tbuckley/cabot-search huggingface dataset:
Natural history of chronic myelomonocytic leukemia treated with hypomethylating agents
Authors: Ana Alfonso, Guillermo Montalban‐Bravo, Koichi Takahashi, Elias J. Jabbour, Tapan Kadia, Farhad Ravandi, Jorge Cortes, Zeev Estrov, Gautam Borthakur, Naveen Pemmaraju, Marina Konopleva, Carlos Bueso‐Ramos, Sherry Pierce, Hagop Kantarjian, Guillermo Garcia‐Manero
Journal: American Journal of Hematology (2017)

Hypomethylating agents (HMA) are the most commonly used therapeutic intervention in chronic myelomonocytic leukemia (CMML). Due to the lack of CMML-specific clinical trials, the impact of these agents in the natural history of CMML is not fully understood. We present the largest retrospective series of CMML (n = 151) treated with HMA. Mean age at diagnosis was 69 years (range 50-88). According to the CMML-specific prognostic scoring system (CPSS): 17 (15%) were low-risk, 45 (39%) intermediate-1 risk, 42 (36%) intermediate-2, and 12 (10%) high-risk. 35 (23%) patients received single agent azacitidine, 73 (48%) single agent decitabine, and 43 (29%) combinations. With a median follow-up of 17 months, overall response rate (ORR) was 75%, with 41% achieving complete response (CR). Median overall survival (OS) was 24 months (95%CI: 20-28) and event-free survival 14 months (95%CI: 11-17). By multivariate analysis, age < 70 years, higher levels of hemoglobin, absence of blast in peripheral blood and lower CPSS cytogenetic risk predicted for better OS. CR was significantly higher in those patients treated with decitabine (58.3%) when compared with azacitidine (20.6%) (P < .001). 13 patients (9%) received allo-SCT after a median of 4 cycles of HMA. 66 patients (50%) had HMA failure: 26 primary (34%) and 50 secondary (66%), including 35 (46%) that transformed to AML. Outcomes after HMA failure were poor with OS of 7 months (95%CI: 3-12). In conclusion, HMA are effective in CMML but new agents and combinations are needed. This data could be a benchmark for further drug development in CMML.
Optimizing formulary decisions.
Authors: Henry Jacob Conter
Journal: Journal of Clinical Oncology (2017)

14 Background: As medication prices rise, the sustainability of health care systems has been increasingly questioned. Health technology assessment (HTA) could be employed to maximize value when budgets are limited. Methods: The pan-Canadian Oncology Drug Review (pCODR) is an evidence-based, cancer drug review process that guides formulary decision-making. As of 10/30/16, data from all 93 reviews and economic guidances were abstracted for price of medication, total health care cost per patient, cost-utility provided by the submitter, and the re-analysis by pCODR. Regression analysis was employed to identify correlations. Expected use of therapy was estimated employing mortality data from the Canadian Cancer Society. An optimal formulary was then developed, with value for money as the primary concern. Results: Of the 93 reviews, 11 were not finalized, 3 were withdrawn, and 1 was suspended. 4 reviews were excluded since the base-case was ambiguous. Of included reviews, 13% were recommended for funding, 66% were recommended conditional on improved cost-effectiveness, and 22% were rejected. The median drug price per 28-day cycle was $7,567 (range $2,800-$18,435), with no annual difference from 2012-2016 (p=0.49). The median best-estimate of cost-utility was $188,537/QALY (IQR $127,399/QALY) with a median net increase in health system cost of $66,069/patient (IQR $90,466). The median difference between pCODR’s best estimate and the submitter’s was $61,240/QALY (IQR $73,656/QALY). The submitter’s estimate of cost effectiveness was correlated with pCODRs assessment (R² = 0.65, p&lt;0.01). Cost per 28-day cycle was a weak predictor of value (R² = 0.01, p&lt;0.01), and not of health system cost (R² = 0.17, p=0.11). In the Canadian context, funding all efficacious medications would require a total of $5.91 billion producing 31,705 QALYs, annually. Funding the system with $1.12 billion for new medicines by first-come-first-served principle, yields 5,966 QALYs over 16 drugs, annually. By prioritizing based on value, $1 billion allows for funding of 22 drugs producing 9,665 QALYs, annually. $2 billion would increase annual QALYs to 15,792 over 26 drugs. Conclusions: Price of medications should not be used as a heuristic for value. An optimized formulary requires practical deployment of HTA.
Fulvestrant in heavily pre-treated breast cancer patients—Single institution experience
Authors: J. H. Schornagel, H. H. Helgason, S. Rodenhuis, J. H. Schellens
Journal: Journal of Clinical Oncology (2006)

13157 Background: Fulvestrant is a selective estrogen and progesterone receptor down regulator with equivalent efficacy, i.e. RR, TTP and OS, in comparison to anastrozole in the 1 st and 2 nd line of hormonal treatment in women with advanced breast cancer. Methods: We retrospectively evaluated all patients with advanced breast cancer who were treated with fulvestrant between 06/2003 and 08/2005 in our institution. Response was evaluated according to the RECIST criteria in case of measurable disease but with bone scintigraphy (new bone metastasis) and/or change in CA 15.3 in case of evaluable disease. Results: In total 32 patients (20 with measurable and 12 with evaluable disease) with advanced breast cancer were identified. Median age was 50 (range: 24 - 72) years, 25 (78%) patients had bone/soft tissue involvement, 17 (53%) had visceral metastases and 1 had CNS metastases. All had received prior hormonal treatments; fulvestrant was the 3 rd , 4 th or higher line of hormonal treatment in 26 (81%) and 20 (63%) patients, respectively. The preceding hormonal treatments mostly included tamoxifen, non-steroidal aromatase inhibitors, steroidal aromatase inhibitors and megestrole acetate, but also ovarian ablation and aminoglutethimide. In total 20 (63%) patients had received prior adjuvant or palliative chemotherapy, 13 (41%) had received 2≥ and 5 patients (16%) had received 4≥ lines of chemotherapy. The chemotherapy contained an anthracycline, a taxane or capecitabine, but also vinorelbine, gemcitabine or high dose chemotherapy. In total 139 administrations of fulvestrant (mean: 4.3; range 1 - 18) were given. Most patients received 3 - 6 administrations except two who received 17 and 18 administrations respectively. In this cohort of 32 patients no objective tumor response or clinical benefit was seen, except in 1 patient, previously treated with tamoxifen, who had stable disease for &gt; 18 months. The patient receiving fulvestrant for 17 months was slowly progressive during treatment. Fulvestrant was well tolerated without treatment discontinuation because of toxicity. Conclusion: Fulvestrant was not effective in our small cohort of heavily pre-treated breast cancer patients and may not be a good treatment option after 3 rd or higher line of hormonal treatment or chemotherapy. No significant financial relationships to disclose.
Reducing overuse of colony-stimulating factors without compromising patient safety: Evidence from a decision-support enabled utilization management in patients with lung cancer receiving chemotherapy.
Authors: Gboyega Adeboyeje, Abiy Agiro, Andrea DeVries, Michael Fisch, Jennifer L. Malin
Journal: Journal of Clinical Oncology (2017)

52 Background: Recent studies suggest significant overuse of colony-stimulating factors (CSFs) for the primary prevention of febrile neutropenia (FN) in patients with cancer receiving chemotherapy. Overtreatment with CSF increases costs without evidence of clinical benefit. We examined the impact of a decision-support tool to promote risk-appropriate CSF use in lung cancer. Methods: A retrospective cohort study design was used to analyze commercial claims data on lung cancer patients. The decision-support tool was implemented at participating oncology practices in staggered phases across 14 U.S states (from July 1, 2014 - November 1, 2014). Study population included adults with lung cancer who initiated chemotherapy from July 1, 2014 through March 30, 2015. Patients were assigned to case and control cohorts according to whether or not they resided in service areas where the tool had been implemented. Patients were followed up to 6 months after initiating chemotherapy in the pre- and post-implementation periods. The primary outcomes: CSF use and FN incidence rates were compared using difference-in-differences (DID) models; adjusting for baseline FN risk factors with generalized estimating equations. Results: The final study population included 3,470 patients (case: 1,857 and control: 1,613; overall mean age (SD), years: 65 (10)). There were no meaningful differences in FN risk factors at baseline between the cohorts. In adjusted results, CSF use decreased from 48.4% to 35.6% in the case compared to a change from 43.2% to 44.4% in control cohort (DID: -8.7% (95% CI: -14.65% to -2.67%), p - &lt; 0.001) in the pre- and post-implementation periods. The rates of FN were consistent for both cohorts in each time period, with no statistical difference in trend for the case (2.8% to 4.3%) as compared with the control (3.1% to 5.1%) cohort (DID: -0.2% (95% CI: -0.63% to -0.33%), p – 0.953). Conclusions: These findings demonstrate the potential for decision-support tools to improve evidence-based guideline adherence and promote risk-appropriate CSF use in patients with lung cancer without adversely impacting patient safety.
Peptide-vaccine treatment associated with imatinib in patients with residual CML disease is able to induce both immunologic response and molecular remission
Authors: E. Abruzzese, M. Bocchia, M. Trawinska, L. Morino, F. Iuliano, G. Orlandi, P. Panetta, G. Del Poeta, F. Lauria, S. Amadori
Journal: Journal of Clinical Oncology (2004)

2517 Background: The main objective in the intent to “cure” chronic myeloid leukemia (CML) is to obtain complete cytogenetic (CCR) and molecular remission (MR). Interferon-A and Imatinib have only partially achieved this goal. An alternative approach to target the residual disease is specific immunotherapy. We associated Imatinib and immunogenic peptides derived form the p210 b3a2 fusion protein in patients on Imatinib with stable disease at cytogenetic level. Methods: Ten patients with CML in chronic phase on Imatinib for a median time of 15.5 months (range 12–24) were enrolled. All patients were on their +2nd line treatment being resistant or refractory to IFN-based previous therapies. They presented with an unchanged residual disease from a median of 10 months (range 6–18) consisting of bone marrow Ph+ metaphases ranging from 2–43%. Vaccination included GM-CSF pre treatment and administration of 500 mcg of 5 different length(8–25 aa)peptides mixture of restricted for HLA class I and class II molecules, associated with immunologic adjuvant QS-21. All patients were tested with peptide mixture at 25 mcg dosage in absence of adjuvants (DTH) prior to vaccine to evaluate their sensitivity; all of them resulted negative. The immunotherapy consisted on 6 vaccinations every 2 weeks and 2 additional boosts at +4 and +10 months. Cytogenetic, FISH and molecular biology, immunologic response, cytokine production and immunophenotype were analyzed during treatment. Results: All patients showed a variable degree of progressive reduction of their residual Ph+ metaphases after 3, 6 vaccinations (3 months) and boosts, with 7/9 becoming CCR and 4/6 evaluable achieving MR. All patients presented with some degree of DTH indicating the in vivo
Treatment sequences in non-small cell lung cancer in the United States from 2014-2016.
Authors: Lisa M. Hess, Zhanglin Lin Cui, Xiaohong Li, Julie Beyrer, Ana Belen Oton
Journal: Journal of Clinical Oncology (2017)

237 Background: A number of important advancements in the treatment of metastatic non-small cell lung cancer (mNSCLC) have increased and diversified options for improved patient care based on individual characteristics. The ability to tailor therapy increases the challenges related to appropriate treatment sequencing. This study was designed to describe these emerging treatment patterns following the approval of novel targeted agents. Methods: Flatiron Health OncoEMR, a nationally-representative electronic medical records database in the US, was used to evaluate treatment patterns by histology (squamous and nonsquamous). Eligible patients were 18+ years of age who initiated 2 nd line therapy for mNSCLC from Dec 2014-Jul 2016. Descriptive statistics were used to characterize the clinical and demographic characteristics of the study population, treatments used by line of therapy, and treatment sequencing. Analyses were conducted using SAS version 9.2. Results: A total of 3498 eligible patients were included in this study: 51.3% male; mean age 66.6 years; 65% white; 25% squamous/70.7% nonsquamous (4.3% not specified); and 93% were treated at community practices. ALK testing was performed on 20.0%/74.8%, EGFR testing on 21.5%/79.8%, and PDL-1 on 8.6%/9.7% of patients with squamous/nonsquamous tumors, respectively. Single-agent PDL-1 inhibitors were used by 54.2% of squamous and 35.2% of nonsquamous patients in the 2nd-line setting; however, there were more than 35 (squamous) and 64 (nonsquamous) unique first-line regimens prior to single-agent PDL-1 treatment. Other 2nd-line regimens included pemetrexed (24.9% of nonsquamous patients) and gemcitabine (18.4% of squamous patients), which were preceded by 70 and 48 unique first-line regimens, respectively. Conclusions: There is interest in understanding treatment sequencing to identify the optimal sequence of care for patients with NSCLC; however, there was considerable heterogeneity in sequencing. Since few patients follow any similar trajectory of care, comparative effectiveness research will be challenged to appropriately balance groups due to insufficient patient numbers in any specific treatment sequence.
Natural history, treatment patterns, and economic burden of cancer therapy induced bone loss (CTIBL) among breast and prostate cancer patients (pts): A study overview
Authors: S. P. Boyce, M. R. Smith, M. K. Raut, M. Duh, J. Chang, J. Sung, M. M. Gupta, D. A. Mallett
Journal: Journal of Clinical Oncology (2004)

8243 Background: Accelerated bone loss has been observed in men and women undergoing cancer treatment. In recent years, the use of aromatase inhibitors and gonadotropin-releasing hormone agonists has dramatically increased in breast and prostate cancer, respectively. Both forms of hormone ablative therapy (HAT) decrease bone mineral density and increase fracture risk, potentially leading to increased health care resource utilization. The disease burden of CTIBL in terms of its direct medical and indirect productivity costs in these settings are unknown. We are conducting a retrospective, observational study that investigates the following objectives for breast and prostate cancer pts on HAT: (1) the prevalence of CTIBL, (2) the natural history of bone complications following HAT, (3) the treatment patterns for CTIBL, and (4) the direct medical (inpatient, outpatient, prescription drugs), indirect productivity (sick leave, short- and long-term disability, worker's compensation), and expected life-time costs of CTIBL. Methods: This study will analyze anonymous medical, pharmacy, disability, and worker's compensation claims for 2 million individuals from 1/98 through 6/03 from 16 US employers. There are 24,877 and 20,707 pts with a breast and prostate cancer claim, respectively, of whom 22,470 and 19,240 received HAT. The mean age was 62 ± 13 and 69 ± 10 years, respectively. Breast and prostate cancer pts on HAT experiencing CTIBL (osteoporotic fracture) will be identified. These pts will be observed from the first treatment-related claim until disenrollment or the study end date (6/30/03), whichever comes first. Univariate and multivariate analyses will be used. The results that will be presented will aid to further the clinical understanding and assess the economic impact of CTIBL. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis Pharmaceuticals Corp. Analysis Group, Inc.; Novartis Pharmaceuticals Corp. Novartis Pharmaceuticals Corp. Novartis Pharmaceuticals Corp.
Politics and leadership in global health delivery: lessons from South Africa's HIV and health insurance initiatives
Authors: Amy Madore, Julie D Rosenberg, Hisham Yousif, Chris Desmond, Rebecca L Weintraub
Journal: The Lancet Global Health (2017)

BackgroundSouth Africa's Health Minister Aaron Motsoaledi inherited an HIV epidemic and a weak public health system when he took office in 2009. His priorities were to establish a national programme to address HIV and to create a system of national health insurance (NHI) to increase access to affordable and high-quality health care. By 2015, Motsoaledi's work on HIV was considered as a success; however, work on the creation of NHI was stymied. Here, we aimed to compare the design, promotion, and implementation of the national HIV programme—a primarily vertical programme—with that of NHI, a horizontal programme.MethodsIn January and February, 2015, we conducted 20 semi-structured interviews in South Africa with government leaders, civil society, researchers, health-care practitioners, private insurers, and international non-governmental organisations. We analysed interviews and available quantitative data from government, academic, and industry sources and distilled key themes in two teaching cases.FindingsWe identified several key differences between the HIV programme and NHI efforts, including the role that leadership and politics play in health policy and care delivery; the effect of historical, economic, and cultural context on outcomes and leaders' ability to institute change; and the importance of strategy in planning and decision making. We noted both contextual barriers (such as public distrust of government) and catalysts (demand for HIV treatment) in the programmes. Furthermore, the approach used by the Minister of Health sometimes hindered programme success (for example, the exclusion of private insurers from NHI design) and sometimes enabled success (such as the engagement of civil society in the HIV response). For both programmes, the availability or absence of outcomes data affected the Minister's ability to advocate for change and to make strategic decisions about how to invest in health.InterpretationThe comparison of South Africa's well known and effective HIV programme with its stalled NHI efforts—both led by the same person with very different results––sheds light on important considerations when approaching complex, large-scale change. Our analysis of the politics of health systems shows how explicit acknowledgement of the political nature of health will lead to more effective health promotion strategies and policies. Political leaders can either drive or hinder the implementation of evidence-based public health practices.FundingThe Ministerial Leadership in Health Program of the Harvard TH Chan School of Public Health, and Children's Investment Fund Foundation (CIFF), UK.
The patient population using the Internet differs from the population of patients found in the clinic: Implications for online clinical matching programs
Authors: S. J. Wei, J. M. Metz, M. K. Hampshire
Journal: Journal of Clinical Oncology (2004)

6138 Background: Enrollment of adult cancer patients into clinical trials remains low. Clinical trials matching services offered through the Internet can potentially increase the rate of clinical trial enrollment. However, data describing the differences between the patient population using the Internet and the general population found in the clinic are limited. Methods: A validated questionnaire assessing basic demographics and attitudes towards clinical trials was offered to 609 patients through the OncoLink website (www.oncolink.org) and two radiation oncology clinics. The questionnaire was completed by 439 (72%) patients online and 166 (28%) patients in the clinic. Results: Online patients were more likely to be female (71% vs. 39%, p<0.001), younger (mean age: 52.8 vs. 55.8 yrs, p=0.02), and Caucasian (89% vs. 65%, p<0.001). More clinic patients were African-American (26% vs. 3%, p<0.001). More online patients were interested in learning about clinical trials (94% vs. 83%, p<0.001); however, there was no difference in the rate of current or previous clinical trial enrollment (23% vs. 24%, p=0.73). Online patients were more likely to have explored any information regarding clinical trials (72% vs. 59%, p=0.002). There was no difference in rates of patients obtaining information on clinical trials from health care professionals, other patients, or other media. Patients also differed in their expectations of clinical trials. More clinic patients indicated they would need a >50% chance of benefiting from a trial (45% vs. 22%, p<0.001) and/or a <10% chance of serious toxicity from a trial (43% vs. 35%, p<0.01) in order for them to enroll on that trial. Conclusions: The population of patients who are using the Internet differs significantly from patients seen in the clinic. These differences may potentially bias patient populations of studies that utilize the Internet to enroll patients. Direct comparisons of patients enrolling in studies through the Internet and those enrolling in studies through the clinic are needed. No significant financial relationships to disclose.
Somatic mutation profiling of advanced breast and ovarian cancers according to germline <i>BRCA1/2</i> mutation status.
Authors: Neda Stjepanovic, Michelle K. Wilson, Amit M. Oza, Blaise Clarke, Hal K. Berman, Eitan Amir, Helen Mackay, Patricia Shaw, Marcus O. Butler, Anna Marie Mulligan, Anca Milea, Lailah Ahmed, Alexandra Volenik, Lisa Wang, Trevor John Pugh, Tracy Stockley, Raymond H Kim, Lillian L. Siu, Suzanne Kamel-Reid, Philippe L. Bedard
Journal: Journal of Clinical Oncology (2015)

1532 Background: The risk of breast cancer (BC) and ovarian cancer (OC) is increased in germline BRCA1/2 mutations carriers (BRCA+). We investigated the somatic mutation profile and clinical impact of targeted sequencing in advanced BC and OC patients (pts) according to germline BRCA1/2 status. Methods: Targeted sequencing with Illumina MiSeq TruSeq Amplicon Cancer Panel (TSACP; 48 non-homologous DNA recombination genes, 212 amplicons, ≥ 500× coverage) was performed using archival tumor and germline DNA from advanced BC and OC pts through an ongoing institutional molecular screening program (NCT01505400). Medical records were retrospectively reviewed for clinical, pathological and germline BRCA1/2 testing results. Results: From May/13 to Oct/14, somatic TSACP testing was completed in 257 pts (106 BC and 151 OC). Germline BRCA1/2 testing was performed in 118 pts (35 BC [33%] and 83 OC [55%]), primarily in those with family history and/or young age at diagnosis. Among these, 25 pts were BRCA+ (21%), including 4 BC (11%; 25% triple negative [TN]) and 21 OC (25%, all type 2) pts. The BRCA-/unknown group (BRCA-/UK) comprised 102 BC (24% TN and 76% non-TN) and 130 OC (31% type 1, 68% type 2) pts. Using the TSACP, 188 pts (73%) had ≥ 1 somatic hotspot mutation with no difference in the number of somatic mutations detected in BRCA+ vs BRCA-/UK (median 1, range 0-3; p = 0.85). More BRCA+ pts had TP53 hotspot mutations compared with BRCA-/UK pts (76% vs 50%, p = 0.01). Somatic hotspot mutations in PIK3CA were more frequent in BRCA-/UK vs BRCA+ (22% vs 4%, p = 0.04). After a median follow up of 8 months, 12 BRCA-/UK pts vs no BRCA+ pts were enrolled in somatic genotype matched targeted clinical trials (5% vs 0%, p = 0.62). Seven BRCA+ pts received PARP inhibitors on clinical trials. Conclusions: In pts with BRCA+ BC and OC, TP53 mutations are common while PIK3CA or other hotspot somatic mutations are rare. Whether the association between germline BRCA1/2 and hotspot mutation status is causal or confounded by histological subtypes should be validated in larger cohorts. Broader genomic sequencing may further highlight biological differences amongst BRCA+ and BRCA- tumors and provide more opportunities for genotype-treatment matching.