tbuckley/cabot-search huggingface dataset:
Progression-free survival as an endpoint for clinical trials in first-line metastatic urothelial cancer.
Authors: Matt D. Galsky, Susanne Krege, Chia-Chin Lin, Noah M. Hahn, Thorsten Ecke, Erin L. Moshier, Guru Sonpavde, James H. Godbold, William K. Oh, Aristotelis Bamias
Journal: Journal of Clinical Oncology (2013)

251 Background: Advances in the first-line treatment of metastatic urothelial cancer (UC) have proven elusive. The lack of appropriate intermediate endpoints to screen the activity of novel regimens may be a barrier to progress, particularly in this disease state characterized by relatively high response rates but short response durations. Progression-free-survival (PFS) at fixed time points may overcome several of the limitations of response rate-based endpoints, but would be further supported by establishing benchmarks and demonstrating a correlation between PFS and overall survival (OS). Methods: Data were pooled from eight phase II and III trials evaluating first-line cisplatin-based chemotherapy in metastatic UC. Landmark analyses for progression at 3, 6, and 9 months after treatment initiation were performed to minimize lead-time bias. A proportional hazards model was used to assess the utility of PFS for predicting OS. Results: 545 patients were included in the analysis. The median PFS was 7.75 months (95% CI, 7.06, 8.18) and the median OS was 12.35 months (95% CI, 10.97, 13.44). The results of the landmark analysis, adjusted for performance status ≥ 1 and presence of visceral metastases, is shown in the Table. By using the Fleischer model, the estimated correlation between PFS and OS was 0.86 (bootstrap standard error 0.001, 95% CI 0.83, 0.89). Conclusions: PFS at 3, 6, and 9 months predicted OS in this analysis of patients with metastatic UC treated with first-line cisplatin-based chemotherapy. This analysis provides benchmarks, and support, for the use of PFS as an endpoint for phase II trials screening the activity of novel regimens as first-line treatment for metastatic UC. [Table: see text]
Risk of Acute Leukemia Post-Autologous Stem Cell Tranplant (ASCT) for Hodgkin’s Lymphoma (HL) Depends on Choice of Salvage Chemotherapy and Use of Radiation.
Authors: N.C. Dhani, T. Roberts, M. Pintilie, J. Kuruvilla, N. Franke, T. Nagy, R. Tsang, A. Keating, Michael Crump
Journal: Blood (2007)
Optimising management approaches for locally advanced oropharyngeal squamous cell carcinoma (LAOPSCC): A retrospective review of prognostic factors and outcomes in an Asian tertiary institution.
Authors: W. M. D. Tai, S. H. Tan, Q. S. Ng, N. Chau, W. T. Lim, E. Tan, D. S. Tan, M. Ang
Journal: Journal of Clinical Oncology (2011)

e16022 Background: LAOPSCC is treated with concurrent chemotherapy and radiation (CRT). However, certain subsets of OPSCC may have favourable prognoses, thus raising the question if all patients require similar CRT. This study aims to identify prognostic factors in Asian LAOPSCC and explore patient outcomes according to treatment modality and chemotherapy type. Methods: A retrospective review of resectable LAOPSCC from 2001-2006 were included in this analysis. Patient demographics, risk factors, treatment modalities were collated. Results: Out of the 130 patients, 87 received CRT, 24 received RT alone whilst 19 underwent surgery followed by adjuvant therapy. 74% of the patients were male with median age of 60. 30% were non-smokers. Median OS was 5.2 years. Univariable cox regression analysis showed that older age, male gender, smokers, history of alcohol consumption, higher cancer stage, higher T-stage, base of tongue tumors, higher Charlson Comorbidity Index (CCI) and low albumin were associated with worse overall survival (OS), progression free survival (PFS) and local relapse- free survival (LRFS). After multivariate analysis, smoking status, CCI scores and cancer stage were independently prognostic for OS. Patients who received RT alone, despite being older, predominantly smokers and having higher CCI, had similar OS, PFS and LRFS compared to CRT: Hazard Ratio (HR) 1.7, p=0.2; HR 1.7, p=0.1 and HR 1.6, p=0.2 respectively on multivariable cox regression analysis. In an exploratory analysis, after adjusting for age, CCI, smoking status and cancer stage, patients who received cisplatin-based CRT (n=70) had superior overall survival compared with RT alone (HR=0.4, p=0.01). However, patients who received non-cisplatin-based CRT (n=17) had similar overall survival compared to RT alone, independent of age, CCI, smoking status and cancer stage (HR=1.5,p=0.3). Conclusions: Asian LAOPSCC consists of a significant proportion of non-smokers and females. Amongst Asian LAOPSCC, cisplatin-based CRT remains the standard of care. In patients unfit for cisplatin-based treatment, RT alone should be considered.
Is there an unmet need for palliative care in cancer patients admitted to hospital?
Authors: Xia Zhu, Patricia Neo, Tan Ying Peh, Zhi Zhen Xu, Alethea Yee, Grace Meijuan Yang
Journal: Journal of Clinical Oncology (2015)

123 Background: Cancer patients who are admitted to hospital often have symptom problems and progressive functional decline, and may benefit from palliative care (PC) input. The aim of this study was to determine the profile of patients admitted under Lung and Gastrointestinal (GI) oncology teams (as their cohorts of admitted patients probably have more symptom problems) and whether they are being referred for PC input. Methods: Patients admitted from 1 March 2015 to 31 March 2015 were included. The following were recorded: primary site of tumor and whether it was metastatic, whether the admission was planned or unplanned, referral for PC input, outcome of admission and unplanned readmission within 7 days and 30 days. Results: See table below. Conclusions: Although 84% of patient admissions had metastatic cancer and 82% were unplanned admissions, only 21% were referred for PC input. This represents a missed opportunity for PC input, which has been shown to improve outcomes in patients with advanced cancer. However, if all advanced cancer patients who had an unplanned hospital admission were referred for PC, there would be a large increase from the current workload of the PC team. Hence, there is a need to pilot a novel model of PC provision, perhaps one in which a PC healthcare professional joins the oncology team to provide integrated palliative oncology care. [Table: see text]
Pretreatment serum ferritin and overall survival in metastatic pancreatic cancer.
Authors: Lindsey Zubritsky, Ahmed Alkhateeb, Kim Leitzel, Suhail M. Ali, Cynthia Campbell-Baird, James Connor, Allan Lipton
Journal: Journal of Clinical Oncology (2013)

171 Background: Ferritin, an iron storage protein, is elevated in the serum of certain types of cancers, including breast and pancreatic. Ferritin has been shown to play a role in tumorigenesis and cancer cell growth and survival through angiogenesis, immune regulation, and iron delivery. Ferritin may serve as a potential biomarker in evaluating survival of pancreatic cancer patients. Methods: This study determined pretreatment ferritin levels in a phase III clinical trial of 162 patients with advanced pancreatic cancer. A quantitative sandwich ELISA (Human Ferritin ELISA (Assaypro, St. Charles, Missouri) was used to measure pretreatment serum ferritin levels in 162 patients with advanced pancreatic cancer. Serum ferritin level was correlated with overall patient survival using log-rank regression and Kaplan-Meier analysis on a continuous and categorical dichotomous basis (median cutpoint). Results: The median pretreatment serum ferritin in 162 patients was 832.6 ng/ml, a 25 th and 75th percentile of 446 and 1735 ng/ml, respectively, and ranged from 51 ng/ml to 35914 ng/ml. When analyzed on a continuous basis, patients with higher serum ferritin had reduced overall survival (p= 0.001). When analyzed on a categorical basis (median 832.6 ng/ml), patients with higher ferritin had shorter overall survival (median 121 days vs. 180 days) (p=0.003). In multivariate analysis with pretreatment serum ferritin, TIMP-1, uPA, and VEGF, TIMP-1 remained the only significant predictive factor (p&lt;0.0001), with ferritin trending toward significance (p= 0.076). Conclusions: Pretreatment serum ferritin in 162 patients with advanced pancreatic cancer was quantified using ELISA. Pretreatment serum ferritin predicted for significantly shorter overall survival in a phase III trial of metastatic pancreatic cancer. Pretreatment serum ferritin level has prognostic biomarker utility in pancreatic cancer, and should be evaluated as a predictive factor for response to novel treatment regimens.
Effect of neoadjuvant chemotherapy on survival in patients with gastric signet ring cell adenocarcinoma: A multicentric comparative study.
Authors: C. Mariette, M. Messager, J. H. Lefevre, V. Pichot, A. Souadka, T. Thibot, D. Brachet, N. Carrere, M. Fernandez, J. Guiramand, B. Tsilividis, R. Flamein, K. Kraft, J. M. Balon, F. Borie, A. Glaise, X. d'Journo, F. Peschaud, F. Vandois, G. Piessen
Journal: Journal of Clinical Oncology (2011)

4036 Background: Perioperative chemotherapy is a standard treatment for gastric adenocarcinoma (GA). Signet ring cell GA (SRC) has been shown to be of poorer prognosis when compared to non-SRC. Although of major importance in this context, chemosensitivity of SRC remains hypothetical. The aim of this study was to evaluate the survival impact of neoadjuvant chemotherapy (NCT) in patients with gastric SRC through a large national comparative cohort. Methods: 1,054 patients were treated for SRC in 18 French centers from 1997 to 2009. Were included patients treated in a curative intent (n=924) with 171 patients who received NCT followed by surgery (NCT arm, 18.5%) compared in intention to treat to 753 patients treated by surgery alone (S arm, 81.5%). NCT, mainly based on a fluorouracil-platinum doublet or triplet, was proposed in some centers in accordance to national guidelines for GA treatment, whereas other centers favored primary surgery for SRC due to the suspected chemoresistance. Results: Both groups were comparable regarding usual prognostic variables such as age, gender, ASA score, malnutrition, tumoral location and TNM stage. Ten patients did not benefit from surgery because of a major tumoral progression meanwhile. At surgical examination, metastases were discovered in 4.8% of patients in NCT group and 8.1% in S group (p=0.130), with no tumoral resection in 50 patients. Among the 864 resected patients, R0 resection rates were 65.9% vs. 62.3%, respectively (p = 0.308). Significantly more patients received adjuvant chemotherapy in the NCT group than in the S group (62% vs. 31%, p<0.001). After a median follow-up of 31.5 months, overall survival was significantly shorter in the NCT group (8.6 vs. 12.7 months, p<0.001). In multivariate analysis, NCT was an independent predictor of poor survival (HR 1.4 95% CI 1.1-1.9, p=0.042). Conclusions: While perioperative chemotherapy is considered a standard treatment for GA regardless of histological subtype, we demonstrate for the first time that NCT provides no survival benefit in SRC. Registered on Clinicaltrial.gov website under identifier NCT01249859.
Updated overall survival analysis of NAPOLI-1: Phase III study of nanoliposomal irinotecan (nal-IRI, MM-398), with or without 5-fluorouracil and leucovorin (5-FU/LV), versus 5-FU/LV in metastatic pancreatic cancer (mPAC) previously treated with gemcitabine-based therapy.
Authors: Andrea Wang-Gillam, Chung-Pin Li, Gyorgy Bodoky, Andrew Dean, Yang-Shen Shan, Gayle S. Jameson, Teresa Macarulla, Kyung-Hun Lee, David Cunningham, Jean-Frédéric Blanc, Richard Hubner, Chang-Fang Chiu, Gilberto Schwartsmann, Jens T Siveke, Fadi S. Braiteh, Victor M. Moyo, Bruce Belanger, Eliel Bayever, Daniel D. Von Hoff, Li-Tzong Chen
Journal: Journal of Clinical Oncology (2016)

417 Background: NAPOLI-1 is a global, randomized Phase 3 study evaluating nal-IRI—a nanoliposomal irinotecan—with or without 5-FU/LV in 417 patients with mPAC previously treated with gemcitabine-based therapy. Primary survival analysis was based on 313 events. Nal-IRI+5FU/LV significantly improved overall survival (OS, primary endpoint), 6.1 months (mo) vs 4.2 mo; with 5-FU/LV (unstratified hazard ratio [HR] = 0.67; P = 0.012). Primary endpoint was supported by improved progression-free survival, time to treatment failure, objective response and CA19-9 tumor marker response rates, and manageable toxicities. An updated analysis of OS, 6- and 12-month-survival estimates, and safety is presented. Methods: The updated descriptive analysis of OS, based on 378 events (25 May 2015), includes data from all randomized patients across the 3 arms. Results: After 378 OS events, nal-IRI+5-FU/LV (n = 117) retained an OS advantage relative to 5-FU/LV (n = 119): 6.2 mo (95% confidence interval [CI], 4.8–8.4) vs 4.2 mo (95% CI, 3.3–5.3) with an unstratified HR of 0.75 (P = 0.0417). In contrast, there was no OS advantage with nal-IRI monotherapy (n = 151) vs 5-FU/LV (n = 149): 4.9 mo [95% CI, 4.2–5.6] vs 4.2 mo [95% CI, 3.6–4.9], HR = 1.08; P = 0.5. Six-month survival estimates were 53% (95% CI, 44–62%) for nal-IRI+5-FU/LV vs 38% (95% CI, 29–47%) for 5-FU/LV; 12-month survival estimates were 26% (95% CI, 18-35%) for nal-IRI+5-FU/LV vs 16% (95% CI, 10–24%) for 5-FU/LV. With events in nearly all patients, the OS curves converge at ~20 mo with 19 patients (16.2%) surviving beyond 20 mo. This is a reason for attenuation of the HR estimate and unstratified log rank p-value. The most common grade 3+ adverse events occurring at a ≥ 2% incidence in the nal-IRI-containing arms were neutropenia, diarrhea, vomiting, and fatigue. Conclusions: In an updated analysis, the median OS benefit for nal-IRI+5FU/LV over 5-FU/LV was maintained, with a similar safety profile. Nal-IRI+5-FU/LV may be a new standard of care for patients with mPAC previously treated with gemcitabine-based therapy. Clinical trial information: NCT01494506.
Changes in prostate volume during neo-adjuvant hormone therapy and definitive radiotherapy.
Authors: Andrew McPartlin, Ali Hosni, Alan McWilliam, Marcel Van Herk, Lucy Kershaw, Ananya Choudhury
Journal: Journal of Clinical Oncology (2016)

e628 Background: Neo-adjuvant hormone therapy (NA-HT) produces profound changes in prostate vasculature and volume. There is little data available on how prostate volumes changes during radiotherapy (RT) after NA-HT. This is highly relevant in the context of adaptive RT and focal boosting. Methods: Eleven patients with intermediate- or high-risk prostate cancer, receiving 3 months NA-HT plus 60 Gy RT in 20 fractions, underwent four multiparametric MRI scans. These were performed before and after NA-HT, then during the third week of RT and 8 weeks after RT. The prostate was contoured on each scan by a radiation oncologist with experience in prostate MRI and reviewed by a second radiation oncologist. Statistical analysis was performed using Spearman correlation and the unpaired t-test with Welch’s correction. Results: One patient declined the post-treatment scan. NA-HT induced a dramatic mean volume reduction of 47%, range -27% to -64%. Volume changes during NA-HT inversely correlated with volume change during RT (r -0.755, p=0.01). Patients with ≥50% vs. &lt;50% reduction during NA-HT experienced significantly different responses to RT with +29.4% vs. -9.1% (p=0.006) mean volume changes respectively from pre-RT size by week three. Absolute volume pre-NA-HT (p=0.64) or pre-RT (0.29) was not predictive for subsequent change. There was a small mean volume change post RT of -5%; range -20% to +15%. Conclusions: In this study a reduction in volume during RT is seen in patients with smaller than 50% prostate shrinkage due to NA-HT. Other patients experienced a mean volume increase of nearly one third by week three. This would be equivalent to an increase of around 4mm for an initial diameter of 40mm. In case of small treatment margins, the radiotherapy should be adjusted for these changes. [Table: see text]
Serum vascular endothelial growth factor A<sub>165</sub> levels in patients with various histological types of breast cancer and benign tumors
Authors: I. Gisterek, K. Szewczyk, R. Matkowski, P. Sedlaczek, U. Staszek, A. Zolnierek, A. Lacko, M. Bebenek, M. Pudelko, J. Kornafel
Journal: Journal of Clinical Oncology (2008)

22166 Background: Vascular endothelial growth factor (VEGF) expression has been reported to have independent prognostic significance and is associated with inferior survival in breast cancer. Since blood biomarkers are minimally invasive, relatively easy to evaluate, and there are several reports suggesting that soluble VEGF might be potential markers of angiogenesis we investigated the differences of serum VEGF A165 in various pathological types of breast cancer and benign breast tumors. Methods: Serum VEGF A165 levels were measured preoperatively in 295 patients with breast tumors using immunohistochemical method (ELISA). Patients were divided into four groups according to histological type of breast pathology. Ductal cancer was diagnosed in 202 patients, lobular in 60, ductal carcinoma in situ (DCIS) in 10 and benign tumors in 23 women. Results: Serum VEGF A165 levels ranged from 156 pg/ml to 1,850 pg/ml. In patients with ductal cancer mean level was 640.6 pg/ml, median 553.3 pg/ml, in lobular cancer respectively 611.1pg/ml and 596.8pg/ml, in DCIS - 748.4pg/ml and 628.7pg/ml, in benign tumors 633.8pg/ml and 569.3pg/ml. Statistical analysis (T-Student test) does not show statistically significant differences between serum levels of VEGF in those four groups. Conclusions: VEGF A serum levels are similar in breast invasive cancer and non malignant tumors. Despite the VEGF role of as a key mediator of normal and pathological angiogenesis, serum VEGF levels can't be a marker of invasive cancer. We observed that in patients with DCIS VEGF A serum levels were higher than in individuals with invasive cancer or benign tumors however these differences were not statistically significant (p=0,15, and p=0,19) and the group of patients with DCIS was small. However, to elucidate this issue studies in larger patient population need to be performed. No significant financial relationships to disclose.
Value of phase II pathway in the ambulatory care setting.
Authors: Diane Schaub, Elizabeth Rebello
Journal: Journal of Clinical Oncology (2014)

115 Background: The aim of the project was to decrease PACU (Post Anesthesia Care Unit) time by implementing a Phase II pathway for patients undergoing port-a-cath placement under Monitored Anesthesia Care in the Ambulatory Setting. Methods: The process improvement interventions were centered on eliminating unnecessary patient care processes and increasing patient flow and consisted of: patient and healthcare provider education, phase II unit utilizing existing bed space, revised charting template in the PACU. Queries of our AIMS database for port-a-cath cases performed between January 1, 2012 and February 28, 2013 (pre-intervention) and then between May 1, 2013 and May31, 2014 (post-intervention) were obtained. March 1, 2013 to May 1, 2013 was a transition period used to implement the process. Only cases performed under monitored anesthesia care were included. Cases with a PACU length of stay greater than 200 minutes were excluded from the study as these patients were no longer fast track. Descriptive statistics were used to summarize PACU length of stay pre/post-intervention. Scatter plots were used to show the variability in PACU length of stay and to illustrate the average trajectory of PACU length of stay over each time frame. A t-test was used to compare the average length of stay in the PACU, pre/post-intervention. Results: There were 917 pre-intervention cases and 362 post intervention cases. Trend of minutes spent in the PACU over time is illustrated (Figure 1). The average number of minutes in the PACU during the pre-intervention was 86.8. During the post-intervention, it was 67 minutes (Difference = 19.6 minutes; p-value &lt; 0.001). Conclusions: As a result of implementing a phase II pathway for patients undergoing port-a-cath placement, there was a significant decrease in average time spent in the PACU. In addition, there was a decrease in the variation associated with PACU length of stay. The phase II pathway allowed a significant subgroup of this patient population to be less sedated after surgery and proceed directly to chemotherapy or their next scheduled appointment in the institution. Time and cost savings to the patient and the institution were additional benefits.
An analysis of preoperative chemoradiotherapy with 5FU/leucovorin for T3-4 rectal cancer on survival in a pooled analysis of EORTC 22921 and FFCD 9203 trials: Surrogacy in question?
Authors: F. Bonnetain, J. Bosset, J. Gerard, G. Calais, T. Conroy, L. Mineur, O. Bouche, P. Maingon, O. Chapet, L. Radosevic-Jelic, N. Methy, L. Collette
Journal: Journal of Clinical Oncology (2011)

3506 Background: Phase III trials of preoperative chemoradiotherapy (CRT) in T3-4 rectal cancer have demonstrated the benefit of adding 5FU/leucovorin to radiotherapy (RT) on pathological complete response (ypT0) and local control (LC). Using these intermediate endpoints for phase III trials requires their validation as surrogates for overall survival (OS). We pooled two large phase III trials to assess the benefit of CRT over RT on progression-free (PFS) and OS with increased statistical power and to explore the surrogacy of ypT0 and LC as well as PFS as early endpoints. Methods: We pooled the data of EORTC 22921 (1,011 pts) and FFCD 9203 (756 pts) trials. Meta-analyses methods (forest plot and stratified analyses) were used to compare neoadjuvant CRT to RT for OS, PFS, LC and time to distant progression (DP). We also used the meta-analytic surrogacy validation approach (15 analysis-units) using weighted linear regression to estimate trial-level association (R²) between treatment effects on early and final endpoints. Results: The median follow-up was 5.6 years. CRT (886 pts) as compared to RT (881 pts) did not prolong OS, DP or PFS. The 5-y OS-rate was 66.3% in the CRT arm vs 65.9% in the RT alone arm (HR = 1.04 [0.88-1.21], p=0.66). CRT significantly improved LC: HR = 0.55 {0.42-0.72}, p<0.0001. LC rates at 1 year, 2 years and 3 years were respectively 97.8%, 93.8% and 89.3% in CRT group and 96.0 %, 92.3% and 84.7% in RT alone group. PFS was the only validated surrogate variable for OS with R² = 0.88 (95% CI 0.77 – 1). LC (R² = 0.17 [95% CI, - 0.19 to 0.52]) as well as DP (R² = 0.31 [95% CI, -0.09 to 0.71]) did not predict preoperative CRT effects on OS. Moreover none of pathological parameters (ypT0 and nodal status ypN0) were validated as surrogate endpoints for LC, PFS and OS. Conclusions: Despite increased statistical power, CRT that prolonged LC as compared to RT alone, failed to prolong OS or PFS. Moreover LC was not a surrogate for OS or PFS. Despite the clinical meaningful of LC, future phase III trials may use OS or PFS as primary endpoint to ensure clinical benefit.