tbuckley/cabot-search huggingface dataset:
Outcome of acute myeloid leukemia in patients with a history of autoimmune disease.
Authors: Courtney Denton Dinardo, Alexis R Ogdie, Elizabeth O. Hexner, Noelle V. Frey, Alison W. Loren, Selina M. Luger
Journal: Journal of Clinical Oncology (2012)

6579 Background: Increased risks of solid and lymphoid malignancies are described in patients with autoimmune (AI) disease. The association between AI disease, AI treatment (particularly anti-TNF therapy), and AML is less established. Moreover, the pathologic characteristics of AML in this population have not been evaluated. Here we describe our AML experience in patients with prior AI disease. Methods: Patients with AML from 1992 to 2011 were identified from our database, and AI disorder was verified through chart review. Patients were included if they had an AI disorder that required systemic treatment, and diagnosed &gt; 1 year prior to AML. Patients were excluded if details including the year of AI diagnosis or treatment(s) received were not documented. A total of 22 patients were included for analysis. Results: Median age at AML diagnosis was 59 years (range 32 – 78), 4 (18%) were men. 10 (48%) had received an anti-TNF agent, for a median duration of 30 months (range 2 – 120). Median latency from AI diagnosis to AML was 9.4 yrs. All FAB subtypes were represented except M0 and M6, 9 (41%) had M4 or M5 disease. 10/21 patients (45%) had normal cytogenetics, and 5 had favorable cytogenetics (2 with acute promyelocytic leukemia (APML)). Standard induction was given to 19 patients, and APML-directed therapy for those with APML. One patient received an autologous transplant in CR1, and 5 an allogeneic transplant (1 in CR1, 4 in CR2). 9 patients are alive in CR1. 13 relapsed, and 4 (31%) are alive in CR2 or CR3 (3 following allogeneic transplant in later CR). Median OS was 68.1 months. In univariate analysis, factors associated with OS were cytogenetics, FAB subtype, and gender. Anti-TNF therapy may be associated with poorer prognosis; this was not statistically significant. Median OS was 14.1 months for poor, 68.1 months for intermediate, and not reached for favorable risk cytogenetics. Conclusions: Median OS was higher (&gt; 5 years) than expected. Younger age and an increased incidence of favorable risk AML may account for this finding: whether this is a meaningful biologic association or stochastic event can only be verified with larger studies. Our observations do not support a label of “secondary leukemia” or therapy-related neoplasm in this population.
Role of cetuximab in conversion therapy in advanced KRAS WT colorectal cancer with liver limited disease: A systematic review and meta-analysis.
Authors: Michelle McMullen, Andrew Davidson, Muhammad Adnan Khattak
Journal: Journal of Clinical Oncology (2017)

748 Background: Majority of advanced colorectal cancer (CRC) patients with liver limited disease (LLD) that undergo curative partial liver resection relapse within 5 years. Peri-operative chemotherapy is currently utilized, however the benefit of this is modest only. The addition of anti-EGFR therapy with cetuximab to chemotherapy has consistently demonstrated improvements in objective response rate (ORR) but its impact on potentially curative R0 resection, progression free survival (PFS) and overall survival (OS) remains debatable. The aim of this study was to evaluate the evidence for the use of cetuximab with chemotherapy, in the peri-operative setting for patients with advanced KRAS-WT CRC and unresectable LLD. Methods: Comprehensive literature search was conducted using PubMed and MEDLINE. Inclusion criteria identified studies evaluating the efficacy of chemotherapy and cetuximab vs. chemotherapy alone in advanced KRAS-WT CRC with unresectable LLD. Phase II studies evaluating chemotherapy-cetuximab without control arms were also included. Pooled data was included in meta-analysis and analysed using the Stata v.7. The primary endpoint was the R0 resection rate. Secondary endpoints were ORR, PFS and OS. Results: 5 trials, describing a total of 617 patients, were included in the analysis 1–5 . Patients receiving cetuximab in addition to chemotherapy were more likely to achieve R0 resection than patients receiving chemotherapy alone (OR 2.13; 95% CI 1.23-3.68, p &lt; 0.05). Patients on cetuximab had improved ORR compared to patients not on cetuximab (OR 2.59; 95% CI 1.74-3.87, p &lt; 0.05). Patients receiving cetuximab had a mean PFS 3.1 months higher than patients not on cetuximab (95% CI 2.76-3.45, p &lt; 0.05). Patients on cetuximab also had a mean OS 0.67 months longer than those not on cetuximab (95% CI 0.44-0.91, p &lt; 0.05). Conclusions: The addition of cetuximab to chemotherapy in the treatment of advanced KRAS-WT CRC with unresectable LLD leads to better outcomes compared to chemotherapy alone.
A prospective phase II study of neoadjuvant FOLFOX6 plus cetuximab in patients with colorectal cancer and unresectable liver metastasis.
Authors: Jun Ho Ji, Young Suk Park, Jeeyun Lee, Tae Won Kim, Yong Sang Hong, Kyu-Pyo Kim, Sun Young Kim, Ji Yeon Baek, Hye Jin Kang, Sang Joon Shin, Byoung Yong Shim
Journal: Journal of Clinical Oncology (2012)

e14072 Background: Colorectal cancer(CRC) with liver-only metastasis is considered potentially curable when liver metastases are completely resectable, while nonresectable liver metastases(NLM) are still incurable. In the latter cases, neoadjuvant chemotherapy could render curability by achieving resectability. We assessed efficacy of neoadjuvant cetuximab combined with FOLFOX6 in colorectal patients with NLM. Methods: Between July 2008 and Dec 2009, 73 patients were enrolled from 11 centers in Korea. Newly diagnosed K-RAS wild type CRC patients with NLM were treated with FOLFOX6 plus cetuximab(provided by Merck Serono) every 2 weeks. Response was evaluated every 3 cycles by CT scan according to RECIST 1.0. Chemotherapy was continued until disease progression or maximum of 12 cycles. Liver metastasectomy was performed at physician’s discretion in patients with enough tumor shrinkage, followed by chemotherapy of same regimen to complete total 12 cycles. The primary endpoint was overall R0 resection rate. The secondary endpoints were the response rates, progression-free survival(PFS), overall survival and toxicity. Results: In total, 73 patients were enrolled and analyzed. The median follow up duration was 28.6 months (range 11.5 to 38.1). Among 53 (72.6%) patients who showed response, surgery with curative intent was attempted in 36 (49.3%) patients. With intention-to-treat analysis, R0 resection rate(RR) was 19.2% (14/73), RFA plus R0, R1 and R2 RR were 8.2% (6/73), 8.2% (6/73), 13.7% (10/73), respectively. Despite neoadjuvant chemotherapy, 37 (50.7%) patients had unresectable hepatic metastases, however. RFA was successfully performed in combination with surgery (n=7) or alone (n=1) in 8 patients of them. Chemotherapy was discontinued in 26 patients due to disease progression (n=13), death (n=2), consent withdrawal (n=10), or protocol violation (n=1). The most common grade 3 and 4 toxicity was neutropenia (10.7%). Median PFS was 14.1 months (range 1.3 - 30.8) in patients received R0 resection and RFA + R0 resection. Conclusions: Neoadjuvant chemotherapy with FOLFOX6 plus cetuximab showed high response rates and increase resection rate in CRC patients with NLM.
Risk-Adapted Treatment of Acute Promyelocytic Leukemia: Results of the PETHEMA LPA2005 Trial Using All-Trans Retinoic Acid and Anthracycline with Cytarabine for High-Risk Patients
Authors: Miguel A. Sanz, Pau Montesinos, Aleksandra Holowiecka, Gustavo Milone, Chelo Rayon, Elena de Lisa, Javier de la Serna, Salut Brunet, Angel Leon, Isabel Krsnik, Concha Rivas, Jose M. Ribera, Jose Gonzalez, Joaquín Díaz- Mediavilla, Javier Bueno, Jose David Gonzalez, Juan Bergua, Marcos Gonzalez
Journal: Blood (2008)
Bevacizumab plus chemotherapy continued beyond first disease progression in patients with metastatic colorectal cancer previously treated with bevacizumab-based therapy: Patterns of disease progression and outcomes based on extent of disease in the ML18147 study.
Authors: Richard Greil, Roger Von Moos, Jaafar Bennouna, Pia J. Osterlund, Thierry André, Eric Van Cutsem, Stefan Kubicka, Dirk Arnold, Jose Maria Vieitez de Prado, Olivier Bouche, Vicente Alonso, Christophe Borg, Christoph Schlichting, Claus-Christoph Steffens, Stuart Osborne, Daniel Waterkamp, Martina Makrutzki, Javier Sastre
Journal: Journal of Clinical Oncology (2013)

3604 Background: ML18147 demonstrated that bevacizumab (BEV) + chemotherapy (CT) continued beyond first disease progression (PD) significantly prolongs overall survival (OS) and progression-free survival (PFS) as second-line treatment for metastatic colorectal cancer (mCRC) [Bennouna et al. Lancet Oncol 2012]. Here we report exploratory analyses of patterns of PD and outcomes based on extent of disease. Methods: In ML18147, patients (pts) with unresectable, histologically confirmed mCRC who progressed ≤3 months after discontinuation of first-line BEV were randomised to second-line CT±BEV. This exploratory analysis evaluated PD patterns, time from discontinuation of study medications to PD, and survival outcome (OS, PFS) based on liver-limited vs extensive disease. Results: Details on patterns of PD and outcome by extent of disease are shown in the table. Conclusions: These exploratory analyses suggest that pts with liver-limited or extensive disease seem to benefit equally from BEV+CT continued beyond PD. Our findings indicate that the pattern of PD does not appear to differ between the two treatment arms following cessation of BEV treatment in this setting. Clinical trial information: NCT00700102. [Table: see text]
Current status of the implementation of gene expression testing in breast cancer management in the United States.
Authors: Julie Ann Lynch, Louis Fiore, Michael J. Kelley, Ann Borzecki, Christopher S. Lathan, Michael Hassett, Hope S. Rugo, Muin J Khoury, Andrew N Freedman
Journal: Journal of Clinical Oncology (2013)

6562 Background: Data on implementation of genetic diagnostic (GDx) tests are lacking yet are crucial to evaluate population differences in access and outcomes. Previous studies identified substantial underuse of GDx tests. Greater access existed in states with NCI cancer centers. This pattern of diffusion may exacerbate disparities. Since 2008, the 21-gene recurrence score (21-gene RS), which assesses the 10-year risk of breast cancer (BC) recurrence in ER+, node-negative, early-stage disease, has been recommended by ASCO/NCCN to guide chemotherapy decisions. This study examines regional and site-of-care differences in use. We report national implementation rate and state-level differences in utilization. Methods: Hospital level data on 2011 orders for the test were provided by Genomic Health. We aggregated this dataset at the state-level and linked it to public datasets (Census and CDC State Cancer Profiles). Using Surveillance Epidemiology End Results (SEER) data, we estimated number of guideline-directed BC cases. The outcome variable, state utilization ratio, was calculated by dividing the number of tests ordered by guideline-directed BC cases. For some states utilization ratios may be higher than 1 because patients may have crossed state boundaries to obtain care. Results: Of approximately 101,702 guideline-directed BC cases nationally, 59,053 patients had the test; a utilization ratio of 0.58. Utilization ratio by state ranged from 0.21 to 1.71 (25 th /75 th percentile range 0.48-0.64). The District of Columbia had the highest utilization ratio at 1.71 (8 institutions ordered 367 tests on an estimated 213 patients); Iowa had the lowest at 0.21 (39 institutions, 458 tests, 2094 patients). Only 7 states had utilization ratios &lt;0.45. Conclusions: In contrast to other GDx tests, 21-gene RS has achieved notable market penetration. Overall, utilization across states is remarkably consistent, especially considering potential variations in age, comorbidities, stage, and incidence of ER+ BC. Despite widespread use, there are likely county-level and site-of-care differences in use. Hospital level analysis is ongoing and will be presented at the meeting.
Efficacy of a genetically modified <i>Salmonella typhymurium</i> against metastatic osteosarcoma in an orthotopic mouse model
Authors: R. M. Hoffman, M. Zhao, K. Hayashi
Journal: Journal of Clinical Oncology (2009)

10543 Background: We have previously developed a genetically-modified strain of S. typhimurium, selected for tumor targeting and therapy in vivo. Normal tissue is cleared of these bacteria even in immunodeficient athymic mice with no apparent side effects. Methods: In this study, the tumor-targeting strain of S. typhimurium, termed A1-R, was administered i.v. to nude mice which have primary bone tumor and lung metastasis. Primary bone tumor was obtained by orthotopic intratibial injection of 5 × 10 5 143B-RFP (red fluorescent protein) human osteosarcoma cells. One group of mice was treated with A1-R and another group was used a as control. A1-R (5 × 10 7 colony-forming units) was injected in the tail vein three times on weekly basis. On day 28, lung samples were excised and observed with the Olympus OV100 Small Animal Imaging System. Results: The size of the primary tumor and RFP intensity of lung metastasis were measured. Primary bone tumor size (fluorescence area [mm 2 ]) was 232 ± 70 in the untreated group and 95 ± 23 in the treated group (P&lt;0.05). RFP intensity of the lung metastasis was 3 ± 1.5 × 10 6 in the untreated group and 0.42 ± 0.33 × 10 6 in the treated group (P&lt;0.05). No toxicity was observed in the treated mice. Conclusions: Therefore, bacterial treatment was effective for both primary bone tumor and lung metastasis. Treatment with the tumor-targeting but non-toxic mutant of S. typhimuriumis a promising approach to therapy of metastatic osteosarcoma. No significant financial relationships to disclose.
The diagnostic and prognostic value of UHRF-1 and p53 in gastric cancer.
Authors: Nalan Akgul Babacan, Reyhan Egilmez, Birsen Yucel, Mehmet Metin Seker, Ilknur Parlak, Turgut Kacan, Aykut Bahceci, Sener Cihan, Bulent Akinci, Saadettin Kilickap
Journal: Journal of Clinical Oncology (2014)

e15082 Background: Gastric cancer is the second leading cause of cancer death for both sexes worldwide. Ubiquitin-like with PHD and ring-finger domains-1 (UHRF- 1) is essential for cellular proliferation and is overexpressed in various cancers. P53 is a well known tumor suppressor gene and many human cancers are found to have a mutant p53 gene. We aimed to examine whether UHRF-1 and p53 over expression could be diagnostic and prognostic markers of gastric cancer. Methods: Immunohistochemistry was used to examine expression of UHRF-1 and p53 in gastric cancers and a control group diagnosed with gastritis. Results: In total, 64 patients with gastric cancer (study group) and 23 patients with gastritis (control group) were evaluated. The median age was 63 years (18–83) in the study group. UHRF-1 was positive in 15 (23%) patients with gastric cancer and 5 (21.7%) patients with gastritis (p=0.559). Thirty-seven (61%) patients with gastric cancer and only one patient with gastritis were p53 positive (p<0.001). After a mean follow-up of 22 months (±2.8), the 2 year overall survival rates were 55% and 30% in negative and positive p53, respectively (p=0.084). Also, the 2 year overall survival rates were 45% and 53% in negative and positive UHRF-1, respectively (p=0.132). Conclusions: This trial demonstrated that UHRF-1 is not a diagnostic and prognostic factor, wherase p53 could be a diagnostic but not a prognostic factor for gastric cancer.
Association of <i>UGT1A1</i> gene polymorphism with the safety and efficacy of irinotecan monotherapy for advanced gastric cancer.
Authors: Toshifumi Yamaguchi, Satoru Iwasa, Hirokazu Shoji, Yoshitaka Honma, Atsuo Takashima, Ken Kato, Tetsuya Hamaguchi, Narikazu Boku
Journal: Journal of Clinical Oncology (2017)

16 Background: The uridine diphosphate glucuronosyltransferase (UGT) 1A1, which transforms SN-38 into SN-38 glucuronide, is a key enzyme involved in the metabolism of irinotecan. Previous studies showed that UGT1A1 genotype is related to the toxicity of irinotecan-based chemotherapy in metastatic colorectal cancer. The purpose of this study was to investigate the relationship between UGT1A1genotype and safety and efficacy of irinotecan monotherapy in patients with advanced gastric cancer. Methods: We reviewed the data of 208 patients who were tested for UGT1A1 genotype and treated with irinotecan-based chemotherapy for advanced gastric cancer from 2009 to 2014. We evaluated the efficacy and safety of irinotecan monotherapy in the three groups with wild-type (WT), single heterozygosity (SH), and homozygosity/double heterozygosity (Homo-DH) classified by the genotypes for UGT1A1*28 or UGT1A1*6. Results: A total of 117 patients received irinotecan monotherapy: 40 patients in second-line, 74 in third-line, and 3 in forth-line therapy. The UGT1A1genotype was WT in 62 patients (53.0%), SH in 41 (35.0%), and Homo-DH in 14 (12.0%). Patients’ characteristics were similar among the three groups. The initial dose of irinotecan was reduced in 10 patients (16%) with the WT genotype, in 11 (27%) with SH, and in 10 (71%) with Homo-DH. Grade 3-4 neutropenia, diarrhea, and febrile neutropenia occurred in 13/22/64%, 6/5/21%, and 2/7/50% of WT/SH/Homo-DH patients. Median time to treatment failure of second-line and third-line therapies were 2.4/2.8/3.3 months and 2.4/2.3/1.3 months in WT/SH/Homo-DH patients. Median overall survival of second-line and third-line therapy were 7.9/9.9/4.6 months and 6.9/6.3/2.8 months in WT/SH/Homo-DH patients. Conclusions: Patients with UGT1A1 Homo-DH displayed high frequency of grade 3-4 toxicities, although the initial dose of irinotecan was reduced in some patients. UGT1A1 polymorphism may be related to the efficacy of irinotecan monotherapy in second- and third-line treatments for advanced gastric cancer.
A phase II study of everolimus (E) and sorafenib (S) in patients (PTS) with metastatic differentiated thyroid cancer who have progressed on sorafenib alone.
Authors: Marcia S. Brose, Andrea B. Troxel, Mark Yarchoan, Aaron Benjamin Cohen, Kathleen Harlacker, Nikolas A Dyanick, Zakkiyya A Posey, Ramkrishna Makani, Parna Prajapati, Larisa M. Zifchak, Carolyn Grande, Christian Michael Squillante
Journal: Journal of Clinical Oncology (2015)

6072 Background: Recently, S became the first drug FDA-approved in 40 years to treat progressive, RAI-refractory thyroid cancer. S inhibits VEFR, PDGFR, Kit and RET. With S, patients achieve a median PFS of 10.8 months. We observed that pts may progress in some sites while maintaining stability in others. We hypothesized that progression on S may depend on increased activity of the AKT/MTOR pathway. Therefore we conducted a Phase II study to see if the addition of everolimus (E), an oral mTOR inhibitor, to S would have activity in pts who had progressed on S alone. Methods: 35 pts with evidence of progression by RECIST criteria on S were enrolled. Pts were started on a dose of S 200mg/d lower than their previously tolerated dose, combined with E 5mg/d. Pts were followed for toxicity; if tolerated, the dose of E and then S were incrementally increased to a maximum daily dose of S 800mg/day and E 10mg/day. The primary endpoint was progression-free survival (PFS). Response was evaluated by RECIST every 8 weeks. Results: Of 35 pts enrolled, 33 were evaluable for PFS and response. 17 pts had papillary, 9 had Hürthle Cell, 1 had follicular and 6 had poorly differentiated subtypes. 13 pts were successfully dose escalated to full dose of both agents: S 800mg/d and E 10mg/d, 5 pts reached S 600mg/d and E 10mg/d, and 8 pts reached S 600mg/d and E 7.5 mg /d. While increased severity of hand foot skin reaction was anticipated, it was rarely seen. The median PFS was 13.7 mos (95% CI: 7.15-24.75). No complete responses were observed, 1 pt achieved a partial response and 18 achieved a best response of stable disease for > = 6 mos. for a clinical benefit rate (CR+PR+SD > = 6 mos.) of 58%. Conclusions: The addition of everolimus to sorafenib at the time of progression was tolerable and allowed pts an additional median of 13.7 mos. of disease stability. The addition of everolimus did not result in dose-limiting hand foot skin reaction as had been seen in prior studies in which both were started at the same time, demonstrating that these agents may be successfully combined if started sequentially. Our approach may have implications in other diseases where the combination of a VEGFR inhibitor and mTOR inhibitor may have added activity. Clinical trial information: NCT01263951.
‘There is nothing more deceptive than an obvious fact’: more evidence for the prescription of exercise during haemodialysis (intradialytic exercise) is still required
Authors: Daniel S March, Matthew PM Graham-Brown, Hannah ML Young, Sharlene A Greenwood, James O Burton
Journal: British Journal of Sports Medicine (2017)

With regard to the recent editorial,1 we applaud the author’s call to arms for nephrologists to ‘prescribe’ exercise during haemodialysis (HD). It is true that exercise has tremendous health benefits, with many likely benefits for HD patients. Staying physically active is essential to maintaining health, and unquestionably clinicians caring for HD patients should be counselling patients to increase physical activity levels. There are, however, unresolved questions that must be answered before structured programmes of intradialytic exercise (IDE) can simply be ‘prescribed’ by clinicians, as Deschamps suggests. The UK Renal Association clinical practice guidelines for cardiovascular disease state that exercise should be encouraged for all HD patients,2 but practical recommendations on prescribing and dosing of exercise (and indeed safest modes of exercise) cannot currently be made based on the available evidence. …