tbuckley/cabot-search huggingface dataset:
Time to targeted therapy after cytoreductive nephrectomy (CN) and surveillance in patients with synchronous unresectable metastases of renal cell carcinoma (RCC).
Authors: Axel Bex, Roderick de Bruijn, Allard Noe, Christian U. Blank, Simon Horenblas, John B. A. G. Haanen
Journal: Journal of Clinical Oncology (2016)

604 Background: VEGF-targeted therapy does not cure metastatic RCC. Guidelines recommend cytoreductive nephrectomy and complete resection of solitary-/oligometastases when feasible to potentially cure patients. However, in patients with low-volume but unresectable multiple metastases at single or more sites surveillance with or without local therapy after debulking CN may be an option to delay non-curative systemic therapy and associated toxicity. Methods: From an IRB approved institutional database of patients with primary metastatic RCC we identified patients with low-volume but unresectable oligometastatic disease in whom surveillance after debulking CN was a local multidisciplinary tumour board recommendation. Patient data, IMDC risk, site and number of sites, time-to-progression (TTP), time-to-targeted therapy (TTT) and overall survival (OS) were retrospectively analyzed. Results: From 203 primary mRCC patients treated since 2006, 28 (13.8 %) were identified who had low-volume multiple metastasis at a single site (13 with 7 lung, 5 bone) or multiple sites (15 with ≥ 2 sites). IMDC risk was favorable in 1, intermediate in 18 and poor in 6. Median TTP was 12 (range 3-36) months and TTT was 14 (range 3-43) months. Of 8 (28.7 %) progressing within 6 months, 2 had sarcomatoid tumours, 4 grade 4, 3 IMDC poor risk and 7 had ≥ 2 sites . In 15 patients TTT was further delayed by surveillance beyond RECIST progression (median time 5 (range 1-15) months) or additional local therapy of the most rapidly progressing lesion (5 radiation, 1 ablation). Median OS was 21.5 (range 4-75) months. Conclusions: Debulking CN followed by surveillance may substantially delay VEGF-targeted therapy and associated adverse events in a subset of patients with primary mRCC and unresectable low-volume metastasis. Local therapy to control the most rapidly progressing lesion or surveillance beyond progression were additional means to delay systemic therapy.
Epidemiology of rectal and small intestinal carcinoids: Two distinct tumors?
Authors: Sharven Taghavi, Senthil N. Jayarajan, John P. Gaughan, Alliric Isaac Willis
Journal: Journal of Clinical Oncology (2012)

399 Background: Gastrointestinal carcinoids (GIC) are most commonly found in the small intestines. However, in this era of screening colonoscopy, the incidence of rectal carcinoids (RC) is increasing. The aim of this study was to determine if differences exist between the two most common carcinoid tumors. Methods: Small intestinal and rectal cancers were reviewed from the Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute from 2000-2007. Factors reviewed included age, gender, ethnicity, and survival. Results: 12,931 small intestinal cancer tumors included 4,731 (36.6%) small intestinal carcinoids (SIC). 57,850 rectal cancer tumors included 4,550 (7.9%) RC. Comparing RC and SIC, RC presented at a younger age (56.2 vs. 64.5 years, p&lt;0.001). RC were more common among women (50.6 vs. 47.0%, p&lt;0.001). The ethnic distribution of SIC and RC were significantly different. SIC were more common among Whites (W) (76.0 vs. 51.0%) while RC were more common among each ethnic minority group: Blacks (B) (19.9 vs. 14.3%), Hispanics (H) (13.0 vs. 6.5%), Asians (A) (14.9 vs. 2.7%), and American Indians/Alaskans (AI) (1.1 vs. 0.4%); p&lt;0.001. RC were more common than SIC among women for every ethnic group (percentage of patients who are women W 48.1 vs. 46.8%, B 59.3 vs. 50.6%, H 50.3 vs. 44.3%, A 46.5 vs. 41.1%, AI 72.0 vs. 47.1%), although this reached significance in only Black females (p=0.001). Mean survival was better in RC (93.4 vs. 65.8 months, p&lt;0.001) by Kaplan-Meir analysis. Conclusions: This study demonstrates that SIC and RC are epidemiologically distinct tumors with different presentations and outcomes. Minority groups and females are more likely to present with RC. In addition, RC have better prognosis. Further studies are needed to investigate potential biological differences between these two tumors. [Table: see text]
Osteonecrosis of the jaw in patients treated with sunitinib and zoledronic acid.
Authors: G. Bozas, V. Allgar, G. Greenwood, A. Maraveyas
Journal: Journal of Clinical Oncology (2011)

e15116 Background: Osteonecrosis of the jaw (ONJ) occurs in 1-10% of cancer patients treated with intravenous bisphosphonates. Mean time of exposure to zoledronic acid (ZA) prior to the event has been reported to be around 22 months. It has been recently suggested that antiangiogenic agents may increase the risk for ONJ. In this context, we explored the incidence of ONJ in patients with metastatic renal cancer treated with ZA and sunitinib (SUT). Methods: Data from 77 consecutive patients treated with SUT for metastatic renal cancer between April 2006 and October 2010 in our centre was retrospectively reviewed. Survival analysis was used to assess the incidence of the event (ONJ) over time. Results: We identified 21 patients who had received at least one complete cycle of SUT (4 weeks) concomitantly with ZA. Median age was 59 (range 29-78) and the majority (n=15,71%) were male. 5 patients developed ONJ (24%) resulting in the immediate discontinuation of ZA. All were male and recent dental work was implicated in two cases (40%). 4 patients (80%) were current smokers. Two patients developed ONJ within the first month of concomitant treatment. Mean duration of concomitant treatment with SUT + ZA was 5.4 months (95%CI: 0.66-10.15) for the patients who developed ONJ and 7.9 months (95%CI: 4.7-11.2) for those who did not (p=0.308). Life table analysis showed a cumulative hazard of 17% (95%CI: 8%-26%) at 6 months of concomitant treatment and 28% (95%CI: 16%-40%) at 12 months. 13 (62%) of the patients had been exposed to ZA prior to the initiation of SUT. Mean duration of prior exposure to ZA was 13 months (95%CI: 6.5-19.5) for the patients who developed ONJ and 15.7 months (95%CI: 10.2-21.2) for those who did not (p=0.452). The cumulative hazard for ONJ was estimated at 5% (95%CI: 0%-10%) for 12 months and 36% (95%CI: 23%-49%) for 24 months of ZA exposure. Conclusions: Compared with published data, the risk for ONJ appeared to be higher and possibly accelerated in our cohort. This suggests a potential synergy of SUT with ZA in inducing this debilitating adeverse effect which merits further investigation.
Discordance between conclusions in the abstract and conclusions stated in the body of the article: An analysis of randomized controlled trials (RCTs) of lung cancer.
Authors: A. K. Altwairgi, C. Booth, W. Hopman, T. D. Baetz
Journal: Journal of Clinical Oncology (2011)

6046 Background: To keep abreast of an expanding literature base of RCTs clinicians may read only the abstract associated with a full article. Here we evaluate whether conclusions as stated in the discussion section of the full article differ from the summary conclusion in the accompanying abstract among a cohort of lung cancer RCTs. Methods: We performed a structured literature search to identify all RCTs of systemic therapy in lung cancer published 2004-2009. Details related to trial design and results were captured. Author conclusions in the article discussion section and in the abstract were independently assigned a score from 1 to 7: 4/7 for a neutral statement, 7/7 for strong endorsement of the experimental arm, and 1/7 for strong endorsement of the control arm. Conclusions were classified as discordant if there was a difference in score of >2; we also evaluated the direction of discordance. Logistic regression was performed to identify factors associated with discordance. Results: 114 eligible RCTs were identified; 24 (21%) small-cell and 90 (79%) non-small cell lung cancer. Sixty (53%) RCTs were published in high profile journals (NEJM, Lancet, JCO, JNCI). The primary endpoint was met in 26 (23%) RCTs. Eighty-three percent (95/114) of RCTs were conducted in the palliative setting, 86% (98/114) used overall survival as the primary endpoint and 67% (76/114) were sponsored by industry. Conclusions in abstracts and article were found to be discordant in 11 (10%) RCTs. Most discordance related to abstract conclusions more strongly endorsing the experimental arm compared to the conclusions stated in the body of the article (9/11, 82%); the converse was considerably less common (2/11, 18%, p<0.001). No trial-related factors were found to be associated with discordance. Conclusions: Important differences in the conclusion of full articles compared to accompanying abstracts were found in 10% of systemic therapy RCTs in lung cancer. Clinicians should be cautious when reading only the abstract of a published RCT.
Open-label, phase II raptor study of everolimus (EVE) for papillary mRCC: Efficacy in type 1 and type 2 histology.
Authors: Bernard J. Escudier, Sergio Bracarda, José Pablo Maroto Rey, Cezary Szczylik, Paul D. Nathan, Sylvie Negrier, Agnese Cattaneo, Claudia Weiss, Camillo Porta, Viktor Gruenwald
Journal: Journal of Clinical Oncology (2014)

410 Background: Prospectively collected data evaluating therapy for papillary mRCC are limited. RAPTOR (NCT00688753) evaluated the efficacy and safety of EVE as first-line therapy for papillary mRCC. Methods: Eligible pts had histologically confirmed type 1 or 2 papillary mRCC, ECOG PS ≤1, and no previous systemic therapy for mRCC. Central histology review was mandatory. EVE 10 mg/d was given until disease progression or intolerable toxicity. The primary end point was the PFS rate at 6 months assessed per RECIST 1.0 (central review) in the first 44 pts of the per-protocol population (PPFF; lack of centrally confirmed papillary histology was a protocol violation). Secondary end points included PFS, OS, and safety. Sensitivity (per protocol [PP] and ITT populations), supportive (local review), and subgroup (type 1 and 2 histology) analyses were performed. Results: 92 pts enrolled (median age, 60 y; 78% men). Among pts with papillary RCC per local review (99%), 58% had type 2 and 16% had type 1 (25% missing). Central review confirmed papillary histology in 76% of pts, 59% with type 2 and 33% with type 1 (9% missing). Reasons for discrepancies will be presented. Efficacy results are shown (Table). In the safety population (n=92), the most common grade ≥3 AEs were asthenia (11%), anemia (5%), and fatigue (5%). Conclusions: The RAPTOR study showed that EVE was well tolerated by and provided clinical benefit to pts with both type 1 and type 2 papillary mRCC, although both PFS and OS were longer in type 1. These results support further evaluation of EVE for pts with papillary mRCC. Clinical trial information: NCT00688753. [Table: see text]
Malignant B Cells from Hairy Cell Leukemia Express an Innate Phenotype and Undergo IgD Class Switching in Response to Innate Environmental Factors, Including BAFF and APRIL.
Authors: April Chiu, Kang Chen, Bing He, Stacey Dillon, Amy Chadburn, Daniel M. Knowles, Weifeng Xu, Andrea Cerutti
Journal: Blood (2007)
The comparison of efficacy and safety of selected diagnostic methods of non-palpable breast lesions: Systematic review and meta-analysis
Authors: M. Hetnal, M. Władysiuk, J. Rutkowski, E. Luczynska, K. Malecki, J. Wechowski, T. Zemelka, R. Plisko
Journal: Journal of Clinical Oncology (2008)

17505 Background: Breast screening results in increased detectability of subclinical lesions. Biopsy precision and defining a lesion as benign or malignant are crucial in determination of the final diagnosis, allowing to make therapeutic decisions. The analysis objective is to compare diagnostic efficacy and safety of following methods used in diagnostics of non-palpable breast lesions: mammotomy (MT), core needle biopsy (LC) and fine needle (FN) aspiration biopsy. Methods: Search of the most important medical databases (June 2007), subsequent verification of the identified abstracts and evaluation of credibility based on the full texts of scientific reports resulted in selection of clinical studies to the analysis of diagnostic efficacy and safety of MT, LC and FN with the golden standard (open surgical biopsy and/or follow-up). The endpoint of analysis was complications rate, sensitivity, specificity, accuracy and diagnostic odds ratio (DOR). Meta-analyses were carried out with the use of Meta-Disc software. Results: Selected 45 studies included 21 708 cases of non-palpable breast lesions, all were assessed with the golden standard. The comparative analysis of MT, FN and LC as optional methods of diagnosis of non- palpable breast lesions demonstrated that MT is characterised by statistically significant higher sensitivity, specificity and accuracy. Additionally, in comparison with FN and LC, MT is associated with significantly fewer patients with nondiagnostic biopsies. Due to insufficient reporting it is impossible to conduct comparative analysis of the incidence of perioperative complications for the methods of percutaneous biopsy. Conclusion: Mammotomy is the method of choice in diagnosis of non-palpable lesions of the breast in woman. It is characterised by the highest accuracy out all analysed methods. The second recommended method should be core needle biopsy. MT LC FN Pooled CI 95% Pooled CI 95% Pooled CI 95% Percentage of nondiagnostic biopsies 0 1.6 1.3-1.8 8.4 7.9-8.9 Sensitivity 98.1 96.1-99.2 89.5 88.2.1-90,8 82.5 81.1-83.9 Specificity 100.0 99.8-100.0 99.2 98,8-99,4 97.9 97.6-98.2 Accuracy 99.6 95.9 94.3 DOR 15779 2868-86813 777 323-1866 256 146-449 No significant financial relationships to disclose.
Moving towards hospital and radiation oncology EMR integration: Results of an institutional survey.
Authors: Abhishek Ashok Solanki, Murat Surucu, Barbara Kaczmarz, Teresita McCoo, John Roeske, William Small
Journal: Journal of Clinical Oncology (2016)

152 Background: We are working to electronically integrate our radiation oncology EMR and our hospital EMR to improve communication and facilitate patient care. To guide integration, we surveyed providers and support staff at our academic cancer center to identify the important encounters/documents and how well these are currently communicated. Methods: We sent an email survey to 182 MDs, nurses, and administrative staff at our cancer center. Respondents identified their role in the patient care team, and rated how important several radiation oncology-specific encounters/documents from “not important at all” to “extremely important” and rated the accessibility of these encounters/documents from “not at all accessible” to “exceptionally accessible.” Encounters/documents are listed in the table. Descriptive statistics were then performed to identify opportunities to improve communication. Results: There were 32 responses to our survey from staff outside of our department, including 18 physicians, 2 APN/PAs, 8 nurses, 2 nutritionists, 1 receptionist, and 1 social worker. Of the physicians, there were 8 medical oncologists, 2 neurosurgeons, 5 urologists, 1 breast surgeon, 1 gynecologic oncologist, and 1 reconstructive surgeon. The table describes the number of respondents who felt the encounter/document was “moderately,” “very,” or “extremely important”, and within this group of respondents, what percent thought each item was “very” or “exceptionally accessible.” Conclusions: We prioritized the importance of encounters/documents for integration between EMRs and identified deficiencies in communication. We will use the results of this study to guide our electronic integration of our two EMR systems. We will repeat the survey after integration is complete to identify improvement. [Table: see text]
Prognostic impact of baseline CEA level and surgery of primary tumor among patients with stage IV denovo colon cancer.
Authors: S. S. Dawood, A. M. Gonzalez-Angulo, C. Eng
Journal: Journal of Clinical Oncology (2011)

503 Background: Surgical resection of primary tumor among pts with stageIV denovo colorectal cancer is controversial. Prognostic role of baseline CEA level in the same cohort has yet to be defined. The objective of this study was to determine the prognostic value of CEA and surgical resection of primary tumor among pts with stage IV denovo colorectal cancer in the era of biologic therapy and to determine subgroups with improved survival outcome. Methods: The Surveillance, Epidemiology and End Results Registry was searched to identify patients with stage IV denovo colorectal cancer diagnosed between 2004-2007. Colorectal cancer specific survival (CCS) was estimated using the Kaplan-Meier product limit method. Cox models were fitted to assess the multivariable relationship of various pt and tumor characteristics and CCS. Results: 19,437 pts were identified with stage IV denovo colorectal cancer. Median CCS was 15M. Median CCS among pts with primary tumor removed was 20M vs 8M (primary intact; p&lt;0.001). Median CCS among pts who had elevated vs. non elevated CEA was 14M vs 23M (p&lt;0.0001). Among pts who had primary tumor surgery median CCS among pts who had elevated vs. non elevated CEA was 19M vs 29M (p&lt;0.0001). Among pts who had primary tumor and distant disease surgically removed, the median CCS among pts who had elevated vs. non elevated CEA was 24M vs 35M (p&lt;0.0001). By multivariable analysis, pts with elevated CEA had a 51% increased risk of death from colorectal cancer compared to those with a non elevated CEA level (HR=1.51, 95%CI 1.40-1.65, p&lt;0.0001). Pts who underwent primary tumor surgery had a 33% decreased risk of death from colorectal cancer compared to those who did not (HR=0.67, 95%CI 0.58-0.78, p&lt;0.0001). Other factors significantly associated with a decreased risk of death from colorectal cancer included low grade disease, non visceral metastases, surgical resection of metastases, younger age and white race. Conclusions: In this large population study, elevated baseline CEA level and surgical resection of the primary tumor had a significant impact on survival outcomes. The best prognostic group were those pts with normal baseline CEA level who proceeded to surgical resection for their primary tumor. No significant financial relationships to disclose.
A phase 1 trial of GSL (gemcitabine, S-1, LV) combination therapy in advanced pancreatic cancer.
Authors: Yousuke Nakai, Hiroyuki Isayama, Takashi Sasaki, Kei Saito, Naminatsu Takahara, Suguru Mizuno, Tsuyoshi Hamada, Koji Miyabayashi, Keisuke Yamamoto, Hirofumi Kogure, Natsuyo Yamamoto, Kenji Hirano, Hideaki Ijichi, Keisuke Tateishi, Minoru Tada, Kazuhiko Koike
Journal: Journal of Clinical Oncology (2014)

290 Background: Our previous randomized controlled trial, GEMSAP study (Br J Cancer. 2012 5;106:1934-9), showed a combination therapy of gemcitabine (Gem) &amp; S-1 (GS) for advanced pancreatic cancer was superior to Gem monotherapy in terms of progression-free survival (PFS) but not overall survival (OS). Leucovorin (LV) is known to enhance efficacy of S-1 and we conducted this phase 1 trial of combination therapy of Gem, S-1 and LV (GSL). Methods: A primary endpoint of this classical “3+3” design phase 1 trial is to determine recommended dose of GSL. Inclusion criteria were 1. histologically-confirmed advanced pancreatic cancer without prior treatment, 2.PS 0-2, 3. age over 20. Treatment schedule was S-1 80 mg/m 2 2x p.o. days 1-7, LV50mg 2x p.o. days 1-7, Gem 600(Level1), 800(Level2), 1000 mg/m 2 (Level3) div 30-min day 1 in a 2-week schedule. Dose-limiting toxicities were Grade 4 hematological and Grade ≥3 non-hematological toxicities, or delay of recovery from treatment-related toxicity for more than 2 weeks. Results: Between May 2012 and Feb 2013, 15 patients (Level 1/2/3: 6/6/3 patients) were enrolled; 7 males, a median age of 66, PS 0/1: 5/10, locally advanced/metastatic: 5/10. DLT was observed in 2/6 in Level 1 (Grade 3 anorexia in 1 and Grade 3 anorexia/stomatitis/diarrhea in 1) and 1/6 in Level 2 (Grade 3 pulmonary embolism). No DLT was observed in Level 3 and RD was determined as 1,000 mg/m 2 of Gem. Tumor response by RECIST was PR 5, SD 9, NE 1 with response rate of 33% and disease control rate of 93%. Overall toxicities greater than 3 were neutropenia 20%, anemia 7%, anorexia 13%, diarrhea 7%, stomatitis 7% and pneumonitis 7%. Conclusions: RD of GSL was determined as GEM 1000 mg/m 2 div 30 min day 1, S-1 80 mg/m 2 2x, LV50mg 2x p.o. days 1-7. GSL was tolerable and showed promising tumor response in advanced pancreatic cancer. Clinical trial information: UMIN000007556.
Population pharmacokinetic modelling of decitabine in patients with myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML).
Authors: B. Mistry, L. Gibiansky, Z. Hussein
Journal: Journal of Clinical Oncology (2011)

6551 Background: Decitabine is a deoxycytidine nucleoside derivative inhibitor of DNA-methyltransferases indicated for treatment of MDS patients and currently being investigated for the treatment of AML patients. Aim of this analysis was to build a population pharmacokinetic (PK) model that describes decitabine PK in MDS and AML patients following two different decitabine IV infusion schedules. Methods: Nonlinear mixed effect modelling was performed on plasma decitabine concentrations from 59 patients in 4 clinical trials; 1 phase 1 trial with decitabine given at 15-mg/m2 as 3-hour infusion every 8 hours on days 1-3 in a 6-week cycle; and 2 phase 2 and 1 phase 3 trials with a convenient dosing schedule of 20-mg/m2 as 1-hour infusion on days 1-5 in a 4-week cycle. Gender, weight, body surface area (BSA), body mass index, total bilirubin concentration, and calculated creatinine clearance (CrCL) were the covariates investigated in the analysis. Results: Decitabine PK was characterized by a linear 2-compartment model with rapid elimination from the central compartment and slow distribution to a peripheral compartment. For a typical patient (weight 70 kg/BSA 1.73 m2) the decitabine PK parameters following 20-mg/m2 regimen were: Vd = 69.1 L (95%CI: 49.7 - 89 L), CL = 298 L/hr (95%CI: 249 - 359 L/hr), Vp= 47.0 L (95%CI: 32.5 – 65.8 L), Q = 32.3 L/hr (95%CI: 24.4 – 43.8 L/hr). Vd was proportional to body weight while CL was proportional to BSA with inter-individual variability for Vd and CL of 70.6% and 55.7%, respectively. Intra-individual variability of decitabine concentrations was moderate (CV=31.6%). CL, Q, and Vp for the 15-mg/m2 regimen were 32.5% (95%CI: 18.4 – 43.9%) lower than for the 20-mg/m2 regimen while Vd was 74.1% (95%CI: 60.3 – 83.7%) lower. Clearance for females was 12.1% (95%CI: 0.5-25.6%) lower than for males but the effect was small relative to the inter-individual variability (55.7%) and clinically not relevant. The PK parameters were independent of time. There was no evidence of parameter dependencies on age, CrCL, total bilirubin concentration, or disease (AML or MDS). Conclusions: The PK of decitabine was well described by a linear two-compartment model.