tbuckley/cabot-search huggingface dataset:
Referral of high risk breast cancer patients to a certified genetics counselor in a large community hospital.
Authors: Natalie S Berger, Shirin Karimi, Dorothy Wakefield, Anne Wein, Joerg Rathmann, James J. Vredenburgh
Journal: Journal of Clinical Oncology (2015)

e12548 Background: With the identification of BRCA1 and BRCA2 mutations as a genetic cause for hereditary breast cancer (BC), The National Comprehensive Cancer Network (NCCN) has established guidelines for clinicians to assess patients' risk factors for breast and ovarian cancer. Appropriate identification of these patients and subsequent genetics counseling is vital for the patient and their family members in order to understand their risk for developing malignancy. Data has shown that physicians still do not refer all appropriate candidates. Our study aims to establish the percentage of BC patients who are properly referred to genetics counseling at a large inner-city community hospital. Methods: We conducted an IRB approved retrospective chart review, identifying all patients diagnosed with BC in 2012 and 2013 through the tumor registry. We then reviewed charts to see if patients were or were not referred appropriately for genetics counseling based on NCCN guidelines by documentation in the oncologists’ notes. This data was validated using the genetics counselor's database to confirm if the patients were referred, attended counseling, and received results. Statistics were analyzed using SAS 9.2. Results: A total of 369 patients were identified. Of this, 205 qualified for genetics referral, however, only 135 were referred (65.85%). Patients who were younger were more likely to be referred appropriately (p < 0.0001, Mean 53. 6) compared to those who were not referred appropriately (p < 0.0001, Mean 66.2). There was no difference in referral rates among different races. All Ashkenazi Jews were referred appropriately (p 0.01). Of the 135 patients who were referred appropriately, 96 attended counseling (71.11%). Of the 96 who attended counseling, 90 received their results (93.75%). Conclusions: Underutilization of genetic testing remains a significant problem. Younger patients are more likely to be referred for counseling. Certain familial risk factors lead to referrals more frequently than others. The results of this study will lead to an educational program for practitioners in an effort to improve referrals. The study will then be repeated to determine if the educational initiative increases referral rates.
Exposure-response (ER) relationship of regorafenib (REG) in patients with hepatocellular carcinoma (HCC).
Authors: Alexander Solms, Bart Ploeger, Isabel Reinecke, Sabine Fiala-Buskies, Adriaan Cleton, Jordi Bruix, Gerold Meinhardt
Journal: Journal of Clinical Oncology (2017)

374 Background: In the phase 3 RESORCE trial (N = 573), REG (160 mg QD, 3 weeks on/1 week off) significantly (P &lt; 0.001) improved overall survival (OS) versus placebo in patients with HCC who progressed during sorafenib treatment (HR 0.63; 95% CI 0.50‒0.79). This exploratory analysis evaluated the ER relationship between REG and both OS and time-to-progression (TTP). Methods: Exposure estimates were available for 327 and 315 patients for the OS and TTP analysis, respectively. A multivariate Cox proportional hazard analysis was used to evaluate differences between exposure quartiles and efficacy, taking into consideration all preselected baseline covariates. Subsequently, the functional form of the ER relationship within the REG group was evaluated. Results: The baseline risk factors ECOG status, AFP category, and AST/ALT baseline levels were significantly associated with OS (P &lt; 0.01), with higher HRs for ECOG category ≥ 1, AFP levels ≥ 400 ng/mL, and AST/ALT levels &gt; 3 x ULN. For TTP, a significant correlation (P &lt; 0.01) with age was observed, with a higher HR for patients &lt; 65 years of age. After adjusting for these baseline risk factors, the average exposure over the first 28 days grouped in exposure quartiles for REG was significantly associated with OS and TTP (P &lt; 0.01), i.e. the HR in all exposure quartiles was &lt; 1 versus placebo. By contrast, the difference in HR between exposure quartiles was found to be small and not significant. While no statistically significant ER relationship could be identified between (continuous) individual exposure and efficacy in the REG group, the analysis of the functional form of the ER relationship indicates that OS and TTP improved with an increase in exposure, under the assumption of a linear and a non-linear ER relationship. Conclusions: In addition to a significant difference in OS and TTP between REG and placebo, a trend towards improved efficacy was observed with an increase in REG exposure in HCC patients, which was not statistically significant when taking into consideration ECOG status, AFP level, and AST/ALT risk factors (OS) or age (TTP). Therefore, similar efficacy was observed in patients with HCC who started on REG 160 mg QD 3 weeks on/1 week off over the entire exposure range. Clinical trial information: NCT01774344.
A comparison of CR versus CRi response following CPX-351 treatment of newly diagnosed AML in elderly patients (pts).
Authors: Jeffrey E. Lancet, Jorge E. Cortes, Tibor Kovacsovics, Donna Hogge, Jonathan E. Kolitz, Martin S. Tallman, Michael Chiarella, Arthur Chin Louie, Eric Jay Feldman
Journal: Journal of Clinical Oncology (2012)

6601 Background: A Phase 2b study randomized untreated elderly AML pts to CPX-351 or 7+3. CPX-351 improved leukemia clearance (88% v 71%, &lt;5% marrow blasts), CR+CRi rate (67% v 51%), and was particularly effective in pts with adverse karyotype and antecedent hematologic disorders (sAML). Survival following CRi is usually inferior compared to CR. CPX-351 markedly prolongs plasma drug levels and maintains the 5:1 molar ratio for optimal leukemic cell killing potentially delaying hematologic recovery among CRi patients. Consequently, we compared the characteristics and outcomes of pts achieving CR v CRi. Methods: Untreated AML pts, aged 60-75, PS= 0-2, S Cr &lt; 2.0 mg/dL, total bilirubin &lt;2.0 mg/dL, ALT/AST &lt;3 x ULN, and LVEF ≥50% were eligible. Pts were randomized 2:1 to receive up to 2 inductions and 2 consolidations with CPX-351 (100 u/m 2 ; D 1, 3, 5; 90 min infusion) or 7+3 (cytarabine=100 mg/m 2 and daunorubicin=60 mg/m 2 ). Consolidation with stem cell transplantation (SCT) was permitted. The 1 o endpoint was CR+CRi rate. The 7+3 control arm had only a single CRi among 21 responders. The CPX-351 arm had 15 CRi (27%) and 41 CR (73%) allowing a CR v CRi comparison to be made. Results: CR and CRi pts were balanced by age, race, and PS. The CRi group had more males (87% v 51%), more baseline WBC&gt;20K (27% v 15%), and more adverse karyotype (40% v 27%) and sAML (47% v 29%). A smaller proportion of CRi pts received post-remission chemotherapy (47% v 73%) but had similar rates of SCT (13% v 20%). Most CRi pts had delayed platelet recovery (80%). By 1-year more CRi pts had relapsed (54% v 39%) and more had died (54% v 34%). Contributing causes included: relapsed AML (7 CRi v 10 CR pts), complications post SCT (1 CRi v 1 CR pt), chemotherapy complications (0 CRi v 2 CR pts) and unknown causes (0 CRi v 1 CR pt). The survival curves were not significantly different (p=0.39). Conclusions: More CRi patients had adverse karyotype and sAML and most (53%) received no post remission chemotherapy. Survival was not significantly different compared to CR patients but was markedly better than that of non-responders. These data suggest that CRi following CPX-351 provides clinically meaningful benefit, a finding that needs to be confirmed in a larger randomized study.
Incidence and survival of chronic myelomonocytic leukemia (CMML) in the United States (US).
Authors: Guru Subramanian Guru Murthy, Raji Venkitachalam, Vijaya Raj Bhatt, Ishwori Dhakal, Jeanette Y. Lee, Yogesh Jethava, Paulette Mehta, Peter D. Emanuel
Journal: Journal of Clinical Oncology (2015)

e18072 Background: CMML is a rare hematological malignancy with characteristics of both myelodysplastic and myeloproliferative disorders. Population level data about its overall survival (OS) in the recent years is sparse. In this study, we aimed to delineate the characteristics and trends in OS of CMML in the US. Methods: The Surveillance, Epidemiology and End Results (SEER-18) database was used to identify patients with age > 20 years diagnosed with CMML (ICD-O-3 code –9945) between 2000 to 2011. Baseline characteristics were described in frequencies. OS was calculated using Kaplan-Meier method and compared by log rank test. Multivariate analysis was performed using Cox proportional hazard regression method. Results: 3520 patients with CMML had a median age of 76 years (range 22-94). Patient characteristics included age > 60 (89.3%), 62.4% males, 88.4% Whites, 6.2% African Americans and 5.2% other racial groups. About 74.7% patients had primary CMML and 25.3% had secondary CMML. Incidence of CMML has increased from 0.5/100,000 to 0.6/100,000 population from 2000 to 2011. Median OS was worse in patients with age > 60 vs. age < 60 (13 months vs.18 months, p < 0.001), males vs. females (13 months vs. 14 months, p = 0.04) and secondary CMML vs. primary CMML (10 months vs. 14 months, p < 0.001). Median OS did not differ significantly with race (Whites -14 months, African Americans- 8 months and other races -15 months; p = 0.07). We found that OS has improved in patients diagnosed from 2007-2011 as compared to diagnosis from 2000-2006 (Median OS – 15 months vs. 12 months, 2-year OS – 35.7% vs. 32.5%, p < 0.01). On multivariate analysis age > 60 years (HR-1.47, 95% CI 1.29-1.68, p < 0.01) and secondary CMML (as compared to primary CMML, HR-1.20, 95% CI 1.10-1.31, p < 0.01) were significantly associated with higher mortality. Diagnosis from 2007-2011 was associated with lower mortality (HR 0.89, 95% CI 0.82-0.96, P < 0.01). Conclusions: Our data suggests that age > 60 and secondary CMML portend worse prognosis. Although the OS of CMML in US seems to be improving in the era of hypomethylating agents, stem cell transplant and supportive care, its dismal prognosis indicates the need for novel therapies.
Prognostic value of “angiogenic” risk score in early-stage NSCLC.
Authors: Elena Sanmartin, Eloisa Jantus-Lewintre, Rafael Sirera, Jose Javier Sanchez, Marta Usó, Sandra Gallach, Ana Blasco, Cristina Hernando, Nieves Martinez, Santiago Figueroa, Christian Diego Rolfo, Ricardo Guijarro, Miguel Martorell, Carlos Camps
Journal: Journal of Clinical Oncology (2012)

10594 Background: Angiogenesis is a key mechanism in tumor growth and dissemination mainly regulated by VEGF family members. We analyze the expression of 11 angiogenic genes in a cohort of resectable NSCLC patients and correlate them with clinico-pathological variables and prognosis. Methods: RNA was obtained from tumor and normal lung specimens from 175 NSCLC patients. RT-PCR was performed to assess the expression of HIF1-A, PIGF, VEGFA, VEGFB, VEGFC, VEGFD, VEGFR1, VEGFR2, VEGFR3, NRP1 and NRP2. Relative expression was normalized by an endogenous gene (GUS) using the Pfaffl formulae. Differences were considered statistically significant at p&lt;0.05. Results: We found that tumor samples had a significant higher expression of PIGF and lower expression of VEGFD, VEGFR2, and VEGFR3 compared with normal tissue (2.76X, 0.035X, 0.417X and 0.426X, respectively). The group of patients with higher expression levels of VEGFA or PlGF had a significantly reduced TTP (p=0.024 and p=0.027, respectively) and OS (p=0.055 and p=0.048, respectively) whereas those patients with values of VEGFB or VEGFD below the median had reduced TTP (p=0.020 and p=0.135, respectively) and OS (p=0.003 and p=0.089, respectively). The multivariate Cox regression analysis revealed that VEGFA, VEGFB and PlGF were independent prognostic markers for TTP and OS and based on these results we generated an “angiogenic” risk score model. TTP and OS were significantly different among the low, medium and high risk score patients (Table). Conclusions: VEGF family members are master control genes of the angiogenic process and have a crucial role in the prognostic of the disease. We found differences in the expression of four genes between tumor and normal lung samples. An “angiogenic” risk score (based on the expression of PlGF, VEGF-A and VEGF-B) significantly predicts OS and TTP in our cohort of early-stage NSCLC patients. Validation in an independent cohort is needed. Supported by grants PS09-01149 and RD06/0020/1024 from ISCIII. [Table: see text]
Commensal Microbes and Hair Follicle Morphogenesis Coordinately Drive Treg Migration into Neonatal Skin
Authors: Tiffany C. Scharschmidt, Kimberly S. Vasquez, Mariela L. Pauli, Elizabeth G. Leitner, Kevin Chu, Hong-An Truong, Margaret M. Lowe, Robert Sanchez Rodriguez, Niwa Ali, Zoltan G. Laszik, Justin L. Sonnenburg, Sarah E. Millar, Michael D. Rosenblum
Journal: Cell Host & Microbe (2017)
Validating the Lower-Risk MD Anderson Prognostic Scoring System (LR-PSS) and the Revised International Prognostic Scoring System (IPSS-R) for Patients with Myelodysplastic Syndromes
Authors: Mikkael A. Sekeres, Paul Elson, Ramon V. Tiu, Yogen Saunthararajah, Anjali S. Advani, Katarina Paulic, Josephine Chan, Sherry Pierce, Elias Jabbour, Hagop M. Kantarjian, Jaroslaw P. Maciejewski, Guillermo Garcia-Manero
Journal: Blood (2011)
Activity of metronomic capecitabine and bevacizumab combination in patients with relapsed peritoneal pseudomyxoma.
Authors: Claudia Maggi, Filippo G. De Braud, Maria Di Bartolomeo, Federica Perrone, Elena Tamborini, Massimo Milione, Marcello Deraco, Shigeki Kusamura, Dario Baratti, Rosa Berenato, Marta Caporale, Monica Niger, Paola Valentina Consonni, Ilaria Bossi, Pietro Bagnoli, Ermanno Leo, Giuseppe Pelosi, Filippo Pietrantonio
Journal: Journal of Clinical Oncology (2015)

e14707 Background: Standard treatment of peritoneal pseudomyxoma (PMP) is based on cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (HIPEC). The establishment of newer treatments is an unmet clinical need for unresectable or relapsed PMP; modern chemotherapy regimens used in gastrointestinal malignancies may improve outcomes of these patients. The aim of our study was to assess the efficacy and safety of chemotherapy with metronomic capecitabine and bevacizumab in this subset of patients. Materials and Methods: Patients were included in a single center, observational study and treated with metronomic capecitabine at the daily dose of 1300 mg/mq and bevacizumab at the dose of 7,5 mg/Kg every 3 weeks, until progressive disease or unacceptable toxicity. All patients were relapsed after peritonectomy procedures and closed abdomen HIPEC with cisplatin and mitomycin C; six patients received one prior treatment with FOLFOX-4 regimen. Ion Torrent next generation sequencing technology (“Hot-spot Cancer Panel”) was used to obtain molecular data. Results: Fourteen patients were included from February 2014 up today. Four patients are not evaluable for response because the treatment was started too early. Partial response was observed in one patient (10%), progressive disease in one case (10%) while radiological stable disease in all remaining 8 (80%). Treatment was associated with a significant decrease of sierological markers (CEA, Ca19.9, Ca125) in all but one of evaluable patients. Median PFS was 7.3 months, while overall survival data are not mature. Safety data were consistent with the literature. By means of Ion-Torrent, 11 patients are evaluable. GNAS mutations were found in 4 (36%) cases and KRAS mutations in 10 (91%), MGMT promoter methylation was found in 4 (36%). Different rare mutations were found: HNF1A in one case; FGF3 and LKB1mutations in another case. Conclusions: Metronomic capecitabine and bevacizumab combination is tolerable and active in patients with PMP when disease is relapsed after peritonectomy and HIPEC. The identification of predictive biomarkers is a priority for the development of evidence-based treatment strategies for this orphan disease.
Impact of diabetes on site-specific oncologic outcome in stage I-III colorectal cancer.
Authors: Justin Y Jeon, Deok Hyun Jeong, Min Keun Park, Jennifer A. Ligibel, Jeffrey A. Meyerhardt, Nam Kyu Kim
Journal: Journal of Clinical Oncology (2012)

e14114 Background: Background: Conflicting results have been reported whether pre diagnosis diabetes mellitus (DM) influence survival of colorectal cancer patients or not. Therefore, we determine the influence of DM on long-term outcomes of stage 1-3 patients with resected colon and rectal cancer. Methods: This prospective study include a total of 4,131 participants who were treated for cancer between 1995 and 2005 in South Korea in a single hospital (Non DM: 3,614 patients, DM: 517 patients) with average follow up period of 12 years. We analyzed differences in all cause mortality, disease free survival (DFS), recurrence free survival (RFS) and colorectal cancer-specific mortality between colorectal patients with DM and those without DM. Results: After adjustment for potential confounders, pre-diagnosis DM significantly associated with increased all cause mortality (HR: 1.46, 95% CI: 1.11-1.92), and recurrence free survival reduced DFS (HR: 1.45, 95%CI: 1.15-1.84) and RFS (HR: 1.32, 95% CI: 0.98-1.76) in colon cancer patients but not in rectal cancer patients. In colon cancer patients, DM negatively affects the survival outcome of proximal colon cancer (HR: 2.08, 95%CI: 1.38-3.13), but not of distal cancer (HR:1.34, 95% CI: 0.92-1.96). Conclusions: To our knowledge, the current study first reported the effects of pre-diagnosis DM on survival outcome of colorectal cancer are site specific (proximal colon, distal colon and rectum). The current study was supported by the National Research Foundation of Korea (KRF) (No. 2011-0004892) and the National R&amp;D Program for Cancer Control, Ministry of Health &amp; Welfare, Republic of Korea (1120230). [Table: see text]
International prevalence of nonmetastatic (M0) castration-resistant prostate cancer (CRPC).
Authors: Alexander Liede, Jorge Arellano, Guy Hechmati, Brian Bennett, Steven Wong
Journal: Journal of Clinical Oncology (2013)

e16052 Background: CRPC represents a growing public health concern that has not been adequately quantified. In the absence of metastases, CRPC represents a transitional disease state defined by increases in prostate specific antigen (PSA) despite castration levels of androgens during androgen deprivation therapy (ADT). We developed a model to estimate M0 CRPC prevalence in selected countries. Methods: A patient-flow model was developed to estimate 5-year limited duration prevalence of prostate cancer (PC) and M0 PC in each country, each year (2008 to 2028) using age-specific incidence and survival data from population cancer registries from 28 countries in North (US, Canada, Mexico) and South America (Brazil), Europe (18 countries), Asia (5 countries), and Australia. The proportion of men with M0 PC treated with ADT was based on literature reports and survey research with physicians treating PC. PSA relapse rates from published literature were used to estimate CRPC among ADT treated. Results: PC prevalence is driven by size and aging of populations, with notable increases predicted within 15 years in regions other than US, Canada, and EU5 (table). The prevalence model, which utilized country-level data, indicates that M0 CRPC represents a relatively small proportion (2-8%) of the total PC population. Nonetheless, widespread screening and demographic changes dictate that the prevalence of CRPC will increase over the next 15 years, assuming current ADT rates. Conclusions: Incidence trends in PC are dependent on PSA screening, which is projected to lead to an increase in M0 PC and PC prevalence in most regions. The number of men treated with ADT and who ultimately develop CRPC will increase accordingly, as demonstrated in the model. [Table: see text]
Telling patients there is nothing wrong
Authors: L. Howard
Journal: BMJ (1996)

Telling patients there is nothing wrong Randomised controlled trials are needed EDrroR,-It is still unclear from the literature whether investigative tests reassure patients with anxieties about the presence of serious disease.' 2 Ray Fitzpatrick discusses some of the possible reasons for this, including psychiatric morbidity, poor communication, and the "wild card effects" mentioned in the study by I G McDonald and colleagues.3Other psychological processes in patients are
Phase 1b study of orteronel in postmenopausal women with hormone-receptor positive (HR+) metastatic breast cancer.
Authors: Murtuza M. Rampurwala, Mark E. Burkard, Kari Braun Wisinski, Sima Ehsani Chimeh, Jamie Zeal, Tamara Koehn, Torie L Champeny, Joan Rettig, KyungMann Kim, Jill Kolesar, Amye Tevaarwerk
Journal: Journal of Clinical Oncology (2014)

538 Background: Endocrine therapies are the treatment of choice for HR+ metastatic breast cancer; novel drugs are needed due to resistance. Reducing both androgens and estrogens may circumvent resistance by reducing androgen receptor stimulation. Orteronel is a selective, reversible, nonsteroidal inhibitor of the 17, 20-lyase enzyme (which generates androgens and estrogens). We conducted a phase 1b study of orteronel in HR+ metastatic breast cancer; the primary objective was the recommended phase 2 dose (RP2D) of orteronel in women. Methods: Key inclusion criteria were postmenopausal status and evaluable or measurable HR+ metastatic breast cancer. Doses escalated via standard 3+3 design. Initial dose was 300 mg BID and escalated to 400 mg BID (the RP2D in men). Cycle length was 28 days. Patients were evaluated every 8 weeks for progression. Correlative studies assessing hormone levels via liquid chromatography-mass spectrometry were performed. Results: Seven patients enrolled (median 56 yo, range 47-71). Patients were heavily pre-treated: 6 had prior endocrine therapy for metastatic cancer (median 4 lines, range 0-5) and 5 had prior chemotherapy regimens for metastatic cancer (median 2, range 0-5). Four received 300 mg BID at dose level 1 (1 was not evaluable per protocol); 3 received 400 mg BID at dose level 2. Orteronel was well tolerated: no dose limiting toxicities were observed. Common adverse events at least possibly related to therapy were: grade 1 hot flashes (28%), grade 1-2 nausea (28%), grade 1 hypokalemia (28%), and grade 1 elevated AST (28%). 6 patients received 14 cycles of treatment. 2 patients remain on therapy with evidence of clinical benefit: 1 with stable disease for > 6 months (best response) and 1 with stable disease for 3 months. Conclusions: Orteronel 400 mg BID is well tolerated in post-menopausal women, and significantly suppresses serum estrogens and testosterone. Clinical benefit was seen among heavily pretreated patients. Clinical trial information: NCT01808040.Mean levels ± standard deviation prior to and after orteronel. Cycle 1, day 1 (n=7) Cycle 2, day 1 (n=6) Cycle 3, day 1 (n=4) Estradiol (pg/ml) 6.2 ± 5.6 4.9 ± 4.4 0.5 ± 1 Estrone (pg/ml) 24.4 ± 12.8 2.7 ± 3.6 5.2 ± 6.4 Testosterone (pg/ml) 131.7 ± 102.9 7.3 ± 9 13.4 ± 25.5
Distinct Immunogenetic Signatures in IgA Versus IgG Multiple Myeloma
Authors: Katerina Gemenetzi, Andreas Agathangelidis, Apostolia Papalexandri, Alejandro Medina, Elisa Genuardi, Theodoros Moysiadis, Evdoxia Hatjiharissi, Maria Papaioannou, Evangelos Terpos, Cristina Jimenez, Chrysavgi Lalayanni, Achilles Anagnostopoulos, Simone Ferrero, Marco Ladetto, Ramon Garcia Sanz, Chrysoula Belessi, Anastasia Hadzidimitriou, Kostas Stamatopoulos
Journal: Blood (2016)