tbuckley/cabot-search huggingface dataset:
Changes in tumor burden and IMDC class after active surveillance (AS) for metastatic renal cell carcinoma (mRCC).
Authors: Davide Bimbatti, Teodoro Sava, Francesco Massari, Chiara Ciccarese, Emanuela Fantinel, Alberto Dalla Volta, Walter Artibani, Giampaolo Tortora, Roberto Iacovelli
Journal: Journal of Clinical Oncology (2017)

435 Background: Targeted therapies (TT) improved survival in mRCC but treatment-related toxicities may worsen quality of life and lead to treatment discontinuation. AS is a feasible strategy in pts with indolent disease but effects on tumor burden (TB) and prognosis have not been investigated. Methods: In this retrospective study we included pts who received AS at our centre. The TB, defined as the number of sites of disease, was collected with the IMDC class, just before and after AS. The time on surveillance (ToS) was defined as the time from the start of AS to the beginning of therapy or last follow-up. The OSs were collected from the start of AS or TT. Results: 48 pts started AS from January 2007 to April 2016. After a median follow up of 37.3 months, 79.2% are still alive. At baseline the main sites of metastases were: lung (56%), nodes (25%), pancreas (14%), adrenal gland (8%), CNS (8%), and bone (6%). TB was one site in 65 %, two in 31%, and &gt;2 sites in 4%. The IMDC prognostic class was favorable in 68,8%, intermediate in 25%, and poor in 6.3% of pts. After a median ToS of 16.7 months (95% CI 9.6-23.7), 34 patients (70.8%) started a TT, only 1/24 patient had progression as the best response. Significant difference in ToS were found where pts with good (19.9 mos) or intermediate (17.7 mos) class were compared to the poor group (5.2 months) (p&lt;0.04). At the beginning of TT, the main sites of metastases were: lung (71%), nodes (44%), bone (15%), adrenal gland (15%), pancreas (15%), and CNS (9%). The TB was one site in 35%, two in 47%, and &gt;2 sites in 18%; and 14 pts had new sites of disease. The IMDC class changed in four patients from good to intermediate. The median OSs was not reached from the start of surveillance and was 64.4 months from the start of TT. Conclusions: AS is an option for management of mRCC pts with good and intermediate prognosis. AS allows to delay the start of TT avoiding toxicity and worsening quality of life. Despite the fact pts in AS have increased TB and rarely a worsening of prognostic class, the survival remains longer and the effectiveness of subsequent therapy seems not to be affected.
Long telomeres protect against age-dependent cardiac disease caused by NOTCH1 haploinsufficiency
Authors: Christina V. Theodoris, Foteini Mourkioti, Yu Huang, Sanjeev S. Ranade, Lei Liu, Helen M. Blau, Deepak Srivastava
Journal: Journal of Clinical Investigation (2017)

Diseases caused by gene haploinsufficiency in humans commonly lack a phenotype in mice that are heterozygous for the orthologous factor, impeding the study of complex phenotypes and critically limiting the discovery of therapeutics. Laboratory mice have longer telomeres relative to humans, potentially protecting against age-related disease caused by haploinsufficiency. Here, we demonstrate that telomere shortening in NOTCH1-haploinsufficient mice is sufficient to elicit age-dependent cardiovascular disease involving premature calcification of the aortic valve, a phenotype that closely mimics human disease caused by NOTCH1 haploinsufficiency. Furthermore, progressive telomere shortening correlated with severity of disease, causing cardiac valve and septal disease in the neonate that was similar to the range of valve disease observed within human families. Genes that were dysregulated due to NOTCH1 haploinsufficiency in mice with shortened telomeres were concordant with proosteoblast and proinflammatory gene network alterations in human NOTCH1 heterozygous endothelial cells. These dysregulated genes were enriched for telomere-contacting promoters, suggesting a potential mechanism for telomere-dependent regulation of homeostatic gene expression. These findings reveal a critical role for telomere length in a mouse model of age-dependent human disease and provide an in vivo model in which to test therapeutic candidates targeting the progression of aortic valve disease.
Biomarkers of amenorrhea and ovarian function in breast cancer survivors.
Authors: Kathryn Jean Ruddy, Shari Gelber, Rulla M. Tamimi, Elizabeth S Ginsburg, Lidia Schapira, Steven E. Come, Meghan E Meyer, Eric Winer, Ann H. Partridge
Journal: Journal of Clinical Oncology (2012)

9071 Background: Ovarian function after treatment of early breast cancer may affect fertility, menopausal symptoms, endocrine therapy decision-making, and subsequent health and psychosocial concerns among young survivors. We aim to improve understanding of ovarian reserve in women with a history of breast cancer by comparing anti-mullerian hormone (AMH), estradiol (E2), and follicle-stimulating hormone (FSH) levels in survivors with and without amenorrhea, a surrogate for ovarian dysfunction and menopause. Methods: As part of an ongoing prospective multi-center cohort study, women diagnosed with breast cancer at age &lt;41 have blood and surveys collected one year after diagnosis. Women who reported that they were receiving ovarian suppression or had undergone hysterectomy or bilateral oophorectomy/ovarian ablation were excluded. Amenorrhea was defined as &gt;6 months between blood draw and last menstrual period. AMH, E2, and FSH levels were compared between those with and without amenorrhea using a Wilcoxon rank sum test with 2-sided p-values. Results: The first 199 eligible women with blood and survey data at one year were included in this analysis. Median age was 37 years (range 22-40). Seventy-two(36%) had received chemotherapy alone, 75 (38%) had received chemotherapy followed by tamoxifen (TAM), 25 (13%) had received TAM alone, and 10 (5%) reported TAM use but did not respond to chemotherapy items. Median AMH and E2 were lower and FSH was higher in women with amenorrhea, and these differences remained significant when those on and off TAM were analyzed separately (Table). Conclusions: AMH, E2, and FSH all are promising biomarkers for amenorrhea and residual ovarian function in young breast cancer survivors. Future research will evaluate whether AMH, E2, and FSH at baseline and early in the survivorship period predict ovarian function later. [Table: see text]
Continuation of EGFR/ALK inhibition after local therapy of oligoprogressive disease in EGFR mutant (Mt) and ALK+ non-small cell lung cancer (NSCLC).
Authors: Andrew James Weickhardt, Benjamin Scheier, Joseph Malachy Burke, Gregory Gan, Robert Charles Doebele, Paul A. Bunn, Laurie E. Gaspar, Brian D. Kavanagh, D. Ross Camidge
Journal: Journal of Clinical Oncology (2012)

7526 Background: This study aimed to investigate the benefits of local treatment of limited disease progression and continuation of crizotinib (C) or EGFR-TKI in patients with ALK+ or EGFR-Mt metastatic NSCLC, respectively. Methods: Patients with advanced ALK+ NSCLC treated with C (n=38) and EGFR-Mt NSCLC treated with EGFR TKIs (erlotinib or gefitinib) (n=27) were identified. Patients were evaluated for initial response, site of first progression (CNS or extra CNS (eCNS)) and median progression free survival (PFS1). A subset of patients with limited sites of progression (oligoprogressive disease) suitable for local therapy received either radiation or surgery to these sites and continued on the same TKI. The subsequent pattern of progression and median progression free survival from the time of first progression (PFS2) were recorded. Results: In 38 ALK+ patients, PFS1=9.0 months on C. In 27 EGFR-Mt patients, PFS1=13.8 months on EGFR-TKI. CNS was the first site of progression in 13/28 (46%) of ALK+ patients and 5/23 (22%) EGFR-Mt patients. 25 of 51 patients who progressed (49%) were deemed suitable for local therapy (15 ALK+, 10 EGFR-Mt; 24 with radiotherapy (Body: 3 XRT, 9 SBRT; CNS: 7 WBRT, 5 SRS), 1 with surgery (adrenalectomy)) and continuation of the same targeted therapy. 19/25 patients progressed post local therapy, median PFS2 = 6.2 months. In patients who progressed at PFS1 only in the CNS, there was a trend to longer PFS2 than patients who progressed at PFS1 in eCNS (7.1 months vs 4.0 months, p=0.26). 60% who progressed only in the CNS at PFS1, progressed eCNS at PFS2 (n=10). Conclusions: Progression of oncogene addicted NSCLC on relevant targeted therapies is often suitable for local therapy (oligoprogressive disease). Continuation of the targeted therapy following local therapy is associated with &gt;6 months of additional disease control. [Table: see text]
Bevacizumab plus irinotecan in patients with recurrent high grade malignant gliomas.
Authors: Jairo Legaspi, Lucia Ceniceros, Jaime Espinós, German Valtueña, Patricia Martin, Eduardo Castanon Alvarez, Javier Aristu, Iosune Baraibar, Diego Salas, Pablo Sala, Itziar Gardeazabal, Leyre Zubiri Oteiza, Alicia Olarte, Ignacio Gil-Bazo, Pablo Dominguez, Juan Pablo Fusco, Maria Isabel Martinez, Jose M. Aramendia, Oscar Fernández-Hidalgo, Marta Santisteban
Journal: Journal of Clinical Oncology (2015)

e13057 Background: Recurrent high grade malignant gliomas (MGs) have a short survival. Initial standard therapy is based on surgery followed by concurrent radiotherapy with Temozolomide (TMZ) and subsequent TMZ, however most patients relapse from their disease. On 2009, the FDA accelerated the approval of humanized IgG1 monoclonal antibody against VEGF bevacizumab as a single agent for patients (pts) with progressive MG following prior therapy, supported by durable objetive response rates. Further studies demonstrated an increased response rate (RR) and PFS with the addition of Irinotecan to Bevacizumab (I+B). Methods: We retrospectively analyzed 62 pts with recurrent MG treated in our hospital with Irinotecan plus Bevacizumab. Pts received Irinotecan 150 mg/m2 and Bevacizumab 10 mg/m2 every two weeks. Study endpoints were safety, RR and survival. Toxicity was scored according to NCI-CTC v4.0. Results: Sixty-two pts were included with a median 54 years old (range: 18-76). 75.8 % of them have the diagnosis of glioblastoma and 24.2% WHO grade 3 gliomas. Regarding the intake of enzyme-inducing antiepileptic drugs (EIAEDs), 10% of the patients; 40% were on non-EIAED and 50% have no needed for AED. Half of the pts were on dexamethasone by the beginning of the schedule (52%). Most of the pts have a good performance status (ECOG 0-2 in 89% versus ECOG 3-4 in 11%). 54 patients (87%) got standard treatment, but 8 (13%) received one more chemotherapy regimen before I+B. Fifty patients were evaluated for response: complete response (CR) was observed in 2 patients (4%), partial response (PR) in 17 (34%), stable disease (SD) over 4 months in 21 pts (42%) and progression in 10 pts (20%). Clinical benefit (CR+PR+SD) was seen in 40 patients (80%). We reported 2 severe toxicities (1 septic death due to a bowel perforation and 1 grade 3 pulmonary embolia) and 39 pts with mild toxicity (grade 1-2) (26% hypertransaminasemmia, 24% asthenia, 21% neutropenia, 8% high-blood pressure, and 6% with diarrhea). Since the start of I+B, median PFS was 9.14 m (95% CI: 6.26-12.02) and median Overall Survival was 13.84 m (95% CI: 9.58-18.10). Conclusions: Irinotecan plus Bevacizumab can be a good option in recurrent MGs with acceptable toxicity and a good outcome.
Anaerobic Bacterial Fermentation Products Increase Tuberculosis Risk in Antiretroviral-Drug-Treated HIV Patients
Authors: Leopoldo N. Segal, Jose C. Clemente, Yonghua Li, Chunhai Ruan, Jane Cao, Mauricio Danckers, Alison Morris, Sarah Tapyrik, Benjamin G. Wu, Philip Diaz, Gregory Calligaro, Rodney Dawson, Richard N. van Zyl-Smit, Keertan Dheda, William N. Rom, Michael D. Weiden
Journal: Cell Host & Microbe (2017)
Out-of-pockets costs for patients receiving targeted agents for metastatic renal cell carcinoma.
Authors: Simon P. Kim, Cary Gross, Robert Abouassaly, Sarah P. Psutka, Holly K. Van Houten, Robert Houston Thompson, Marc C. Smaldone, Quoc-Dien D Trinh, Maxine Sun, Leona C Han, Nilay Shah
Journal: Journal of Clinical Oncology (2014)

e15598 Background: Although targeted agents have drastically changed clinical practice for metastatic renal cell carcinoma (mRCC), the variations in out-of-pocket costs for these expensive agents remain poorly described. To address this, we sought to assess the economic burden from out-of-pocket costs for oral targeted agents among mRCC patients. Methods: Using outpatient and inpatient claims from a large private health insurance database, we identified all patients who were diagnosed with mRCC and received oral targeted agents (Sunitinib, Sorafenib, or Pazopanib) within six months of diagnosis from 2004 to 2010 in the U.S. The primary outcome was out-of-pocket costs at six months, which were ascertained from the difference of total costs and amount reimbursed for each specific oral targeted agent, adjusted to 2010 U.S. dollars. General estimated equations were used to determine the mean out-of-pocket costs adjusting for patient age, gender, Elixhauser comorbidity index, and geographic region. Results: Among 566 patients diagnosed with mRCC, 433 (77%), 159 (28%) and 18 (3%) mRCC patients received Sunitnib, Sorafenib, and Pazopinib, respectively. Additionally, 135 (23%) patients underwent cytoreductive nephrectomy. Overall, the mean out-of-pocket costs for mRCC patients at six months for all oral targeted agents were $1,341 (SE: $250). On multivariable analysis, there was significant variation in the adjusted mean out-of-pocket costs at six months for Sunitinib ($1,354 {SE: $307}), Sorafenib ($1,350 {SE: $242}), and Pazopanib ($555 {SE: $151}). Conclusions: Patients diagnosed with mRCC experienced high out-of-pocket costs for oral targeted agents from 2004 to 2010. Our findings have important implications since patients are becoming increasingly responsible for higher deductibles. High out-of-pocket costs may make the availability of targeted agents difficult, or possibly introduce economic harm for mRCC patients.
Fertility preservation in children newly diagnosed with cancer: Existing standards of practice in Australia and New Zealand
Authors: J. A. Heath, C. J. Stern
Journal: Journal of Clinical Oncology (2006)

9047 Background: Over the past two decades, rapid advances have occurred in both the successful treatment of childhood cancers and reproductive medicine. We sought to establish the current level of clinical practice for sperm, oocyte and gonadal tissue collection and storage in children newly diagnosed with cancer in Australia and New Zealand (ANZ). Methods: A cross-sectional survey of all pediatric oncology services in ANZ was performed. Comparisons to recently published North American practices and to current recommendations for best practice were also made. Results: Of the 13 centers invited to participate, 12 (92%) completed the survey. All centers had offered sperm conservation, but only ten (83%) had offered oocyte/ovarian tissue conservation. Available methods of gamete collection and storage were not consistent. Two centers were using GnRH agonists as fertility protection in post-pubertal females. Forty-two per cent had offered fertility conservation to males and females prior to completion of sexual development. All centers were more likely to offer sperm conservation than oocyte conservation for any given disease. The most common diseases for which conservation was offered were lymphomas and sarcomas. The anticipated cumulative dose at which centers elected to offer fertility preservation varied widely, both for the alkylator cyclophosphamide (1g/m 2 to 10g/m 2 ) and for abdominal/pelvic irradiation (any to 12 Gy) and spinal irradiation (any to 18Gy). Fertility counseling was offered in a variety of settings by 82% of centers. Despite 92% of centers agreeing that fertility preservation guidelines would be helpful, only two (17%) had any in place. Overall, there was greater uptake and consistency of utilization of fertility services in ANZ when compared with published North American data. Conclusions: There are inconsistencies regarding the indications for and methods of gamete conservation in pediatric oncology centers throughout ANZ. Unresolved medical, legal and ethical issues suggest the development of guidelines and a voluntary code of practice would be helpful. No significant financial relationships to disclose.
Contents Vol. 69, 2000
Authors: Giovanni A. Fava, Fedra Ottolini, Ulrich Schnyder, Stefan Büchi, Tom Sensky, Richard Klaghofer, G.N. Meldolesi, A. Picardi, E. Accivile, R. Toraldo di Francia, M. Biondi, Kirsi Honkalampi, Jukka Hintikka, Pirjo Saarinen, Johannes Lehtonen, Heimo Viinamäki, Luigi Grassi, Katia Magnani, Valdo Ricca, Edoardo Mannucci, Teresa Zucchi, Carlo M. Rotella, Carlo Faravelli, Moshe Kotler, Hagit Cohen, Dov Aizenberg, Mike Matar, Uri Loewenthal, Zeev Kaplan, Hanoch Miodownik, Zvi Zemishlany, Caterina Novara, Salvatore Casari, Silvia Compostella, Stella Dorz, Ezio Sanavio, Claudio Sica, M. Balestrieri, B. Nacmias, S. Sorbi, G. Marcon, M.G. Carta, W. Orrù, M.C. Hardoy, B. Carpiniello
Journal: Psychotherapy and Psychosomatics (2000)
Awareness of HPV and its vaccine among lesbian, gay, bisexual, transgender, and queer (LGBTQ) populations.
Authors: Caroline Ong, Joel Winer, Liz Margolies, Feng Dai, Eric Patridge, Anees B. Chagpar
Journal: Journal of Clinical Oncology (2013)

e17597 Background: HPV is a sexually transmitted virus that is known to cause of a number of malignancies, including anorectal and oral cancers. However, there is a paucity of data regarding the knowledge of HPV and its now FDA-approved vaccine amongst LGBTQ populations. We sought to compare awareness of HPV and the vaccine in an LGBTQ sample to the general population. Methods: An anonymous electronic survey was conducted through well-known LGBTQ organizations. The survey was designed to replicate verbatim questions regarding HPV fielded in the 2010 National Health Interview Survey (NHIS) Cancer Supplement. Data from the LGBTQ survey was compared to the nationally representative population surveyed in the NHIS. Results: A total of 323 LGBTQ people responded to the survey; 148 were female (90 lesbian, 25 bisexual, and 33 queer/other), 158 were male (141 gay, 5 bisexual and 12 queer/other), 13 were transgender and 4 identified themselves as other/queer in gender. The median age of the cohort was 34.4 (range; 16-74). Of this population, 297 (92.0%) had heard about HPV (vs. 61.5% in the general population in NHIS). Both LGBQ men and women were equally likely to have heard about HPV (92.4% and 91.3%, respectively), whereas knowledge regarding HPV was more disparate between men and women in the general population (47.2% and 75.6%, respectively). Of the 11 transgender people who responded to the questions regarding HPV, all had heard about the virus. 88.5% of the LGBTQ cohort had heard about the vaccine; compared to 51.3% in the general population in NHIS. Again, there was less of a gap in knowledge between men and women in the LGBQ community (90.6% and 87.3%, respectively) than there was in the general population (68.1% and 34.0%, respectively). 10 of the 11 transgendered people who responded to questions regarding HPV (90.9%) were aware of the HPV vaccine. Conclusions: The LGBTQ community appears well-educated regarding HPV and its vaccine, compared to the general population. These findings are gratifying given the potential increase in risk of HPV-related malignancies in these populations, but further work is needed to explore whether this increased awareness translates into increased HPV-vaccination rates.
The efficacy and safety in elderly patients with advanced renal cell carcinoma: Real-world use of sorafenib in Japan.
Authors: Katsunori Tatsugami, Mototsugu Oya, Koki Kabu, Hideyuki Akaza
Journal: Journal of Clinical Oncology (2017)

476 Background: Multiple treatment options are available for patients with advanced renal cell carcinoma (RCC). However, the safety and efficacy data of these agents in elderly patients are limited. In this study, the data, which prospectively collected practical use of sorafenib amongst all RCC patients as a nationwide post-marketing surveillance, were analyzed using propensity-matched cohorts. Methods: A total of 3,255 patients with advanced RCC were enrolled and 772 patients selected by propensity score were matched for &lt;75 (n=386) and ≥75 year old patients (n=386). Progression free survival (PFS), tumor response, adverse events (AEs), doses of sorafenib, and estimated glomerular filtration rate (eGFR) were analyzed. Results: The median PFS in &lt;75 and ≥75 year old patients was 233 days (194, 274) vs. 219 days (190, 263), respectively. The mean starting dose (702 mg vs. 688 mg) and median treatment duration (222 days vs. 175 days) were similar in two groups, but mean dose intensity (70.3% vs. 61.4%, p&lt;0.001) was lower in ≥75 year old patients than that in &lt;75 year old patients. Complete response rates were 0.9% and 3.7%, partial response rates were 27.9% and 27.1%, stable disease rates were 58.4% and 55.6%, progressive disease rates were 12.8% and 12.8% in &lt;75 and ≥75 year old patients, respectively. Objective response rate (CR+PR) was comparable in both groups (28.8% and 30.8%). Safety was analyzed for 772 patients, and any grade AEs observed ≥20% were hand-foot skin reaction (HFSR) (55.8%), hypertension (36.7%), rash (27.4%), and increase in lipase / amylase (26.2%), and diarrhea (21.8%). The common serious AEs were rash (7.4%), HFSR (6.0%), hepatic dysfunction (5.6%), cytopenia (4.9%), and hypertension (2.8%). The incidence of these common AEs was similar between the two groups. The discontinuation due to AE and drug related death rates were 65.3% vs. 74.9% (p&lt;0.01) and 3.4% vs. 4.9% in &lt;75 and ≥75 year old patients, respectively. In both groups, the eGFR value did not change from the baseline, and even slightly increased after 12 months of sorafenib treatment. Conclusions: This study indicated that sorafenib provides clinical benefits and is tolerable amongst patients with advanced RCC regardless of age.