tbuckley/cabot-search huggingface dataset:
Lead-time from diagnosis to start of radiation shortened by 44% for head and neck cancer when patients go through a multidisciplinary clinic.
Authors: J. S. Parzuchowski, J. Jordon, L. Burgess, M. Witsell, L. Sobol, M. Rontal, S. Balaraman, R. Ignatius, P. Venuturumilli, D. Krauss, P. Chen, J. Fontanesi, J. Akervall
Journal: Journal of Clinical Oncology (2011)

e16627 Background: Head and neck cancer (HNC) is a multidisciplinary condition. Multi-modality treatment is standard, especially the use of chemoradiation. Proper imaging (CT, MRI and PET), more accurate pathologic assessment and thoroughly tailored treatment plans that limits radiation fields and doses and take into consideration surgical options that minimize morbidity (endoscopic and robotic procedures) are essential. Furthermore, dental, swallowing, speech, nutritional, financial and social support are also cornerstones in this comprehensive approach. However, the most important function might be the role of the nurse navigator in order to offer true coordinated care for our patients. Within William Beaumont Oncology Network we initiated multi-disciplinary clinics for HNC in January 2010 in which our specialists meet the patients together after discussion at the tumor board to streamline management. Methods: In this initial analysis we studied 15 randomly chosen patients’ way through our health care system in 2009, and compared with 15 randomly chosen patients in 2010, after the initiation of the Multi-Disciplinary Clinic. All patients had biopsy verified HNC, the vast majority being squamous cell carcinomas, and were stage III or stage IV. The radiation techniques were unchanged during study and treating physicians remained the same as well. Results: The first group of patients that did not go through our multi-disciplinary clinic had a mean time of 59 days (range 4-156) from pathologic diagnosis to start of radiation. Corresponding mean time for patients going through the multi-disciplinary clinics was 33 days (range 18-86), a decrease of 44%. Conclusions: Coordinated care is of uttermost importance for patients with HNC. The complex treatment options, significant potential morbidities and complications along with complicated socio-economic conditions, underline the necessity of a comprehensive work-up for these patients. We show a significant decrease in time for management of HNC patients when a multi-disciplinary clinic is used in which specialists and a nurse navigator see the patients together.
Last year of life of cancer patients who are adolescents and young adults (AYA): Inpatient patterns and disparities in a population-based study.
Authors: Emily E. Johnston, Elysia Marie Alvarez, Olga Saynina, Lee Sanders, Smita Bhatia, Lisa J. Chamberlain
Journal: Journal of Clinical Oncology (2016)

126 Background: Cancer is the leading cause of non-accidental death among adolescents and young adults (AYA) in the US. The last year of life involves significant inpatient resources for older patients. We sought to determine the quantity and pattern of inpatient care for AYA cancer decedents in the last year of life to learn their healthcare system impact and groups to target for intervention. Methods: Using the California Office of Statewide Health Planning and Development private administrative database linked to death certificates, we performed a retrospective cross-sectional population-based analysis of patients aged 15-39 with cancer who died between 2000-2011. We calculated the number of admissions, hospital days, and percent of the cohort admitted each day in the last year of life. We determined the bed-day distribution across the population and the clinical and socio-demographic factors associated with high inpatient utilization. Results: The 9562 AYA cancer decedents were 45% non-Hispanic white, 30% Hispanic; 20% had hematologic malignancies, 70% had solid tumors. They were hospitalized, on average, 4.3 times and 40.6 days in the last year of life, increasing 3 months before death. Bed day occupation was skewed: 5% of the patients occupied 20% of the bed days and 18% occupied 50%. Factors associated with increased odds of being a top 5% utilizer were being Hispanic (OR: 1.48, 95% CI: 1.15-1.90, ref: non-Hispanic white), and having Acute Myelogenous Leukemia (AML) (2.7, 1.74-0.67, ref: Acute Lymphoblastic Leukemia (ALL). Factors associated with decreased odds were rural residence (0.39, 0.23-0.67, ref: urban), HMO insurance (0.58, 0.38-0.88, ref: private non-HMO), no hospitalizations at specialty centers (0.72, 0.53-0.97, ref: specialty center only), and having lymphoma or a solid tumor (ORs 0.035-0.39, CI range 0.005-0.56, ref: ALL). Conclusions: AYAs dying of cancer spent 40.6 days in the hospital in their last year of life (more than 1 in 9 days) with higher rates for Hispanics, AML patients, those with urban residence, and those hospitalized at specialty centers. Further research needs to determine what is driving these patterns, if they are preventable, and if they align with patient and family wishes.
Racial disparities in breast cancer mortality among the regions of California.
Authors: Carol Parise, Vincent Caggiano
Journal: Journal of Clinical Oncology (2015)

106 Background: Racial/ethnic disparities in breast cancer mortality have been described. Geographic variation in breast cancer mortality has also been observed. The purpose of this study is to determine if there are racial disparities in breast cancer survival among eight regions in California, the most populous state in the U.S. Methods: Of 245,701 cases of first primary female invasive breast cancer from the California Cancer Registry (CCR) diagnosed in 2000-2011, we identified 143,184 with complete data. The regions of California were classified as North, Sacramento, San Francisco and Bay Area (SFBA), Central Valley, Tri-County, Desert Sierra, Los Angeles (LA), and San Diego/Orange. Cox Proportional Hazards was conducted to assess risk of mortality of African Americans, Hispanics, Asian/Pacific Islanders, and American Indians when compared with whites. The region X race interaction was tested. Analyses were adjusted for year of diagnosis, stage at diagnosis, grade, age, and socioeconomic status. Hazard ratios and 95% confidence intervals were reported. Results: The region X race/ethnicity interaction was statistically significant so separate models were fitted for each region. Blacks has increased mortality in SFBA (HR = 1.36; 1.20, 1.56), LA (HR = 1.37; 1.24, 1.51) and San Diego/Orange (HR = 1.31; 1.07, 1.60). American Indians had an increased risk of mortality in the Tri-County (HR = 3.90; 1.73, 8.78) and San Diego (HR = 1.93; 1.04, 3.64) regions. Hispanics had a reduced risk mortality only in the Tri County region (HR = 0.71; 0.55, 0.93). Asians had a lower risk of mortality in San Diego/Orange (HR = 0.81; 0.70. 0.94) and LA (HR = 0.78; 0.70; 0.87). Race was not a statistically significant factor for risk of mortality in the North, Sacramento, Central Valley, and Desert Sierra regions. Conclusions: Racial disparities in breast cancer mortality California vary by region and appear to be more prevalent in large urban areas.
A decision-analytic model of idelalisib in relapsed or refractory patients with follicular lymphoma in the United States.
Authors: Nathaniel Smith, Alexander Xenakis, Rachel Beckerman, Jagpreet Chhatwal, Stephanie A. Gregory, Andrew Briggs
Journal: Journal of Clinical Oncology (2014)

30 Background: There are currently few treatment options for relapsed/refractory (RR) indolent non-Hodgkin’s lymphoma (iNHL) patients. Idelalisib (IDELA) is a first-in class PI3Kδ inhibitor with substantial clinical efficacy in iNHL patients refractory to rituximab and an alkylating agent. A single-arm clinical trial (Study 101-09) showed RR iNHL patients treated with IDELA have a median of 11 and 20.3 months of progression-free and overall survival (PFS and OS), respectively. Efficacy was also demonstrated in patients with iNHL subtypes such as follicular lymphoma (FL). The objective of this study was to project the health outcomes of IDELA versus the current standard of care for US FL patients. Methods: A partitioned survival model simulated a cohort of RR FL patients over 10 year time horizon. Patients first received IDELA or an aggregate comparator of current RR iNHL chemotherapy regimens in a progression-free state before transitioning to a progressive-disease state where they received palliative care until death. Survival data was fit and extrapolated from Study 101-09 (IDELA) for FL patients. A real-world database claims analysis provided survival, disease- and treatment-related adverse event (AEs) profiles, and medical resource utilization data for RR iNHL patients for the comparator. All outcomes were discounted at 3%. Results: Claims data predicted a median of 6.16 and 13.04 months of PFS and OS, respectively, for the comparator. Our model suggests that IDELA treatment improved health outcomes over 10 years versus the comparator, increasing life-months (LMs) and progression-free life-months (PFLMs) by 9.94 and 4.63 mos, respectively. Over 1 year, IDELA reduced both AEs and hospitalisations in FL patients by 40.3% and 49.8%, respectively. Deterministic and probabilistic sensitivity analyses demonstrated the model results are robust across different methods of survival extrapolation. Conclusions: IDELA was projected to improve health outcomes in RR FL patients compared to current treatments, largely driven by improved PFS and OS; short-term reductions in AEs and hospitalisation were specifically related to a delayed disease progression.
Association of interval appendectomy with risk of neoplasm.
Authors: Matthew Jason Furman, Mitchell Cahan, Philip Cohen, Giles Francis Whalen, Laura A. Lambert
Journal: Journal of Clinical Oncology (2012)

430 Background: The role of interval appendectomy after conservative management of perforated appendicitis remains controversial. Determining the etiology of perforated appendicitis is one reason to perform interval appendectomies. This study hypothesizes that there is an increased rate of neoplasm in patients undergoing interval appendectomy. Methods: This is a retrospective review of all patients over 18 years of age who underwent appendectomy for presumed appendicitis from January, 2006 to December, 2010 at a single, tertiary care institution. Demographic data, pathologic diagnosis, clinico-pathologic characteristics, interval resection rate, and complication data were collected and analyzed. Results: During the study period, 376 patients underwent appendectomy. The mean age was 41 years (range 18 to 94). Interval appendectomy was performed in 18 patients (5.0%) (age 28 to 74). Neoplasms were identified in 14 patients (3.7 %); 6 were found in patients who had undergone interval appendectomy (33%). Nine were mucinous tumors (69.2%), 5 of which were associated with interval appendectomies. Neoplasms were identified in 8.3% of patients between 35 and 55 years old. Conclusions: Mucinous neoplasms of the appendix were found in 33% of patients undergoing interval appendectomy. Interval appendectomies should be considered in all patients 35 years and older due to increased risk of appendiceal neoplasm. [Table: see text]
JNK/MKP-1 and PI3K/NF-κB: Critical pathways controlling cellular response towards cisplatin in non-small cell lung cancer (NSCLC)
Authors: J. Albanell, S. Chattopadhyay, M. Tapia, A. Rovira, C. Belda-Iniesta, J. de Castro, C. Manguán-García, R. Machado, M. Gonzalez Barón, R. Perona
Journal: Journal of Clinical Oncology (2005)

2033 Background: Cisplatin induces cell death via JNK in NSCLC. However, MKP-1, a MAPK phosphatase that negatively regulates JNK activity, is highly expressed in many NSCLCs and might limit cisplatin activity. Furthermore, cisplatin activates the PI3K/Akt/nuclear factor(NF)-κB pathway, resulting in an antiapoptotic effect that might also counteract cisplatin cytoxicity. Methods: NSCLC cell lines (H460, H1299 and H727) were assayed for cisplatin cytotoxicity. Total and phosphorylated proteins of JNK/MKP-1 and PI3K/Akt/NF-κB pathways were assayed by WB and NF-κB activity by EMSA. siRNA of MKP-1 and pharmacological inhibition of PI3K/NF-κB were used to study the dependence of cisplatin activity on both pathways. Results: H460 cells lacked constitutive phospho-Akt, had low NF-κB expression and activity and were highly sensitive to cisplatin. In contrast, H1299 and H727 cells showed higher IC50s towards cisplatin than H460, expressed constitutive phospho-Akt, had high NF-κB expression (including p65, p50, NEMO) and activity. MKP-1 expression was high in H460 and H727 cells and very low in H1299. BAY11–7082, an NF-κB inhibitor that irreversibly inhibits IκB-alpha phosphorylation, enhanced cisplatin effects in H1299 cells but not in cells with high MKP-1. However, by expressing a siRNA vector for MKP-1, transfected H460 cells exhibited a 10-fold higher sensitivity to cisplatin, increased activation of JNK following cisplatin, and enhancement of the chemo-sensitization effects of NF-κB inhibition (IC50 of cisplatin was lowered 10-fold by BAY-11–7082). MKP-1 inhibition by siRNA in H727 cells also lowered (100-fold) the IC50 of cisplatin by BAY-11–7082. In the low MKP-1 expressing H1299 cells transfection of siRNA/MKP-1 did not further improve chemo-sensitization. Similar results for all three cell lines were obtained with the PI3K inhibitor LY294002. Conclusions: An activated PI3K/Akt/NF-κB pathway was linked to reduced sensitivity to cisplatin in NSCLC cells. Inhibition of NF-κB potently enhanced cisplatin cytotoxicity in cells with endogenous or genetically induced low MKP1. Cisplatin activity could be improved significantly by co-targeting NF-κB and MKP-1. No significant financial relationships to disclose.
Identification of unique somatic mutations with functional relevance through genetic characterization of gallbladder cancer (GB ca).
Authors: Milind M. Javle, Asif Rashid, Siddhartha P Kar, Kurt Schalper, Nicholas Wang, Myron Peto, Jean-Nicolas Vauthey, Thomas A. Aloia, Xavier De Aretxabala, Gordon B. Mills, Paul Spellman, Ivan Roa
Journal: Journal of Clinical Oncology (2013)

214 Background: GB Ca is the leading cause of cancer mortality in Chilean women and its incidence is high in Southeast Asia. Molecular characterization of this disease is limited to small retrospective studies of prognostic biomarkers. Methods: 54 surgically resected GB Ca cases were selected. DNA was extracted from microdissected tumors; genetic mutations analyzed using two platforms a) Sequenom MassARRAY, a mass spectrometry-based approach for 90 targetable mutations including PIK3CA, KRAS, EGFR, FGFR, CTNNB1, MET, ALK and AKT and b) Exome sequencing using the Illumina HiSeq2000 sequencer for novel genetic variants in the coding regions. Sample preparation followed the standard Agilent SureSelect XT protocol with the 71Mb +UTR capture library. A stepwise filtering approach was used to identify variants by screening for nonsynonymous substitutions, comparison of exomes to matched control and dbSNP database to exclude common variants. Variants not predicted to affect protein function were excluded. KM survival curves and log rank test were used to correlate genotyping results with survival. Results: 46 cases were selected for Sequenom MassARRAY and whole exome sequencing performed on 8 cases and control non-tumor tissue. Sequenom identified mutations in KRAS (3 cases), IDH1 (4), ALK1 (1), MET (1), NRAS (3) and PIK3CA genes (2). Overall survival was poorer in KRAS [24 vs. 75 weeks, p=0.008] and IDH1 [27 vs. 80 weeks, p=0.0008] mutation carriers. Exome sequencing after filtering revealed genetic variants in 6 cases with an overall low mutation rate. There were no overlapping mutations and we identified 45 functional mutations in STK11, CDKN2A, IKZF3, GRM6, TP53 and CTNNB1 genes, known to be prognostic in other cancers. ABCB1 transporter, TP53 and STK11mutations were predicted to have high functional impact. Ingenuity pathway analysis identified p53, WNT/ ß-catenin, GBM and thyroid cancer signaling and cell cycle regulation to be the top hits. Conclusions: This first high-throughput genomic screening of GB Ca using different platforms identifies known and unique variants in cancer genes. Sequencing of additional cases and efforts to develop a GB Ca-specific somatic mutation panel are ongoing.
Prognostic factors in locally advanced, unresectable esophageal cancer patients treated with chemoradiotherapy (exploratory analysis of JCOG0303).
Authors: Tatsuya Okuno, Junki Mizusawa, Ken Kato, Masayuki Shinoda, Hiroshi Katayama, Hiroyasu Igaki, Yasuhiro Tsubosa, Takashi Kojima, Hiroshi Okabe, Yusuke Kimura, Tatsuyuki Kawano, Shinichi Kosugi, Yasushi Toh, Hoichi Kato, Kenichi Nakamura, Haruhiko Fukuda, Satoshi Ishikura, Nobutoshi Ando, Yuko Kitagawa
Journal: Journal of Clinical Oncology (2015)

150 Background: The prognosis of patients (pts) with locally advanced esophageal squamous cell carcinoma (LAESCC) is generally dismal. Definitive chemoradiotherapy (CRT) with cisplatin plus 5-fluorouracil (CF-RT) is the standard treatments especially for the pts with unresectable LAESCC. The aim of this study is to investigate the possible prognostic factors and predictive accuracy of the Glasgow Prognostic Score (GPS) in the pts with unresectable LAESCC treated with CRT. Methods: 142 patients were enrolled to JCOG0303, and assigned to standard CF-RT group and low-dose CF-RT group. 131 pts with sufficient data were used for this analysis. Cox regression model was used for an analysis of prognostic factors of the pts with unresectable LAESCC treated with CF-RT. GPS was classified by baseline CRP and serum albumin. Pts with a CRP ≤ 1.0 mg/dL and albumin ≥ 3.5 g/dL were allocated to GPS0 group. If only CRP was increased or albumin decreased,pts were allocated to the GPS1 and pts in whom CRP was &gt; 1.0 mg/dL and albumin level &lt; 3.5 g/dL were classified as GPS2. Results: The pts background was as follows: median age (range), 62 (37-75), male / female, 119/12; ECOG PS 0/1/2, 64/65/2; clinical stage (UICC 6th) IIB/III/IVA/IVB, 3/75/22/31. As a result of multivariable analysis including all variables, the factors which became statistically significant were shown in the table. In several sensitivity multivariate analyses, only esophageal stenosis was indicated as a common poor prognostic factor. In addition, overall survival tended to decrease according to GPS subgroups (median survival time(m): GPS0/GPS1/GPS2 16.1/14.9/8.7). Conclusions: Presence of stenosis was thought to be one of the candidates for stratification factor in randomized trial for unresectable LAESCC pts. Furthermore, GPS represents a prognostic fator in LAESCC pts treated with CRT. Clinical trial information: 000000861. [Table: see text]
Role of palliative resection in patients with incurable advanced gastric cancer unfit for chemotherapy.
Authors: Wataru Takagi, Yutaka Tanizawa, Hayato Omori, Noriyuki Nishiwaki, Keiichi Fujiya, Fumiko Hirata, Taichi Tatsubayashi, Shinsaku Honda, Makoto Hikage, Rie Makuuchi, Masanori Tokunaga, Etsuro Bando, Taiichi Kawamura, Masanori Terashima
Journal: Journal of Clinical Oncology (2016)

114 Background: Recently, REGATTA trial showed that debulking surgeries followed by chemotherapy did not improve survival outcomes compared to chemotherapy alone for incurable advanced gastric cancer (AGC). Therefore, the standard treatment for incurable AGC without emergent symptom is not gastrectomy plus chemotherapy but chemotherapy alone. However, in patients who are unfit for chemotherapy due to poor performance status (PS), age, or comorbid chronic diseases, the role of palliative gastrectomy remains controversial. The aim of this study is to determine the role of palliative resection in patients with incurable AGC unfit for chemotherapy. Methods: Two hundred and twelve gastric cancer patients having any cause of incurable factors and underwent palliative gastrectomy or bypass operation between November 2002 and December 2014 were enrolled. Of these 212 patients, 64 patients who did not receive any chemotherapy were divided into two groups; Gastrectomy group with 45 patients who underwent palliative gastrectomy (distal gastrectomy in 18, total gastrectomy in 27) and Bypass group with 19 patients who underwent gastrojejunostomy. Survival outcomes and clinicopathologic features were compared between the two groups. Results: The reasons why unfit for chemotherapy were age (15), patients’ refusal (14), poor PS (11), postoperative complications (11), comorbidity (10), disease progression (3). There was no significant difference of clinicopathologic features between the two groups such as, age (MAN; 74.1 vs 77.1, p = 0.198), gender (male/female: 37/8 vs 13/6, p = 0.321), and number of incurable factors 2 or more (51.1% vs 63.2%, p = 0.422) except for postoperative complications of C-D grade 3 or more (24.4% vs 0%, p = 0.025). Median survival time of Gastrectomy group and Bypass group were 154 days (95%CI: 124-253) and 86 days (95%CI: 71-166), respectively, and significantly longer in Gastrectomy group (p = 0.002). Conclusions: These results suggest that palliative gastrectomy may improve survival in patients with incurable advanced gastric cancer unfit for chemotherapy.
Examining the use of PET scans in the diagnosis and management of non-small cell lung cancer patients.
Authors: Cheryl Louzado, Kristen DeCaria, Jose Hernandez, Rami Rahal, Jin Niu, Gina Lockwood, Heather E. Bryant
Journal: Journal of Clinical Oncology (2014)

311 Background: PET Scans are increasingly used in the diagnosis and management of non-small cell lung cancer (NSCLC) patients. However, uptake of PET at provincial level is not well studied. This project, led by the Canadian Partnership Against Cancer, established processes and indicators to describe utilization of PET in patients with NSCLC. These indicators support the monitoring of uptake and highlight areas for quality improvement strategies at the national and provincial level. Methods: Cases of NSCLC, diagnosed in the study period of 2009-2011, were identified from cancer registries and linked to PET utilization data. PET scans were identified as indicated for diagnosis/staging or treatment response, based on the timing of scans relative to diagnosis and treatment dates. Scans conducted three months prior to and up to four months post-diagnosis but before start of treatment (surgery or radiation) were identified as diagnosis/staging. Scans conducted after the start of treatment to ten weeks post-treatment were identified as management and follow-up of treatment. Results: A total of 27,984 cases of NSCLC were identified. Preliminary analysis revealed that 8,947 (32.0%) of NSCLC patients had at least one PET scan. Some variation was seen in age, with those 18 to 69 years more likely to receive a scan than those 70 years and older. PET scan use was higher among stages I and II (52.3% to 50.6%) compared to stage IV (17.98%). A majority of PET scans were performed for diagnosing/staging NSCLC (91.1%). PET scans for diagnosis/staging were highest for patients with stage I (36.7%) followed by stage IV (24.6%). Conclusions: This study provided information on the current use of PET technology across Canada, allowing for identification of opportunities for increasing evidence-based use while decreasing extra-evidential use, and forming a baseline for future monitoring as evidence evolves.