tbuckley/cabot-search huggingface dataset:
Surgical treatment and outcome of patients with invasive breast carcinoma age 80 or older.
Authors: Nikola Besic, Jan Zmuc, Barbara Peric, Gasper Pilko, Rok Petric, Andraz Perhavec
Journal: Journal of Clinical Oncology (2012)

171 Background: Because the population ages, the proportion of breast cancer (BC) patients over age 80 is increasing. To date, there is no consensus as to what the best treatment is for older patients with BC. The aim of our retrospective study was to analyze data about surgically treated BC patients with ≥80 years of age and their outcome. Methods: A chart review of 158 early BC patients (mean age 83; range 80-90) that were surgically treated at our institute from 2000 to 2008 was performed. The data on the extent of disease, morphologic characteristics, mode of therapy, recurrence and survival were collected. Correlation between possible prognostic factors, mode of therapy and cause-specific survival was analyzed by univariate and multivariate test. Results: Extension of BC was local, locoregional and unknown in 37%, 46% and 17% of cases; pT1/pT2 and pT3/pT4 tumor stage was present in 75% and 25%, respectively. Conservative breast surgical procedure, mastectomy, axillary lymphadenectomy, sentinel lymph node biopsy and no lymph node surgery was done in 27%, 73%, 57%, 18%, and 25%, respectively. Adjuvant hormone therapy (tamoxifen in 56 and aromatase inhibitors in 47 cases), chemotherapy and external radiotherapy were used in 65%, 1.2% and 15% of patients. Recurrence occurred in 23% of cases during the follow-up period of 0.2-11 years (median 4.3 years); local, regional and/or distant in 10%, 6% and 22% of cases, respectively. Because of BC and other reasons died 20% and 20% of cases, respectively. The 5-year cause-specific survival in patients with local and regional extension of BC was 86% and 74%, respectively. Univariate statistical analysis showed that pT3/pT4 tumor, pN1 stage, mastectomy, sentinel node biopsy and lymphadenectomy correlated with shorter cause-specific survival. Multivariate analysis showed that only pT3/pT4 tumor and pN1 stage correlated with shorter cause-specific survival. Our results indicate that our patients were locoregionally treated adequately to tumor stage Conclusions: Short cause-specific survival indicates that BC in patients with ≥80 years of age and regional metastases may be aggressive. Adjuvant chemotherapy might be considered in selected cases to prolong survival.
MRI accurately predicts histopathology of pelvic masses.
Authors: A. E. Ford
Journal: Journal of Clinical Oncology (2011)

e15534 Background: Pelvic MRI is often used to preoperatively characterize adnexal masses, and can predict the nature of the mass (benign or malignant), but also, its specific histologic subtype. We aimed to determine the accuracy of MRI by correlating MRI predictions with the final pathology diagnoses for a series of pelvic masses. Methods: We reviewed patients who had pelvic MRI for an adnexal mass between 2008-2010 at our tertiary care institution, including demographics, CA-125 levels, and extent of clinical or surgical follow up. Results: We identified 238 female patients meeting inclusion criteria. Of these patients, 84 (35%) underwent surgical intervention, while 152 (64%) were followed conservatively. Of the 69 women who were identified as having a benign mass on pre-operative MRI, 65 (94%, 95% CI 0.84-0.97) had benign pathology and of the 15 women whose MRI predicted a malignant lesion, the surgical pathology showed malignancy in 14 (93%, 95% CI 0.68-0.99). The predicted histologic subtype was accurate in 47/69 women (68%) with an anticipated benign diagnosis and in 7/15 patients (47%) with an anticipated malignancy. However, 4 patients (4.8%) were incorrectly classified on MRI diagnosis as benign when the pathology was either borderline (1 patient, or 1.2%) or malignant (3 patients, or 3.6%). Of those that had surgical intervention with a benign MRI interpretation, the average CA-125 level was 80.4 U/mL (n=34) for those with an eventual benign diagnosis, and of those that ultimately had a borderline or malignant lesion, the average CA-125 level was 37 U/mL (n=3). For comparison, the average CA-125 level was 175.3 U/mL for all malignant lesions. Conclusions: In this tertiary care center, MRI is often used to further characterize adnexal masses. Our data indicates that MRI is accurate in this regard, but more importantly is also highly correlative of the actual histopathology for patients who underwent surgical intervention. Furthermore, 63% of patients in our cohort were able to be managed expectantly based on reassuring results of the MRI. Our data indicates that, when available, MRI is an important tool in providing more detailed patient counseling, appropriate referral to gynecologic oncologists, and appropriate surgical planning.
A novel p53-based strategy for protection of gastrointestinal track and bone marrow (BM) from 5-fluorouracil (5-FU).
Authors: C. S. Ha, S. Ganapathy, Z. Yuan
Journal: Journal of Clinical Oncology (2011)

213 Background: Acute toxicity from DNA damaging agents such as radiation and chemotherapy is mainly mediated by p53 which, upon activation, induces massive apoptotic cell death in sensitive tissues such as GI track and BM. Expanding from our recent finding that low-dose arsenic can temporarily and reversibly suppress p53 activation and subsequent tissue damages in normal tissues but not in carcinomas due to distinct differences in p53 status, we used a mouse tumor xenograft model to test the potential of arsenic in protecting the GI track and BM from one of the most commonly used chemotherapeutic agents for GI malignancies, 5-FU, without compromising tumor control. Methods: Arsenic pretreatment was done by feeding sex-matched mice (4-6 weeks old) with water with or without 1.0 mg/L sodium arsenic for 3 days. Mice were randomized into 4 groups: A. control; B. arsenic only; C. 5-FU (30 mg/kg body weight i.v. for 5 days) only; D. arsenic and 5-FU. 5- FU-induced GI track and BM damages were analyzed histologically with H&amp;E staining 4 weeks after last treatment. Body weight was monitored as a measure of toxicity. Lung carcinoma NCI-H358 was used to generate a mouse xenograft model. Treatments were initiated 3 weeks after implantation when the lung carcinomas reached an average volume of 100 mm 3 . Tumor volumes were measured periodically. Two independent experiments were done with10 mice per group. Results: Tumor sizes at 9 weeks were (mean±SE in mm 3 ): 528.1±62.81, 504.04±55.19, 133.02±35.74, 114.47±17.49 for groups A,B,C and D respectively (p=ns, C vs. D). The corresponding body weights were (in gm): 34.6±1.5, 36.4±2.1, 31±1.2, and 35.4±1.8 (p=0.0001, t-test, C vs D). 5-FU treatment was associated with severe damages to small intestine and BM, and such damages were significantly reduced by low-dose arsenic pretreatment by histological examination. Conclusions: Our data demonstrate that a brief treatment with low-dose arsenic is associated with a marked protection of GI track and BM without compromising the ability of 5-FU to kill carcinoma cells.Our data have provided proof-of- principle for the use of low-dose arsenic to protect GI track and BM from toxicity of 5-FU, and for potential 5-FU dose intensification in clinical settings. No significant financial relationships to disclose.
Pattern of recurrence after partial and total nephrectomy in non-metastatic renal cell carcinoma (RCC) of low, intermediate and high risk: Implications for follow-up.
Authors: Axel Bex, Yvette Kuijpers, Allard Noe, Ruud Bosch, Simon Horenblas, Richard Meijer
Journal: Journal of Clinical Oncology (2016)

601 Background: Guidelines recommend risk-adapted follow-up (FUP) after (partial) nephrectomy in non-metastatic RCC. VEGF-targeted therapy does not cure multiple metastatic RCC. FUP should therefore focus on local recurrences or single-/-oligometastases that may potentially be cured by local therapy. The rate of potentially curable recurrences per risk group is unknown and their pattern and management were analyzed in this study. Methods: From an IRB approved database non-metastatic RCC patients who underwent (partial) nephrectomy from 2004 to 2011 with a minimum FUP of ≥4 years and regular cross-sectional imaging were identified. Risk stratification was assigned to Leibovich- (clear-cell ) or UICC-stage- (non-clear cell) risk groups . Local recurrence, solitary and oligometastases defined as &lt; 3 lesions at a single site were considered potentially curable by local therapy modalities. Recurrences were recorded as was the time to detection of recurrence (TDR) and their management. Results: From 230 patients identified, 191 (clear-cell) and 39 (non-clear cell) were assigned to the Leibovich- or UICC-risk groups respectively. Together, 69 developed recurrences (30 %), of whom 29 (42 %) were potentially curable. Of low-risk patients (32.6 %), only 9 (12 %) had recurrences of which 5 (55.6 %) were potentially curable. In high-risk (19.1 %), of 26 (59.1%) recurrences, the majority were multiple and rapid at a median TDR of 8.4 months (IQR 13.7) with only 6 (23.1 %) potentially curable at a median TDR of 17.6 (IQR 53.8) months. Of 24 recurrences (33.8 %) in intermediate risk, 12 (50 %) potentially curable lesions were detected after a median TDR of 26 (IQR 36.2) months. Together, of 29 potentially curable lesions 15 (51.7 %) were not treated because of comorbidity, poor performance or prognosis and irresectability. Conclusions: High-risk patients predominantly develop multiple metastases early during FUP. A benefit of FUP might derive from identifying potentially curable lesions which develop with latency especially in intermediate and high risk. With only 48 % of potentially curable lesions treated locally the impact of FUP on OS remains controversial.
Phase II trial of weekly irinotecan and carboplatin for relapsed ovarian cancer: A Kansai Clinical Oncology Group study.
Authors: H. Tsubamoto, K. Inoue, R. Kawaguchi, K. Ito, S. Takeuchi, T. Shiozaki, Y. Itani, A. Arakawa, T. Tabata, S. Toyoda
Journal: Journal of Clinical Oncology (2011)

5089 Background: Irinotecan has shown favorable activities in combination with carboplatin for patients with advanced or recurrent epithelial ovarian cancer (EOC). Thus a multicenter phase II trial was conducted to evaluate the activity and toxicity. Methods: Intravenous administrations of 60 mg/m2 of irinotecan (Days 1 and 8 ) and carboplatin at AUC of 5 mg-min/mL (Day 1), repeated every 21 days, were given to patients with either radiological or serological recurrent EOC. The primary endpoint was response rate (RR) determined by RECIST and GCIG criteria, while the secondary endpoints were adverse events (AEs; NCI-CTCAE ver 2.0) and progression-free survival (PFS). Results: From 2005 to 2009, 40 patients were enrolled in the trial. Their median age was 59 years old (range, 33-78) and histological findings were serous (68%), endometrioid (17%), and others (15%). The number of previous regimens were 1 in 45%, 2 in 30%, and 3 or 4 in 20%. 35 patients (88%) had measurable disease. Overall RR was 31% and median PFS was 5.5 months (range, 1-15) in patients with TFI <6 months, while those were 56% and 10 months (range: 3-16), respectively, in patients with TFI ≥6 months. Grade 3 or 4 toxicities encountered during the first cycle included G3/G4 neutropenia in 14/13 (68%), G3/G4 thrombocytepenia in 17/0 (43%), G3 febrile neutropenia in 2, G3 fatigue in 2, G3 nausea in 1, and G2 diarrhea in 1. Delay of the second cycle in 28 (70%), and the actual dose intensity (DI) of irinotecan and carboplatin during the first 12 weeks were 30.5 mg/m2/week (range,15-40) and 1.4 AUC of 1.4 (range 1.1-1.7), respectively. Conclusions: Our results showed that combination chemotherapy with irinotecan and carboplatin was efficacious in regard to RR and PFS. Severe hematologic toxicity was often observed, but was controllable. We concluded that the regimen was useful as second-line chemotherapy, while the recommended regimen is 60 mg/m2 of irinotecan (Days 1 and 8 ) and carboplatin at an AUC of 5 (Day 1), repeated every 28 days.
Unravelling Endogenous MicroRNA System Dysfunction as a New Pathophysiological Mechanism in Machado-Joseph Disease
Authors: Vitor Carmona, Janete Cunha-Santos, Isabel Onofre, Ana Teresa Simões, Udaya Vijayakumar, Beverly L. Davidson, Luís Pereira de Almeida
Journal: Molecular Therapy (2017)

Machado-Joseph disease (MJD) is a genetic neurodegenerative disease caused by an expanded polyglutamine tract within the protein ataxin-3 (ATXN3). Despite current efforts, MJD's mechanism of pathogenesis remains unclear and no disease-modifying treatment is available. Therefore, in this study, we investigated (1) the role of the 3′ UTR of ATXN3, a putative microRNA (miRNA) target, (2) whether miRNA biogenesis and machinery are dysfunctional in MJD, and (3) which specific miRNAs target ATXN3-3′ UTR and whether they can alleviate MJD neuropathology in vivo. Our results demonstrate that endogenous miRNAs, by targeting sequences in the 3′ UTR, robustly reduce ATXN3 expression and aggregation in vitro and neurodegeneration and neuroinflammation in vivo. Importantly, we found an abnormal MJD-associated downregulation of genes involved in miRNA biogenesis and silencing activity. Finally, we identified three miRNAs—mir-9, mir-181a, and mir-494—that interact with the ATXN3-3′ UTR and whose expression is dysregulated in human MJD neurons and in other MJD cell and animal models. Furthermore, overexpression of these miRNAs in mice resulted in reduction of mutATXN3 levels, aggregate counts, and neuronal dysfunction. Altogether, these findings indicate that endogenous miRNAs and the 3′ UTR of ATXN3 play a crucial role in MJD pathogenesis and provide a promising opportunity for MJD treatment. Machado-Joseph disease (MJD) is a genetic neurodegenerative disease caused by an expanded polyglutamine tract within the protein ataxin-3 (ATXN3). Despite current efforts, MJD's mechanism of pathogenesis remains unclear and no disease-modifying treatment is available. Therefore, in this study, we investigated (1) the role of the 3′ UTR of ATXN3, a putative microRNA (miRNA) target, (2) whether miRNA biogenesis and machinery are dysfunctional in MJD, and (3) which specific miRNAs target ATXN3-3′ UTR and whether they can alleviate MJD neuropathology in vivo. Our results demonstrate that endogenous miRNAs, by targeting sequences in the 3′ UTR, robustly reduce ATXN3 expression and aggregation in vitro and neurodegeneration and neuroinflammation in vivo. Importantly, we found an abnormal MJD-associated downregulation of genes involved in miRNA biogenesis and silencing activity. Finally, we identified three miRNAs—mir-9, mir-181a, and mir-494—that interact with the ATXN3-3′ UTR and whose expression is dysregulated in human MJD neurons and in other MJD cell and animal models. Furthermore, overexpression of these miRNAs in mice resulted in reduction of mutATXN3 levels, aggregate counts, and neuronal dysfunction. Altogether, these findings indicate that endogenous miRNAs and the 3′ UTR of ATXN3 play a crucial role in MJD pathogenesis and provide a promising opportunity for MJD treatment.
Development of intermediate and high-risk prostate cancer after testicular cancer.
Authors: Andrew John Riggin, Mohummad Minhaj Siddiqui
Journal: Journal of Clinical Oncology (2015)

177 Background: Men with a history of testicular cancer are known to have an increased risk of developing prostate cancer (PCa) in epidemiologic studies. We hypothesized they may also have an increased risk of developing intermediate to high-risk PCa. Herein, we present a case-control study to assess the association of a history of testicular cancer and intermediate to high-risk PCa. Methods: We used the eighteen Surveillance, Epidemiology and End Results (SEER) registries to compare men with a history of testicular cancer to a control population of men with a history of melanoma. Melanoma was used as a control group because, to our knowledge, there is no association of melanoma and PCa. Men were excluded if they were not 60 years of age or older to allow for sufficient PCa diagnosis. PCa incidence was only counted if it occurred at least 5 years after the diagnosis of their primary cancer to allow for possible temporal effect of the primary malignancy. Incidence of total and intermediate to high-risk PCa(Gleason score ≥ 7) was compared using Kaplan-Meier (KM) curves. Cox proportional hazards models were utilized to assess for associations of PCa (JMP 10, SAS Inc). Results: 119,781 men with melanoma and 10,365 men with testicular cancer were identified. The incidence of all PCa by age 80 was 2.7% in the control melanoma cohort and 12.3% in the case cohort of men with history of testicular cancer (p&lt;0.0001 for KM survival curves). For intermediate/high-risk disease, the incidence was 1.1% versus 5.7% for each cohort respectively (p&lt;0.0001 for KM survival curves). Testis cancer (versus the control melanoma cohort) was associated with an increased risk of all PCa (HR 4.7, p&lt;0.0001) and intermediate/high-risk PCa (HR 5.5, p&lt;0.0001). These associations persisted even when controlling for race. Conclusions: A history of testicular cancer is associated with a significantly increased risk of developing both PCa and intermediate/high risk PCa.
DPD deficiency: Medicoeconomic evaluation of pretreatment screening of 5-FU toxicity.
Authors: Sory Traoré, Michele Boisdron-Celle, Gilles Hunault, Thierry Andre, Alain Morel, Veronique Guerin-Meyer, Olivier Capitain, Erick Gamelin
Journal: Journal of Clinical Oncology (2012)

410 Background: Deficiency of DPD activity is associated with severe toxicity or even death after the first two cycles 5-fluorouracil (5-FU) based of chemotherapy. The objective of this study was to assess the cost-effectiveness of a screening test before treatment of the deficiency of DPD activity combining two approaches (genetic and phenotype (UH 2 / U)). The main measure of effectiveness was the number of avoided severe toxicities (grade 3-4), but the number of quality adjusted life days was the secondary endpoint. Methods: The analysis was based on retrospective data from a population of patients treated for colorectal cancer. 856 patients were screened (5-FU ODPM Tox , ODPM, France) before being treated with adjusted doses (5-FU ODPM Protocol , ODPM, France) versus a population of 886 patients treated according to standard doses (2400 mg/m²). The main point of view was society perspective and the time horizon was 2 cycles of chemotherapy. A multi-state Markov-type was used to estimate the mean cost and results for each of the two strategies. The cost of the strategy with screening was composed of the cost of the screening test and the cost of remaining toxicities, the cost of the standard strategy was just the cost of toxicities. The incremental cost-effectiveness ratio (ICER) was calculated: (COST Standard - COST WithScreening )/(Eff Standard - Eff WithScreening ) COST A : Cost of the strategy A, Eff A : Effectiveness of the strategy A. Results: In the screened and adapted arm, the prevalence of severe toxicities at 1 cycle of chemotherapy was 0.5%, at 2 cycles was 0.9%. In the arm with standard doses, they were 5.80% and 6.90%, respectively. Any toxicity associated death was observed in the screened arm versus 1 death in the standard arm. The screening strategy was dominant, it allowed avoiding toxicities and saving money. The avoided cost per patient screened was 313 € for two cycles of treatment and a saving of 2780 € per toxicity avoided. The incremental net benefit (INB) per patient screened is 426 €. Conclusions: Pre-treatment screening test combining genetic and phenotype reduced the incidence of toxicities associated with 5-FU, it avoided deaths due to 5-FU and its additional cost was less than the cost of care of toxicity that it avoided.
Implementation of electronic chemotherapy ordering: An opportunity to improve evidence-based oncology care.
Authors: Kerin Adelson, Randall F. Holcombe, Kristine Lutkowski, Damaris Peralta-Hernandez, Michael McLean, Anika Evans-Smith, Denise Wynter, Patricia Spencer-Cisek
Journal: Journal of Clinical Oncology (2012)

323 Background: On April 20, 2012, Mount Sinai Medical Center was the 63rd site to go-live with the Beacon chemotherapy module of the EPIC EMR. EPIC support reports that ours was one of the most successful launches to date. Previously, all our chemotherapy orders were handwritten with variable adherence to evidence-based chemotherapy and supportive care guidelines. Our goals were 1) reduce errors and improve patient safety, 2) increase use of evidence-based treatment, 3) optimize supportive care and 4) improve practice efficiency. Methods: Fourteen months prior to the go-live we formed a Chemotherapy Council, made up of Oncology physician, nursing and pharmacy leadership and a Beacon-trained Build Team, including an oncology nurse and two chemotherapy pharmacists. Individual disease groups submitted lists of their regimens with references, which were used to create paper orders. The council met weekly to review the orders, references, nursing communications, and NCCN treatment, antiemetic and supportive care guidelines. Once approved, these paper orders served as templates for more than 400 electronic protocols. Each protocol was validated by a utilizing physician. Results: 98% of patients had electronic orders entered prior to go-live (394 chemotherapy and 116 supportive). There were no patient safety issues during the go-live period. In a survey one-month post go-live, 72% of users felt that Beacon had improved their day-to-day efficiency and 72% of users felt that the quality of patient care had improved. Conclusions: The transition to electronic chemotherapy ordering offers an institution the chance to develop evidence-based oncology practice, standardize supportive care and enhance patient safety. It is essential to develop procedures to avoid electronically immortalizing unproven regimens or chemotherapy dosing errors. The key elements that made our Beacon transition so successful were: 1) extensive involvement of oncology leadership, 2) use of a chemotherapy council to enforce evidence-based practice, 3) clinician validation of every protocol and 4) ongoing collaboration between clinical operations and IT regarding the impact of electronic ordering on downstream operations.