tbuckley/cabot-search huggingface dataset:
Outcomes of radical cystectomy in potential candidates for bladder-preservation therapy.
Authors: Eugene J. Pietzak, Zachary L. Smith, S. Bruce Malkowicz, Thomas J. Guzzo
Journal: Journal of Clinical Oncology (2014)

357 Background: Outcomes for Bladder Preservation Therapy (BPT) in urothelial-type bladder cancer (UBC) are often compared to those achieved by Radical Cystectomy (RC). However, BPT patients are usually “carefully selected” which may limit comparisons. Our objective was to analyze the outcomes of RC within a “carefully selected” patient cohort. Methods: We identified 471 consecutive patients with UBC who underwent RC with curative intent from 1987 to 2008 at a single academic center. Patients were considered eligible for BPT if tumors were clinical T2 without carcinoma in-situ (CIS), hydronephrosis, multiple invasive tumors, or mixed histology. Patients with ≥1 contraindications were considered ineligible. Renal function was not factored into eligibility. Clinicopathologic characteristics and survival outcomes for BPT eligible patients were compared to ineligible patients. Results: 275 patients had cT2 tumors, of which 157 (57.1%) were ineligible for BPT (CIS=54; hydro=77; multiple tumors=29; mixed histology=55; ≥2 contraindications=51). BPT eligible and ineligible patients did not statistically differ with regards to age, gender, race, BMI, smoking, ASA score, or neoadjuvant chemotherapy. At time of RC, BPT eligible patients were less likely to have positive lymph nodes (p=0.01), pathologic LVI (p=0.02), &amp; upstaging to pT3/pT4 (p=0.002). 2 and 5 year overall survival (OS) for all cT2 patients was 65.2% and 40.3%. 2 and 5 year OS was 76.7% and 44.2% for BPT eligible patients, but only 57.1% and 37.4% for ineligible (p=0.07). No statistical difference was seen in distant Recurrence Free Survival (RFS) (p=0.9), but BPT eligible patients had better local-RFS (p=0.05). 2-year Cancer Specific Survival (CSS) for all cT2, BPT eligible, and BPT ineligible patients was 71.8, 85.4%, and 62.3% respectively. Fine-Gray competing risk analysis revealed significantly better CSS for BPT eligible patients compared to those ineligible (Sub-HR=0.46 [CI=0.29-0.72] p=0.001). Conclusions: RC provides excellent CSS for patients potentially eligible for BPT. This should be included in an informed discussion of treatment options. In the absence of randomized trials, comparisons between RC and BPT must factor in selection bias.
Risk of progression to myelofibrosis and acute myeloid leukemia in patients with essential thrombocythemia and polycythemia vera with prior malignancy.
Authors: M. A. Cherry, H. Pham, H. Kantarjian, J. E. Cortes, S. Pierce, L. Zhou, S. Verstovsek
Journal: Journal of Clinical Oncology (2011)

6597 Background: Essential thrombocythemia (ET) and polycythemia vera (PV) are chronic myeloproliferative neoplasms (MPN) associated with a risk of transformation to myelofibrosis (MF) and acute myeloid leukemia (AML). The clinical relevance of prior malignancy (PM) in patients (pts) with ET and PV is largely unknown. We report the prevalence of PM in ET or PV pts and its clinical implications. Methods: We performed retrospective chart review of all pts with ET and PV seen at MD Anderson Cancer Center (diagnosis according to WHO criteria) between January, 1960 and September 2010, for evidence of PM. We recorded the prior pathological diagnosis of PM, and performed a univariate analysis of age at diagnosis of MPN, sex, JAK2 status, CBC, and cytogenetics in pts with or without PM. Results: A total of 437 pts charts (ET 263, PV 174) were evaluated. 40% of pts were male (ET 33% and PV 49%). 45 pts had PM [26 ET (10%), 19 PV (11%)] with median time to diagnosis of 65 months (4-435) in ET pts and 75 months (4-570) in PV pts. 2 pts had 2 PM. Majority had solid tumors [14 Skin (ET 8, PV 6), 7 prostate (ET 4, PV3), 5 gynecologic (ET 4, PV 1), 4 breast (ET 3, PV1), 4 melanomas (ET 3, PV 1), 3 colon (ET 1, PV 2), 3 thyroid (ET 2, PV 1), 3 sarcomas (ET 2, PV 1), 4 other cancers]. Median age at diagnosis of MPN was higher in pts with PM (years; all pts: 60 vs. 48 (p<0.001); ET 57 vs. 47 (p=0.001); PV 67 vs. 50 (p<0.001), respectively). No significant difference in abnormal cytogenetics frequency between 2 groups was observed (13% for PM vs 7%; p = 0.21). The risk of progression to AML (2% vs 0.8%) or MF (9% vs 3 %) was higher in pts with PM (p=0.027). Median overall survival from MPN diagnosis was lower in PM pts(months; all pts: 182 vs. 324 (p<0.001); ET: 268 vs. 474 (p =0.01); PV: 182 vs. 322 (p=0.003), respectively), perhaps due to their age difference. No differences were found in the frequency of JAKV617F2 mutation and blood counts at diagnosis between 2 groups. Conclusions: In our experience, ET and PV pts with PM are older at MPN diagnosis and harbor increased risk of progression to MF or AML. Larger studies are needed to confirm our findings
An evaluation of the possible interaction of gastric acid suppressive medication and the EGFR tyrosine kinase inhibitor erlotinib.
Authors: J. F. Hilton, L. Seymour, A. Le Maitre, D. Tu, F. A. Shepherd, P. A. Bradbury
Journal: Journal of Clinical Oncology (2011)

7523 Background: NCIC CTG BR21 trial demonstrated a 2 -month overall survival (OS) benefit from erlotinib (E), when compared to placebo (P), in advanced NSCLC patients after the failure of 1st or 2nd line chemotherapy. Gastric acid suppression (AS), through the use of proton pump inhibitors (PPIs) and H2 receptor antagonists (H2RA), increases gastric pH which may reduce the absorption of E. Methods: We retrospectively evaluated the impact of AS use on E drug levels, progression-free survival (PFS) and OS using the BR21 trial database. Patients were allocated to the AS cohort if they received PPIs or H2RAs at baseline or at any time during protocol treatment. PFS and OS comparisons were performed using Cox models with a time-dependent covariate for AS use and adjusting for known covariates. Results: Of 731 patients randomized to BR21, 267 received PPIs or H2RAs (AS cohort: 191 randomized to E and 76 to P; non-AS cohort 297 randomized to E and 167 to P). Within the E and P cohorts, no statistically significant differences were found in baseline characteristics between those patients receiving AS and those who did not. In the AS cohort, the mean of median E plasma levels over the study were not significantly lower compared with the non-AS cohort (1551.3 vs.1655.3 ng/mL, p=0.96). AS was prognostic for inferior OS and PFS compared to the non-AS cohort, regardless of which arm patients were randomized to. Therefore, this finding does not appear to be due to an interaction between AS use and E. Conclusions: Based on participants from the BR21 trial, these results suggest that, although the use of H2RAs and PPIs may reduce the absorption of E, the impact on median plasma levels is modest and this does not appear to reduce its efficacy significantly. Group and outcome AS usemedian in months (95% CI) Non-AS use median in months (95% CI) Adjusted HR (95% CI) P value Erlotinib OS 5.52 (4.14; 7.52) 7.20 (5.95; 8.28) 1.69 (1.37; 2.09) <0.0001 PFS 2.20 (1.91; 3.29) 2.27 (1.91; 3.38) 1.77 (1.45; 2.16) <0.0001 Placebo OS 3.33 (3.02; 4.67) 5.88 (4.57; 7.59) 1.98 (1.45; 2.69) <0.0001 PFS 1.84 (1.74; 1.91) 1.81 (1.77; 1.87) 1.53 (1.14; 2.07) 0.005 Interaction OS 0.81 PFS 0.16
Safety profile of poxviral vaccines: NCI experience.
Authors: Joseph W. Kim, Jennifer L. Marte, Marijo Bilusic, Nishith K. Singh, Christopher Ryan Heery, Ravi Amrit Madan, Mary Pazdur, Sheri McMahon, Myrna Rauckhorst, Jeffrey Schlom, James L. Gulley
Journal: Journal of Clinical Oncology (2013)

85 Background: Recombinant poxviruses have been developed as therapeutic cancer vaccines. Here, we report the safety data from NCI clinical trials with poxviral vaccines. Methods: We evaluated all vaccine injections from 215 patients in 8 clinical trials involving poxviral viral vaccines. The Office of Biotechnology Activities, National Cancer Institute (NCI) Institutional Review Board, and NCI Scientific Review Committee approved all of these trials. Vaccines were consisted of recombinant vaccinia and recombinant fowlpox encoded with 3 human costimulatory molecules (TRICOM), and prostate specific antigen (PSA), or carcinoembryonic antigen, and/or mucin-1. Vaccines were administered at doses between 1.2x10 8 to 2x10 9 pfu, subcutaneously, in all patients. Twenty-one patients were also vaccinated intra-tumorally. 84 patients also received other concurrent treatment modalities, such as radiation, celecoxib, ipilimumab, samarium-153, or flutamide on 4 of these trials. All 8 clinical trials involved granulocyte-macrophage colony-stimulating factor (GM-CSF) 100mcg, or recombinant fowlpox encoding GM-CSF at 1x 10 8 pfu as an immune adjuvant. Here, we report here the grade 2 or higher adverse events given at least a possible attribution to vaccine. Results: A total of 1,348 poxviral injections were given in 215 patients. No contact transmission, inadvertent inoculation, or any serious adverse events (AEs) related to vaccinia was observed. Below is the summary of proportion of vaccine administrations associated with specific AEs. Conclusions: These data demonstrate a favorable safety profile of the poxviral vaccines at a broad range of doses, routes of administration, in combination with other treatments, and in various tumor types. Clinical trial information: NCT00060528, NCT00096551, NCT00088413, NCT00081848, NCT00113984, NCT00450619, NCT00450463. [Table: see text]
Retrospective cohort study on the safety and efficacy of panitumumab (Pmab) for patients with metastatic colorectal cancer (mCRC): The HGCSG1002 study—Analysis of clinical early predictor for the efficacy.
Authors: Susumu Sogabe, Hiraku Fukushima, Satoshi Yuki, Yoshimitsu Kobayashi, Takuto Miyagishima, Hiroyuki Okuda, Takaya Kusumi, Ayako Doi, Yasushi Tsuji, Yasuyuki Kawamoto, Nobuyuki Ehira, Masahiko Koike, Takashi Meguro, Yasuo Takahashi, Koji Yoshizaki, Shuichi Muto, Atsushi Ishiguro, Sosuke Kato, Yuh Sakata, Yoshito Komatsu
Journal: Journal of Clinical Oncology (2013)

593 Background: Inhibition of the EGFR pathway has become a key part in the treatment of colorectal cancer. There were few studies for clinical early predictive markers. To investigate the early magnesium (Mg 2+ ), calcium (Ca 2+ ), albumin (Alb), CEA and CA 19-9 plasma level reductions as a predictor for clinical outcome in terms of progression free survival (PFS) and overall survival (OS). Methods: 200 patients (pts) with mCRC treated by Pmab contained chemotherapy were retrospectively registered from 20 centers in Japan (HGCSG 1002 study). Of these, the pts that were refractory to or intolerant for 5-FU/ irinotecan/ oxaliplatin, and were never administered anti-EGFR-antibody, were included in this analysis. Mg 2+ , Ca 2+ , Alb, CEA and CA19-9 plasma levels were obtained from medical records. The differences in terms of PFS and OS according to the presence of Mg 2+ , Ca 2+ , Alb, CEA and CA19-9 reductions were evaluated by the log-rank test. Results: Of 67 pts were able to evaluate for this analysis. Pts’ characteristics were as follows: male/female 38/29, median age 64 (range 45-81), ECOG PS (0/1/2- ) 45/17/5. Response rate and disease control rate were 16.4% and 65.7%, PFS and OS were 4.3 m and 12.4 m, respectively. There were no correlations between Ca/Alb plasma level reductions and PFS/OS. Mg 2+ reduction of at least 50% respect to the basal value during the course of treatment was significantly correlated with improved OS and PFS (OS, P=0.03; PFS, P=0.01), but the early reduction (until the 4th week or the 8th week after start of chemotherapy) was not correlated with OS and PFS. An early CEA serum level reduction of at least 40% until the 8th week was significantly correlated with improved OS and PFS (OS, P=0.04; PFS, P=0.07), moreover of at least 30% until the 4th week was correlated to longer PFS (P=0.053). Similar results were seen in CA19-9. Conclusions: An early CEA plasma level reduction of at least 30% or 40% was suggested to be a predictor for PFS in Pmab containing chemotherapy for mCRC pts. Although Mg 2+ serum level reduction was correlated to clinical outcome, but could not show that is an early predictor for PFS and OS in our study.
Efficacy of anamorelin in cachectic patients with non-small cell lung cancer (NSCLC) and low BMI (&lt; 20 kg/m<sup>2</sup>): Post-hoc analysis of two phase III studies.
Authors: David Christopher Currow, Jennifer S. Temel, Amy Pickar Abernethy, Ruben Giorgino, John Friend, Kenneth Fearon
Journal: Journal of Clinical Oncology (2016)

203 Background: Patients with advanced cancer frequently experience anorexia/cachexia, which can be characterized by weight loss or low BMI, and is associated with reduced function and quality of life. The randomized, phase III, double-blind ROMANA 1 [NCT01387269; N = 484] and ROMANA 2 [NCT01387282; N = 495]) trials in cachectic NSCLC patients demonstrated that the ghrelin receptor agonist anamorelin improved LBM, body weight, fat mass (FM), and symptom burden compared with placebo, and was well tolerated. The aim of this analysis was to assess the response to anamorelin specifically in patients with BMI below 20 kg/m 2 . Methods: Stage III/IV NSCLC patients with cachexia ( ≥ 5% weight loss during prior 6 months or BMI &lt; 20 kg/m 2 ) were randomly assigned (2:1) to daily oral 100 mg anamorelin or placebo for 12 weeks. A post-hoc pooled analysis of efficacy data from both trials was conducted in patients with BMI &lt; 20 kg/m 2 (N = 182) and with BMI ≥ 20 kg/m 2 (N = 647). Endpoints included changes in lean body mass (LBM), fat mass (FM), and changes in self-reported anorexia/cachexia symptoms/concerns and fatigue. Results: Compared with placebo, anamorelin significantly increased LBM both in patients with low BMI (treatment difference: 1.71 kg [95% CI 0.88 – 2.54]) and in those with normal/high BMI (1.47 kg [1.00 - 1.94]) (p &lt; 0.001). Greater increases in FM were observed in the BMI &lt; 20 kg/m 2 (1.66 kg [0.86 – 2.46], p &lt; 0.001) than in the BMI ≥ 20 kg/m 2 subgroup (0.79 kg [0.30 - 1.28], p = 0.002). Significant improvements in anorexia/cachexia symptoms/concerns were observed in the BMI &lt; 20 kg/m 2 subgroup (5.27 [2.11 - 8.43], p = 0.001), while in the BMI ≥ 20 kg/m 2 subgroup these were not significant (0.91 [(-0.56) - 2.37], p = 0.224). In patients with low BMI, anamorelin also improved fatigue (3.94 [0.56 – 7-32], p = 0.023), while this was not significant in patients with BMI ≥ 20 kg/m 2 (-0.42) [(-2.07) – 1.23], p = 0.616). Conclusions: In patients with BMI &lt; 20 kg/m 2 anamorelin increased lean and fat mass as well as improved anorexia/cachexia symptoms/concerns. Additionally, improvements in fatigue were also noted in patients with BMI &lt; 20 kg/m 2 . Clinical trial information: NCT01387282; NCT01387269.
EORTC QLQ CR-29 evaluation in 500 patients with colorectal cancer.
Authors: José Pedro Carvalho Moreira da Silva
Journal: Journal of Clinical Oncology (2012)

429 Background: Colorectal cancer represents the 4 th most frequent cancer in the world and is the 2 nd leading cause of death due to cancer. This disease has a negative impact in the Quality of Life (QoL), due to its associated symptoms and due to the used treatments (surgery, chemotherapy and radiotherapy). Therefore it is fundamental to evaluate and assure a good quality of life of this patients and define the best QoL instrument in Colorectal cancer. Methods: Type of study: Transversal study The main objective was: validate for Portuguese population CR29 instrument. The QLQ-CR29 was administered with the QLQ-C30, core questionnaire, to 500 portuguese patients. Questionnaire scaling and reliability were established and clinical and psychometric validity examined. Patient acceptability and understanding were assessed with a debriefing questionnaire. Results: 57.4% (287) are male with a median of age of 66,67 years (Min.: 34 e Máx.: 88), 55.2% had rectal cancer (35.7% were Stage III disease at diagnosis. 46.4% had adjuvant and 27.4% had neoadjuvant treatment. The mean value of the QLQ-C30 Global Health Status was 58,75. The CR29 Multi-trait scaling analyses and face validity refined the module to four scales assessing urinary frequency, faecal seepage, stool consistency and body image and single items assessing other common problems following treatment for colorectal cancer identifying different groups of patients. High scores of cognitive and social functioning scales (QLQ C30), Subscale Corporal Image and the functional item Female Sexual function (QLQ-CR29) were related with good QoL. Low scores of Emotional Functioning subscales (QLQ C30) and Anxiety (QLQ-CR29), were related with poor QoL. A multivariable analysis reveals that sex, scholarship, marital status, distance between home and hospital and disease recurrence affect significantly the global health score. Conclusions: QLQ-CR29 Scale did not correlate with QLQ-C30 scales, demonstrating construct validity and it is a good instruments to identify a poor QoL in patients with colorectal cancer.
Stromal characterization of small bowel adenocarcinomas.
Authors: Katrina Pedersen, Thomas C. Smyrk, Robert R. McWilliams
Journal: Journal of Clinical Oncology (2016)

288 Background: Programmed-death 1 (PD-1) receptor and its corresponding ligand, PD-L1, have been found to be clinically relevant in maintaining immune tolerance to malignant cells in an increasing number of tumor types. We have previously shown that nearly half of 48 randomly selected, resected small bowel adenocarcinomas at any stage exhibit positive PD-L1 expression. Furthermore, a larger quantity of tumor infiltrating lymphocytes (TILs) within the tumor stroma or microsatellite instability (MSI-H) have been associated with improved likelihood of response to PD-1 and PD-L1 inhibitors. We have descriptively characterized the stromal components of small bowel adenocarcinomas to determine if similar tumor/stromal features to drug-responsive tumors can be seen. Methods: 30 tumors were immunohistochemically stained for CD8 (T-lymphocytes), CD68 (macrophages), and e-cadherin. They were morphologically screened for MSI-H status with light microscopy. PD-L1 staining was previously performed and reported. Results: Of the 30 tumors, there was no correlation between the density of macrophages and T-lymphocytes, nor was there a correlation with the burden of immune cells with e-cadherin expression. 14/30 (47%) tumors had 3+/4+ expression of CD8+ lymphocytes. 7/14 (50%) of these tumors were morphologically MSI-H. No tumors with low CD8+ cells (1+/2+) were MSI-H. PD-L1 expression colocalized exclusively with macrophages and not with lymphocytes. Conclusions: There appears to be no association between the proportions of immune cells and basement membrane integrity. MSI-H tumors are more likely to have a greater quantity of CD8+ lymphocytes in the stroma; however, PD-L1 stromal expression appears to colocalize with macrophages. Further pathologic characterization is needed in patients treated with PD-1 and other immune checkpoint inhibitors to determine the clinical significance of these observations.
Neutrophiles-to-lymphocytes ratio (NLR): Prognostic value in non-muscle invasive bladder cancer (NMIBC).
Authors: Jacques Irani, Damien Thillou, Simon Bernardeau, Clément Biscans, Maxence Sarradin, Pierre-Olivier Delpech
Journal: Journal of Clinical Oncology (2016)

360 Background: The aim of this retrospective study was to evaluate the prognostic value of NLR in NMIBC as it was recently suggested in the literature. Methods: Patients included in the study were diagnosed between 1992 and 2013 with a T1 stage bladder cancer either primarily or following progression. NLR was calculated using the pre-operative (TURB or cystectomy) work-up. Results were expressed as median and interquartile range (IQ) unless indicated otherwise. Results: Seventy-eight patients were analyzed (12 females and 67 males). Mean age: 68.3 years. At diagnosis (1 st TURB): median grade according to the WHO 1973 classification: 3 (IQ = 1), median NLR: 3.1 (IQ = 2.4 and range 1.0- 25.7). There was no significant difference between NLR when comparing stage, grade and gender subgroups. During FU (median 6.2 years): median number of TURB: 3.3. Observed NLR was higher in the highest risk groups, however the difference was significant only for grade progression and when comparing pT0 stage vs pTa or higher at the last biopsy/TURB (see table). NLR variation for each patient (NLR at diagnosis – NLR at the last TURB) was not associated with bladder tumor evolution. Conclusions: We found that NLR was higher in NMIBC with a high risk of progression. These data warrant a further evaluation of this potential, readily available prognostic marker in NMIBC. [Table: see text]
Geriatric assessment of older adults (&gt; age 65) with diagnosed or suspected malignancy in a cancer center clinic.
Authors: T. A. Jolly, W. K. Chiu, S. M. Alston, A. C. Lacy, H. B. Muss
Journal: Journal of Clinical Oncology (2011)

e19546 Background: Although the majority of cancer incidence and death occur in adults age 65 and older they are seldom offered entry into clinical trials (CT). Some decisions to not offer CT are based on the inability of clinicians to adequately assess functional age. The goal of this study is to create a registry of older adults with diagnosed or suspected malignancy, describe baseline characteristics, and obtain a measure of their functional status by using a Geriatric Assessment (GA). Methods: All English speaking patients ≥ 65 years referred to the North Carolina Cancer Hospital were eligible. The GA included a self administered questionnaire (Hurria et al Cancer 2005 104:1998) given to enrollees before, during, or after treatment. Medical staff performed a mental status exam and timed get-up and go test. Data from the questionnaire including measures of functional status, comorbidity, psychological status, nutrition, social status and support were analyzed to evaluate the feasibility of the GA process in a busy cancer center clinic. Results: 170 evaluable respondents participated in this study. Median age was 72 (range 65-92), 147 (87%) were white, 17(10%) black, 92 (54%) married, 126 (74%) retired, and 121 (71%) had at least some college education. Overall, 87% reported at least one comorbid condition and 75% took ≥ 4 concomitant medications. The mean number of comorbidities was 3 (SD=1.9). The most frequent conditions were arthritis (56%), hypertension (46%) and other cancers or leukemia (39%). Though 110 (65%) respondents had minor or no symptoms, 69 (41%) were dependent with at least one instrumental activity of daily living, 40 (24%) had ≥ 1 fall and 49 (29%) lost an average of 6 lbs in the last six months. Thirty-nine patients (23%) reported limitations in social activities due to physical or emotional problems. While 95% were satisfied with the length, 10% felt that some questions were difficult. Conclusions: A GA can be easily administered in a busy multidisciplinary clinic and the results used to evaluate outcomes in the study population. Further work will focus on interventions for the most vulnerable and correlating GA with outcome. Supported in part by the Breast Cancer Research Foundation, New York, NY.