bluuebunny/crossref_metadata_2025_split huggingface dataset:
Caring for Alaska native prostate cancer survivors in primary care: A survey of Alaska Tribal Health System providers.
Authors: Tilburt Jon C. , Kim Simon P. , Kelley Stacey , James Katherine , DeCourtney Christine , Marino Gregory , McCormick Lynn 
Published: March 2020

6126 Background: Little is known about the actual constraints of doing so in the distinctive geographic context of Alaska. We performed a survey of primary care providers (PCPs) within the Alaska Tribal Health System (ATHS) to learn more about their attitudes and practices surrounding prostate cancer (PC) survivorship care. Methods: We surveyed primary care physicians, nurse practitioners, and physician assistants practicing in the ATHS. We administered surveys to assess attitudes about PSA monitoring, responsibility for long-term surveillance, supporting emotional health and medical needs, their degree of confidence in managing patients on androgen deprivation therapy (ADT), as well as their comfort level in managing common side effects of treatment. Results: Of the 221 providers surveyed, 114 responded (52%). Most PCPs indicated a preference for annual PSA monitoring (69%), but several (27%) indicated monitoring every 6 months, and a few (4%) indicated monitoring every 24 months. Most (60%) thought PCPs should manage cancer surveillance, but many (40%) thought a specialist (urologist or medical oncologist) should perform that function. When asked about supporting patients’ emotional needs, PCPs indicated that support groups (63%) followed by survivorship clinics (16%) or on-site specialist visits (14%) were the most appropriate venues to address these concerns. Most respondents thought that medical needs of PC survivors could be addressed locally with appropriate specialty input (71%) or potentially through dedicated survivorship clinics (14%). Only 46% indicated being "moderately" or "very" confident managing ADT. Most PCPs indicated being moderately or very comfortable monitoring for recurrence (59%), managing erectile dysfunction (66%), addressing urinary incontinence (63%), and addressing emotional needs (61%). Conclusions: PCPs practicing in the ATHS express comfort with monitoring for PC recurrence, but express some concerns about the full range of issues in PC survivorship. Constructing cancer survivor care models in geographically dispersed and resource-limited contexts for Alaska Natives is an ongoing clinical and policy challenge.
Sociodemographic and patient disparities in use of first-line chemotherapy (CT) in older adult patients (pts) with advanced non-small cell lung cancer (AdvNSCLC): Analysis of Surveillance, Epidemiology, and End Results (SEER)-Medicare data.
Authors: Feliciano Josephine Louella , Gardner Lisa , Edelman Martin J. , Davidoff Amy J. 
Published: March 2020

6131 Background: Clinical trials have demonstrated that CT improves survival and quality of life in pts with AdvNSCLC. Our prior studies suggest that only 26% of older pts diagnosed with AdvNSCLC received CT through 2002. In this study, we examined more recent patterns, and the effect of socio-demographics, race, and age on receipt of CT in older pts with AdvNSCLC. Methods: Medicare pts diagnosed with AdvNSCLC from 2001-2005 were identified in SEER registries. Medicare enrollment data provided demographic information (age, race, sex, marital status), augmented with census tract level data on median household income. Comorbid conditions at baseline were identified by ICD9-CM diagnoses on claims. Receipt of 1st line CT was identified based on agent-specific procedure codes in claims. Logistic regression examined predictors of 1st line CT. Results: Of 31,341 pts with Adv NSCLC, 34% received 1st line CT. As reflected in the table, poor predicted PS (PredPS), multiple medical comorbidities, and black race were associated with lower likelihood of CT receipt. Being female, married, having higher income, and being diagnosed at a later year were associated with a higher likelihood of receiving CT. Conclusions: Even when controlling for factors such as PS, our results suggest the presence of age, race, and socio-economic disparities in the receipt of 1st line CT for older patients with AdvNSCLC. [Table: see text]
Predictors of retention in a cervical cancer survivorship study.
Authors: Wenzel Lari B. , Osann Kathryn , Hsieh Susie , Sappington Sandra , Marquez Diana , Chase Dana Meredith , Nelson Edward L. 
Published: March 2020

6132 Background: Women with cervical cancer experience numerous quality of life (QOL) disruptions. A completed pilot study indicated that QOL and key biomarkers could be improved with psychosocial telephone counseling (PTC). A confirmatory trial has recently completed accrual.The purpose of this study is to identify predictors of retention in this large biobehavioral trial, and examine retention differences between the pilot and confirmatory trial. Methods: Women with stage I – III cervical cancer diagnosed 9 – 30 months earlier were randomized to either PTC or usual care. PROs and biological specimens were collected prior to randomization (N=204), and 3 (T2) and 9 months post baseline. Sociodemographic, clinical and QOL variables were evaluated from baseline to T2 to identify predictors of study retention. Multiple measures, including the PROMIS Depression and Anxiety scales were entered into a multivariate stepwise logistic regression model to predict study retention. Results: In the multivariate model, being randomized to counseling (OR=4.4, 95% CI: 1.5-12.6), having clinically significant depression, defined as >1 SD above the 50th percentile (OR=4.2, 95% CI:1.7-10.5) and being single (OR=3.4, 95% CI: 1.3-9.2) were the most significant predictors of drop-out in the study overall. Among those in the counseling arm, depression is the strongest predictor of dropout, with a five times higher dropout rate (OR=5.2, 95% CI:1.9-15.6) than those with low to moderate levels of depression, or no depression. However, retention rates improved substantially overall from the pilot study (72%) to the confirmatory study (84%), in both study arms, and retention increased among Latinas from 60% in the pilot study to 83% in the current study, and from 52% to 81% among those with less than a high school education. Conclusions: Results from this analysis of predictors of retention indicate that enhanced attention to sociocultural disparities can improve study retention. Attending to baseline clinical depression may be a further consideration.
Phase I/II trial of primary chemotherapy with nonpegylated liposomal doxorubicin, paclitaxel, and lapatinib in patients with HER2-positive, early-stage breast cancer.
Authors: Kuemmel Sherko , Aktas Bahriye , Krocker Jutta , Elling Dirk , Lantzsch Tilmann , Bischoff Joachim , Fersis Nikos , Boehme Michael , Belau Antje , Lampe Dieter , Schmid Peter 
Published: March 2020

624 Background: Combinations of trastuzumab and anthracyclines in HER2-positive breast cancer are highly active but associated with a high incidence of cardiotoxicity. The risk of cardiac damage can be significantly reduced through liposomal encapsulation of anthracyclines. This phase I/II study was initiated to evaluate the combination of non-pegylated liposomal doxorubicin (NPLD), paclitaxel and lapatinib as primary treatment for patients with early stage, HER2-positive primary breast cancer. Methods: Patients with newly diagnosed HER2-positive (IHC 3+ or FISH+) early stage (T1c N1-2 or T2 N0-2) breast cancer were treated with NPLD (60mg/m2; day 1), paclitaxel (175mg/m2, day 1) and lapatinib (750-1500 mg orally daily) in 3-week intervals for up to 6 cycles. The primary endpoints were dose-limiting toxicities (DLT) and pathological complete response (pCR). Secondary endpoints include safety, incidence of cardiac events, and clinical response. Exploratory endpoints include molecular markers for sensitivity or resistance to chemotherapy and/or lapatinib evaluated. Results: A total of 84 patients have been included to date.No DLTs were observed and the maximum tolerated doses were NPLD 60mg/m2, paclitaxel 175mg/m2 and lapatinib 1500mg. Recommended phase 2 doses (P2D) were NPLD 60mg/m2, paclitaxel 175mg/m2 and lapatinib 1250mg. The treatment was generally well tolerated and associated with toxicities that were consistent with the known side-effects of the individual agents. No cardiac event has been observed to date. Preliminary efficacy data confirm a pCR breast rate of 41.7% and pCR rate in breast and lymph nodes of 37.5%, in 24 evaluable patients treated at ≥P2D. Conclusions: The combination of NPLD, paclitaxel and lapatinib is well tolerated and has high antitumour activity in patients with HER2-positive primary breast cancer. The phase II part of the study is ongoing and updated results will be presented.
Impact of single/dual HER2 inhibition and chemotherapy (CT) backbone upon pathologic complete response (pCR) in patients receiving neoadjuvant CT for operable/locally advanced breast cancer (O/LABC): A treatment-interaction analysis of randomized trials.
Authors: Furlanetto Jenny , Vaccaro Vanja , Caliolo Chiara , De Laurentiis Michele , Bonomi Maria , Pilotto Sara , Massari Francesco , Nortilli Rolando , Cianniello Daniela , Cognetti Francesco , Giannarelli Diana , Tortora Giampaolo , Bria Emilio 
Published: March 2020

630 Background: Although the addition of trastuzumab to neoadjuvant CT for O/LABC have dramatically increased pCR, clinical research is moving forward to further improve the overall outcome. In this regard, the DUAL inhibition of the HER-2 pathway and the choice of the best CT backbone may represent an issue to be addressed. Methods: Phase II randomized/Phase III trials were considered. pCR events/rates were extracted from papers/presentation and cumulated (R[pCR]) according to a random-effect model; 95% confidence intervals (CI) were derived. A sensitivity analysis according to SINGLE/DUAL HER-2 inhibition and to administered CT (anthracyclines-taxanes: anthra-TAX; TAX alone) was accomplished, in order to test for interaction. Results: 7 trials (2155 pts) were gathered; 1855 pts were enrolled in arms where anti-HER-2 targeted therapy was administered. HER-2 inhibition was obtained with trastuzumab, lapatinib and pertuzumab (alone or combined). Results according to HER-2 inhibition follow in the table below. With regard to CT, a significant interaction (p=0.0001) in favour of the addition of Anthra to TAX was found in the context of SINGLE HER-2 inhibition subgroup (R[pCR] 46.5%, 95% CI 37-51, vs 26.9%, 95% CI 23-31), while no significant interaction was determined in the context of the DUAL subgroup (R[pCR] 49.0%, 95% CI 26-72, vs 49.0%, 95% CI 43-55). A significant interaction (p=0.0001) in favour of the addition of Anthra to TAX was found for pts receiving trastuzumab (R[pCR] 45.5%, 95% CI 37-53, vs 26.5%, 95% CI 21-32) as well. Conclusions: Although biases in the pCR definition, the DUAL inhibition of HER-2 pathway may significantly increase pCR, regardless of the CT backbone; if confirmed, this strategy allows to reduce toxicities by sparing Anthra. For pts receiving SINGLE HER-2 inhibition, Anthra-TAX-based CT should be still considered the best treatment option. [Table: see text]
Effect of acquired resistance to lapatinib in HER2-positive breast cancer cells on the Bcl-2 family members MCL-1 and BAX.
Authors: Eustace Alex J. , Browne Brigid , Madden Stephen F. , O'Driscoll Lorraine , McDermott Martina , O'Brien Neil A. , Watson William , Crown John , Walsh Naomi , O'Donovan Norma 
Published: March 2020

633 Background: Lapatinib (L) is approved for the treatment of trastuzumab (T) resistant HER2 positive metastatic breast cancer. Not all HER2 positive tumors respond to L and patients who initially respond frequently relapse, due to the development of resistance to L. Understanding the molecular changes associated with L resistance may lead to the identification of targets to overcome resistance. Methods: SKBR3 cells were treated with either 250 nM L, or 125nM L and 5 µg/ml T twice weekly for 6 months to establish the resistant cell lines SKBR3-L and -TL. We measured by TUNEL assay the effect of L on apoptotic induction in SKBR3, -L and -TL cells. Gene array analysis of the SKBR3, -L and -TL cells identified differences in the expression of apoptosis-related genes, which were validated by immunoblotting. Finally using combinations of obatoclax (O) and L were tested in L resistant cells. Results: In SKBR3 cells, L (500 nM) induces apoptosis (15.8 ± 2.0%) compared to untreated controls (4.6±2.7%), whilst in SKBR3-L and -TL cells L did not induce significant apoptosis compared to controls. Gene array analysis showed that BAX mRNA is down regulated 3.2 fold in SKBR3-L cells compared to the parental cells. In SKBR3-TL cells, MCL-1 mRNA expression is increased 2.1 fold, whilst BAX mRNA is down regulated 2.1 fold compared to the parental cells. Immunoblotting confirmed that BAX protein expression was reduced in the SKBR3-L (1.5 fold, p=0.058) and significantly reduced in SKBR3-TL cells (2.0 fold, p=0.039) compared to SKBR3. MCL-1 protein expression was significantly increased in the SKBR3-L (1.6 fold, p=0.035) and -TL cells (2.3 fold, p=0.031) compared to SKBR3. Combining O (200 nM) and L (500 nM) in both SKBR3 and SKBR3-L cells produced greater growth inhibition than either drug on its own (SKBR3: 86.9±1.0% vs 73.5±3.1% for L (p<0.01) and 44.7±7.7% for O, (p<0.01); SKBR3-L: 54.2± 8.6% vs 26.9±2.4% for L (p=0.027) and 33.8±10.7% for O (p=0.04)). Conclusions: Extended exposure to L in SKBR3-L and –TL cells alters the apoptotic response to L. O alone and in combination with L results in growth inhibition in L resistant cells.
Evaluation of Ile655Val HER2 polymorphism associated with cardiac toxicity following the administration of trastuzumab in women with breast cancer.
Authors: Diorio Caroline , Lemieux Julie , Cote Marc-Andre , Provencher Louise , Nadeau-Larochelle Corinne , Jacob Simon , Demers Eric , Tremblay-Lemay Rosemarie , Saint-Pierre Christine , Beauchemin Michel , Barabe Frederic , Laflamme Christian 
Published: March 2020

634 Background: Trastuzumab is well tolerated without major side effects except for cardiac toxicity. Although a number of clinical parameters have been associated with trastuzumab-associated cardiac toxicity (TACT), there is some indication that genetic variation of the HER2 gene may play a toxic role in a population of metastatic breast cancer patients. However, this finding needs confirmation and we looked at a population of non-metastatic breast cancer. This study aimed to evaluate the association between cardiac toxicity and HER2 [Ile655Val] polymorphism in non-metastatic breast cancer patients treated with trastuzumab. Methods: The Ile655Val HER2 polymorphism was assessed in 73 women using TaqMan technology. For this study, the genotyping was performed using DNA extracted from normal breast tissue located at more than 1 cm of any other lesions. Charts review was used to collect information on TACT which was defined as any decline in LVEF > 10 % from the baseline to < 55 % or a decline in LVEF > 5 % to < 50 % (lower limit of normal). The Fisher exact test was used to evaluate the association between cardiac toxicity and HER2 polymorphism. Results: No deviation from the Hardy-Weinberg equilibrium has been observed for the allele and genotype frequencies. The distribution of HER2 polymorphism was 3 Val/Val (4%), 18 Ile/Val (25%) and 52 Ile/Ile (71%). In this population, 19% (14/73) developed a cardiac toxicity. We found that 29% (6/21) of Ile/Val or Val/Val carriers compared to 15% (8/52) of Ile/Ile carriers showed TACT, but this association did not reach statistical significance (P = 0.21). Conclusions: HER2 Ile655Val polymorphism may be an efficient marker of TACT considering this tendency with this small cohort of patients. Larger sample is needed to strengthen this conclusion, since this result may influence on prescribing decision for adjuvant chemotherapy and anti-HER2 therapy in HER2 positive patients.
A randomized phase II study of sapacitabine in MDS refractory to hypomethylating agents.
Authors: Garcia-Manero Guillermo , Luger Selina M. , Goldberg Stuart , Altman Jessica K. , Arellano Martha Lucia , Wetzler Meir , Seiter Karen , Chiao Judy H. , Kantarjian Hagop 
Published: March 2020

6520 Background: Sapacitabine is an orally administered nucleoside analogue which causes single-strand DNA breaks and induces G2 cell cycle arrest. A multi-center, randomized phase 2 study was conducted to evaluate 3 dose regimens in older patients with MDS refractory to hypomethylating agents. The primary endpoint is 1-year survival. Secondary endpoints include the rate of CR, CRp, PR, major hematological improvement (HI) or stable disease and their corresponding durations. The study uses a selection design to identify a dose regimen which produces a better 1-year survival rate in the event that all three dose regimens are active. The planned sample size is 60 patients (20 patients in each arm). Methods: Eligible patients must be ≥ 60 years with intermediate-2 or higher risk MDS previously treated with hypomethylating agents and 6 - < 20% blasts in bone marrow, ECOG 0-2, adequate renal and hepatic functions. Patients were randomized 1:1:1 to receive sapacitabine every 4 weeks at 200 mg b.i.d. x 7 days (Arm G), 300 mg q.d. x 7 days (Arm H), or 100 mg q.d. x 5 days per week x 2 weeks (Arm I). The number of cycles is not limited. Results: As of January 2012, 61 patients were enrolled and 56 had ≥ 30 days of follow-up. Mean follow-up was 173 days. Median age was 71. Two or 3 cytopenias were present in 42 patients and 14 have received both azacitidine and decitabine. Baseline bone marrow had 6-10% blasts in 31 patients and 11-19% blasts in 25 patients. Median number of cycles was 2 and 18 patients received ≥ 4 cycles. To date, 8 patients have responded (2 CRs, 2 CRp, and 4 major HIs): 15% (Arm G), 16% (Arm H) and 12% (Arm I). Time to response is 1-3 cycles. Additionally, 6 patients achieved stable disease lasting longer than 16 weeks. More than 50% of patients have lived 16 weeks or longer. Three deaths occurred within 30 days of randomization and 1 death was considered to be related to sapacitabine. Common adverse events (all grades, regardless of causality) included fatigue, nausea, diarrhea, constipation, edema, dyspnea, pyrexia, pneumonia, febrile neutropenia, anemia, neutropenia and thrombocytopenia, most of which were mild to moderate. Conclusions: Sapacitabine appears to be safe and active across all 3 dose regimens. Updated data will be presented at the meeting.
Use of single polymorphism arrays (SNP-A) to modify prognostic scoring systems for myelodysplastic syndromes.
Authors: Bupathi Manojkumar , Elson Paul , Valeria Visconte , Traina Fabiola , O' Keefe Christine , Tabarroki Ali , Hasrouni Edy , Advani Anjali S. , Sekeres Mikkael A. , Maciejewski Jaroslaw P. , Gondek Lukasz , Tiu Ramon Velasquez 
Published: March 2020

6521 Background: MDS are hematologic neoplasms characterized by dysplasia and cytopenias. Two commonly used risk stratifications, IPSS (Greenberg et al Blood 1997) and IPSS-R are based on clinical factors (marrow blasts, number of cytopenias and genetic abnormalities determined by conventional karyotyping), with the IPSS based on 4 cytogenetic risk groups and the IPSS-R based on 5 cytogenetic risk groups defined by Schanz et al JCO 2012. A drawback to metaphase cytogenetics (MC) is its inability to detect small cryptic chromosomal defects and uniparental disomy (UPD). SNP-A can identify these small cytogenetic lesions/UPD and has been shown to be of prognostic value in MDS. The goal of this investigation was to determine if SNP-A detected defects could be used to refine the IPSS and IPSS-R. Methods: SNP-A karyotyping was performed as previously described (Tiu et al, Blood, 2011). We reviewed data from 327 patients idenfitying SNP-A results, MC, and the IPSS/IPSS-R-related clinical factors were identified. Overall survival (OS) measured from the date of sampling for SNP-A karyotyping was the primary endpoint. Data were analyzed using Cox proportional hazards models. Results: SNP-A lesions not detected by MC were grouped as 1) none or only gains/losses; 2) UPD only or gains+losses but no UPD; and 3) UPD+other defects. The frequencies/median os in months (mo) of the groups were: 66%/20.0, 23%/12.7 and 11%/5.8, respectively, p<.0001 for OS. Combining the SNP-A groups with MC resulted in revised definitions of cytogenetic risk that had better discrimination than the underlying models; and when combined with the relevant clinical factors resulted in refined IPSS (IPSSSNP-A) and IPSS-R (IPSS-RSNP-A) risk stratifications (Table). Conclusions: Detection of chromosomal gains, losses, and UPD by SNP-A has prognostic value in MDS and can be used to refine current risk stratifications. [Table: see text]
Allogeneic stem cell transplantation for patients over age 65 with acute myelogenous leukemia and myelodysplastic syndrome.
Authors: Conter Henry Jacob , Rondon Gabriela , Nguyen Nhu-Nhu , Chen Julianne , Shpall Elizabeth J. , Khouri Issa F. , Giralt Sergio , Champlin Richard E. , De Lima Marcos J.G. 
Published: March 2020

6529 Background: ASCT represents a potentially curative approach for AML and MDS, diseases that primarily affects patients in 7th and 8th decade of life. Here, we report outcomes of patients older than 64 treated at the MD Anderson Cancer Center from 1996 until December 2011. Methods: 182 patients older than 64 received an ASCT for AML (n=143) or MDS (n=39). Outcomes of interest were transplant-related mortality (TRM), incidence of acute and chronic graft-versus-host disease (GVHD), incidence of relapse, and overall survival (OS) - which were estimated from the date of transplant. Results: The median age of patients was 67 (range 65-79). Most patients were transplanted with active disease (table). Median follow-up for alive patients was 12.6 months (n=63; range 0-118). The cumulative incidence of 100-day, 1 year, and 3 year TRM was 14%, 18%, and 21%, respectively. 26% of patients developed grade II-IV acute GVHD and 35% suffered from chronic GVHD. The actuarial incidence of relapse was 46% at 1 year and 53% at 3 and 5 years. Actuarial OS was estimated to be 45% at 1 year, 28% at 3 years, and 21% at 5 years. 3 year OS for patients transplanted in CR and with active disease was 40% versus 23% (p=0.02). OS of patients age 65-69 or >69 was 30% vs. 20% (p=0.06) at 3 years for all patients; compared to 38% versus 27% (p=0.23) for patients in those age groups transplanted in CR. Conclusions: Although a significant minority of patients older than 64 years may achieve long-term disease control, new approaches are needed to reduce TRM and relapse in this cohort of patients. [Table: see text]