tbuckley/cabot-search huggingface dataset:
Quality of lymphadenectomy for esophageal cancer in the United States: An analysis of the SEER database.
Authors: B. M. Stiles, A. Nasar, F. Mirza, J. L. Port, P. C. Lee, S. Paul, N. K. Altorki
Journal: Journal of Clinical Oncology (2011)

4068 Background: The Worldwide Esophageal Cancer Collaboration (WECC), a consortium of institutions to pool data on EC, reported recommendations regarding the optimal number of lymph nodes removed during esophagectomy. This study was performed to assess how often optimal lymphadenectomy (LAN) was performed in a national EC registry. Methods: From the SEER-17 cancer registry (1988-2007), patients undergoing esophagectomy with “T-classification” and “number of resected lymph nodes (LN)” recorded were analyzed. The WECC recommended optimal LAN as ≥10 LN for T1, ≥20 LN for T2, and ≥30 LN for T3 or T4 tumors. Optimal LAN and survival were primary outcomes. Log-rank was performed for univariate comparisons and Cox regression for multivariate analysis. Results: 5792 patients with resected EC were appropriate for analysis. Median number of lymph nodes resected was 9. Optimal LAN was achieved in 951 patients (16%) of the cohort and in only 164 (5%) of those with T3 or T4 EC. Optimal LAN was more likely achieved with lesser T-classifications (OR for T1=13.43, CI:11.12-16.23), in patients <65 yo (OR 1.26, CI:1.08-1.47), and in patients with adenocarcinoma (OR 1.20, CI:0.98-1.47). Despite identifying more N+ disease, 5-yr OS was improved in each T-classification for patients who underwent optimal LAN (Table). Conclusions: The SEER database provides insight into practice patterns at US hospitals. In that context, LAN for EC is grossly underperformed when held to the standard of the WECC recommendations. Patients who undergo an optimal LAN have improved survival, likely due to identifying the need for further treatment or to a therapeutic effect of the LAN. Efforts should therefore be made by surgeons to perform a more extensive LAN during esophagectomy to ensure that patients are appropriately staged and treated. pT Extent of lymphadenectomy No. of patients (%) Positive lymph nodes (%) 5-year OS p value (OS) T1N=1520(26%) Optimal 46 (42%) 134 (21%) 62.1% <0.001 Suboptimal 874 (58%) 124 (14%) 53.8% T2N=1106 (19%) Optimal 141 (13%) 74 (52%) 39.1% 0.009 Suboptimal 965 (87%) 415 (43%) 31.8% T3/T4N=3166 (55%) Optimal 164 (5%) 122 (74%) 24.3% 0.015 Suboptimal 3,002 (95%) 2,000 (67%) 19.8% *11 patients with missing value.
The RADICAL-PC trial.
Authors: Jehonathan H Pinthus, Laurence Klotz, Himanshu Lukka, Wilhelmina CM Duivenvoorden, Shirley Pettit, Kayla Pohl, D. Robert Siemens, Vincent Fradet, Marina Mourtzakis, Peter Kavsac, PJ Devereaux, Darryl Leong
Journal: Journal of Clinical Oncology (2016)

178 Background: Cardiovascular disease (CVD) occurs frequently in men with prostate cancer (PC), but the reasons are unclear. Specifically, the role of androgen deprivation therapy (ADT) in promoting CVD remains uncertain. There is a lack of evidence to inform preventive strategies against CVD in this high risk group. It is unknown if the evidence to support CVD preventive strategies in the general population can be validly extrapolated to men with PC. Methods: RADICAL-PC combines two prospective studies, one of which is embedded in the other. The Role of Androgen Deprivation Therapy in Cardiovascular Disease – A Longitudinal Prostate Cancer Study (RADICAL PC1) is a prospective cohort study of men within one year of their first diagnosis of PC, or who are within one month of commencing ADT for the first time. Its goal is to identify factors associated with the development of CVD among men with PC, with a particular focus on ADT. The Randomized Intervention for Cardiovascular and Lifestyle Risk Factors in Prostate Cancer Patients (RADICAL PC2) is a randomized, controlled trial embedded in RADICAL PC1. RADICAL PC2 will test a systematic approach to modifying CV and lifestyle risk factors. The intervention group will receive: 1) Standardized advice on healthy diet and exercise; 2) Low-dose antiplatelet agent; 3) Low- to moderate-dose statin; and 4) ACE-I for baseline systolic blood pressure ≥ 130mmHg. Results: The study has been recently funded by Movember clinical trial program of Prostate Cancer Canada, and is launched across Canada. The primary outcome is the occurrence of the composite of cardiovascular death, myocardial infarction, stroke, heart failure, or arterial revascularization. For RADICAL-PC1, 6000 participants will have 90% power to detect a hazard ratio 0.86 for a given exposure. For RADICAL-PC2, 4116 participants randomized, with 434 primary outcome events will have 85% power to detect a hazard ratio of 0.75 in the intervention group. Conclusions: RADICAL PC will be one of the largest prospective studies of CVD – the main competing risk – in men with PC. It will clarify the determinants of CVD in these men, the role of ADT in CVD, and will simultaneously test an intervention to lower the CVD risk in this high-risk population.
Comparison of microscopic versus molecular approaches in classifying the relatedness of synchonous and metachronous cancers.
Authors: D. M. Smith, E. M. Ellsworth, W. Spence, S. D. Finkelstein
Journal: Journal of Clinical Oncology (2010)

e21091 Background: Oncologists are increasingly challenged with resolving whether separate cancers discovered synchronously or metachronously in patients represent metastasis or second primaries. This dilemma confounds proper patient care. Comparative mutational profiling (CMP) can address this need. We reviewed medical records to define the status of how this issue is currently managed and compared these findings with the results of CMP. Methods: We reviewed clinical records and pathology reports on 126 unselected, problematic patients with greater than 1 cancer, sent to us to determine the cancers' relatedness. Based on pathology reports, we assigned each cancer pair to 1 of 4 groups of relatedness: metastasis, independent primaries, unknown, or not stated in report. We performed quantitative CMP (RedPath PathFinderTG) using 17 markers on the DNA from cellular targets dissected from routine tissue or cytology slides. Results: CMP showed 63 of 126 (50%) patients had new primary cancers; 63 (50%), recurrent disease. Pathology reports did not state a relationship in 65 of 126 (52%) patients; 28 of these 65 (22%) reports nevertheless staged the lesion pathologically as a new primary. 36 of 126 (29%) reports expressly stated that the microscopic analysis was indeterminate. The remaining 25 (20%) reports classified the relatedness; however, CMP reclassified the relationship in 9 (36%). 14 (11%) patients with metachronous cancers had latency intervals exceeding 5 years; CMP showed 6 (43%) of these patients had recurrent disease including 2 with intervals of 13 and 17 years. Conclusions: Optimal patient management requires correct pathologic staging and definitive discrimination between cancer recurrence and new cancer formation. Traditional microscopic methods often fail, especially for small specimens or for origin from a single organ. Quantitative CMP fills this void. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration RedPath Integrated Pathology RedPath Integrated Pathology
Second-line combination chemotherapy: A phase I study of ixabepilone, mitoxantrone, and prednisone in patients with metastatic hormone-refractory prostate cancer (HRPC) refractory to docetaxel-based therapy
Authors: A. L. Harzstark, V. K. Weinberg, J. Sharib, D. C. Smith, M. H. Hussain, T. M. Beer, C. W. Ryan, P. Mathew, C. J. Ryan, E. J. Small, J. E. Rosenberg
Journal: Journal of Clinical Oncology (2008)

5151 Background: Mitoxantrone and prednisone (MP) and ixabepilone (Ix) both have modest activity as single agents for 2nd-line chemotherapy in docetaxel-refractory patients with HRPC and have demonstrated evidence of non-cross resistance, suggesting the potential for benefit with a combination of the two agents. Methods: Patients with metastatic HRPC and progression after 3 or more cycles of docetaxel were enrolled in a phase I multicenter study of the combination of Ix and MP administered on day 1 every 21 days along with prednisone 5 mg BID daily. Dose levels are listed below in a standard 3+3 phase I design. Toxicity was evaluated using CTC v3 criteria and responses were evaluated using PSA Consensus Criteria. Results: 32 pts have been treated on dose levels I through VIa to date. 20/32 pts (62.5%) had grade 3/4 neutropenia, 1 pt had grade 3 febrile neutropenia, and 1 pt had a grade 5 infection. Non-hematologic serious adverse events related to study drug included 1 episode of grade 3 diarrhea with dehydration and one episode of grade 3 emesis. DLTs are listed below. Due to prolonged neutropenia not identified until after dose-escalation, dose levels V and VI were repeated with pegfilgrastim on day 2 of each cycle (levels Va, VIa). Eight patients have experienced PSA responses, all at dose level 3 or higher; 6/17 (35%) of patients receiving full dose mitoxantrone (12 mg/m2) have had a PSA response. Conclusions: These results suggest that the combination is feasible and active and may require dosing with pegfilgrastim. Further exploration of activity will occur during the phase II expansion cohort once the MTD has been determined. This study was supported by the Cancer Therapy Evaluation Program of the NCI and the DOD Prostate Cancer Clinical Trials Consortium. Dose Level Mitoxantrone (mg/m2) Ixabepilone (mg/m2) Pegfilgrastim (mg) DLTs PSA Responses I 8 20 - 0/3 0/3 II 8 25 - 0/3 0/3 III 10 25 - 0/3 1/3 IV 10 30 - 0/6 1/6 V 12 30 - 2/6: Grade 3 diarrhea, grade 4 neutropenia 2/6 VI 12 35 - 2/5: Grade 4 neutropenia (x2) 3/5 Va 12 30 6 0/3 1/3 VIa 12 35 6 1/3: Grade 5 infection 0/3 No significant financial relationships to disclose.
Choice of starting dose for molecular targeted agents (MTA) evaluated in phase I cancer clinical trials (P1T)
Authors: L. Vidal-Boixader, C. Le Tourneau, L. L. Siu
Journal: Journal of Clinical Oncology (2008)

3586 Background: One tenth of the LD10 (dose lethal to 10% of mice) has been conventionally used to identify a safe human starting dose (SD) in P1T with cytotoxic agents. There is no consensus on which preclinical models and parameters would best predict for a safe SD for MTA. Methods: We reviewed a total of 61 MTA evaluated in 86 P1T for which preclinical data were available. Our objectives were to evaluate which animal models and parameters were used to establish a safe human SD, to compare the SD with the maximum administered dose (MAD), and to calculate the number of dose levels required to achieve MAD. We also analyzed if higher SD would shorten dose escalation while guaranteeing safety. Results: Of the 86 P1T reviewed, the SD was based on data from rodent (33), non- rodent (30), healthy human volunteers (10), other ongoing P1T (5) and not specified (8). For the 44 agents in which animal data were available, 25 followed a modified Fibonacci dose escalation design and 19 used alternative designs. To assure comparability, we only analyzed the 25 agents which utilized the modified Fibonacci design in 29 P1T. Among these 29 P1T, 17 used rodent parameters to determine SD (13 used LD10, 4 used toxic dose low [TDL]), while 12 used non-rodent parameters (6 used no observed adverse event level [NOAEL], 4 used LD10, 2 used TDL). The median ratio to MAD to SD for all 25 agents was 11.4 (1- 45): 11 and 12 for agents with SD based on rodent and non-rodent data respectively. The median number of dose levels to reach MAD from SD was 5.3 (1–9). The table below illustrates the safety and number of dose levels to reach MAD, with varying SD (1x, 2x and 3x SD). Conclusions: Unlike cytotoxic agents, the derivation of SD for MTA is based on different practices using a variety of preclinical parameters. No significant differences are observed in the number of dose levels to reach MAD using SD based on rodent versus non-rodent data. Non-rodent data appear to better predict for a safe human SD than rodent data in P1T of MTA. Starting dose No of dose levels to reach MAD Rodents median (range) No of dose levels to reach MAD Non-rodents median (range) No of unsafe* trials Rodents (n=17) vs non-rodents (n=12) No of unsafe agents* Rodents (n=14) vs non-rodents (n=11) 1x 5.2 (1–9) 5.3 (2–9) 4 vs. 0 4 vs. 0 2x 3.2 (1–6) 3.6 (1–6) 4 vs. 1 4 vs. 1 3x 2.4 (1–5) 2.4 (1–5) 8 vs. 3 7 vs. 3 * Unsafe trial or agent is arbitrarily defined if SD = MAD No significant financial relationships to disclose.
Diabetes mellitus and risk of cancer-specific mortality among patients with clear cell renal cell carcinoma undergoing nephrectomy.
Authors: Sarah P. Psutka, Suzanne B. Stewart, Christine M. Lohse, Matthew K. Tollefson, Stephen A. Boorjian, John C. Cheville, Bradley C. Leibovich, R. Houston Thompson
Journal: Journal of Clinical Oncology (2014)

516 Background: The impact of diabetes mellitus (DM) on outcomes in patients with renal cell carcinoma (RCC) is controversial. Herein, we evaluated the association of DM with survival among patients with RCC. Methods: We reviewed 2,589 patients treated with nephrectomy for sporadic, unilateral, M0 RCC between 1990 and 2008 and compared demographic and tumor characteristics in patients with and without DM (nonDM). Patients with DM (n=313) were matched 1:2 to nonDM patients according to date of surgery, age, smoking status, obesity, ECOG performance status (PS), CKD stage, histological subtype, and nuclear grade. Cancer-specific (CSS) and overall survival (OS) were compared by Kaplan-Meier analysis. The association of DM with outcomes was evaluated with Cox proportional hazards regression models. Results: A total of 313 (12%) patients had DM. DM patients were significantly older at RCC diagnosis, more likely to be obese, and had higher Charlson scores, CKD class, rates of smoking, and worse PS at surgery (p&lt;0.001). Patients with DM were also more likely to have ccRCC (83% vs. 76%, p=0.02) and to undergo nephron-sparing surgery (42% vs. 35%, p=0.01), while other pathologic features were similar in DM and nonDM. Among the 939 matched cases and controls, 463 patients died within a median of 5.5 years after nephrectomy. Median follow-up for survivors was 8.6 years. Five-year CSS was not significantly different among DM patients 84% vs. nonDM patients 87% (p=0.11), although 5-year OS was significantly worse among DM patients (66% vs. 75%; p&lt;0.001). Indeed, even after adjusting for Charlson score, DM patients were noted to have a significantly increased risk of all-cause mortality (HR 1.33; p=0.004). In a subanalysis of patients with clear cell RCC, DM patients were more likely to die from RCC compared with nonDM patients after adjusting for the SSIGN (Stage, Size, Grade, Necrosis) score (HR 1.44; p=0.034). Conclusions: In this surgical cohort, DM was independently associated with decreased CSS among patients with ccRCC and with decreased OS in all RCC subtypes. Further studies to determine the potential biologic mechanism for this interaction are warranted.
Urinary osteopontin as a marker for localized and metastatic prostate cancer.
Authors: A. J. Prager, C. R. Peng, E. Lita, D. McNally, A. Kaushal, M. Sproull, K. Compton, W. L. Dahut, W. D. Figg, K. A. Camphausen
Journal: Journal of Clinical Oncology (2011)

e15147 Background: Prostate cancer is the second most common cause of cancer related death for men in the United States. Osteopontin (OPN) is an extracellular structural protein that is over-expressed in various cancers and is associated with tumor angiogenesis and metastasis. We investigated whether normalized OPN levels can be used as a noninvasive biomarker for localized and metastatic prostate cancer. Methods: Urine samples were collected from healthy men (n=19) as well as men with localized cancer prior to receiving radiation therapy (n=65) and men with metastatic prostate cancer (n=36). Samples were assayed in duplicate via an Enzyme Linked Immunosorbent Assay specific to Osteopontin-1 (R&D Systems). Osteopontin values were corrected for urinary creatinine levels obtained using Bayer DCA 2000+ Analyzer (Bayer Healthcare). Results: The mean normalized OPN levels for healthy men (mean: 532.4 ng/mg, range: 51.0 – 1559.0), men with localized cancer (mean: 613.6 ng/mg, range: 2.3 – 2716.0) and men with metastatic cancer (mean: 1024.0 ng/mg, range: 123.6 – 3304.0) were significantly different from each other (p=0.016, Kruskal-Wallis nonparametric ANOVA test). Furthermore, the urinary OPN levels were significantly different between healthy and metastatic groups (p=0.006), as well as between the localized and metastatic groups (p=0.0086). The area under the ROC curve distinguishing between healthy and metastatic groups was 0.70 (p=0.01392, 95% confidence interval of 0.56 to 0.85) and between localized and metastatic groups was 0.65 (p=0.01389, 95% confidence interval of 0.53 to 0.77). Conclusions: Urinary osteopontin levels can be used to identify patients with prostate cancer and differentiate between patients with localized and metastatic disease.
Correlates of capillary leak syndrome (CLS) in patients with cutaneous T-cell lymphoma (CTCL) during treatment with denileukin diftitox (DD) in a placebo (PBO)-controlled phase III trial.
Authors: T. Kuzel
Journal: Journal of Clinical Oncology (2010)

e18509 Background: Interleukin-2 therapy is associated with capillary leakage which manifests as hypoalbuminemia, hypotension/intravascular signs of dehydration, with concurrent edema/fluid retention. DD is a recombinant fusion toxin composed of sequences of human IL-2 and diphtheria toxin and is approved for the treatment of CD25+ CTCL. In open-label studies of DD, CLS has been noted. To learn more about the possible association of DD with CLS, we analyzed data from a Phase III trial in CTCL pts with recurrent or persistent stage Ia-III disease. Methods: We examined the clinical reporting of adverse events in any single cycle of therapy for the components of CLS of any severity, identifying 1) hypoalbuminema, 2) dehydration or low blood pressure, and 3) fluid retention or edema. The trial included 144 pts, 44 receiving PBO (mean cycles per pt = 5.1), 45 receiving DD 9 μ g/kg qd × 5 every 21 days (LD) (mean cycles per pt = 5.7), and 55 receiving DD 18 μ g/kg daily × 5 every 21 days (HD) (mean cycles per pt = 5.7). Median age was 57, 58, and 60 in the arms respectively. Results: In the PBO arm, 10/4/1 pts experienced 1/2/3 components of CLS, respectively, and no pt experienced all 3 components in a single cycle. In the LD arm 12/2/4 pts experienced 1/2/3 components, respectively, and the 4 pts with 3 components were all during same cycle (9%). In the HD arm, 13/4/8 pts experienced 1/2/3 components, respectively, and 6 pts with 3 components (11%) during single cycle. Of the 10 pts with single-cycle CLS, 5 (50%) were stage IIb or greater (overall incidence of ≥stage IIb CTCL in trial was 47/144=33%), and median age 60. There were 2 responders in the 10 pts (20%) with single-cycle CLS (vs the overall response rate (RR) in the LD and HD arm combined 44/100, 44%). Conclusions: CLS, especially when all components are during a single cycle, is associated with DD treatment. No pt in the placebo arm had single-cycle CLS, whereas rates of 9% and 11% of CLS (of any severity) were noted in the LD and HD arms, respectively. Higher stage CTCL (≥stage IIb) may be more likely to lead to CLS. RR trends lower in pts with single cycle CLS, but this may be due to dose-limiting toxicity. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Eisai
Outcomes and efficiency of national gastric cancer screening program in Korea: Single-center, large-scale study.
Authors: Beom Jin Kim, Chae Heo, Bong Ki Cha, Jae G. Kim, Sang-Jung Kim
Journal: Journal of Clinical Oncology (2012)

29 Background: Gastric cancer is a major cause of death and a substantial socioeconomic burden in Korea. The National Cancer Screening Program for Medicaid recipients was initiated in 1999 and has contributed to reduction of cancer-related mortality in Korea. Endoscopy may be cost-effective screening tool in Korea, where the cost of endoscopy and UGIS are similar and the incidence of gastric cancer is high. Most of Japanese studies on the efficiency of mass screening for gastric cancer have dealt with photoflurography as a screening tool. Although biennial gastric cancer screening by endoscopy has been increasing in Korea as part of the National Cancer Screening Program, few studies have evaluated its efficiency. Therefore, we analyzed the outcomes and efficiency of the National Gastric Cancer Screening Program using endoscopy in Korea. Methods: We reviewed medical records from the National Gastric Cancer Screening Program at Chung-Ang University hospital in Korea from January 2007 to December 2010. The study population was comprised of Medicaid recipients ≥ 40 years of age who were taken from the National Health Insurance Corporation. Results: A total of 41,150 asymptomatic subjects underwent endoscopy for gastric cancer screening. The mean age of the screened subjects was 56.3 years for men and 48.9 years for women. The male to female ratio of the screened subjects was 1.57:1. Gastric cancer was diagnosed in 102 (0.24%) of 41,150 subjects (60 men and 42 women). Their mean age was 54.4 years. Of these, 76 subjects (0.18%) were diagnosed as early gastric cancer and 26 subjects (0.06%) as advanced gastric cancer. The proportion of early gastric cancer among total gastric cancers was 74.5%. During the period, only 6,586 (16.0%) subjects participated in the biennial gastric cancer screening (59% for men and 49% for women). Conclusions: Despite accomplishments of the National Gastric Cancer Screening Program in Korea, low compliance to the screening program remains an issue. Furthermore, its cost-effectiveness analysis will be needed for successful progression.
Contrast-enhanced U.S.-guided biopsies following MRI in men with elevated PSA and previous negative biopsy.
Authors: G. Pasticier, G. Rigou, C. Deminiere, J. Bernhard, J. Riviere, G. Robert, H. Wallerand, J. Ferriere, Y. Lebras, N. Grenier, A. Ravaud
Journal: Journal of Clinical Oncology (2011)

e15130 Background: A first set of US-guided biopsy does not exclude prostate cancer in men with elevated PSA. Repeated biopsy detection rate is only 10 to 30% and increases risks of complications. Localization of suspected targets on MRI with subsequent sonography may be difficult. Therefore, we addressed the ability of contrast-enhanced US-guided biopsies in detecting prostate cancer after MRI localization. Methods: 79 patients (mean age 62y) with elevated PSA value (mean = 12.9 ng/ml) and prior negative biopsy (1-5, mean 2.3) were included in a prospective study. They underwent prostate MRI examination: T1-weighted, T2-weighted, diffusion-weighted and dynamic contrast-enhanced sequences. A single physician performed a first set of targeted biopsies (TB) on MRI-suspected lesion and identified on contrast-enhanced US as well, and subsequently performed a set of sextant randomized “non targeted biopsies” (NTB). Diagnostic efficacy of each biopsy approach – TB or NTB- was evaluated regards to pathological results. Results: 92/1090 non-targeted biopsies (8,4%) and 54/174 targeted biopsies (31%) were positive for cancer. Mean cancer detection rate was 51,9% (41/79 patients), growing up to 57,9% and 58,3% for the third and fourth set of biopsy (11/19 and 7/12 patients). 6/41 patients with cancer were identified by targeted biopsy only (14,6%) versus 16/41 identified by systematic biopsy only (39%) and 19/41 by both (46,4%). Conclusions: In men with elevated PSA and prior prostate negative biopsy, detection rate of contrast-enhanced US-targeted biopsy is superior to repeated systematic biopsy after MRI, with a decreased number of samples.