal: Journal of Clinical Oncology (2016)

306 Background: The ASCO Choosing Wisely Campaign and other published guidelines recommend avoidance of aggressive treatments in early-stage cancer patients with limited life expectancy. However, patients with more advanced cancers are likely to benefit from aggressive treatment. The population-based SEER-MHOS (Medicare Health Outcomes Survey) provides unique data to allow assessment of aggressiveness of cancer treatment by cancer stage and patient frailty. Methods: MHOS includes patient-reported functional deficits in a sample of Medicare beneficiaries, and has been linked with SEER data which provide diagnostic and treatment data. This analysis included 2605 patients diagnosed with non-metastatic breast cancer from 1999-2006 who had pretreatment frailty data  which was calculated using a validated index based on age, comorbidity, and functional deficit. Each patient was classified as healthy, intermediate, or frail. Treatment aggressiveness was examined for each group. Results: Comorbidity and functional deficits were very common. For example, 11% had chronic lung disease, 17% diabetes, 52% low back pain, 50% reported difficulty walking several blocks, and 11% difficulty bathing. Almost all individuals with localized and regional breast cancers had surgery (Table 1). However, frail patients with localized cancers were less likely to receive post-lumpectomy radiotherapy (RT, p &lt; .001); frail patients with regional cancers were less likely to receive post-mastectomy RT (p = .02). A sizable proportion of healthy patients (25-32%) do not receive post-lumpectomy RT. Conclusions: Comorbidities and functional status limitations are common in Medicare breast cancer patients. There appears to be an underutilization of adjuvant RT in healthy breast cancer patients, and use is less in frail patients. [Table: see text]
Cetuximab-related skin toxicity in metastatic colorectal cancer (mCRC) patients and its correlation with molecular markers: Results from the German AIO CRC 0104 trial.
Authors: Sebastian Stintzing, Christine Kapaun, Ruediger P. Laubender, Andreas Jung, Jens Neumann, Dominik Paul Modest, Clemens Albrecht Giessen, Nicolas Moosmann, Andreas Wollenberg, Thomas Kirchner, Volker Heinemann
Journal: Journal of Clinical Oncology (2012)

491 Background: Skin toxicity is a frequent adverse event of EGFR targeting agents. The role of cetuximab induced skin toxicity (Cet-ST), for the most acneiform skin rash, as a prognostic or a predictive factor of treatment efficacy is currently under discussion. Methods: The prognostic and predictive value of Cet-ST in relation to treatment response and survival of patients of a randomized trial investigating CAPIRI plus cetuximab versus CAPOX plus cetuximab as first-line treatment of mCRC was analyzed. Cet-ST was grouped into clinically relevant (grade 2-3) and non relevant (grade 0-1) toxicity (NCI-CTCAE 3.0). KRAS mutations in codons 12 and 13, EGFR-FISH, EGFR-IHC and EGFR intron-1 polymorphism were evaluated in tumor specimens. Results: A total of 149 patients got cetuximab until the first tumor assessment (6 weeks) and were used for this analysis. Overall response rate was higher in patients with grade 2-3 Cet-ST when compared to grade 0-1 (62.1% vs. 41.3%). Patients without Cet-ST (grade 0) had a short PFS (1.9 months) and OS (11.0 months). PFS (7.8 months vs. 5.2 months) and OS (30.3 months vs. 18.0 months) were longer in patients with Cet-ST grade 2-3 than in patients with grade 0-1 Cet-ST. Almost 90% of Cet-ST occurred during the first two cycles of treatment. When only KRAS codon-12 mutated tumors which are thought not to be sensitive to cetuximab were investigated, Kaplan-Meier differences in PFS and OS times between patients with grade 0-1 Cet-ST and grade 2-3 Cet-ST became statistically significant. In a multivariate analysis, male gender, age and EGFR intron-1 polymorphism were significantly correlated with Cet-ST. Conclusions: Cetuximab related skin toxicity is a strong predictor of outcome. It is proposed that Cet-ST is rather a prognostic than a predictive factor since this effect is most evident in patients with KRAS codon-12 mutated tumors. EGFR intron-1 polymorphism appears to be a predictor of Cet-ST.
Immunohistochemical expression of receptor-tyrosine-kinase in patients with gastric cancer: A multicenter study in Japan.
Authors: Yutaka Kimura, Yukinori Kurokawa, Nariaki Matsuura, Junya Fujita, Hiroshi Imamura, Chikara Ebisui, Yoichiro Nushijima, Shinichi Adachi, Kazuhiro Nishikawa, Toshirou Nishida, Shuji Takiguchi, Masaki Mori, Yuichiro Doki
Journal: Journal of Clinical Oncology (2013)

41 Background: Treatment of HER2 positive gastric cancer (GC) with trastuzumab, receptor-tyrosine-kinase (RTK) inhibitor, has led to significant gains in overall survival. Several other targeted therapies are currently undergoing preclinical and clinical testing in some malignancies and GC, directed against diverse oncogenic RTK, therefor it is important to define the expression pattern of target RTK in GC. A multicenter retrospective study was conducted to evaluate the correlation between the expression of some RTKs, HER2, EGFR and c-KIT, and clinicopathological features in GC. Methods: A total of 153 cases with GC which was surgically resected between 2000 and 2006 were registered from nine hospitals. The neoadjuvant treatment cases were excluded. Tumors were centrally examined for HER2, EGFR and c-KIT status with immunohistochemistry (IHC) and fluorescence in-situ hybridization (FISH) for HER2. The relation between the expressions of HER2, EGFR and c-KIT and clinicopathological factors was examined by Fisher’s exact test. The hazard ratio (HR) for death was estimated, and overall survivals (OS) were compared between positive and negative cases of HER2, EGFR, and c-KIT using log-rank test. Results: The proportion of positive cases with IHC of HER2, EGFR and c-KIT was 7.8%, 14.4% and 11.1%, respectively. There was no significant correlation between the expression of HER2, EGFR and c-KIT and differentiation, location and depth. HER2-positive cases tended to be more frequent in differentiated type tumors. EGFR-positve cases were more frequent in lymph node metastasis (P=0.013). c-KIT-positive cases tended to be more frequent in T1-T2 tumors. OS in HER2-positive cases were clearly worse than in HER2-negative cases (HR 2.23 (95%CI, 1.16-4.38); P=0.014). EGFR-positive cases had a tendency to be worse than in EGFR-negative cases (HR 1.60 (95%CI, 0.94-2.71); P=0.082). c-KIT-negative cases were worse than in c-KIT-positive cases (HR 0.42 (95%CI, 0.17-1.02); P=0.048). Conclusions: This study showed that HER2 expression is a factor of poor prognosis and that EGFR-positive status and c-KIT-negative status tended to be associated with worse outcomes in resected GC.
Economic analysis of pegfilgrastim in patients receiving cancer chemotherapy
Authors: L. E. Cosler, A. Eldar-Lissai, D. C. Dale, J. Crawford, G. H. Lyman
Journal: Journal of Clinical Oncology (2005)

6041 Introduction: Randomized controlled trials (RCTs) have demonstrated that the prophylactic granulocyte colony-stimulating factors (pG-CSFs) are capable of reducing the risk of febrile neutropenia (FN) in patients receiving cancer chemotherapy. A meta-analysis of the 14 RCTs of pG-CSFs including filgrastim and pegfilgrastim has confirmed significant reductions in FN and infection-related mortality (IRM) along with improved chemotherapy dose intensity. Methods: An economic analysis was conducted based on risk and efficacy estimates from the meta-analysis and direct US cost estimates for hospitalization and outpatient care. Expected costs along with estimates of incremental cost savings and cost-effectiveness (CE; $/life saved) were generated. Threshold and sensitivity analyses for all variables and Monte Carlo simulation based on lognormal hospital cost distributions were performed to assess the robustness of the model. Results: Under baseline conditions, a net cost savings with pegfilgrastim of $578 was estimated. A net cost savings was observed for an FN risk >16.4%, daily cost of hospitalization >$1,282 and a relative risk reduction >72%. Cost savings thresholds are found to decrease further with increasing IRM, longer hospital lengths of stay or cost/day and greater estimated efficacy. In Monte Carlo simulation, lower costs were observed with pegfilgrastim in two-thirds of patients with an average cost savings with pegfilgrastim [±95%CL] of $600 [-1000,3600]. Further distribution analysis based on Monte Carlo simulation along with a cost-effectiveness analysis based on the reduction in IRM will be presented. Conclusions: Incorporation of risk and efficacy estimates from a recent meta-analysis along with updated cost estimates into clinically relevant models demonstrates that pegfilgrastim reduces overall costs associated with moderately myelosuppressive chemotherapy. Further increases in healthcare costs or the use of validated FN risk models for targeted therapy should further increase the estimated cost savings. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Amgen Amgen Amgen
Mutational profiling of the oncogenome in non-small cell lung cancer (NSCLC)
Authors: W. Pao, M. D. McLellan, D. K. Pham, B. Singh, V. W. Rusch, M. F. Zakowski, V. A. Miller, M. G. Kris, R. K. Wilson, H. E. Varmus
Journal: Journal of Clinical Oncology (2005)

7021 Background: Cancers arise from a multistage process during which tumor cells acquire activating mutations in proto-oncogenes and inactivating mutations in tumor suppressor genes. In NSCLC, somatic mutations have been detected in genes such as EGFR, HER2, PIK3CA, BRAF, KRAS, and p53. Two of these mutations are now known to have direct clinical relevance; mutations in the EGFR tyrosine kinase domain are associated with tumor responses to targeted therapies such as gefitinib and erlotinib (Lynch et al, NEJM ’04, Paez et al, Science ’04, Pao et al, PNAS ’04), while KRAS mutations are found in tumors refractory to these agents (Pao et al, PLoS Med ‘05). Moreover, EGFR and KRAS mutations are mutually exclusive (Shigematsu et al, JNCI ‘04). To identify new predictors of response as well as novel targets for therapy, we have initiated a comprehensive large-scale re-sequencing analysis of genes potentially mutated in NSCLC, i.e. the NSCLC oncogenome. Methods: Genomic DNA was extracted from 188 early-stage resected untreated NSCLCs. All tumors were obtained on IRB-approved protocols and with patients’ consent. High-throughput PCR-based re-sequencing was performed on a high priority list of ∼100 genes, with particular focus on genes in the ERBB signaling pathway. Results: Thus far, 110 tumors have been analyzed for EGFR (exons 2–28) and KRAS2 (exons 1–6) mutations. 11 tumors (10%) had EGFR mutations (exons 19 and 21), while 19 (17%) had KRAS mutations (exon 2). EGFR and KRAS mutations were mutually exclusive. No mutations were identified among 11 never smokers analyzed for changes in FLT3 (exons 2–24). Conclusions: Mutational profiling of NSCLC can distinguish clinically relevant molecular subsets of lung cancer, and may reveal novel targets for therapy. Further re-sequencing of the NSCLC oncogenome is in progress. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genentech AstraZeneca AstraZeneca
Uptake of <i>BRAF </i>and <i>ALK</i> mutation screening versus HER2 overexpression testing.
Authors: Savanna D. Steele, Austin J. Combest, Marie-Edith Anne Bonneterre, Joseph Walt Adair, Eric Barefield, Dirk J. Reitsma
Journal: Journal of Clinical Oncology (2012)

101 Background: Genetic mutation testing in cancer has become standard practice with the advent of targeted therapies such as vemurafenib, crizotinib, and trastuzumab and their associated companion diagnostics. We observed a rapid uptake in BRAF mutation screening in melanoma compared to ALK mutation in NSCLC and HER2 overexpression in breast cancer. Hypothesizing this discrepancy may be related to the overall impact the drugs had on standard of care within their respective indications, we evaluated the relationship between mutation screening frequency and hazard ratios (HRs) from pivotal clinical trials (Shaw Lancet Oncol 2011; Gerber Cancer Cell 2010; Slamon NEJM2001). As a historical control, we also assessed HER2 screening trends. Methods: BRAF, ALK, and HER2 screening data were collected via Ipsos’ Tandem Oncology Monitor, a commercial system in which oncologists in US (500) and EU (783) enter de-identified data on actual prescriptions and mutation screening orders by indication for cancer patients from their practice. Results: Our results show an increase in mutation testing from 42 to 83% for BRAF and from 13 to 34% for ALK from Q1 2011 to Q4 2011. HER2 testing has increased from 56%, Q1 2001, to 95%, Q4 2011. Correlation in uptake in testing vs. PFS/TTP HR endpoints in the US was -0.866. This implies a relationship between outcomes and the propensity for mutation testing. Conclusions: While it is likely that the potential for benefit drives mutation testing, clinicians may also be less likely to screen for an uncommon mutation (~5% of NSCLC patients), or may choose to test only those patients with known predisposing factors. Additionally, oncologists may go through a testing algorithm for NSCLC patients where mutations that are more common are screened first (i.e., EGFR – KRAS – ALK). BRAF testing reached nearly 90% in one year compared to nearly 10 years for HER2 and emphasizes the impact vemurafenib has had on standard of care. ALK mutation screening increased, but not to the same extent as BRAF. These results are encouraging, but also demonstrate that mutation testing in all patients is not yet a reality. [Table: see text]
In Acute Myeloid Leukemia (AML), Targeting the Histone Methyltransferase EZH2 Promotes Differentiation, Impairs Clonogenic Survival and Augments the Anti-Leukemic Effects of the Retinoid, All-Trans-Retinoic Acid (ATRA)
Authors: Ronan T. Swords, Aymee Perez, Ana Rodriguez, Justin M. Watts, Tino Schenk, Fernando Vargas, Roy Elias, Arthur Zelent
Journal: Blood (2015)
The German study group of intravesical hyperthermia-chemotherapy in non-muscle-invasive bladder cancer presents their long-term results in efficacy and tolerability for optimized adjuvant therapy and bladder preservation.
Authors: Gerson Lüdecke, Florian Hasner, Herbert Hanitzsch, Matthias Schmidt
Journal: Journal of Clinical Oncology (2013)

268 Background: In NMIBC recurrence and progression in high-risk BC are the dominant aspects for the clinical management. Intravesical chemotherapy and BCG treatment are the techniques to reduce both risks. HTC has a potentiating synergistic action in BC cell death induction. In consequence we proved HTC in the adjuvant indication and the ablativ indication in high-risk BC. Methods: We treated 138 patients in 1,443 treatment sessions in 3 institutions with intravesical hyperthermia-chemotherapy with Mitomycin C applied with the Synergo device. After an initial inductive weekly therapy for 6 to 8 weeks maintenance followed once every 6 weeks 6 times and cystoscopy every 3 month. Results: In the adjuvant indication 52 patients were treated. The over all recurrence free rate was 78.3% over 2.9 years in mean (3.6m – 6.9y). Only 10 patients recurred but none progressed or needed a cystectomy. In the ablative indication 86 patients were treated. For efficacy 69 could be evaluated. 17 patients must be excluded because of protocol violation or extra-vesical TCC or simultanious second malignancy. 85.5% of the patients (58) reached CR and this persited for 26.1 months in mean. 48 patients (69.6%) were tumor free over the hole investigation time. In total 8 patients (11.6%) needed a cystectomy. 3 patient (4.3%) progressed to metastatic disease and the other 5 demonstrated low-risk new tumors again treated transurethral. In total 53 patient (76.8%) achieved organ preservation in high-risk situation. Side effects included allergy, UTI, spasm, difficulties with catheterization and nocturia ascending from 1.4% to 5.6%. Conclusions: HTC is a safe and effective therapy in NMIBC to prevent intermediate risk BC patients for recurrence and to ensure organ preservation in high-risk BC patients in more than 75% with a long lasting efficacy.
Predictive models for improved prognostication and selection of neoadjuvant and adjuvant systemic chemotherapy in upper tract urothelial cell carcinoma.
Authors: Simone Lucia Vernez, Yair Lotan, Shahrokh F. Shariat, Arthur I. Sagalowsky, Jacob B Morgan, Jay D. Raman, Christopher G. Wood, Alon Z. Weizer, Marco Roscigno, Francesco Montorsi, Christian Bolenz, Wassim Kassouf, Vitaly Margulis, Ramy F Youseff
Journal: Journal of Clinical Oncology (2016)

456 Background: Chemotherapy is still underutilized in management of upper tract urothelial carcinoma (UTUC). We created pre and post-operative predictive tools combining independent prognostics to guide selection of patients for neoadjuvant and adjuvant chemotherapy. Methods: From the UTUC collaboration database (1,453 patients who underwent radical nephroureterectomy [RNU] at 13 academic institutions); a preoperative predictive model was created using 659 patients in whom all preoperative prognostic variables were available and a post-operative model was created using 586 patients with non-metastatic/ high-grade UTU. After multivariable survival analyses, a backward step-down selection process was applied to create a preoperative nomogram. Internal validation was performed using 200 bootstrap resamples. For the postoperative model, TALL score was created based on the sum of the independent prognostic variables. Results: Preoperative model: Grade, architecture and location of the tumor were independently associated with nonorgan confined disease. A nomogram including these 3 variables achieved 76.6% accuracy in predicting nonorgan confined upper tract urothelial cancer. Postoperative model: TALL score (1-7) was the sum of T ( ≤ T1 = 1, T2 = 2, T3 = 3 and T4 = 4), A (papillary = 0 and sessile = 1), LVI (absent = 0 and present = 1) and L (lymphadenectomy = 0 and no lymphadenectomy = 1). Five-year disease-free survival (DFS) and cancer-specific survival (CSS) were stratified into four risk categories according to the TALL score: low (TALL 0-2; 86 % DFS and 90 % CSS), intermediate (TALL = 3; 71 % DFS and 75 % CSS), high (TALL = 4; 57 % DFS and 58 % CSS) and very high risk (TALL ≥ 5; 34 % DFS and 38 % CSS) using Kaplan-Meier survival analyses. TALL score was externally validated in a single-center cohort of 85 UTUC patients. Conclusions: We developed validated multivariable prognostic tools for prediction of locally advanced UTUC and oncological outcomes after RNU for UTUC. These prediction models can be used for patient counseling, selection for neoadjuvant/adjuvant systemic therapies and design of clinical trials.
Survival outcomes in U.S. patients with metastatic colorectal cancer (mCRC).
Authors: Kevin Knopf, Sheikh Usman Iqbal, Stephen F Thompson, Elisabetta Malangone, Magdaliz Gorritz-Kindu, Lee Stern, Steven A Sherman, Sarah Naoshy, Michael Wooten, Michael L. Andria
Journal: Journal of Clinical Oncology (2013)

559 Background: The increase in survival seen in recent years in patients with mCRC has been attributed to improvements in treatments, including the introduction of targeted biologic agents. The objectives of this retrospective, observational study are to investigate recent treatment patterns in US mCRC patients and examine real-world survival outcomes. Methods: Data were obtained from a large U.S. database (SDI/IMS Health) of mCRC patients diagnosed from January 1, 2004 to June 30, 2011, ≥18 y at diagnosis, and who received chemotherapy and/or biologic treatment. Complete follow-up was defined as those who either died before June 2011 or who had at least 1 claim within 30 days of June 30, 2011. Kaplan-Meier curves were generated to determine overall survival (OS) from the date of mCRC diagnosis. Results: 1,066 stage IV mCRC patients with complete follow-up were identified (57.5% male; mean age, 61.6 y). Approximately 80% were diagnosed with mCRC after 2006; 51.7% had liver metastases. The most common 1L, 2L, and 3L regimens were FOLFOX plus bevacizumab (34.52%), FOLFIRI plus bevacizumab (21.83%), and irinotecan plus cetuximab (15.83%), respectively. A total of 445 patients died during the study period, yielding a mortality rate of 41.74%. Mean time from diagnosis to first treatment was 3.31 months (SD=7.13). All patients received 1L therapy; OS from diagnosis was 35.77 months (95% CI: 32.57-38.10); 5-year survival was approximately 28%. After 1L, 591/1066 (55%) patients went on to receive 2L therapy; for these patients, median survival from diagnosis was 37.13 months (95% CI: 34.07-40.43) and 5-year survival was approximately 25%. After 2L, 278/591 (47%) patients received 3L therapy; for these patients, median survival from diagnosis was 38.10 months (95% CI: 34.83-43.13); 5-year survival was approximately 25%. Conclusions: In this study, OS (35.77 months) was longer than for other mCRC observational studies that have reported survival from start of treatment, but is more comparable when the ~3 months from diagnosis to start of treatment are not included. Addition of targeted agents and novel chemotherapy has prolonged OS in mCRC patients. Because of poor 5-year survival rates, the need for additional agents in later lines of therapy still exists.
Infectious Disease Associations in Advanced Stage, Indolent Lymphoma (Follicular, FL and Non-Follicular, nFL): Developing a Lymphoma Prevention Strategy.
Authors: Carol S. Portlock, Paul A. Hamlin, Ariela Noy, Maria Lia Palomba, Lisa Rosenzweig, Darren Walker, Stacie Corcoran, William D. Chey, Charlotte A. Gaydos, Ira Schwartz, Genovefa Papanicolaou, Arnold Markowitz
Journal: Blood (2006)