tbuckley/cabot-search huggingface dataset:
Derivation of a prognostic model for chemotherapy-induced febrile neutropenia.
Authors: Shin Ahn, Yoon-Seon Lee, Jae-Lyun Lee
Journal: Journal of Clinical Oncology (2014)

e20624 Background: Object of this study was to develop a simple and objective prognostic model for patients with chemotherapy induced febrile neutropenia (FN). Methods: A total of 718 patients with FN were prospectively collected from January 2012 to December 2013.We derived our prediction model using logistic regression with adverse outcome as the primary outcome, and patient demographic and clinical data routinely available at presentation as potential predictor variables. We compared the performance of our model in predicting outcome with that of the Multinational Association for Supportive Care (MASCC) risk score. Results: Risk factors and their points for adverse outcome included in the model were age ≥60 (2), serum procalcitonin ≥0.5 (5), Eastern Cooperative Oncology Group (ECOG) performance score ≥2 (2), Mucositis grade ≥3 (3), initial systolic blood pressure <90 mmHg (3), and initial respiratory rate ≥24/min (3). Total score has its range between 0 and 18 theoretically, however, actual sum of scores ranged from 0 to 15. Our prediction rule stratifies patients with FN into three severity classes, with complication rate of 5.97% in class I, 27.27% in class II, and 67.86% in class III. Mortality rate were 0.4% among patients in class I and 17.96% in class III. The area under the curve for our model and the MASCC risk index score were 0.837 (95% CI 0.797 – 0.878) and 0.823 (95% CI 0.795 – 0.87) respectively. Conclusions: We have developed a new prognostic model for FN, through which we can classify patients with FN into 3 classes of increasing adverse outcomes. Further validation of the rule is important before its implementation.
Deletions in <i>HSP110</i> and prognosis in colorectal cancers with microsatellite instability.
Authors: David Tougeron, Karline Guilloteau, Aurelie Ferru, Lucie Karayan-Tapon
Journal: Journal of Clinical Oncology (2014)

e14577 Background: Microsatellite instability (MSI) is found in 12% of colorectal cancers (CRC) and associated with a low recurrence rate after curative surgery. In MSI CRC, adjuvant chemotherapy with 5-FU seems ineffective, but FOLFOX could be effective. HSP110 is a chaperone protein that promotes the survival of CRC malignant cells. A recent study demonstrates that MSI CRC with large deletions in HSP110 T17 (T17 repeat in intron 8) have improved response to adjuvant chemotherapy (Collura et al., 2013). The aim of this study was to analyze prognosis and efficacy of adjuvant chemotherapy with 5-FU or FOLFOX according to the HSP110 T17 status in MSI CRC. Methods: This study included all patients with MSI CRC in our institution (n=151). The polymorphic status of the HSP110 T17 was evaluated using polymerase chain reaction and fragment analysis. Tumors were divided between large (more than 4) and small (up to 4) HSP110 T17 deletions. Prognostic factors of relapse-free survival (RFS) were analyzed in univariate analysis using Cox model. Results: A total of 136 MSI CRC tumors, with tumoral DNA available, were analyzed. Overall, 31% (n=42) of the results were not assessable due to the lack sensibility of the technique (estimated between 15% and 50% on MSI CRC cell lines). Among the remaining tumors (n=94), 35% had large deletions (n=33) and 65% small deletions (n=61). Mean age of patients was 62 ± 14 years. Characteristics of the patients (sex, age, Lynch syndrome) and tumors (T stage, N stage, grade, tumor location, BRAF mutation) were not different according to the size of HSP110 T17 deletion. In our series, large HSP110 T17 deletions were not associated with better RFS. Moreover, in patients with adjuvant chemotherapy (35%), large HSP110 T17 deletions were not associated with better RFS (HR=0.23, 95% CI 0.01-3.77 ; p=0.30). Conclusions: In this study, HSP110 T17 large deletions were not associated with better outcome and response to adjuvant chemotherapy.
Tanespimycin (T) + Bortezomib (BZ) in Multiple Myeloma (MM): Confirmation of the Recommended Dose Using a Novel Formulation.
Authors: Paul G. Richardson, Asher Chanan-Khan, Sagar Lonial, Amrita Krishman, Michael Carroll, G.F. Cropp, K. Kersey, M. Abitar, R.G. Johnson, Alison L. Hannah, Kenneth C. Anderson
Journal: Blood (2007)
BAP1 tumor predisposition syndrome: Preliminary data from a laboratory-based multigene panel testing cohort.
Authors: Carrie Horton, Holly LaDuca, Patrick Reineke
Journal: Journal of Clinical Oncology (2017)

490 Background: Germline mutations in BAP1 have recently been shown to cause a tumor predisposition syndrome characterized by renal cell carcinoma (RCC), uveal melanoma, cutaneous melanoma, and mesothelioma. However, mutations have thus far been identified in highly enriched cohorts and the tumor spectrum among individuals with a broader phenotype undergoing multi-gene panel testing (MGPT) has not been described. Other genes associated with familial RCC have been established, such as FLCN (Birt-Hogg Dube syndrome) and VHL (von Hippel Lindau), but the proportion of BAP1 mutations in individuals with RCC is not yet known. Here we aim to describe the clinical features of individuals with BAP1 mutations identified from a clinical laboratory cohort, and to estimate the frequency of BAP1 mutations in individuals with kidney cancer. Methods: Since May 2015, a total of 6956 tests have been ordered that include BAP1 at our diagnostic laboratory. Retrospective data review yielded molecular and clinical details for individuals with identified mutations. Results: Thirteen individuals with BAP1 mutations have been identified. Cancer diagnoses in probands and family members consist of breast cancer (reported in 69.2% of kindreds), RCC (61.5%), melanoma (61.5%), mesothelioma (46.2%), lung cancer (46.2%), non-melanoma skin cancer (30.8%), and cholangiocarcinoma (15.4%). Among probands with kidney cancer undergoing MGPT (n = 1012), there is no difference in mutation rate of BAP1 compared to VHL (n = 3; OR 2.01 p = 0.51) or FLCN (n = 10; OR 0.598 p = 0.45). Conclusions: Cancer histories in our laboratory-selected cohort of BAP1 mutation carriers are consistent with those reported in the clinical literature, lending credence to the notion that BAP1 tumor predisposition syndrome is highly penetrant and consists of a constellation of several core cancers. The observation of breast, lung, non-melanoma skin cancer, and cholangiocarcinoma has also been reported in the literature and warrants further study. Our results suggest that BAP1 mutations are found at a similar frequency as other well-known kidney cancer genes, supporting its position as an important differential when considering genetic testing for RCC.
Randomized, open-label, phase III study of pemetrexed plus carboplatin followed by maintenance pemetrexed (Arm A) versus paclitaxel plus carboplatin and bevacizumab followed by maintenance bevacizumab (Arm B) in patients with advanced nonsquamous (NS) non-small cell lung cancer (NSCLC).
Authors: Ralph Zinner, Helen J. Ross, Robert Weaver, Ramaswamy Govindan, Viran R. Holden, Naveed Mahfooz Chowhan, J. Thaddeus Beck, David Michael Waterhouse, Manuel Modiano, Vijay Phooshkooru Rao, Jingyi Liu, Andrew Koustenis, Symantha Melemed, Susan C. Guba, Waldo Feliu Ortuzar, Durisala Desaiah, David R. Spigel, Coleman K. Obasaju
Journal: Journal of Clinical Oncology (2013)

LBA8003 The full, final text of this abstract will be available at abstract.asco.org at 7:30 AM (EDT) on Monday, June 3, 2013, and in the Annual Meeting Proceedings online supplement to the June 20, 2013, issue of Journal of Clinical Oncology. Onsite at the Meeting, this abstract will be printed in the Monday edition of ASCO Daily News.
Delay from surgery until first adjuvant treatment and prognosis of women with invasive breast cancer in a Brazilian public health service.
Authors: Damila Cristina Trufelli, Leandro Luongo Matos, Patricia Xavier Santi, Auro Del Giglio
Journal: Journal of Clinical Oncology (2014)

e17589 Background: Several studies showed that delays in the initiation of treatment since diagnosis of breast cancer may lead to worse prognosis.The purpose of this study was to evaluate if time from surgery until first adjuvant treatment (chemotherapy, radiotherapy or hormone therapy) in patients with breast cancer is a risk factor for lower overall survival (OS). Methods: Five-year retrospective cohort study in which data from medical records of all women diagnosed with invasive breast cancer attended at an academic oncology service were collected and analyzed. Results: Three-hundred and forty eight consecutive women were included. The median time from surgery to first adjuvant treatment was 2 months. Cox regression analysis showed that time form surgery until first adjuvant treatment was a risk factor for shorter overall survival (HR = 1.3, CI95% 1.06-1.71, P = 0.015), along with negative estrogen receptor, presence of lymph-vascular invasion and greater tumor size, meaning that the risk of death is increased in 1.3 times for each month of delay, independently of other well established factors. Time from surgery until first adjuvant treatment longer than 4 months was also associated with shorter overall survival (cumulative survival of 80.9% for delay ≤ 4 mo. vs. 72.6% for delay > 4 mo.; P = 0.041, LogRank test). Conclusions: Each month of delay from surgery to first adjuvant treatment worsens progressively overall survival among women with invasive breast cancer, independently of all other well established risk factors. Based on these results we recommend further public strategies in order to decrease interval to adjuvant treatment.
Impact of comorbidity and PSA doubling time on the risk of death in men experiencing PSA failure following radiation therapy with or without androgen deprivation therapy for unfavorable-risk prostate cancer.
Authors: Sagar Anil Patel, Ming-Hui Chen, Marian Loffredo, Andrew A. Renshaw, Philip W. Kantoff, Anthony Victor D'Amico
Journal: Journal of Clinical Oncology (2017)

68 Background: The optimal management of men with PSA failure following initial prostate cancer therapy based on comorbidity is unknown. We investigated the impact that PSA doubling time (DT) and comorbidity had on the risk of all cause (AC), prostate cancer-specific (PCS) and other cause mortality (OCM) following PSA failure. Methods: Between 1995 and 2001, 206 men with unfavorable-risk PC were randomized to receive radiation therapy alone or in combination with 6 months of androgen deprivation therapy (ADT). After a median follow up of 16.2 years, 108 men experienced PSA failure (85, no or minimal; 23, moderate to severe comorbidity) and formed the study cohort. Cox and Fine-Gray regression analysis was used to determine whether PSA DT was associated with the risk of ACM and PCSM/OCM respectively, stratified by ACE-27 comorbidity score. Results: After a median follow up of 13.71 years following PSA failure, 81 of the 108 men (75%) died. Longer PSA DT was associated with a decreased risk of PCSM in men with no/minimal (AHR 0.33, 95% CI 0.17-0.65, p= 0.001) and moderate/severe comorbidity (AHR 0.014, 95% CI 0.002-0.129, p= 0.0002) with a trend toward an increased risk of OCM in men with no/minimal (AHR 1.42, 95% CI 0.94-2.16, p= 0.10) and moderate/severe comorbidity (AHR 1.68, 95% CI 0.85-3.35, p= 0.14). However, increasing PSA DT was only associated with a decreased risk of ACM in men with no/minimal (AHR 0.69, 95% CI 0.50-0.96, p = 0.03) but not moderate/severe comorbidity (AHR 0.95, 95% CI 0.51-1.78, p= 0.87). Conclusions: The extent and natural history of comorbidity as well as PSA DT should be taken into consideration when deciding on appropriate management and/or clinical trial eligibility at the time of PSA failure. Specifically, randomized studies are needed to determine whether survival is prolonged in men with life-shortening comorbidity with salvage ADT at the time of PSA failure versus surveillance and reserving ADT use for symptomatic progression. For all other men, trials comparing ADT with or without novel agents shown to prolong survival in men with metastatic castrate resistant PC is warranted.
Dose adjustment of axitinib based on AUC monitoring in sunitinib-refractory advanced renal cell carcinoma.
Authors: Yuji Miura, Chiyo K. Imamura, Keita Uchino, Takeshi Kishida, Nobuaki Matsubara, Toshiaki Shinojima, Mototsugu Oya, Noboru Nakaigawa, Kenichi Yoshimura, Toshimi Takano, Yusuke Tanigawara
Journal: Journal of Clinical Oncology (2014)

TPS4598 Background: Axitinib is a standard second-line treatment after sunitinib in patients (pts) with metastatic or advanced renal cell carcinoma (RCC). The previous results of pharmacokinetic (PK) and pharmacodynamic (PD) analysis of axitinib showed that higher exposure and diastolic blood pressure (dBP) were independently associated with longer progression free survival (PFS) and overall survival in metastatic RCC pts (Rini et al., J Clin Pharmacol, 2013). These findings support that axitinib dose titration to increase plasma exposure in pts who tolerate axitinib, and also demonstrate dBP as a potential marker of efficacy. In clinical practice, axitinib dose titration based on dBP is recommended; however, it has limitations because underlying hypertension and anti-hypertensive agents usually affect daily dBP. Therefore, we hypothesize that the dose adjustment of axitinib based on its exposure is more adequate than that based on dBP. Methods: A prospective single arm trial is conducted at 6 institutions in Japan. The starting dose of axitinib is 5mg BID and blood samples are taken at 2h, 4h, 8h, and 12h after the first administration to assay axitinib levels and calculate the area under concentration-time curve from 0 to 12 hours (AUC0-12) on day 1. We target AUC0-12 value at the steady state over 150 ng*hr/mL, and suggest a sufficient dose to reach the 150 ng*hr/mL for each patient. After day 15, dose adjustment of axitinib to keep over the target value is performed according to adverse drug reaction for each patient. The primary endpoint is 6-month PFS rate based on axitinib AUC monitoring, and secondary endpoints include toxicity and objective response rate. The target AUC0-12 value in sunitinib-refractory pts is also investigated, because the value of 150 ng*hr/mL is referred from the previous PK/PD analysis in which the first-line treatments were not only sunitinib. Major eligibility criteria include (1) metastatic or advanced clear cell RCC or RCC with clear cell component; (2) previously treated with sunitinib; and (3) disease progression on sunitinib or within 6 months of last dose of sunitinib. Prior treatment with cytokines is permitted. Twelve of planned 32 pts have been enrolled as of February 2014. Clinical trial information: UMIN000009579.
Systematic analysis of potential targets for immunotherapy in acute myeloid leukemia.
Authors: Christopher Simon Hourigan, Meghali Goswami, Nawal Alkharouf, Medha Bhagwat, Heidi May Sardon, Ann L Williams, J. Phillip McCoy, Sawa Ito, Stephen Anthony Strickland, Bipin N. Savani, James W Fraser, Hossein Sadrzadeh, Amir Tahmasb Fathi, Lu Qin, Allan Hess, B Douglas Smith, Judith E. Karp, A. John Barrett
Journal: Journal of Clinical Oncology (2013)

3104 Background: The ability to target myeloid malignancies using immunotherapy, without allogeneic transplantation, depends on the capability to target leukemic clones while sparing normal tissues. A variety of putative leukemia associated antigens (LAA) have been identified but an evidence-based list of targets for acute myeloid leukemia (AML) has not yet been established. Methods: De-identified, clinically annotated, samples of peripheral blood and/or bone marrow aspirate from untreated AML patients were collected under IRB-approved protocols from three NCCN cancer centers. Samples were analyzed for commonly observed somatic mutations in ASXL1, DNMT3A, FLT3, IDH1/2, KIT, NPM1, NRAS, RUNX1, TET2, and WT1. Gene expression of 75 consensus LAAs were determined using a custom-designed RT-PCR array. 12 samples underwent extended LAA analysis by flow sorting into “bulk leukemia” and “stem cell enriched” populations. LAA expression was normalized using the geometric mean of three control genes. Results: Samples from 48 AML patients (30 blood, 22 marrow) were suitable for analysis. Average age of patients was 53 (24-86), 50% were female. Cytogenetics were favorable (17%), intermediate (65%) or adverse (19%); 29% presented with a white blood cell count &gt;50,000. Over 10,000 individual data-points were collected. Five distinct patterns of LAA expression were observed in blood from AML patients compared to healthy donors. Conclusions: Understanding the heterogeneity and patterns of AML LAA expression between individuals allows the rational prioritization of potential targets for immunotherapy. Based on our data we predict that targeting any single LAA will likely often be ineffective but that it may be possible to create an inclusive panel of multiple targets with coverage of most AMLs, eliminating the need for individualized personalization of therapy. Such AML antigen signatures may also have utility for minimal residual disease monitoring. [Table: see text]
Secondary bladder cancer after anticancer therapy for prostate cancer: Reduced comorbidity after androgen-deprivation therapy.
Authors: Masaki Shiota, Akira Yokomizo, Ario Takeuchi, Kenjiro Imada, Keijiro Kiyoshima, Junichi Inokuchi, Katsunori Tatsugami, Saiji Ohga, Katsumasa Nakamura, Hiroshi Honda, Seiji Naito
Journal: Journal of Clinical Oncology (2015)

e16002 Background: Radiotherapy for prostate cancer has been shown to be related to an increased incidence of secondary bladder cancer (BC). This study investigated the incident rate of BC and renal cancer (RC) comorbid with prostate cancer according to radiotherapy, surgical therapy, and androgen-deprivation therapy (ADT), as well as the clinicopathological characteristics and the prognosis of secondary BC. Methods: This study included 1,334 Japanese patients with prostate cancer treated with radiotherapy (n=631), surgical therapy (n=437), and primary ADT (n=266). The comorbidity rate of BC and RC with prostate cancer as well as clinicopathological characteristics and the prognosis of secondary BC were investigated. Results: During the median follow-up period of 51.2, 44.8, and 45.5 months, secondary BC occurred in 14 (2.3%), 5 (1.1%), and 0 (0%) of patients with prostate cancer treated with radiotherapy, surgical therapy, and ADT, respectively. The 10-year BC-free survival rate was 91.3% in the radiotherapy group, 97.4% in the surgical therapy group, and 100% in the ADT group. Only three (0.5%) cases of secondary RC occurred in the radiotherapy group, while none occurred in the surgical therapy or ADT groups. The rates of intravesical recurrence, progression to muscle-invasive BC, and BC-specific death were higher in secondary BC after radiotherapy compared with after surgical therapy. Conclusions: There was a significant difference in the incident rate of secondary BC among different therapeutic modalities for prostate cancer in Japanese men, indicating possible higher and significantly lower comorbidity rates of secondary BC after radiotherapy and ADT for prostate cancer, respectively. Incidence of BC and the temporal relationship with prostate cancer diagnosis. Therapeutical modality n Preceding (n=10) Concurrent (n=20) Subsequent (n=19) Total (n=49) Radiotherapy 631 4 (0.6%) 5 (0.8%) 14 (2.2%) 23 (3.6%) Surgical therapy (without radiotherapy) 437 2 (0.5%) 4 (0.9%) 5 (1.1%) 11 (2.5%) ADT (without radiotherapy) 266 4 (1.5%) 11 (4.1%) 0 (0.0%) 15 (5.6%)
Relapse Following Initial Remission and Subsequent Outcome for Children with Relapsed Acute Myeloid Leukemia on the AAML0531 Phase III Study of Gemtuzumab Ozogamicin: A Report from the Children's Oncology Group
Authors: Todd M Cooper, Robert B. Gerbing, Todd A. Alonzo, Jessica Pollard, Lillian Sung, E. Anders Kolb, Richard Aplenc, Soheil Meshinchi, Alan S. Gamis
Journal: Blood (2016)
Profile of <i>BRCA1/2</i> variants in patients from CEMIC and the University of Buenos Aires including novel findings, deleterious mutations, variants affecting protein function, and recurrent germline mutations.
Authors: Angela Rosaria Solano, Florencia Cecilia Cardoso, Fernando Poletta, Juan Martin Marques, Lina Maria Nunez, Vanesa Romano, Silvia Quiroga, Jorge Lopez Camelo, Ernesto Jorge Podesta, Oscar Gaspar Mandó
Journal: Journal of Clinical Oncology (2015)

e12515 Background: Sequence data related to inherited cancers associated genes is scarce for South America population. Genetic variants of the BRCA1/2 genes, as a result of 15 years of experience in patients with diagnostic and/or family history of breast/ovarian cancer (HBOC) will be depicted. We found novel variants with clinical significance benign, uncertain (UN) and deleterious, surprisingly, even after more than 1700 causal mutations listed in the Breast Cancer Information Core (BIC), that might emphasize our hypothesis about regional variants. Methods: Massive parallel sequencing (Ion Torrent) with Sanger confirmation in DNA samples extracted from blood, analyzing the full coding sequence and 30bp of the introns of the BRCA1/2 genes, this is since two years, before that we performed Sanger sequence. Results: We analyzed 524 patients (including 144 healthy women). We detected near 400 genetic variants including 71 of them novel (30% intronics). Among the 148 mutated patients we detect three recurrent mutations: c.181T > G and c.211A > Gin BRCA1 and c.2808_2811delACAA in BRCA2. We found 24 novel mutations as follows: sixteen (7 in BRCA1 and 9 in BRCA2) are deleterious; eight variants c.4484+3A > G and p.S114C in BRCA1 and p.G173C, c.7426_7428delGAA (in frame deletion), p.D2680N, p.K426T, p.S1106G and p.A2387P in BRCA2 which resulted in either putative altered splicing (the intronic +3 variant and the base change affecting the last base of the exon c.517 C > T at the G173C), or as result of the in silico analysis probably/possibly damaging. Conclusions: a) The few recurrent mutations makes unviable the design of a panel for our population; b) The high number of novel variants reinforces the necessity for the full sequencing and the report of all the variants detected; c) This data will contribute with South American genetic variants enlarging knowledge in worldwide bases that have been (and certainly are), so generous in our development.