tbuckley/cabot-search huggingface dataset:
Trends in lymph node (LN) harvest for colon cancer in routine clinical practice: Does node count matter in the real world?
Authors: Joseph Cosimo Del Paggio, Sulaiman Nanji, Xuejiao Wei, Christopher M. Booth
Journal: Journal of Clinical Oncology (2015)

e14635 Background: International guidelines recommend 12+ LNs be resected during surgery for colon cancer. Here we report practice patterns in routine care and evaluate whether LN harvest is associated with survival in the general population. Methods: Electronic records of treatment were linked to the population-based Ontario Cancer Registry to identify all patients with colon cancer who underwent surgical resection during 2002-2008 in Ontario. Surgical pathology reports were reviewed for a random sample of cases representing 25% of all patients treated over the study period. Patients with metastases or unstated number of LNs were excluded. Modified Poisson regression was used to identify factors associated with LN harvest; Cox models were used to explore association between LN harvest and survival. Results: 30,643 patients underwent resection of colon cancer during the study period. Pathology reports were reviewed for 7514 (25%) randomly selected cases; 6759 met eligibility criteria. Over the study period median LN harvest increased from 11 to 17 nodes (p < 0.001) and the proportion of patients with 12+ LNs increased from 45% to 86% (p < 0.001). Despite the increase in LN harvest the proportion of patients with node positive disease did not change (from 43% to 42%, p = 0.569). On adjusted analysis the following factors were associated with 12+ LNs: age (RR 0.85 > 80 vs < 50 years, p < 0.001); co-morbidity (RR 0.87 moderate vs none, p < 0.001); year of surgery (RR 1.90 2008 vs 2002, p < 0.001); laterality (RR 1.22 right vs left, p < 0.001); and hospital volume (RR 0.89 low vs high volume, p < 0.001). After controlling for relevant co-variates (including hospital volume), < 12 LNs was associated with inferior overall survival (OS) and cancer-specific survival (CSS). This association was seen in stage 2 (OS HR 1.43, p < 0.001; CSS HR 1.60, p < 0.001) and stage 3 (OS HR 1.45, p < 0.001; CSS HR 1.51, p < 0.001) disease. Conclusions: Despite a temporal increase in LN harvest the proportion of cases with node positive disease has not changed. LN harvest is associated with survival in patients with stage 2 and stage 3 colon cancer. These data suggest that the association between LN harvest and survival is not due to stage migration.
Myeloablative Conditioning Haploidentical Stem Cell Transplantation (MAC-HAPLO) with Post-Transplant Cyclophosphamide (PTCy) As GvHD Prophylaxis in High Risk Leukemias/Myelosdysplastic Syndromes (MDS): Geth Experience
Authors: Jorge Gayoso, Pascual Balsalobre, Mi Kwon, Pilar Herrera, Arancha Bermúdez, Antonia Sampol, Santiago Jimenez, Lucia Lopez-Corral, David Serrano, Pau Montesinos, Maria-Jesús Pascual, Inmaculada Heras, Leyre Bento, Rosario Varela, Karem Humala, Amaya Zabalza, Almudena Laiglesia, Mariana Bastos-Oreiro, Ana Pérez-Corral, Carolina Martínez-Laperche, Jose Luis Diez-Martin
Journal: Blood (2016)
Use of the mitotic kinase aurora-A activation to predict outcome for primary duodenal adenocarcinoma.
Authors: Jie Chen, Jing-Yun Wen, Zhan-Hong Chen, Qu Lin, Xiao-Kun Ma, Li Wei, Xing Li, Tian tian Wang, Dan-Yun Ruan, Ze-Xiao Lin, XiangBo Wan, Quentin Liu, Xiang-Yuan Wu
Journal: Journal of Clinical Oncology (2013)

4131 Background: We and others had proved that hypoxia-inducible factor-1α (HIF-1α) and transcriptionally upregulated Aurora-A were required for disease progression in several tumors. Methods: We addressed the clinicopathologic value of HIF-1α and Aurora-a in primary duodenal adenocarcinoma (PDA). Aurora-a and HIF-1α expression were semi-quantitative evaluated by immunohistochemistry in 140 PDA. Among which, 76 patients from one institute acted as training set, and 64 cases from another two institutes were used as testing set to validate the prognostic effect of Aurora-a and HIF-1α. Results: We found that Aurora-a was high or sufficient expressed in tumor zone, whereas low-expressed in the normal adjacent epithelia. Moreover, Aurora-a high expression, classified by training set ROC analysis-generated cutoff score, predicted an inferior overall survival both in testing set and training set. Multivariate Cox regression confirmed that Aurora-a was indeed an independent prognostic factor (Table). Contrary to previous studies, we did not detect any correlation between Aurora-a and HIF-1α in PDA. Additionally, survival analysis showed that HIF-1α level was not correlated with patient outcome (p = 0.466). Conclusions: Activation of Aurora-A, an independent negative prognostic biomarker, might be used to identify particular patients for more selective therapy. [Table: see text]
Targeted therapy for renal cell carcinoma (RCC) with brain metastasis: Overall survival (OS) and safety.
Authors: Diogo Assed Bastos, Ana M. Molina, Xiaoyu Jia, Susanne Velasco, Sujata Patil, Martin Henner Voss, Darren Richard Feldman, Robert John Motzer
Journal: Journal of Clinical Oncology (2013)

e15517 Background: Brain metastases (b-met) in RCC are associated with poor prognosis and median OS of about 7 months in the pre-targeted therapy (TT) era (Culine, Cancer 1998). The role of TT in this setting is not well established since patients (pts) with b-met were excluded from most clinical trials. The primary objective was to assess OS and central nervous system (CNS) safety of pts with b-met treated with TT. Methods: Pts with mRCC treated with ≥ 28 days of TT after b-met diagnoses were retrospectively identified. Kaplan-Meier method and Cox proportional hazards model were used to analyze the association between clinical features and OS. Results: 65 pts were identified, 52 (80%) treated with anti-angiogenic agents and 13 (20%) treated with mTOR inhibitors. Most pts had extracranial metastasis (98%) and 54% had ≥ 2 brain lesions. Fifty seven pts (88%) had local therapy for b-met before TT including surgery in 3 (5%), radiation therapy (RT) in 36 (55%) and both surgery and RT in 18 (28%). Median follow-up was 12.3 months (1.1 – 58.8) and median time from RCC diagnosis to b-met was 17.8 months (0 – 192.2). Median TT duration was 3.4 months (0.3 – 31.9) for 1st line and 1.9 months (0.2 – 23.6) for 2nd line. Median OS was 12.2 months (95% CI 8.0 to 15.5). On univariate analysis using various clinical and treatment variables, MSKCC risk group (P= 0.001), histology subtype (clear vs other) (P&lt; 0.0001), and number of b-met at diagnosis (P= 0.004) correlated with OS and retained statistical significance on multivariate analysis (Table). CNS complications were identified in 5 pts (8%), including 2 with radiation necrosis and 3 with b-met hemorrhage. Conclusions: The use of TT in the multimodality treatment of pts with RCC and b-met appears safe with OS that compares favorably to historical results in the pre-TT era. Clear cell RCC, favorable MSKCC risk status, and solitary b-met are associated with better outcome. [Table: see text]
Determination of the BRAF V600E mutation in Uruguayan melanoma patients.
Authors: Maria Eugenia Mazzei, Jimena Hochman, Gonzalo Manrique, Ana Luisa Marino, Lucia Beatriz Delgado, Miguel Angel Martínez
Journal: Journal of Clinical Oncology (2012)

e19007 Background: Vemurafenib approval by the FDA determines a new era for the treatment of metastatic melanoma in those patients with BRAF V600E mutation. This mutation is reported in about 50% of melanomas and is more common in melanomas on skin without chronic sun induced damage. The aim of this study was to evaluate the frequency of BRAF V600E mutation in Uruguayan melanoma patients, in order to analyze whether the use of vemurafenib would impact on our population. Methods: Formalin fixed, paraffin embedded tissues from 27 primary cutaneous melanomas, were obtained from files of the the Dermatopathology Unit, Department of Dermatology, Hospital de Clínicas in Montevideo, Uruguay. Most were Superficial Spreading Melanomas from skin without chronic sun induced damage. Microdissection of melanoma cells from paraffin embedded tissue was performed under microscopic visualization using a micromanipulator equipment. ADN extraction was performed and the BRAF V600E was detected by ASO-PCR. Results: Of the 27 melanoma samples analyzed, we detected the BRAF V600E mutation in 21. This determines a 77.8% frequency of mutation, a higher percentage than reported in the literature. This could be explained in different ways. The demographic characteristics of Uruguayan population are very peculiar, complying with a genetic admixture of Europeans(mostly from Spain), Amerindians (10%) and alow percentage of Africans (6%), which could explain the high incidence of BRAF V600E mutation. On the other hand, these melanomas were from skin without chronic sun induced damage, this type of melanomas have the highest rate of mutation. Finally, this mutation was analyzed in samples microdissected from melanoma biopsies, the fact that the cells were precisely removed from the tumor could also explain the high frequency of mutation. Conclusions: In this study we found a high frequency of BRAF V600E mutation in Uruguayan malignant melanoma patients, this could be explained by population genetic admixture, the melanoma subtype or technical characteristics. Further studies comparing techniques should be performed in our country to clarify this point.
Impact of bevacizumab added to temozolomide-chemoradiation on time to health-related quality of life deterioration in unresectable glioblastoma: Results of a phase II randomized clinical trial.
Authors: Franck Bonnetain, Tienhan Sandrine Dabakuyo, Astrid Pozet, Loic Feuvret, Luc Taillandier, Didier Frappaz, Herve Taillia, Roland Schott, Jerôme Honnorat, Michel Fabbro, Isabelle Tennevet, Francois Ghiringhelli, Chantal Campello, Daniel Castera, Marc Frenay, Cecile Dalban, Jeremy Skrzypski, Olivier L. Chinot, Bruno Chauffert, Amelie Anota
Journal: Journal of Clinical Oncology (2015)

2018 Background: Two clinical trials investigating the addition of bevacizumab (BEV) to TMZ treatment (Chinot et al., NEJM 2014; Gilbert et al., NEJM 2014) for unresectable glioblastoma (GB) highlighted an improvement of progression-free survival (PFS) but no effect on overall survival. Health-related quality of life (HRQoL) results were divergent and compromised the conclusion about clinical benefit of bevacizumab. A phase II clinical trial evaluated BEV and irinotecan (IRI) in addition to TMZ-based chemoradiation for unresectable GB (Chauffert et al., Annals of Oncology 2014) was conducted. The primary objective 6-month PFS rate from 50% to 66% was not reached. This present study focuses on the HRQoL analysis (secondary endpoint). Methods: EORTC QLQ-C30 and its BN20 brain cancer module were used at baseline, during treatment and every 4 weeks until progression. Time until definitive HRQoL score deterioration (TUDD) was used as a modality of longitudinal HRQoL analyses (Bonnetain et al., EJC 2010), with a 10-point Minimal Clinically Important Difference including or not death as an event. TUDD was estimated with the Kaplan-Meier method. Cox model was used to estimate Hazard Ratios (HR) and its 95% confidence interval (CI). Multivariate Cox model investigated factors associated with TUDD. Results: Among the 134 patients included from 2009 to 2011, 101 patients (75%) filled the baseline HRQoL questionnaires (51 in BEV/IRI arm, 50 in TMZ arm). For TUDD or death, patients in BEV/IRI arm presented a longer TUDD than those of TMZ arm for 10/15 dimensions of the QLQ-C30 and 10/11 dimensions of the BN20. As an example, patients in BEV/IRI arm presented a longer TUDD of motor dysfunction than those of TMZ arm (Median 4.6 months (95%CI 3.2-9.4) for BEV/IRI vs. 3.3 (95%CI 2.8-6.7) for TMZ, HR = 0.70 (95%CI 0.45-1.08)). A sensorial deficit is associated with shorter TUDD of Weakness of legs dimension or death (HR = 2.74 (95%CI 1.41-5.30). Conclusions: Patients in BEV/IRI arm presented a longer TUDD than those of the TMZ arm. These HRQoL results are consistent to those obtained with AVAGLIO trial suggesting HRQoL benefit for patients with BEV. Clinical trial information: 2008-002775-28.
Mitigation of iatrogenic risk in young women Hodgkin’s survivors, acceptability of a structured information process.
Authors: François Eisinger, Agnes Boyer-Chammard, Laurence Gonzague, Diane Coso, Patrice Viens, Reda Bouabdallah
Journal: Journal of Clinical Oncology (2012)

TPS1613 Background: Long term follow up of cancer survivors uncovers iatrogenic risk. Higher risk for second cancers should be mainly observed for cancer with a high rate of therapeutic efficacy, using aggressive therapeutic and for cancers occurring in young people. Hodgkin lymphoma fits all these criteria. Consistent data about higher risk for breast cancer in these women had been published. However, risk management is not yet often carried out. Methods: We plan to carry out a national program aiming both at offering counselling and screening protocol and to assess key parameters allowing to better estimate risk, and offering acceptable and effective risk management option. Our National program will start in January 2013. We are now in a pilot phase in a single medical institution in which we offered women previously affected with an Hodgkin lymphoma to have access to risk analysis and information and if they agree to a specific breast cancer screening program. We present some of our psychosocial questionnaire analysis based on 27 women (aged 19-50 years old) fulfilled at the end of the information consultation and one month latter. Results: There was few or no negative assessment: no one stated that they express regrets to have been informed, nor they better ignore some delivered information, no one feel that risk management description is unsatisfying and no one will advice an other women against that kind of consultation. Only 4 out 27 i.e. 15% stated that there was in delivered information a source for anxiety. However positive assessment was only fairly high and not stable after one month. Information process to inform women survivors from Hodgkin lymphoma of their higher risk of being affected with a breast cancer and the current recommendation for earlier breast cancer screening reach a high level of satisfaction at the initial stage of the process. However it could decrease with time and thus, need to be monitored. [Table: see text]
Baseline characteristics from two ongoing phase III trials for the prevention and treatment of muscle wasting in NSCLC.
Authors: Mitchell S. Steiner, Richard J. Gralla, Carla M. M. Prado, Michael L. Hancock, James T. Dalton, Mary Ann Johnston, Jeffrey Crawford
Journal: Journal of Clinical Oncology (2013)

e19100 Background: Although muscle wasting and cancer cachexia occur in &gt; 80% of patients with advanced cancer, few well-powered scientifically-based trials have been conducted. Using enobosarm, a novel SARM, we have now enlisted 650 patients (pts) with advanced NSCLC in two phase III trials. Recent studies indicate major advantages for supportive care in NSCLC at chemotherapy initiation (Temel, NEJM 2010).This presentation examines the feasibility of pt enlistment at chemo initiation, the major characteristics of these pts and trial design for the prevention and treatment of muscle wasting. Methods: Both double-blind, placebo-controlled, international trials evaluate the effect of enobosarm in NSCLC. ˜300 pts with stage III or IV NSCLC were randomized in each trial at initiation of first-line chemo to receive additionally enobosarm or placebo for 5 months. Pts were males and postmenopausal females ≥30 years, ECOG ≤1. First line chemo: a platinum + taxane (Power 1) or platinum + non-taxane (Power 2). Co-primary endpoints at Day 84 are physical function assessed by stair climb power (SCP) and lean body mass (LBM) by DXA. Baseline characteristics are available on 634 pts (98%), as in the Table. Results: See Table. Conclusions: These results indicate that it is feasible to enlist pts receiving first-line chemo in trials designed to prevent or treat muscle wasting and cachexia; their presenting characteristics are typical for NSCLC. Median weight loss at baseline was 5% even though weight loss was not required for study inclusion. LBM and SCP were lower than typically observed in healthy individuals indicating significant functional decline before starting chemo for NSCLC. These phase III trials will determine the effect of enobosarm on preventing and treating muscle wasting in NSCLC. Clinical trial information: NCT01355484 and NCT01355497. [Table: see text]
Temporal versus probabilistic approach to survival estimation: Physician’s accuracy over time.
Authors: Pedro Emilio Perez-Cruz, David Hui, Renata dos Santos, Kelly L. Kilgore, Thiago Buosi Silva, Gary B. Chisholm, Raphael de Almeida Leite, Camila Souza Crovador, Egidio Del Fabbro, Maria Salete de Angelis Nascimento, Donna S. Zhukovsky, Fabiola de Lourdes GonÃƒÂµaves de Freitas Seriaco, Suresh K. Reddy, Luciana Machado Frascari, Shalini Dalal, Carlos Eduardo Paiva, Rony Dev, Stacy Hall, Julieta Fajardo, Eduardo Bruera
Journal: Journal of Clinical Oncology (2012)

e19584 Background: Physicians are inaccurate in estimating survival. Both Temporal and Probabilistic approaches have been used for prediction. Serial prognostication might improve accuracy. In this study we compare these two approaches and assess whether serial prognostication improves accuracy. Methods: Physicians prognosticated survival daily for cancer patients admitted to palliative care units in two hospitals until death/discharge, using two prognostic tools: Temporal (What is the approximate survival of this patient in days?) and Probabilistic (What is the probability that this patient will be alive in 24 hrs?, 0% to 100%) (Hui et al. Oncologist 2011). Temporal prognosis was accurate if it fell within ± 33% of the actual survival. Probabilistic prognosis was accurate if the clinician selected a survival probability ≥70% and the patient survived in ≤24 hours or the clinician endorsed a survival probability ≤30% and the patient died. We compared physicians’ accuracy with each method at specific time points using Mc Nemar’s test. We assessed accuracy for each method over time comparing the accuracy at each time point with day -14 using a test of proportions. Results: Baseline characteristics of 306 patients included mean age 58 (18-88), female 69%, Caucasian 76%. Physicians were significantly more accurate in prognosticating survival with the Probabilistic v/s Temporal approach (p&lt;.001 at each time point). The accuracy of Temporal approach was stable over time (Table). The accuracy of Probabilistic approach decreased close to death (Table). Conclusions: Physicians were more accurate at estimating probability of survival at 24 hrs than at estimating days to death. The accuracy of the probabilistic approach decreases as patient approaches death. Serial prognostication does not improve accuracy of survival estimation. [Table: see text]
Impact of angiotensin system inhibitors (ASI) on outcome in sunitinib (SU)- treated patients for metastatic renal cell carcinoma (mRCC): Gustave Roussy experience.
Authors: Lisa Derosa, Hassane Izzedine, Gwenael Le Teuff, Laurence Albiges, Bernard Escudier
Journal: Journal of Clinical Oncology (2014)

4584 Background: ASIs are widely used for hypertension (HTN) and proteinuria. Limited data for their anti-angiogenic effect exists in combinations with targeted therapy. We aimed to evaluate the role of ASI on outcome in mRCC. Methods: Patients (pts) treated with SU as first line at Gustave Roussy from 04/04 to 11/13 with available data about the use of ASI before, or during treatment (defined as during first month) were included. Overall survival (OS) and progression free-survival (PFS) were compared with log-rank test and hazard ratios (HR) and 95% confidence interval (CI) through a multivariable Cox model adjusted on age, gender, histology, IMDC risk groups and history of HTN. Results: N=213 pts with a 44 month median follow-up received SU as first line. Median age was 59, most pts were male (78%), with clear-cell histology (86%), intermediate IMDC risk group (61%). N=102 (48%) pts were ASI-users either before SU (n=61, 29%) or during SU (n= 41, 19%). ASI use was associated with improved OS and PFS when compared to ASI nonuser pts. Among ASI users, OS and PFS were not significantly different. Conclusions: Use of ASI in mRCC pts receiving SU significantly improves outcome (PFS and OS). There is no difference between pts who receive ASI before starting SU or those who received ASI within one month of SU. ASI users compared to nonusers. OS median (months) PFS median (months) ASI nonusers (n=109) 18 [12, 23] 7 [5, 8] ASI users (n=102) 44 [30, 55] 15 [12, 17] Log rank test p<0.0001 p<0.0001 HR user / non user [95%CI] 0.32 [0.21, 0.49] 0.45 [0.32, 0.63] ASI users (n=102) ASI users during SU only (n=41) 51 [38, 92] 15 [10, 20] ASI users before SU (n=61) 37 [27,55] 15 [11, 17] Log rank test p=0.30 p=0.41 HR user / non user [95%CI] 0.91 [0.39, 2.11] 1.12 [0.62, 2.02]
Institutional series of selective internal radiation therapy (SIRT) for liver predominant metastatic colorectal cancer (MCRC)
Authors: M. Huie, L. Greiner, J. Thomas, D. Mulkerin, R. Smith, J. Welsh, J. McDermott, R. Neider, J. Bianco, K. Holen
Journal: Journal of Clinical Oncology (2004)

3665 Background: SIRT using yttrium (Y-90) microspheres infused through hepatic artery circulation was introduced in 1989 and FDA approved for MCRC to the liver in 2002. While used primarily in China and Australia for both hepatocellular and MCRC (Ann Onc 12: 1711–1720, Cancer 83: 1894–1907), few patients have been treated in the US. Methods: Patients with ECOG performance status ≤2 and suitable hepatic vascular anatomy were treated between 2/03 and 12/03. Hospital charts were reviewed for disease status, liver function, toxicity, response, and survival. Results: Twenty patients (16 m, 4 f) with MCRC refractory to standard chemotherapy and extensive hepatic metastases age 47 to 88 yrs (median 63) received treatment. Six patients were treated sequentially to both lobes of the liver, 8 concurrently to both lobes, and 6 to the right lobe only. Most toxicities documented within a two-week post-procedure period were transient and < grade 3, including nausea/vomiting in 5 patients, abdominal pain in 6 patients, fatigue in 6 patients, and fever in 2 patients. One patient had a hypertensive urgency requiring intravenous therapy. Six patients developed hyperbilirubinemia (4 pts grade 2 and 2 pts grade 3). Two of these progressed to hepatic failure (1 attributed to therapy, the other to progression). Grade 3 transaminitis was seen in one other patient. One patient developed a duodenal ulcer with biopsy evidence of Y-90 spheres in the ulcer. Fourteen patients were evaluable by CT scan ≥ 1 month post-SIRT. Three patients had a partial response and 10 had stable disease while 1 patient with initial regression of tumor had progression after 6 months. Five patients with liver control had progression of disease outside the liver. Of the 6 patients not evaluated by CT, 3 declined clinically and died or were discharged to hospice, 3 had recent treatment and have not had a repeat CT. Conclusions: SIRT is an FDA approved novel therapy for liver tumors that has demonstrated promising activity with acceptable toxicity. Monitoring of liver function, blood pressure, and PUD is recommended. Further evaluation of SIRT with chemotherapy and in other settings is warranted. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Sirtex Medical Limited