tbuckley/cabot-search huggingface dataset:
Long-term follow-up results of imatinib mesylate therapy in chronic phase chronic myeloid leukemia (CML-CP) after interferon alpha (IFN) failure.
Authors: J. Shan, S. M. O'Brien, G. Garcia-Manero, S. Faderl, F. Ravandi, E. Jabbour, J. E. Cortes, H. Kantarjian
Journal: Journal of Clinical Oncology (2011)

6550 Background: The very long-term outcome of pts on imatinib post IFN failure is not described. Methods: 368 pts; median age 54 yrs; median follow-up 114 mos. Pts received imatinib 400 mg daily. Results: 247 pts (67%) had complete cytogenetic response (CCyR) as best response. 207 / 327 pts (63%) had major molecular response (MMR) and 99 (30%) had undetectable levels. The 10-yr survival (OS) rate is 68%, progression-free survival rate 67% (PFS; progression = accelerated or blastic phase, or death at any time on or off imatinib), event-free survival 51% (EFS; event = any occurence that results in discontinuation of imatinib). By multivariate analysis, age ≥ 60 yrs, (hgb < 10g/dl, marrow basophils ≥ 5%, any peripheral blasts, and clonal evolution were independent adverse factors for survival. The 7-yr OS with none (n=154), 1-2 (n=190), or ≥ 3 factors (n=24) were 93%, 70%, and 25% (p <0.01). Achievement of major cytogenetic response MCyR or better at 12 months were associated with better 10-yr OS by landmark analysis (10-yr OS 80-90%) vs. achieving minor cytogenetic response or complete hematologic response (CHR) (10-yr OS 55-65%) vs. other response (10-yr OS 10%). Using landmark analysis to include imatinib response at 12 months, achievement of MCyR or better (hazard ratio 0.12; p< 0.001) and CHR or minor CyR (hazard ratio 0.36; p=0.003) were significant favorable prognostic factors. The 10-yr OS of 68% suggests improved outcome with imatinib post-INF failure vs. historical data (median OS of CML-CP post-IFN failure 3-4 yrs; Clinical Cancer Research 10: 68-75; 2004). Conclusions: Pts with CML-CP post IFN failure have improved OS vs. historical experience. Prognostic factors defining survival may help advise pts.
Recovery of cancer patients' social lives upon referral to palliative care units.
Authors: Takeshi Terui, Yasuo Hirayama, Takayuki Machino, Toshiro Kusakabe, Kenji Nakamura, Hiroyoshi Mihara, Satoko Itoh, Kunihiko Ishitani
Journal: Journal of Clinical Oncology (2016)

107 Background: Our hospital is a cancer-specific facility that treats patients from diagnosis to terminal care. We evaluate the possibility of effective cancer chemotherapies for patients referred to our palliative care unit from other hospitals through case conferences in our institution. Even the patients referred to the palliative care unit of our institution are sometimes assessed as “very likely to be improved by standard or semi-standard treatment” by the palliative care and oncologic teams in our institution. We surveyed inappropriate cases that were mistakenly assessed as indicated for terminal care in their previous hospital. Methods: We reviewed 1535 patients referred to our palliative care unit from other hospitals because of anticancer chemotherapy contraindications over a 3-year period. We determined the number of the patients who were thought to actually have indications for cancer chemotherapy. Results: During the case conferences, 31 (2.0%) of the 1535 patients were thought to have indications for cancer chemotherapies. Standard chemotherapies were administered in our hospital to 6 patients. Four of the 6 patients were alive at one year and recovered their social life. Conclusions: Prudent assessment using updated guidelines are needed at the time of patient referral of a hospice. Ethical problems clearly exist with patients who were mistakenly assessed as indicated for terminal care in their previous hospital. There remains room for discussion of whether it is an ethical problem to overturn the will of a patient having chosen best supportive care (including those for whom it was presented as the only option by previous doctors or those who made positively the choice themselves) and proceed with cancer treatment.
Breast cancer with synchronous metastases: Impact of locoregional radiotherapy (LRR) on survival
Authors: R. Le Scodan, D. Stevens, M. Tubiana-Hulin, B. De La Lande, C. Cohen-Solal, E. Brain, M. Gutierrez, A. Boudinet, F. Spyratos, J. Munck, A. Labib
Journal: Journal of Clinical Oncology (2008)

1038 Background: Breast cancer with synchronous metastases is considered as a noncurable disease for which systemic treatment remains the cornerstone of management. However several observational studies have reported a survival benefit for those patients (pts) who were offered a complete excision of the primary tumor. In such setting, locoregional treatment (LRT) may also consist of exclusive locoregional radiotherapy (LRR), as favoured in our institution for the past 2 decades. From our database, we have evaluated the impact of this alternative LRT to surgery on survival of breast cancer pts presenting with synchronous metastases. Methods: Among 18,753 cases diagnosed and treated at Rene Huguenin Cancer Center between 1980 and 2004, 598 pts (3.2%) presented with initial simultaneous distant metastasis. Information regarding demographics, tumor characteristics, site(s) of metastases and treatments were prospectively recorded in the database. The impact of delivery of LRT on overall survival (OS) was evaluated in a multivariate analysis after adjustment for other prognostic factors. Results: Of 581 pts who survived more than 30 days and selected for the analysis, 320 received LRT (group A) while 261 pts had no LRT (group B). LRT consisted mainly of exclusive LRR (directed to the breast and regional lymphatics): exclusive LRR, 249 pts (78%); surgery of the primary tumor with adjuvant LRR, 41 pts (13%); exclusive surgery of the primary tumor with or without axillae dissection, 30 pts (9%). With a median follow-up of 39 months (range 6–138) for the whole population, 3-year OS rates were 43.4% and 26.7% for group A and group B respectively (p=0.00002). This beneficial effect of LRT was particularly evident for women with initial visceral metastases (3-year OS: 34.2% vs 17.8%, p=0.0005). LRT was a prognostic factor in multivariate analysis (HR, 0.74 [95%CI 0.61–0.89]; p=0.001) but could not be analyzed according to type of LRT given the small number of pts by sub-groups. Conclusions: In our experience, LRT consisted mainly of LRR and improved significantly OS of breast cancer women with synchronous metastases, particularly among women with visceral metastases at diagnosis. Therefore it may represent an active alternative to the more traditional surgery. No significant financial relationships to disclose.
Pre-treatment serum folate levels and toxicity in colorectal cancer patients treated with 5-fluorouracil and folinic acid.
Authors: Michael Yan, Mark David Vincent, Cheryl Ho, Eric Winquist, Derek J. Jonker, Daniel Rayson
Journal: Journal of Clinical Oncology (2016)

755 Background: 5-fluorouracil (5-FU) chemotherapy is associated with severe and unpredictable toxicity in a significant proportion of patients.We hypothesized that susceptibility to 5-FU toxicity might be related to individual differences in components of reduced folate metabolism affecting intracellular 5,10-MTHF levels, detectable in blood prior to treatment. Methods: A prospective cohort of chemo-naive colorectal cancer patients planned to receive IV 5-FU and folinic acid for five consecutive days every four weeks were studied. Baseline clinical and laboratory data were collected prior to treatment. Biochemical data associated with folate metabolism was also collected and not revealed to treating physicians. The primary endpoint was occurrence of &gt; grade 3 toxicity and/or toxicity mandating dose delay or reduction. Results: Of 78 eligible patients studied, 68% experienced &gt; grade 3 toxicity, 69% had schedule modification, and 81% had either or both. Multivariable analyses identified only a higher pre-treatment serum folate level as an independent predictor of toxicity &gt; grade 3 and/or mandating schedule modification (p = 0.016). An increasing toxicity trend was observed amongst folate-stratified patient cohorts, with an odds ratio of 2.87 (p = 0.09) comparing the highest and lowest quartiles. Concurrently, overall survival and relapse-free rates also increased with pretreatment folate levels in the adjuvant cohort with log rank values of 3.60 (p = 0.06) and 7.20 (p = 0.007) between the highest quartile and the lower quartiles, respectively. Conclusions: The incidence of severe toxicity with this schedule of 5-FU and folinic acid was high and positively correlated with the pretreatment serum folate level. Interestingly, a concurrent increase in overall and relapse free survival is observed with increasing serum folate levels. These results suggest that an optimal pretreatment folate level exists that balances chemotherapy treatment efficacy and toxicity.
Long term outcome in patients with advanced malignant peritoneal mesothelioma (AbM) treated with a pemetrexed/platin combination.
Authors: Meinolf Karthaus, Kambiz Taghizadeh
Journal: Journal of Clinical Oncology (2016)

295 Background: Advanced mesothelioma is associated with a short overall-survival (OS 9-12 mo). Peritoneal mesothelioma is a rare and aggressive cancer of the peritoneum. Data on long-term outcome of AbM are rare. Pemetrexed (Pem)+cisplatinum (DDP) has been reported effectively for AbM previously with the optimal ctx duration remaining still undetermined. We evaluated the efficacy and safety of Pem + Platinum for the treatment of AbM prospectively. A part of our data has been published previously (ASCO GI 2006). This is a 10-year OS update. Methods: We analyzed the long-term OS of a cohort of AbM that started treatment between 02/2002 and 03/2006. All AbM pts received Pem (500 mg/m 2 ) +DDP (75 mg/m 2 ) or carboplatin (AUC 5) prospectively on d1 (repeated on d22 for 6 cycles or disease progression). Folinic acid 400 μg po/d and vit B12 1000 μg i.m. qw 9 wks was administered to prevent AE. Study endpoints were best response (CR/PR), time to progression (TTP), OS and safety. Results: A total of 95 mesothelioma pts were observed from 12/2002 until 05/2006 in a single institution. Four patients (1 AbM, 1 MPM, 2 MPM+AbM) were excluded due to renal impairment (n = 1) or death prior to chemotherapy (n = 3). Staging procedures revealed AbM in 22 patients, while this was pleural mesothelioma in 64 patients. Five additional patients had malignant mesothelioma on both sites of the diaphragm. Initial ctx was with DDP in all pts with AbM, except one who died prior to therapy initiation. Pem was administered a median of 6 cycles (range 1 –33+). Major toxicity (WHO &gt; III/IV) was nausea and neutropenia (2/11). Benefit for AbM was observed in 77%, with objective RR in 36% while a response or stabilization was observed in 4 out 5 pts with AbM + MPM (80%). Mean time to progression was 11.5 months (range 0 to 35+) in AbM vs 15.4 pts with AbM +MPM. Mean survival was 32.6 months (range 1 to 147+ months) in AbM and 48.4 months in pts with AbM + MPM (18-146+ months). Conclusions: The natural course of AbM is different from pleural mesothelioma. Pts with an AbM had a much longer TTP and overall survival when compared to pleural mesothelioma. Pemetrexed with platinum is well tolerated and has substantial activity for malignant peritoneal mesothelioma.
Genetic evaluation of fatigue in pazopanib-treated patients (pts) with advanced renal cell carcinoma (RCC).
Authors: S. M. Glass, L. Huang, K. King, L. J. Ragone, H. A. Ball, P. L. De Souza, J. Wagstaff, C. F. Spraggs, V. E. Mooser, L. N. Pandite, C. Xu
Journal: Journal of Clinical Oncology (2011)

e15072 Background: Fatigue is a common adverse effect of many cancer drugs, which can be debilitating for pts and have negative implications on their physical, mental, and social well-being. Pazopanib is an oral angiogenesis inhibitor indicated for the treatment of advanced RCC. Pts treated with pazopanib experience fatigue to varying degrees. This study sought to explore genetic factors which may contribute to treatment related fatigue in RCC. Methods: DNA was collected from consenting pts with advanced RCC for genetic study from three pazopanib clinical studies; VEG102616 (ph II), VEG105192 (ph III), and VEG107769 (open label extension study of VEG105192). Pts were defined as fatigue cases (NCI-CTCv3 grade ≥ 2) or fatigue controls (no event). A total of 1999 SNPs in 58 candidate genes were evaluated. These genes were selected for a role in the pharmacokinetic and pharmacodynamic pathway of pazopanib or for a suggestive association with fatigue in the literature. Logistic regression was used to evaluate the effect of the genotypes on the case-control status of fatigue. Results: None of the SNPs were associated with fatigue at the multiple-testing corrected significance level (p<6 x 10-6). However, 11 SNPs in four cytokine-encoding genes (IL1A, IL1RN, IL17RA, and IL8RA) met pre-specified criteria for a suggestive association with fatigue (p<0.01). The minor alleles in IL1A, IL17RA, or IL8RA were more often observed in individuals without fatigue event, suggesting that these alleles may confer a protective effect. Conversely, IL1RN minor alleles were observed at a higher frequency in individuals with moderate to severe fatigue (grade ≥ 2), and therefore pts carrying these alleles may be at a higher risk of developing fatigue with pazopanib treatment. IL1RN rs315948 genotypes also showed a suggestion association with fatigue severity. Conclusions: Candidate gene analyses revealed that SNPs in cytokine-encoding genes may be associated with pazopanib related fatigue. However, as none of the SNPs passed the significance level of multiple testing corrections, further evaluation in independent data sets is required to confirm or refute these findings.
Peroxiredoxin-2: A Novel Factor Involved in Iron Homeostasis
Authors: Alessandro Mattè, Luigia De Falco, Enrica Federti, Sonia Levi, Achille Iolascon, Giorgia Federico, Narla Mohandas, Anne Janin, Mariasole Bruno, Christophe Leboeuf, Soo Young Choi, Dae Won Kim, Francesco Dima, Angela Siciliano, Lucia De Franceschi
Journal: Blood (2015)
Presenting characteristics of insured and uninsured patients with anorectal malignancy referred for radiotherapy at an urban safety net hospital.
Authors: Romaine Charles Nichols, Christopher G. Morris, Robert Anthony Zaiden, Ziad Awad, Rovel Colaco, Bradford S. Hoppe, William M. Mendenhall, Nancy Price Mendenhall
Journal: Journal of Clinical Oncology (2013)

363 Background: This retrospective study compares: presenting characteristics; time intervals between symptom emergence, tissue diagnosis and initiation of therapy; and survival, for insured (IP) and uninsured patients (UP) with anal (22) or rectal (39) malignancy referred for radiotherapy at University of Florida Shands Hospital in Jacksonville. Methods: From 5/2002 to 8/2012, 63 newly diagnosed patients were evaluated. 2 patients were excluded due to mental illness. Records were reviewed to capture: 1.) Patient demographics; 2.) Stage at diagnosis; 3.) Weight loss at diagnosis; 4.) Patient reported date of symptom onset; 5.) Date of tissue confirmation of malignancy; 6.) Date of first therapeutic intervention (i.e. surgery, chemotherapy or radiotherapy); 7.) Insurance status at each of the above time points; and 8.) Survival data. Results: At the time of symptom emergence, 32 patients were uninsured and 29 were insured. Median age of UP was 52 years vs. 64 years for IP (P=0.0005). UP experienced median intervals of 258.5 days between symptom emergence and tissue confirmation of malignancy vs. 58 days for IP (P=0.0013). UP experienced median intervals of 314.5 days between symptom emergence and treatment initiation vs. 120 days for IP (P=0.0024). UP presented with T4 primary tumors in 41% of cases vs. 7% for IP (P=0.0027). UP presented with a median weight loss of 10 lbs vs. 0 lbs for IP (P=0.0158). UP presented with lymph node metastasis in 66% of cases vs. 45% for IP (P=0.1264). With a median follow up of 22 months for UP and 32 months for IP, 2 year actuarial overall survival was 87% for UP and 74% for IP (P=0.5503). Conclusions: UP presented at a younger age than IP (P=0.0005) and demonstrated:1.) Longer intervals between symptom emergence and tissue confirmation of malignancy (P=0.0013); 2.) Longer intervals between symptom emergence and treatment initiation (P=0.0024); 3.) Greater likelihood of presenting with a T4 tumor (P=0.0027); 4.) Greater weight loss at presentation (P=0.0158); 5.) A trend toward a greater likelihood of presenting with lymph node metastasis (P=0.1264); 6.) No difference in actuarial 2 year survival from date of diagnosis compared to IP. (P=0.54).
Evaluating the relationship between progression-free survival (PFS) and overall survival (OS) in clinical trials of patients (pts) with metastatic colorectal cancer (mCRC).
Authors: R. Sidhu, A. Rong, S. Dahlberg
Journal: Journal of Clinical Oncology (2011)

3617 Background: Analyses of combined data from clinical trials of chemotherapy (CT) regimens in mCRC have shown that PFS is strongly positively correlated with OS. (Buyse M, et al. J Clin Oncol. 2007;25:5218–5224; Tang P, et al. J Clin Oncol. 2007;25:4562-4568.) Here, we examine this relationship further by including data from published trials of targeted agents plus CT in the first- and second-line setting. Methods: A MEDLINE search was conducted using the keywords "neoplasm metastasis" and "colorectal neoplasm." The search limited to "randomized controlled trial," "clinical trial phase II or III" and a publication date between "2000 and present." Published trials of fluoropyrimidine-based regimens enrolling at least 100 pts, and reporting mature PFS and OS data were included. A manual search (matching the MEDLINE search criteria) was performed for bibliographies of published overviews and conference abstracts. The correlation (R2) between log(PFS) and log(OS) was estimated using a linear regression model. The analysis uses OS and PFS as defined in the publication. Results: In total 22 trials (∼17,000 patients) were included. The R2 value between log(PFS) and log(OS) was: 0.74 for all trials; 0.78 among 11 trials of targeted agents in combination with oxaliplatin or irinotecan-based CT; and 0.79 among 8 first-line phase III trials of targeted agents, including 4 in which epidermal growth factor receptor (EGFR)-targeted agents were used in patients with wild-type KRAS tumors. Conclusions: In this analysis of clinical trials of CT and targeted agents plus CT in the first or second-line treatment of pts with mCRC, improvements in PFS were highly correlated with improvements in OS. These results are consistent with those previously reported for trials of CT alone.
Reduced expression of DENND2D through promoter hypermethylation as an adverse prognostic factor in squamous cell carcinoma of the esophagus.
Authors: Soki Hibino, Mitsuro Kanda, Hisaharu Oya, Hideki Takami, Dai Shimizu, Shuji Nomoto, Masahiko Koike, Suguru Yamada, Goro Nakayama, Tsutomu Fujii, Hiroyuki Sugimoto, Michitaka Fujiwara, Yasuhiro Kodera
Journal: Journal of Clinical Oncology (2014)

58 Background: Esophageal cancer ranks sixth in cancer mortality worldwide and patients with ESCC have a poor prognosis with a 5-year survival rate of less than 10%. Elucidation of the mechanisms of carcinogenesis and tumor progression in esophageal cancer is urgently needed to develop targets for therapy and prognostic biomarkers. In the present study, the expression and regulatory mechanism of the Differentially Expressed in Normal and Neoplastic cells Domain containing 2D (DENND2D), which is a regulator of Rab GTPases, were investigated to explore its potential as a tumor suppressor gene for esophageal squamous cell carcinoma (ESCC). Methods: The level of DENND2D mRNA expression in ESCC cell lines and surgical specimens was determined using a quantitative real-time reverse transcription-polymerase chain reaction assay, and the relationship between the expression level of DENND2D mRNA and clinicopathological factors was evaluated. The expression and distribution of DENND2D were determined using immunohistochemistry. DNA methylation analysis was performed to determine the regulatory mechanism of DENND2D expression in ESCC. Results: The level of DENND2D mRNA expression was reduced in 8/9 ESCC cell lines and in 59/65 surgical specimens, and the mean expression level was significantly lower in cancerous tissues than in corresponding normal tissues (p&lt;0.001). The expression pattern of DENND2D protein and mRNA was consistent. Downregulation of DENND2D mRNA in ESCC tissues was identified as an independent prognostic factor in multivariate analysis (hazard ratio: 2.194; p=0.039). The DENND2D promoter was methylated in five out of nine ESCC cell lines, and DNA demethylation reactivated DENND2D mRNA expression. Hypermethylation of DENND2D was frequently detected in ESCC tissues (64.6%) and was significantly associated with downregulation of DENND2D mRNA expression (P = 0.008). Conclusions: Our data suggest that DENND2D is a candidate tumor suppressor gene that was inactivated by promoter hypermethylation in patients with ESCC and may serve as a novel biomarker of ESCC.
Stratifying risk of urinary tract malignant tumors in patients with asymptomatic microscopic hematuria.
Authors: Ronald Loo, Violeta Rabrenovich, Ann Michelle Aspera, Steven Jacobsen, Howard Landa, Stephen F. Lieberman, Albert J. Mariani, Gary Nicolaisen, Jeff Slezak, Mark StLezin
Journal: Journal of Clinical Oncology (2013)

223 Background: AMH in the general population is common, occurring in up to 9-18%. Even low degrees of AMH have been considered a risk factor for UTMT. Although the prevalence of UTMT is low (.01-3%), many asymptomatic patients undergo unnecessary and hazardous evaluations. In 2007, the Kaiser Permanente (KP) Urologists started a multi-year QI effort to research and develop a risk stratified evidence-based approach in the evaluation of AMH. Methods: The group first conducted a retrospective analysis to determine the incidence of urinary cancer, and stratify risk according to age, gender, smoking history, and degree of hematuria. A multi-regional prospective, observational study was then conducted over a two year period. We used a data collection tool embedded within an EMR to determine patients with AMH who are at greatest risk for UTMT, and patients who might benefit from urologic evaluation or safely avoid unnecessary workup and radiation exposure. Results: 4,414 patients had full urologic work up. Overall, 100 bladder cancers were diagnosed among 4,414 patients (2.3%), and only 11 renal cancers (0.2%) were pathologically confirmed. Multivariable logistic regression was conducted for 5 common parameters: age, gender, smoking history, degree of microscopic hematuria, and history of gross hematuria within the past 6 months. The two most important risk factors were age &gt; 50, and prior history of gross hematuria. A hematuria risk index (HRI) was developed, which significantly improved predictability (AUC = .809-HRI vs .532-AUA guideline). Overall, 32% of the population was identified as low risk with only 0.2% cancer detected; 14% of the population was identified as high risk, of whom 11.1% had a cancer diagnosed. Conclusions: These results suggest that a considerable proportion of patients may safely avoid hazardous evaluation using multivariate risk stratification. An evidence-based algorithm was developed for the management of asymptomatic microscopic hematuria and implemented within KP. We expect to significantly improve patient safety and improve reliability of patient evaluation.