bluuebunny/crossref_metadata_2025 huggingface dataset:
Strategies to minimize wastage of expensive drugs in expensive times: Cabazitaxel, a single center experience.
Authors: Fallah-Rad Nazanin , Lee Roy , Ng Pamela , Smith Alan D. , Hansen Aaron Richard , Joshua Anthony M. , Sridhar Srikala S.
Published: September 2018

e18297

Background: Although approved for metastatic castrate-resistant prostate cancer (mCRPC), the use of cabazitaxel has been limited due to concerns over drug wastage. In Canada, Cabazitaxel costs $96.7/mg and comes prepackaged in 60 mg single-dose vials, a quantity higher than the average prescribed and provincially reimbursed dose based on body size. Despite a discount offered by Sanofi to help cover the costs of drug wastage, many centers still cannot afford to administer it. We investigated whether aggressively batching patients (pts) on the same day, and allowing for excess drug to be used for subsequent pts can result in cost-savings. Methods: Between 09/2015 and 09/2016, all mCRPC pts receiving cabazitaxel at Princess Margaret Cancer Center were only treated on Mondays. Left over drug in opened vials was used for subsequent pts treated on the same day. Pts were dosed according to clinical parameters and BSA, at a dose of 20mg/m2 every 3 weeks. We calculated the total number of vials used daily and the amount of drug (mg) wasted. We then compared costs of the new batching system to the standard practice of opening one vial per treatment session. Results: During the trial period, 28 patients, mean age 72.3 (range 45-91) received cabazitaxel as 2nd line (23 pts) or 3rd line (5pts) therapy until disease progression or toxicity. In total, they required 117 individual treatment sessions, administered on 53 treatment days. With the batching system, 91 cabazitaxel vials were used, in comparison to 117 vials required with standard practice. As a result, 26 vials were unopened, $149,760 CAD were saved, equating to a 22.2% cost reduction over a year. In terms of wastage, $121,154 CAD of Cabazitaxel was wasted compared to $251,808 CAD wasted without batching, a difference of $130,656 CAD. Conclusions: Batching of mCRPC pts receiving cabazitaxel on the same day was feasible at a single center and significantly reduced drug wastage. This approach could be applied to centers with adequate patient volumes to save costs and reduce a key barrier to the use of cabazitaxel. A similar strategy can also be applied to other drugs across the field of oncology and has similar implications for cost-savings.
Impact of value of research analyses on SWOG’s clinical trial capsule scoring.
Authors: Carlson Josh John , Kim David , Guzauskas Gregory F. , Bennette Caroline Savage , Hershman Dawn L. , Baker Laurence H. , Hendrix Nathaniel , Basu Anirban , Veenstra David Leroy , Ramsey Scott
Published: September 2018

e18311

Background: The Institute of Medicine has called for approaches to help maximize the return on research investments in cancer clinical trials. Value of Research (VOR) analysis is a health economics technique that estimates the clinical and economic returns for research investments and can inform research prioritization. Our objective was to evaluate the impact of VOR estimates on SWOG executive committee’s (EC) clinical trial proposal review scores. Methods: We used a previously developed minimal modeling approach to calculate per-patient and population-level (based on US cancer incidence) VOR estimates for 9 phase II and III SWOG research proposals between February 2015 and December 2016. VOR estimates were presented to EC members who determine which studies to submit to the National Cancer Institute (NCI) for funding approval. EC members scored proposals on scientific merit and potential impact before and after receiving VOR estimates. Scores ranged from 1 (best) to 5. We used the Wilcoxon signed rank test to evaluate the change in pre-post scores. Results: Study characteristics, VOR estimates, and pre-post scores are below. EC scores changed after receiving VOR estimates for 8 of 9 proposals. There was no association between VOR estimates and the magnitude of the change in proposal scores (all p > 0.2). Proposals with larger planned annual enrollment had larger changes in scores (0.3 more points [95% CI: 0.2, 0.56] per 100 patient increase; p = 0.04). Conclusions: Presenting VOR estimates influenced EC scores for SWOG trial proposals. VOR may add important data to inform reviews of trial proposals within NCI Cooperative Clinical Trials group settings. [Table: see text]
Comparison of treatment characteristics between patients diagnosed with immune thrombocytopenia (ITP) and treated with thrombopoietin receptor agonists (TPO-RA).
Authors: Lokhandwala Tasneem , Bhor Menaka , Stafkey-Mailey Dana , Chen Herman , Elliott Brian Marc
Published: September 2018

e18314

Background: There is limited real-world information on the utilization of TPO-RAs, eltrombopag (ELT) and romiplostim (ROM), for the treatment of ITP. Methods: The study employed a retrospective, longitudinal cohort design using integrated healthcare claims data from July 2008-June 2015. Adults diagnosed with ITP initiating TPO-RA therapy from Jan 2009-July 2014 were included. Patients not continuously enrolled in benefits for 6-months prior and 12-months post the index date (first TPO-RA claim date) were excluded. Index TPO-RA discontinuation rates, concomitant therapy, restarts, subsequent therapy, and treatment free periods were assessed. Results: Of the 1,067 patients included, 26.5% (283) received ELT and 73.4% (784) ROM. Age (58.8 vs 59.3; P= 0.705) and gender (males: 45.9% vs 46.6%; P= 0.858) were similar between cohorts. Among ELT and ROM patients 35.7% and 27.6% continued therapy (no gap of ≥30 days) for ≥1 year ( P= 0.010). The average duration of continuous therapy (up to gap ≥30 days) was 131 and 108 days, respectively ( P= 0.001). During continuous course of index TPO-RA treatment 52.7% ELT and 47.2% ROM patients received concomitant ITP-related treatment ( P= 0.115). Following discontinuation, 42.9% of ELT patients restarted ELT, 22.0% did not initiate any subsequent ITP treatments, and 35.2% started a new ITP treatment. Among patients who discontinued ROM, 38.4% restarted, 26.9% did not receive any subsequent therapy, and 34.7% initiated a new treatment. Treatment free periods (≥30 days with no ITP treatment) were experienced by 52.7% of ELT patients and 61.6% ROM patients ( P= 0.009). Mean duration of treatment free period was 109 and 137 days ( P< 0.001), respectively. Conclusions: ITP patients receiving ELT had a longer duration of treatment and shorter treatment free periods compared to patients receiving ROM. Further research is needed to compare clinical outcomes (e.g., platelet counts, bleeding symptoms and remissions) among ITP patients receiving ELT and ROM, in the real-world setting.
The value of cancer treatments: Patient and clinician perspectives.
Authors: Briggs Andrew , Baba Camilla , Kaltenboeck Anna , Lipitz Snyderman Allison Nicole , McIntosh Emma , Bach Peter
Published: September 2018

e18320

Background: A number of frameworks for assessing the value of cancer treatments such as the National Comprehensive Cancer Network’s evidence blocks, Memorial Sloan Kettering Cancer Center’s Drug Abacus and ASCO’s value framework have been developed to help address the rising cost of cancer treatments. Yet the methodological basis for the inclusion of differing attributes, how to incorporate other contextual considerations and understand stakeholder trade-offs is unclear. This qualitative study aimed to identify contextual factors prioritized by stakeholders for inclusion in oncology value frameworks. Methods: A scoping review identified attributes currently included in value frameworks. Nominal group technique methods were then used in 3 focus groups representing cancer patients, oncology nurses, and physicians across a range of cancer specialties. Each group was tasked with ‘identifying important treatment features’ based on their own experience. Following discussions, participants ranked attributes in order of importance and group consensus identified the ‘top 6’ factors. Results: Twenty-one attributes were identified by the patient (n = 9), nurse (n = 10) and physician (n = 6) focus groups. All identified efficacy and safety/toxicity. Long-term adverse effects, alternative treatment options, quality of evidence and reputation of the treating oncologist/center were prioritized by patients. Nurse preferences centered on mode of administration, quality of life, communication and treatment innovation. Physicians focused on the burden and inconvenience of treatments to patients, functional outcomes, financial toxicity to patients, and societal costs. Conclusions: Although efficacy and safety/toxicity were prioritized in all groups, the prioritization of contextual factors across stakeholders highlights the need to further understand the relative value of possible ‘other’ attributes currently not reflected in frameworks thus, possibly failing to reflect the preferences of stakeholders.
Predictors of advanced imaging use during breast cancer surveillance.
Authors: Miles Randy C. , Lee Christoph I. , Sun Qin , Bansal Aasthaa , Fedorenko Catherine R. , Specht Jennifer M. , Ramsey Scott David , Lyman Gary H. , Lee Janie M.
Published: September 2018

e18337

Background: Our objectives were to determine advanced imaging use (whole body imaging with bone scan, CT, or PET-CT and breast MRI) during breast cancer surveillance, and to identify drivers of potential imaging overuse as outlined by ASCO’s Choosing Wisely initiative. Methods: Cancer registry records for 2923 women diagnosed with primary breast cancer in Washington State from January 1, 2007 to December 31, 2014 were linked with claims data from two regional commercial insurance plans. Inclusion criteria included women with AJCC stage 0-3 disease treated with curative intent. Women without continuous insurance enrollment from 3 months prior to diagnosis until 14 months after diagnosis were excluded. Surveillance began 4 months after the end of primary therapy and lasted for 15 months or until restart of treatment. Women’s (age, race, family history) and tumor (grade, receptor status, stage) characteristics were collected. Evaluation and management codes from claims data were used to determine mammography, advanced imaging, and tumor biomarker use during the peri-diagnostic and surveillance periods. Multivariate logistic regression models were used to identify factors associated with advanced imaging use during surveillance. Results: Of eligible women, 80.0% (2332/2923) received mammography, 16.5% (483/2932) received whole body imaging, and 21.5% (670/2932) received breast MRI during the surveillance period. Whole body imaging was significantly associated with increasing stage of disease (stage 3: OR = 3.39, 95% CI: 2.30-5.02), peri-diagnostic whole body imaging (OR = 1.80, 95% CI: 1.36-2.38), and surveillance tumor biomarker use (OR = 1.83, 95% CI: 1.46-2.31). Significant predictors of surveillance breast MRI included young age ( < 45 years: OR = 2.40, 95% CI:1.78- 3.25), family history (OR = 1.58, 95% CI:1.26-1.98), peri-diagnostic breast MRI (OR = 2.01, 95% CI: 1.56-2.59), and surveillance tumor biomarker use (OR = 1.74, 95% CI:1.41-2.17). Conclusions: Peri-diagnostic use of advanced imaging and surveillance use of tumor biomarkers are associated with advanced imaging use during surveillance, and may represent targets for interventions to increase adherence to Choosing Wisely clinical guidelines.
Method for definition of CIS-TRANS status in double CEBPA mutations.
Authors: Mitne-Neto Miguel , Moreira Caroline Mônaco , Fraga Ana Maria
Published: September 2018

e18511

Background: Acute myeloid leukemia (AML) is characterized by infiltration of blood and bone marrow by proliferative, clonal and abnormally differentiated hematopoietic cells, affecting 3 in 100.000 adults. CEBPA is a transcription factor and a biomarker for cytogenetically normal (CN) patients. Somatic CEBPA mutations occur in 10% of CN patients and recent studies have shown that a favorable outcome may only be obtained in those carrying CEBPA mutations in different alleles ( trans). The evaluation of double mutations and the definition of bi-allelic ( trans) versus mono-allelic ( cis) status applies long protocols, involving gene cloning and sequencing, which are challenging for the diagnostic routine and negatively impacts the turnaround time (TAT). The present study aimed the development of an alternate method for the identification of double mutations in CEBPA and its CIS- TRANScondition. Methods: A previously screened sample carrying double CEBPA mutations was selected and its DNA was extracted. This sample and a DNA control were quantified and diluted in order to obtain ½ DNA molecule per well for amplification, using digital PCR rationale. Samples were distributed in 40 wells of a 96 well plate. A pair of primers was used to amplify the entire CEBPA coding region in a Real-Time PCR using SYBR green-based detection in QuantStudio System. A subset of primers was used to amplify and to sequence the regions of interest. The entire process was repeated three times, in order to prove its reproducibility. Results: The above described dilution allowed an estimation that half of the wells had no DNA and half contained a single DNA molecule. An average of 18 wells presented amplification. Five of the positive wells were used as templates for a nested PCR followed by Sanger sequencing analysis. Since each mutation was identified as the result of distinct well amplification, we concluded that the mutations were in trans. Conclusions: Our results show that it is possible to determine the CIS- TRANS allelic configuration of CEBPA dual-mutation in a cost-effective process and with a short TAT, avoiding gene cloning systems. Additionally, the process is reproducible, can be easily implemented as a routine analysis and has a great impact for AML patients’ diagnosis.
CD19 targeted chimeric antigen receptor T (CAR-T) cell immunotherapy has demonstrated significant anti-leukemia activity in pediatric patients with relapsed/refractory acute lymphocytic leukemia: A multicentre study in China.
Authors: Xiao Lei , Tang Yongmin , Zhu Xiaofan , Chen Jing , Wu Zhao
Published: September 2018

e18512

Background: Patients with relapsed/refractory B-ALL are difficult to be treated. Autologous CD19 CAR-T may overcome many limitations of conventional therapies and induce remission in patients with relapsed/refractory disease. We explored treatment of 11 pediatric cases (come from Multicenter) with r/r B-ALL and assessed the clinical safety and efficacy. Methods: We infused autologous CD19 CAR-T in patients at doses of 0.45 × 106 to 10.51 × 106cells per kilogram of body weight. Between Oct. 23 2015 and Jan. 12 2017, a total of 11 children from 3 clinical centers (in China) cases were treated with CAR-T cells (Table1). Patients were monitored for a response, toxic effects, and remission rate. Statistical analysis involving categorical or continuous covariates, univariates, or multivariates analyses. Results: 73% (8/11) of the patients achieved complete remission (CR) and MRD negative between Day7-14 after CD19 CART cell infusion. 4 patients received a repeat infusions following initial ones since they have endured the Cytokine release syndrome (CRS) and have no safety concerns. Cytokine release syndrome (CRS) was seen in 73% (8/11) of patients and severe CRS occurred in 18% (2/11) of patients. Severe CRS was relieved gradually when the anti-IL6R agent tocilizumab and Methylprednisolone were administrated. 1 patients performed bone marrow transplant after they achieved MRD negative. The median CR maintenance is 121 day. Conclusions: This effort provides the first large set of pediatrics data that describes the potential for CART19 therapy to benefit Chinese population. Autologous CD19 CAR-T was effective in treating relapsed/refractory B-ALL not only low leukemia burden, but also high-burden leukemia patients. The method also can associated with a high remission rate. Importantly, While the multicenter trial involves 3 clinical centers in China, the variable clinical settings do not seem to impact patient outcomes due to the highly standardized CAR T cell preparation protocol and manageable CRS in most. (NCT 02813837) Clinical trial information: NCT 02813837.
Clinical utilization of the Myeloid Malignancies Mutation Panel.
Authors: Arain Saad A , Hall Aric C. , Mattison Ryan J.
Published: September 2018

e18523

Background: The scientific community has made tremendous progress in discovering genetic changes that drive myeloid malignancies and elucidating the effect of these mutations on prognosis. Still, the links between mutational profiling and management decisions remain unclear. In an effort to determine its clinical utility, we evaluated the use of the Myeloid Malignancies Mutation Panel (MMMP) at our institution. Methods: The MMMP is an assay of 57 genes with possible diagnostic, prognostic, or therapeutic implications for myeloid malignancies run by ARUP Laboratories. The assay was run on 30 patients at the University of Wisconsin – Madison between 6/2015 and 8/2016: 18 with leukemia, 5 with myelodysplastic syndrome, and 7 with “other” diagnoses (unexplained cytopenias, myeloproliferative disorders, or myelodysplastic/myeloproliferative overlap syndromes). Separate questionnaires for hematologists and hematopathologists were created asking 1) if the results of the MMMP were expected and 2) if the results changed diagnosis or management for each patient. Results were coded in a binary “yes/no” system and further subdivided by disease risk and category of response. Results: Hematologists considered the MMMP results expected for 8 patients and unexpected for 22. Per hematologist assessment, test results affected management (changed risk assessment, monitoring parameters, or drug therapy) for 14 of the 30 patients. Per the hematopathologists, the MMMP results were expected for 17 patients and unexpected for 13. For 11 patients, the diagnosis was affected (confirmed a suspected diagnosis or reassured against malignancy), while for 19 patients, the diagnosis was unchanged. Notably, in half of this group for whom diagnosis was unchanged, the hematopathologists believed there were significant prognostic implications. Conclusions: This data suggests the MMMP had significant implications in the diagnosis and management of myeloid disorders for nearly half of our patients. Clarifying this utility further to determine optimal cost-effective application of this expensive testing will require additional evaluation.
A single center experience with two decades of follow-up on patients with hairy cell leukemia.
Authors: Ilhan Osman , Atilla Erden , Ataca Atilla Pinar , Civriz Bozdag Sinem , Kurt Yuksel Meltem , Toprak Selami Kocak , Topcuoglu Pervin , Demirer Taner , Arslan Onder , Ozcan Muhit , Akan Hamdi , Beksac Meral , Gurman Gunhan
Published: September 2018

e18530

Background: HCL is a rare chronic lymphoid malignancy and frequency is 2% in all leukemia and diagnosed mostly in middle ages. Patients generally respond to purine analogues treatment. In this study our aim is to present our HCL patients with demographic features, treatment modalities and responses. Methods: 39 HCL patients who were diagnosed and treated at Ankara University Department of Hematology between 1984 and 2016 were retrospectively evaluated. Ki-square test and student t test were used in comparison. P < 0.05 was considered statistically significant. Results: Median age of patients were 51 (range, 31-79). 30 of patients (77%) were male. The average leucocyte, hemoglobin, platelet, lactate dehydrogenase (LDH) levels and the spleen size at diagnosis were as follows: 5,1 x 10^9/L (range, 1,5-20), 12,5 g/dl (range, 9-17,5), 116x10^9/L (range,15-300), 178 IU (range,107-394), 155 mm (range,110-290). BRAF mutation could be evaluated in two patients and revealed as positive. 9 patients (23%) underwent splenectomy prior to chemotherapy. All patients received cladribine (0.1mg/kg, 7 days) as a first line treatment; 8 patients (21%) had two courses for remission. 11 patients (30%) had treatment related febrile neutropenia, 2 patients (0.05%) had transient skin rash after infusion. 8 patients (21%) had a relapse and 1 patients received pentostatin (4mg/m2, 1 dose every 2 weeks, 6 months), 7 patients were retreated with the first line treatment and achieved complete response. The overall survival was 67 months, respectively. Leucocyte, hemoglobin, platelet levels were lower, LDH levels were higher and spleen size was increased in patients with relapse however no statistical difference were detected. The patients with splenectomy had improved survival compared to patients without splenectomy (144 vs 329 months, P = 0.024). Conclusions: We detected 18% relapse rate in our series and all patients were followed in remisson after second line purine analogue treatment. Splenectomy has improved overall survival and possibly still has a role to play in HCL therapy. Generally, HCL is a chronic disease with a favorable prognosis.
A prospective study to evaluate outcomes of AIDS-related lymphomas at a tertiary referral cancer centre.
Authors: Dhir Aruna Alahari , Sawant Sheela , Sengar Manju , Daddi Anuprita , Damania Blossom , Mishra Surya , Dittmer Dirk , Shet Tanuja
Published: September 2018

e19012

Background: AIDS related non Hodgkin’s Lymphoma (ARL) remains a major cause of morbidity and mortality .There are limited prospective studies on ARLs in Indian population. We studied the clinical profile and outcome of patients with ARL . Methods: Consecutive patients diagnosed with ARL in the period February 2014-march 2016 who were treatment naïve were included in the study. Details of HIV and ARL, treatment details , complications and outcome were recorded. The primary objective was overall survival(OS), secondary objectives were response rates correlation of overall survival with CD4 count, IPI, duration of HIV, histopathology and stage of NHL. Survival was described with the Kaplan-Meier method, and effect of predictor variables was tested with the log-rank test. Results: 42 patients(28 males) with a median age 45.5 years were included in the study . The commonest types of NHL were DLBCL 22 (52.38 %) and plasmablastic lymphoma 14 (33.33%). HIV infection was detected at the time of lymphoma diagnosis in 21 (50%). The median CD4+ T cell count was 137 cells/mm3 . 32 (76.19%) had stage III/IV disease and and 35(83.3%) had extranodal involvement. IPI score was >2 in 20/40(50%). 30/42 patients received chemotherapy of these 21 received atleast 4 cycles. 19 patients received CVEP regimen , 8 REPOCH and 3 others . NNRTI plus 2 NRTI combination was the HAART regimen in 26/30(86.6%) patients. Grade 3-5 febrile neutropenia was seen in 17/30 (56.6%) . Response was assessed using PET-CT scan in 22 patients ,16 (72.7%) had complete response .16/30 patients expired , 8 of these were due to infections . Median survival was 10 months (0.0-20.4 months). The estimated 2 year overall survival is 43.6 % . Patients with early stage disease had better overall mean survival (p=0.01). Type of NHL, IPI, CD 4+ T cell count, HAART prior to NHL treatment did not affect overall survival . Conclusions: Patients of ARL present at a younger age ,with higher grade and advanced disease. Higher proportion of plasmablastic lymphomas were seen in our study as compared to western data. Though most patients achieve complete response the overall survival is low . Myelosuppression and associated infections continues to be a challenge in the management of ARL.
A cost-effectiveness analysis of DA-EPOCH-R versus R-CHOP for the treatment of diffuse large B-cell lymphoma.
Authors: Gokul Ashni , Boyce Maria , O'Mahony Deirdre , Bird Brian Richard
Published: September 2018

e19018

Background: Clinical trials have indicated that dose adjusted etoposide, prednisolone, vincristine, cyclophosphamide, doxorubicin and rituximab (DA-EPOCH-R) may improve clinical outcomes when compared to standard rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone (R-CHOP) treatment in diffuse large B-cell lymphoma (DLBCL). The cost-effectiveness of the newer regimen, DA-EPOCH-R when compared to R-CHOP has not been assessed. Methods: Patients who received either DA-EPOCH-R or R-CHOP treatment at the Bon Secours Hospital from 2008-2016 for DLBCL were identified. The overall survival (OS), progression free survival (PFS) and event free survival (EFS) was determined for each treatment group using Kaplan-Meier survival estimation curves. Direct costs per treatment for each regimen were obtained from public hospital sources. Results: 71 patients were identified, 40 received DA-EPOCH-R, 31 received R-CHOP therapy. The DA-EPOCH-R group had a mean age at diagnosis of 62 years and a higher overall proportion under 70 years old (70%). The mean age for R-CHOP patients was 66 years and the patient age was largely equal for above and below 70 years at diagnosis. The majority of DA-EPOCH-R patients (77.5%) were stage III or higher at diagnosis compared to approximately half of R-CHOP patients (48.4%). Using a 6-year time horizon, there was no significant difference in Kaplan-Meier survival estimates between the two treatment groups for OS (p=0.58), PFS (p=0.48) or EFS (p=0.23). DA-EPOCH-R was found to be a more expensive treatment option in terms of total drug costs and hospital stay costs. Conclusions: DA-EPOCH-R was shown to have no significant difference in OS, PFS and EFS when compared to standard R-CHOP treatment overall in this population yet it is a significantly more expensive treatment option. The results of this study have not shown an economic or clinical advantage to the use of DA-EPOCH-R. It would be of interest to investigate this question in other high grade lymphomas.
Role of neutrophil to lymphocyte ratio in addition to revised international prognostic index (R-IPI) in patients with extranodal diffuse large B-cell lymphoma of head and neck.
Authors: Cisak Kamila Izabela , Gill Amitoj , Faber Erin , Redman Rebecca A. , Dunlap Neal E , Rai Shesh , Wu Xiaoyong , Perez Cesar Augusto
Published: September 2018

e19032

Background: Diffuse large B-cell lymphoma (DLBCL) is the most prevalent subtype of non-Hodgkin lymphoma (NHL). One third of DLBCLs cases have a primary extranodal origin and head and neck localization is second most common localization after gastrointestinal tract. The Revised-International Prognostic Index (r-IPI) is commonly used as prognostic tool, but there is growing evidence that neutrophil to lymphocyte ratio (NLR) also has prognostic significance in DLBCL. Methods: We retrospectively reviewed all cases of extranodal DLBCLs diagnosed between 2006 and 2016 at a single academic institution. Collected data included race, gender, primary site, baseline laboratory data, IPI score, pathology, treatment and survival. Results: A total of 33 patient were included, with 18 (54.5%) being females. Median age at diagnosis was 68 (range 28-92). 15% of patients had a r-IPI of 0, 30% a r-IPI of 1-2, 12% a rIPI of 3-5 and 36% a not evaluable (NE) r-IPI. Twelve (36%) patients had germinal center B cell subtype (GCB) and 17 (51%) patients had activated B cell subtype (ABC) by immunohistochemistry. Among all patients, 13 (39%) had pretreatment NLR equal or more than 3.5 and 11 (33%) patients had NLR less than 3.5 and 9 patients had a NE NLR. . Among deceased patients, 5 (56%) of them had NLR of more that 3.5 (p =0.011). Nine (27%) patients had pretreatment monocyte count less than 700/mm3 and 14 (42%) patients had monocyte count at least 700/mm3 (p=0.611). The 2-year overall survival was 77% (95% CI 0.61 - 0.93). Conclusions: (R-IPI) is the most common tool to predict outcome in DLBCL and our study showed that pretreatment NLR can be used as additional poor prognosis marker for patients with extranodal DLBCL of the head and neck. [Table: see text]
Impact of FDA approval of lenalidomide maintenance therapy in the first-line treatment of multiple myeloma after autologous stem cell transplant on total healthcare costs.
Authors: Xie Jipan , Parikh Kejal , Chen Christina , Yang Chelsey , Farrukh Adina , Cockrum Paul , Agarwal Amit Balkrishna , Abouzaid Safiya
Published: September 2018

e19509

Background: Lenalidomide maintenance therapy after autologous stem cell transplant (ASCT) in the first-line treatment has been shown to improve progression-free survival (PFS) and overall survival (OS) in multiple myeloma (MM) patients (pts). This study assessed the impact of FDA approval of lenalidomide maintenance therapy on total healthcare costs of a US health plan. Methods: A model was developed to estimate the incremental (additional) total plan costs (in 2016 USD) for maintenance therapy in each year for the first 3 years after lenalidomide monotherapy (R) maintenance therapy approval. The number of post-ASCT adult MM pts eligible for initiating maintenance therapy was estimated from published epidemiological data and an analysis of Connect MM Registry data. Clinical endpoints for R-maintenance, including time on treatment, PFS and OS, were obtained from a meta-analysis of published clinical trials (CALGB, IFM, and GIMEMA). The use of common off-label maintenance therapies was considered. Types of costs included in the model were drug, drug administration, adverse events (AE), AE monitoring, one-time progression and terminal care costs. Results: In a hypothetical health plan with 1 million members, the number of adult MM pts eligible to initiate post-ASCT maintenance therapy was estimated to be 28. Among them, 14.8 pts initiated R-maintenance in Year 1, 15.2 in Year 2, and 15.3 in Year 3, representing an incremental increase of 2.9%, 4.2% and 4.4% after R-maintenance therapy approval, respectively. After considering additional costs of maintenance, as well as potential offsets resulting from delayed progression the incremental total healthcare costs by year are listed in the table. Conclusions: Approval of lenalidomide monotherapy for maintenance after ASCT in the first-line treatment of MM has minimal impact on total plan costs, primarily due to the small incident population and the already common use of lenalidomide in post-ASCT maintenance. [Table: see text]
Differential response to carfilzomib based on initial therapy with bortezomib in multiple myeloma.
Authors: Yellapragada Sarvari , Ifeorah Chizoba , Fletcher Luke , Rivero Gustavo , Yasin Zahida , Krieger Jordan , Mulchandani Alka , Catic Andre , Mims Martha P.
Published: September 2018

e19515

Background: Proteasome inhibitors (PIs) are efficacious in multiple myeloma (MM). In randomized phase 3 studies Carfilzomib doubled the progression free survival (PFS) compared to Bortezomib from 9.4 mo to 18.7 mo (ENDEAVOR study) in relapsed and refractory MM. However concern for suboptimal Carfilzomib based therapy (CBT) response in patients (pt) progressing on Bortezomib based therapy (BBT) suggests “cross-resistance”. Methods: AfterIRB approval, all pt with symptomatic MM over the last 10 years at the Michael E. DeBakey VA Medical Center with initial BBT followed by salvage CBT at progression were included. The primary aim was to evaluate ORR (PR + VGPR+CR) and and PFS by the IMWG criteria, among relapsed/refractory pt treated with salvage CBT whether or not they had an initial BBT response (i.e., primary refractory+stable vs CR+PR+VGPR). Results: In this cohort, the median overall survival was 45 mo. Pt initially treated with BBT had an ORR of 17/19 (89.4%) and median PFS of 7.7 mo. For 12 pt attaining PR, PFS was 4.3 mo, whereas for those achieving CR/VGPR was 9.1 mo, p= 0.03. Two pt were primary refractory to BBT and also to CBT. For initially treated BBT responders the ORR with CBT was 68.4% (13/19), median PFS was 5.26 mo. 6/19 pt (32%) were CBT refractory. PFS during BBT for CBT responders versus CBT refractory patients was not statistically different. Among those who responded to both CBT and BBT there was no significant correlation between the PFS or depth of response (CR vs VGPR vs PR) with initial BBT and PFS with CBT. Conclusions: In our retrospective analysis, pt who exhibited primary resistance to initial BBT did not benefit from salvage therapy with CBT, raising the possibility that hard-wired PI-resistance mechanisms exist. Among BBT responders, CBT ORR was 68%. However the PFS with CBT was significantly shorter than the published literature of CBT in RRMM naïve to PI leading us to hypothesize that uncharacterized resistance mechanisms from “priming” bortezomib leads to inferior outcome with salvage CBT. We conclude that CBT can be attempted in those who respond to BBT independent of depth of response or PFS duration. However, alternative therapies should be considered in pt with primary refractoriness to BBT.
Blocking the formation of induced multiple myeloma stem-like cells through PI3K/AKT/mTOR pathway.
Authors: Liu Bingshan , Wang Danyang , Song Yongping
Published: September 2018

e19518

Background: Multiple myeloma (MM) is still an incurable disease. There are many different treatment options and most patients in the early treatment will have a good effect, but some patients will relapse due to acquired drug resistance. The purpose of this study is to investigate the existence of MM stem cells and its relationship with drug resistence. Methods: A total of 53 patients were recruited who underwent MM between 2010 and 2012. We analysed the expression of stem cell markers (Nanog, Oct4 and Sox2) and their relationship with clinical characteristics and 3– year disease free survival (DFS) or overall survival (OS). Then we chose MM cell line RPMI 8226 for the study, explored the possible mechanism of chemotherapy tolerance. Results: We found that that expression levels of Nanog, Oct4 and Sox2 were 11.3% (6/53), 17.0% (9/53) and 20.8% (11/53), respectively. Only positive expression of Sox2 had relationship with ISS stage ( p= 0.049). Furthermore, positive expression of Sox2 ( p= 0.039) was significantly associated with poor DFS. And after induced treatments, RPMI 8226 cells changed, including cell morphology, cell cycle, apoptosis, stem cell markers and changes in signal transduction pathways. Inhibiting PI3K/AKT/mTOR pathway can improve sensitivity to chemotherapy and radiotherapy. Conclusions: These findings demonstated stem cells markers had significant meanings in MM patients’ prognosis. There may be stem-like cells in MM, which is insensitivity to radiotherapy or chemotherapy, and blocking PI3K/AKT/mTOR pathway can reverse it.
Targeted radiopeptide therapy Re188-P2045 to treat neuroendocrine lung cancer.
Authors: Adams Christopher Peter , Saif Wasif M.
Published: September 2018

e20016

Background: : Despite the recent success of checkpoint inhibitors, there continues to be a significant medical need for lung cancer therapies that can be directed to the patients most likely to respond. Somatostatin receptor subtype 2 (SSTR2) is the most widely up-regulated subtype in both small and non-small cell lung cancers and is also expressed in tumoral (but not mature) blood vessels. Peptide targeted radiotherapy has advantages over traditional targeted therapies in that targeted tumor cells as well as surrounding cancer cells and supporting stroma are selectively killed. This study was conducted to determine the ability of Rhenium Re 188 P2045, a radiolabeled somatostatin analog specific for SSTR2 to both image (to select the most appropriate patients) and treat lung cancer patients who over-express somatostatin receptors. Methods: In an open label, single arm study, refractory lung cancer patients to standard of care therapy were identified by image analysis using Rhenium Re 188 P2045, a radiolabeled somatostatin analog. 25 Patients received the imaging dose of 10uCi of Re188 and 265ng of peptide by intravenous injection. Three patients were selected based on high SSTR expression levels to receive 30uCi of Re188 P2045 as a therapeutic dose 14 days after imaging. Patients were followed for 8 weeks post treatment. Results: The imaging study revealed a high density of expression of the somatostatin receptor in the lungs of patients. Patients in the imaging and therapeutic treatment groups reported no adverse advents or signs of toxicity. The image analysis using Re188 P2045 was compared to CT images and demonstrated accurate detection of lung tumor lesions. The images obtained using Re188 P2045 were of sufficiently high quality to enable identification of receptor expression at the tumor site as shown in Figures 1&2. Conclusions: Rhenium Re 188 P2045, a radiolabeled somatostatin analog, may be used to both identify and treat lung cancer tumors. The ability to image and dose patients with the same targeted molecule enables a personalized medicine approach and this highly targeted patient therapy may significantly improve treatment of tumors that over express somatostatin receptor.
Predicting tumor-immune response to checkpoint inhibitors using a novel patient-derived live tumor explant model.
Authors: Radhakrishnan Padhma , Goldman Aaron , Ulaganathan Baraneedharan , Thaya Kumar Allen , Maciejko Laura , Gertje Hans , Shanthappa Basavaraja U , Mehrotra Debapriya G G , Biswas Manjusha , Thiyagarajan Saravanan , Majumder Biswanath
Published: September 2018

e20035

Background: Immunotherapy has emerged as a powerful treatment paradigm wherein therapies primarily target immune components. For example, blockade of PD-1 and PD-L1 offers effective treatment options for patients with aggressive tumors such as head and neck squamous cell carcinoma (HNSCC) and in non-small cell lung carcinoma (NSCLC). However, clinical responses to immotherapy vary widely among patients. There is an unmet need to understand these disparities at the individual patient level. Rationally combining checkpoint inhibitors may address many of these underlying challenges. Methods: Here, we describe a patient-derived ex-vivo platform technology CANscript™, which captures the 3D profiles of native tumor microenvironment by incorporating tumor tissue, autologous immune cells, and immune-targeted agents. Utilizing late stage HNSCC and NSCLC patient tumors we interrogated the phenotypic changes in the tumor-immune contexture in response to standard-of-care agents, PD-1 and PD-L1 inhibitors. Flow cytometry and immunohistochemistry profiling of CD8, CD45, FOXP3, CXCR4, CD68, PDL1, PD1), cytokine profile (IL6, IL8, IFN-g, IL12 and others), and tumor proliferation/apoptosis were measured. Results: The data suggest that PD-1 and PD-L1 blockade induced patient-specific response, which was characterized by differential distribution and infiltration of CD8+ and CD4+ lymphocytes, distinct patterning of cytokines linked to functional dysregulation, and changes in tumor proliferation and apoptosis. Interestingly, the data demonstrated unique immune signatures associated with single agent vs. combination therapy that imply functionally distinct mechanisms of orchestration of response. Conclusions: Our data highlights the translational underpinnings of of CANScript™ as an ex vivo platform for predicting patient driven therapeutic response of immune checkpoint inhibitors where distinct tumor-immune networks influence clinical response to therapy. Information obtained from this study can re-shape our understanding of patient selection and rational combinations for novel immune checkpoint inhibitors.
Real-world data evaluating the value of PET-CT for mediastinal staging in patients diagnosed with non-small cell lung cancer in an area with high prevalence of granulomatous diseases: The LACOG-0114 study.
Authors: Fritscher Carlos Cezar , Zanini Mara Lise , Berdichevski Eduardo Herz , Vilas Eduardo , Hochhegger Bruno , da Silva Vinicius Duval , Pinto José Antônio Figueiredo , Fritscher Leandro Genehr , Hartmann Louise , Alba Marcos , Sartori Guilherme Parisotto , Matushita Cristina , Vieira Arthur , Bortolotto Vanessa Rezende , do Amaral Rayssa Ruszkowski , Zaffaroni Facundo , Martínez-Mesa Jeovany , Werutsky Gustavo , Barrios Carlos H. , Debiasi Marcio
Published: September 2018

e20065

Background: Evaluation of the mediastinum is critical for therapeutic decision in patients with operable non-small cell lung cancer. This analysis aims to evaluate specificity and positive predictive value (PPV) of PET-CT in mediastinal staging of patients diagnosed with NSCLC in South Brazil, an area with high prevalence of infectious granulomatous disease, such as tuberculosis (estimated incidence of 45 cases/100.000 and only 63.7% of cure rate) (http://www.saude.rs.gov.br/upload/1459169540_RELATÓRIO%20TUBERCULOSE%202016.pdf). Methods: Patients with stages I-III NSCLC underwent 18FDG PET-CT before invasive mediastinal staging. Different SUV cut-offs were evaluated, but for the purpose of this analysis were considered positive all PET-CTs showing any mediastinal uptake > 5 SUV. This abstract shows the specificity and the PPV associated with PET-CT when this high-uptake cut-of is considered. Results: From Aug/2014 to Aug/2016, 100 patients were enrolled, all treated at the Brazilian Public Health System, of which 85 were submitted to mediastinoscopy after PET-CT. Median age was 65 years (range 47-80). At baseline, 49 (58%) patients were male and 68 (80%) white. Current or former smokers accounted for 94% (80/85) of the sample. The prevalence of mediastinal involvement was 27% (23/85) confirmed by histopathological evaluation. PET-CT showed specificity of 79% (95% CI 67%–88%) and PPV of 54% (95% CI 40%–67%) when a SUV > 5 was used as cut-off for positivity (see table). Conclusions: These findings consolidate the clinical impression that a positive PET-CT does not confirm the diagnosis of mediastinal involvement in NSCLC patients treated in areas with high prevalence of infectious granulomatous diseases. In this scenario, all positive findings should be confirmed with histopathological evaluation to assure the diagnosis. Clinical trial information: NCT02664792. [Table: see text]
Concurrent chemoradiation (CChRT) for locally advanced stage III non-small cell lung cancer (NSCLC) with cisplatin and vinorelbine and thoracic radiotherapy: A phase II study from the Galician Lung Cancer Group.
Authors: Gomez Garcia Susana , Costa Rivas Marinha , Areses Manrique Mª Carmen , Fernández Núñez Natalia , Garcia Jorge , Caeiro Manuel , Castro Enrrique , Formoso Ines , Calvo P , De Dios Alvarez Noemi , Firvida Jl , Campos Begoña , Azpitarte Cristina , Afonso Francisco Javier , Amenedo Margarita , Casal Rubio Joaquin
Published: September 2018

e20067

Background: Platinum-based CChRT is recommended as the evidence-based approach for the management of patients (p) with locally advanced stage III NSCLC and a good performance status, although a clearly superior regimen has not been identified. The aim of our study was to evaluate the effectiveness and toxicities of CChRT with Cisplatin (C) and intravenous and oral vinorelbine (V) and thoracic radiotherapy. Methods: 39 p with histologically confirmed inoperable locally advanced NSCLC, stage IIIA (T4 or N2)/IIIB, PS 0-1 and adequate lung function (FEV1 > 1.1, V20 < 30%) were included in CChRT with: C 80 mg/m2 day 1 and intravenous V 25 mg/m2 day 1 and oral V 60 mg/m2 day 8 for three cycles, during conformal radical thoracic radiotherapy (66 Gys, 180 cGy/day). The primary objective was overall survival (OS); secondary objectives were progression free survival (PFS), response rate (RR) and toxicity. Median follow-up: 20,4 months. Results: The p characteristics were: mean age 69,8 years (44-75); male/female: 33/6; ECOG PS 0/1: 7/32; adeno/squamous/large cell carcinoma: 20/13/6; stage IIIA 19 p and stage IIIB 20 p. All p were evaluable for response and toxicity. RR: 3 CR, 27 PR (RR 77%; 95% CI: 64-90), 5 SD (12.8%) and 4 PD (10.2%). The median PFS was 12 months (95% CI: 7-17) and median OS was 36 months (95% CI: 14-58). The PFS at 1/3 years were 46%/22% and the OS at 1/3 years were 75%/47%. Main toxicities (NCI-CTC 4.0) per p in CChRT (109 cycles of chemotherapy, 2.9 per p; mean doses RT: 65,3 Gys) grade 1-2/3-4 (%) were: neutropenia 32.4/25.6; anemia 32.4/10.8; thrombocytopenia 13.5/2.7; nausea/vomiting 27/2.7; fatigue 28.2/0; esophagitis 43.5/5.4 and pneumonitis 17.9/0; hospitalizations were necesary in 13 p: the most important were febrile neutropenia (6 p) and grade 3 esophagitis (2 p). Conclusions: CChRT with Cisplatin and intravenous and oral Vinorelbine during thoracic radiotherapy is a feasible treatment option for inoperable locally advanced stage III NSCLC, showing good clinical efficacy and tolerability with excellent long-term survival.
Spatio-temporal distribution of lung cancer mortality rate in Peru: 2005-2014.
Authors: Flores Claudio J. , Torres-Roman Junior S , Mas Luis , Ruiz Mendoza Rossana Esther , Samanez Cesar Augusto , Aguilar Alfredo , Vallejos Sologuren Carlos
Published: September 2018

e20081

Background: Lung cancer still remains as the principal death cause in many regions around the world. Its mortality varies according to the regions and study periods. In Peru it represents the sixth most frequent malignant neoplasm and the fourth cause of cancer related death. We reported the spatial autocorrelation and the temporal variation in lung cancer mortality rate in Peru. Methods: Data of lung cancer mortality in Peru between 2005-2014 was obtained from the Ministry of Health. Information on the number of inhabitants was obtained from National Institute of Statistics and Informatics. Age standardized mortality rate (ASMR) was calculated based on the 2011 world standard population. Spatial autocorrelation was determined according to Moran’s Index and the Local G Cluster Map to explore the cluster patterns between regions. Results: During the study period 16,839 deaths due to lung cancer were reported. The lung cancer mortality rate in Peru increased from an ASMR of 12.8 (95% CI: 11.9-13.7) by 100,000 persons in 2005 to 13.4 (95% CI: 12.5-14.3) in 2014. According to the quartiles, the ASMR was higher in the north, south and east, and lowest in others regions. The spatial distribution of the ASMR showed a significant spatial autocorrelation (Moran´s I: p = 0.025). Also, during the study period, the ASMR showed a significant increase and decrease in some regions and in others it was constant. Conclusions: In Peru, lung cancer mortality rate showed a spatial and temporal variation in different regions. The increase in mortality rate in some regions requires identification of risk factors in order to establish public measures to reduce the risk of lung cancer mortality.