bluuebunny/crossref_metadata_2025 huggingface dataset:
How effective is telephonic case management of cancer patients undergoing active therapy?
Authors: Wu Charlotte , Bannister Wade M , Chan Hungching , Schumacker Pam , Rosen Michael W , Blair Kelly L , Rossof Arthur H
Published: March 2020

e17519

Background: The Cancer Support Program (CSP) of Optum provides patients and their caregivers with telephonic case management by experienced oncology nurses, social workers and appropriately-trained physicians. Goals include reducing emergency department visits and hospitalizations, and helping patients comply with treatments and more effectively manage symptoms. The intent of this study is to evaluate the effectiveness of CSP from both quality and financial perspectives. Methods: The study used a case control approach to compare participants and non-participants of the Optum CSP program. Propensity score method was applied to adjust for baseline differences between the two groups. The study population consisted of cancer patients (N=8,833) enrolled in commercial health plans through self-insured employers. The patients were referred into CSP between July 2009 and June 2011. Outcomes of cost and hospice days were estimated with generalized linear models. We also compared the group of CSP participants (N=3,716) to active cancer patients enrolled in a general CM program (N=2,867) on the topics the nurses discussed with patients. Results: For program participants who were under active treatment and survived at least 6 months after referral , medical cost per patient per month during the six month of engagement was reduced by 9.8% (95% confidence interval [3.7%, 15.6%], p-value 0.002). The decedent’s cost during the last 3 months of the life was reduced by 19.9% (95% confidence interval [2.8%, 34.1%], p-value 0.025). Average hospice days of all deceased CSP participants increased by 42.3%, (95% confidence interval [13.9%, 77.8%], p-value 0.002). CSP nurses, all of whom had cancer management experience, addressed 56 topics of cancer-related support compared to only 11 for general CM nurses. Among the topics that both groups addressed, 35% of the topics were addressed 10% or more frequently by CSP nurses, including “Cancer Treatment Choices Outlined” and “Education Provided: Cancer Medications” etc. Conclusions: We conclude the Optum CSP program is effective in reducing medical cost, promoting use of hospice and providing cancer-specific patient support for a population of cancer patients under active treatment.
The cost of treatment-related adverse events in metastatic breast cancer therapy: Taxanes versus capecitabine.
Authors: Hansen Ryan N , Brammer Melissa G. , Ramsey Scott David , Lalla Deepa , Hurvitz Sara A. , Sullivan Sean D
Published: March 2020

e17527

Background: Over 73,000 women annually experience new or recurrent metastatic breast cancer (mBC) in the U.S. Chemotherapy can prolong survival with mBC but adverse events (AEs) from chemotherapy are common, costly to manage and may lead to changes in clinical outcomes. We evaluated the difference in cost of treatment for taxane- (TAX) and capecitabine-based (CAP) treatments for mBC patients in the U.S. focusing on the incremental impact of AEs on the cost of care. Methods: A cohort of mBC patients diagnosed from 2008-2011 was identified from the Truven Marketscan® Database. Patients were grouped into chemotherapy categories of either TAX (paclitaxel or docetaxel) or CAP using claims data. Common chemo-related AEs were identified by ICD-9 codes. Healthcare costs were tabulated from a payer perspective, adjusted to 2011 U.S. dollars. To control for selection bias, propensity scores for treatment selection were calculated using age, diagnosis, health plan type, and renal or hepatic insufficiency as predictors. Generalized linear models estimated the cost of treatment by medication type and the presence/absence of AEs. Results: From 52 million subjects, we identified 13,474 mBC patients that met inclusion criteria. We identified 11,902 patients treated with TAX and 1,572 treated with CAP. At least one AE was experienced by 69% (S.D. = 0.46) of TAX users and 56% (S.D. = 0.50) of CAP users. The most common AEs were infection (39%), neutropenia (27%), and anemia (20%) for TAX users. CAP users most commonly experienced infection (36%), anemia (11%), and dyspnea (11%). Average incremental monthly costs were $3,082 and $6,793 for TAX and CAP patients with an AE compared to those who did not experience an AE, respectively. Costs increased by $1,358 for patients with 1-2 AEs (p=0.0002), $2,433 for 3-4 AEs (p<0.0001), and $5,294 for 5+ AEs (p<0.0001). Conclusions: Among community-treated patients, AEs are common in women with mBC receiving TAX and CAP based chemotherapy regimens. Persons experiencing these AEs have substantially higher healthcare costs which increase with the number of AE’s reported. Better management of AEs may represent an opportunity to significantly reduce costs and improve outcomes for women with mBC.
Factors affecting time to seeking medical advice and start of treatment in breast cancer (BC) patients in Turkey.
Authors: Ozmen Vahit , Boylu Sukru , Ok Engin , Canturk Zafer , Celik Varol , Kapkac Murat , Girgin Sadullah , Tireli Mustafa , Ihtiyar Enver , Demircan Orhan , Baskan Mazhar Semih , Koyuncu Ayhan , Tasdelen Ismet , Dumanli Esra , Ozdener Fatih
Published: March 2020

e17529

Background: One of the most important reasons of BC mortality is delay in treatment. Due to lack of BC awareness and organized screening programs, total delay time (from first symptoms of BC to initiation of treatment; TDT) is longer in low-middle income countries. The primary goal of this survey was to identify factors affecting TDT in patients with BC. Methods: As a part of previously presented multinational survey, a total of 1.031 BC patients from 12 cities of 5 districts in Turkey were surveyed using a uniform questionnaire. TDT was determined using 8 individual scales, including one pertaining to patient delay and 7 related to subsequent steps in a typical diagnostic process. Regression models were constructed using 17 variables concerning diverse contextual and personal patient characteristics. Time between first symptom and first medical visit (Patient Delay Time; PDT) and time between first medical visit and start of therapy (System Delay Time; SDT) were modeled separately with multilevel regression. Results: Mean PDT, SDT and TDT were 4.8, 10.5 and 13.8 weeks respectively, with 42% of the patients with a delay of >12 weeks. Multilevel regression equation indicated that disregard of discovered symptoms (p<0.001) and having at least secondary level of education (p=0.021) were significantly correlated with longer PDT. Patients with stronger self-examination habits (p=0.009), reporting more support from friends and family (p<0.001) and living in metropolitan areas (>500k) (p=0.006) had shorter PDT. Predictors of longer SDT included disregard (p<0.001) and having a PDT>4 weeks (p<0.001). Shorter SDT was correlated to being older than 60 years of age (p=0.027). Results revealed that diagnosis during periodic check-up or opportunistic mammography vs. symptomatic BC (p<0.001) and having first medical examination by a surgeon resulted in shorter SDT. Conclusions: TDT in Turkey is unacceptably long and system delay accounted for a substantial part of the total delay experienced by breast cancer patients. This points to a need for shortening clinical pathways if possible. A long patient delay calls for research into patient awareness of BC.
Past medical history (PMH) in oncology: Which is the best source, the doctor or the patient? A prospective double blind study.
Authors: Montiel Monica , Garcia Gerardi Carlos Fernando , Gil Deza Ernesto , Morgenfeld Eduardo L. , Martin Reinas Gaston , Rivarola Edgardo G. J. , Gercovich Felipe G.
Published: March 2020

e17539

Background: The usual way in which Argentinean doctors (Dr) register a patient’s (Pt) PMH in the Clinical record (CR) is the anamnesis. It has proved to be quite heterogeneous. At the Instituto Oncológico Henry Moore (IOHM) a PMH form was designed to be filled out by the Pt before the interview. The objective of this paper is to compare and contrast the amount and quality of PMH information registered by Pt and Dr through a double blind study in order to assess the usefulness of the PMH form. Methods: Between Dec 13th and Dec 20th, 2012, data was collected from all new Pt assisted at the IOHM. In the case that the PMH registered a severe pre-existing condition that was not present in the CR, the physician in charge was made aware of this fact. By indication of the IRB, an interim analysis had to be carried out a week after the study had begun. If the quantity of information proved to be 25% greater or the quality proved to be 5% greater in favor of Pt, the study should be finished. Results: A total of 73 P were included in a prospective double blind study. Sex: 42 males/31 females; Mean age 58.7y (range 21-88); Tumor diagnosis: urological 24, gynecological 17, gastrointestinal 11, other 21. PMH forms filled out by Pt showed 878 pre-existing medical conditions: mean 12 (range 1-35); the CR filled out by Dr showed 453 pre-existing medical conditions: mean 6 (range 0-21). In 3 CR, Dr registered data that Pt had not. A total of 67 CR (92%) showed less data than the PMH, Mean 6 (range 1-21). Quality analysis demonstrated that 15% of the unregistered data could be relevant in medical decisions. Due to the overwhelming differences between registries, the study was finished and the Pt´s PMH form was included as part of the CR at the IOHM. Conclusions: 1) The quality and quantity of data acquired by using the PMH form far exceeds that of the data registered by doctors in CR. 2) In 15% of all the cases, this information could be relevant in medical decision making. 3) In only 3 cases, doctors registered more data than patients using the PMH form. 4) A form filled out by the patient and reviewed by the doctors could be a significant tool on preventing malpractice.
Adherence and patients’ attitude toward oral anticancer drugs: A prospective series of 226 patients focusing onto targeted therapies.
Authors: Barthelemy Philippe , Dourthe Louis-Marie , Serra Sebastian , Asmane-De la Porte Irene , Prim Nathalie , Ame Shanti , Litique Valere , Giron Cathy , Goldbarg Veronica , Fornecker Luc , Duclos Brigitte , Kurtz Jean Emmanuel
Published: March 2020

e17543

Background: Patients’ adherence has been identified as a challenge in oncology and hematology practice. Hormone therapy data in breast cancer suggest insufficient adherence and poor persistence. Limited data is available for targeted therapies such as tyrosine kinase (TK) and mTOR inhibitors whereas poor adherence to TK treatment was linked to treatment failure in GIST and CML. Methods: We report the result of a prospective survey in 226 patients (pts), with solid tumors and hematologic malignancies receiving oral anticancer therapy including chemotherapy or hormone therapy (CT), and targeted therapies (TT). Treatment duration and setting (adjuvant vs metastatic), cancer type, age, co-medication were analyzed. Patients were given a 15-item questionnaire and asked to anonymously answer questions regarding their attitude towards oral anticancer drugs. To analyze adherence, patients were asked whether they voluntarily or not missed any drug dosing during the last month. Results: 226 patients (median age 65.5 y.o) participated, 115 with TT and 111 with CT, with a median time of drug intake of 10.5 months. Both TT and CT patients stated to be well informed about treatment modalities in (92%), mostly by their oncologist or hematologist (87%). Written information was more frequently given in TT pts (67.0 vs 27.0%, p<0.0001). TT pts declared to be more often fully adherent to therapy (84.3 vs 66.7%, p=0.01) despite experiencing more side-effects (p<0.0001) and taking more concomitant oral medication (p=0.029). The mean treatment duration was 28.0 vs 20.3 months in TT vs CT pts (NS), but in both groups non-adherence was observed at any time since initial prescription. Conclusions: Despite advances in patients’ information leading to better treatment adherence in TT pts, efforts are still warranted such as the onset of dedicated staff for early and prolonged monitoring of outpatient anticancer oral therapy.
Economic growth of BRIC nations and access to early-phase oncology clinical trials: An overview.
Authors: Rodrigues Heloisa Veasey , Ganesan Prasanth , Liu Xiaochun , Subbiah Vivek
Published: March 2020

e17554

Background: With increasing globalization we have witnessed exponential economic growth in the BRIC (Brazil, Russia, India and China) nations. Concurrently, clinical trials have been outsourced to these countries. We sought to investigate the current status of early phase oncology clinical trials in the BRIC countries, exemplifying the impact of these emerging economies and global markets in health care. Methods: We reviewed the clinicaltrials.gov database for registered early phase trials (Phase I/II) in the BRIC countries; 2. We looked at research from these countries collectively. 3. We reviewed specific challenges and prognosticated the road ahead through a literature review. Results: We identified374 active early phase clinical trials in BRIC countries as of October 2012. China had 68% (255/374) of the trials, Brazil 14% (51/374), Russia 12% (47/374) and India 6% (21/374). Twenty-three trials were registered in more than one BRIC; therefore we analyzed 348 different trials. Gastrointestinal (20%, 70/348), lung (19%, 67/348) and breast (17%, 57/348) cancers were the most studied. Most of the trials were sponsored by universities or hospitals (51%, 176/348) and most conducted in a single country (73%, 247/348) with 70% of therapy intended to be palliative (243/348). Combined agents were most commonly studied (57%, 199/348). Among the 217 targeted-agent trials, 23% targeted the EGFR pathway, 18% the VEGFR, 11% involved multi-tyrosine kinase inhibitors and 10% the PI3K-mTOR pathway. Funding mechanisms and sponsorship of studies were disparate. Industry-sponsored studies comprised 24% (62/255) in China, 96% (45/47) in Russia, 80% (41/51) in Brazil and 57% (12/21) in India. Conclusions: Despite theeconomic explosion and shift of non-oncology clinical trials to BRIC nations, USA and Europe still lead in conducting early phase clinical trials in oncology. China accounts for 19% of world’s population and has the majority (68%) of trials while India (17% of World’s population) has only 6%. A dominance of industry-sponsored studies in BRIC countries other than China was found. Significant challenges in infrastructure and trained personnel remain, but efforts to overcome them are underway.
Usability testing of the PRO-CTCAE measurement system in patients with cancer.
Authors: Fawzy Maria R. , Abernethy Amy Pickar , Schoen Martin W. , Rogak Lauren J. , Mendoza Tito R. , St. Germain Diane C. , Paul Diane B. , Baumgartner Paul , Gangoli Vinay , Chilukuri Ram , Mitchell Sandra A. , Reeve Bryce B. , Castro Kathleen M. , Shalley Eve , Basch Ethan M.
Published: March 2020

e17560

Background: Use of electronic Patient-Reported Outcomes (ePROs) are increasingly employed in patient care and oncology research. However, these systems can be difficult to use, preventing adoption and deployment. The objective is to evaluate the patient usability of the National Cancer Institute’s (NCI) Patient Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) Measurement System. Methods: PRO-CTCAE is an item bank of 124 questions evaluating 78 symptomatic adverse events, as well as a software system that includes a web-based and interactive voice response system [IVRS] to administer these items to patients, and electronic features to customize survey creation, schedule survey administration, export data, and generate alerts and reports. A protocol was developed for two rounds of usability testing to evaluate understanding and ease of navigation reported by patients undergoing cancer treatment. Software was refined between rounds and retested. Patients were asked to login and complete PRO-CTCAE items either in clinic or at home, then were immediately debriefed (semi-scripted) by a trained interviewer. Results: 173 patients at 3 cancer centers and affiliated community network sites were enrolled in the study between 1/11-5/12 (45% male; 32% non-white; 26% high school or less). Usability issues identified in Round 1 (N=37) included difficulty in using radio buttons, absence of survey progress indicators, and problems with system login. Modifications included increasing size of buttons, improving the progress bar feature, and simplifying the interface to focus users on survey questions. In Round 2 (N=136), remaining issues were related to general difficulty with Internet use, such as navigating to the URL. IVRS testing indicated high scores of ease of use and completion of items, but users had difficulty adding unique symptoms to the system. Conclusions: Iterative usability testing identified improvements to web-based and IVRS for patient self-reporting and achieved a more favorable user experience. The feasibility of integrating PRO-CTCAE into trials to gather symptomatic adverse events directly from patients is currently being evaluated in the cancer cooperative groups.
Patient barriers to participation in clinical trials in a community cancer center.
Authors: Ramakrishnan Geethakumari Praveen , Ackler Joann R. , Gooptu Mahasweta , Braitman Leonard E , Tester William J.
Published: March 2020

e17578

Background: Clinical trials are fundamental to research and innovative oncology treatment. Participation rates in trials have declined nationally to < 5%. Barriers to participation exist at patient, physician and protocol levels. Methods: We conducted a descriptive cross-sectional study in a community cancer center serving a diverse patient population. A total of 160 eligible patients offered enrollment in various clinical trials from July 2010-December 2012 were included. A standardized questionnaire was delivered by mail or in person. Electronic medical records and patient charts were used for disease specific data. Acceptors and decliners were compared using Fisher’s exact test for nominal variables and t test for normally distributed continuous variables. Results: Forty-nine patients (males: 9, females: 40) returned the questionnaire. Twenty-eight had accepted and 21 declined trial participation. Mean age of acceptors was 56.2 ± 2.2 compared to 63.96 ± 1.6 for decliners (p=0.007). Acceptance was highest for stage IV disease (85.71%) [p=0.077]. Of foreign-born patients, 71.4% patients were decliners [p=0.122]. Of those “comfortable with randomization,” 85.2% were acceptors compared to 22.7% who were not [p<0.001]. Of respondents encouraged by knowing that they could leave the study at any time and receive standard treatment, 79.4% were acceptors [p<0.001]. Of patients who valued trust in their doctor, 85.7% accepted compared to 19.05% who did not [p<0.001]. Among most important reasons for their decision, acceptors valued altruism, contribution to research, trust in doctor and hope for cure while decliners mentioned uncertainty in research, drug side effects, depression and need for family support. Conclusions: Results confirm barriers among diverse patients treated in a community cancer center and suggest the type of patient likely to participate in clinical trials. Study limitations include small sample size and majority of female respondents. Key factors included age, patient’s insight into the conduct of randomized trials, perceived drug side effects and the doctor-patient bond. Success lies in bridging knowledge and communication gaps, careful protocol design, and establishing trusting relationships.
Unescheduled visits in cancer patients treated in a clinical trials unit (CTU).
Authors: Gaba Lydia , Victoria Iván , Reig Óscar , Lopez Sandra , Gascon Pedro , Vidal Laura
Published: March 2020

e17580

Background: A number of unscheduled visits may occur in addition to the predefined protocol-specific visit calendars in a CTU. The aim of this prospective study was to characterize and assesss the frequency, causes and the probable relationship of the emergencies with the investigational products (IPs). Methods: A consecutive sample of patients treated in a CTU who presented an urgent medical consultation from July 2012 to January 2013 was registered. Epidemiological data, characteristics of emergency visits and relationship with IPs were revised. Results: 141 patients were registered; 75 men (53.2%) and 66 women (46.8%) with a median age of 61.4 years. Most of them had metastatic cancer and 63 patients (44.7%) had been included in phase III clinical trials. Tumors which produced a higher number of events were melanoma (n=53, 37.6%), colorectal (n=24, 17%) and breast cancer (n=21, 14.9%). Those treatments associated with more unscheduled consultations were chemotherapy agents, Braf inhibitors and antiEGFR antibodies. Of those, 45.4% were in-person consultations, whereas the 54.6% were performed by phone. The main causes were pain (18.4%), diarrhea (12.1%), fever (12.1%) and skin symptoms (10.6%). 48.9% were related to an adverse event of the IPs. 78.7% of the consultations were oriented and specifically treated at the moment of the appointment, whereas the 21.3% had to be referred to another service. 36.2% of the unscheduled visits were directly related with the IPs. Of those, 30% were 3-4 graded. Conclusions: Patients treated on a clinical trial generated an elevated number of unescheduled visits and a significant percentage of them are related to the IPs. Most of them should be managed by staff with the appropriate knowledge and training.
HIV-associated lung cancer in New York City.
Authors: Levy Benjamin , Chintapatla Rangaswamy , Suarez Jaime , Connery Cliff P. , Bhora Faiz Y. , Evans Andrew , Choi Walter , Rohs Nicholas , Becker Daniel Jacob
Published: March 2020

e17589

Background: Recent evidence suggests that HIV may be a risk factor of lung cancer, independent of smoking . Due to the expanding population of HIV patients with lung cancer, there is a need to define the clinical course and tumor biology of these patients. Our analysis seeks to characterize the clinical and molecular features of HIV associated non small cell lung cancer (HIV-NSCLC) and evaluate outcomes in a New York City Cancer center that serves a racially and economically diverse population. Methods: We searched the Continuum Cancer Center Registry for cases of HIV-NSCLC diagnosed from 2002 to 2012. Charts were reviewed to determine patient and tumor characteristics, treatment and outcomes. Kaplan-Meier curves were constructed for survival and compared by means of the log rank test. Patient characteristics were compared to national data from the SEER database. Mutational analysis of archival tissue was performed by OnkoMatch Tumor genotyping. Results: HIV-NSCLC was idenfied in 74 patients. Median age (MA) was 55 compared to MA of 70 for non HIV-NSCLC. Patients were predominantly male (72%). Histology distribution was reflective of the non-HIV population (SEER): adenocarcinoma [31 (42%)], squamous [18 (24%)], NSCLC NOS [8 (11%)], poorly differentiated [6 (8%)], and other [9 (15%)]. Distribution of stage was similar to SEER with 39 (53%) patients presenting with stage IV. Lowest recorded CD4 count was <200 in 34 patients (68%) with available CD4 counts. Chemotherapy and radiation were administered to 28 (49%) and 19 patients (31%), respectively. Median survival was 5.2 months. Kaplan-Meier curves were not statistically different by CD4 count (> or < 200), or by receipt of chemo or radiation. Mutational analysis on 7 patients demonstrated 3 with cMet overexpression, 2 KRAS mutations and 1 BRAF mutation. Conclusions: Among our HIV-NSCLC cohort, patients were diagnosed at younger age, but had similar stage and histology distributions as SEER database averages. HIV associated lung cancer appears to have a poor prognosis similar to that of the general population. Rates of treatment were low in our cohort and the potential for undertreatment warrants further study. Observed increased rate of cMET overexpression should prompt further molecular profiling in this population.
The risk of debilitating falls (DF) in Manitobans living with cancer.
Authors: Gingerich Joel Roger , Lambert Pascal , Doupe Malcolm , Pitz Marshall W. , Daeninck Paul Joseph
Published: March 2020

e17596

Background: Falls and fall-related injuries pose important patient safety challenges. We sought to measure if cancer patients are at increased risk of DF. Methods: This retrospective population-based study was conducted by linking the Manitoba Cancer Registry with health care use records from Manitoba, Canada. All community-dwelling patients who were diagnosed with cancer from 2005-08 were matched with up to three cancer-free controls. DF were defined as falls requiring hospitalization and were identified using ICD-9 and -10 billing codes. A competing risk model was used to compare DF between cancer and cancer-free cohorts and expressed as sub-hazard ratios (SHR). Comparisons across groups were adjusted for age, sex, medication use, region of residence, and the presence of co-morbidities. Results: 22,327 cancer patients were matched to 67,927 controls. The median age was 66.5 years, and the median length of follow-up was 1.98 years. The cumulative 1 and 3-year incidence of DF are shown in the Table. (The adjusted risk of DF was significantly decreased in cancer patients versus matched controls ≥ 80 years old; SHR = 0.82 (95% CI: 0.57 – 0.97, p = 0.03). The adjusted SHR for stages I, II, III and IV in those ≥ 80 were 0.83 (95% CI: 0.64 - 1.09, p 0.18), 0.69 (95% CI: 0.51 - 0.93, p = 0.02), 0.56 (95% CI: 0.38 - 0.83, p < 0.01), and 0.45 (95% CI: 0.31 - 0.66, p < 0.01), respectively. Conclusions: The risk of DF in cancer and non-cancer patients increases with age. When compared to matched controls, only cancer patients ≥ 80 with advanced stage cancers were at decreased risk of DF. This finding is likely due to the higher competing risk of death in cancer patients (i.e., of those ≥ 80, 40.2% with cancer versus 4.0% without cancer die within one year). [Table: see text]
Survival trends among patients with acute myeloid leukemia in the United States.
Authors: Uprety Dipesh , Ghimire Krishna Bilas , Nepal Barsha , Shah Binay Kumar
Published: March 2020

e17598

Background: The chemotherapy regimen for acute myeloid leukemia (AML) has not changed significantly over the last two decades. Better patient care may have improved survival in AML patients. This study was conducted to evaluate the relative survival rates in AML patients over two decades in the United States. Methods: Adult patients (age≥20 years) diagnosed with AML were selected from the Surveillance, Epidemiology, and End Results (SEER) database. Several cohorts categorized by race (Caucasians & African-Americans (AA)), gender & age (20-59, ≥60 years) were compared to see survival differences from 1992-2000 & 2001-2009. We used SEER Stat software to calculate 1- and 5-year relative survival rates (RS). The survival rates accompany standard errors. Results: The database comprised of 28,217 patients. The relative survival rates of AML improved significantly during 2001-2009 compared to 1992-2000 1-year 39.2±0.4 vs 33.7±0.5,( Z score 9.079, p<0.0005); 5- year 20.1±0.4 vs 15.3±0.4, (Z score 10.357, p<0.0005). The 1-and 5-year RS for men during 1992-2000 vs 2001-2009 were 32.3±0.7% vs 39.2±0.5% (Zscore=8.392, p<0.0005) & 13.9±0.5% vs 18.7±0.5% (Zscore= 8.710, p<0.0005) respectively. For women, the survival rates during 1992-2000 vs 2001-2009 were 35.3±0.7% vs 39.1±0.5% (Zscore=4.318, p<0.0005) at 1-year & 16.9±0.6% vs 21.7±0.5% (Z score=5.917, p<0.0005) at 5-years. For younger patients (<60 years), relative survival rates at during 1992-2000 and 2001-2009 were: 1- year: 56.7±0.9 vs 63.5±0.6, (Z score=6.462, p<0.0005); 5- year: 33.0±0.8 vs 40.6±0.7, (Z score= 7.070, p <0.0005). Similarly, the survival rates were significantly better for older patients and for all ethnic groups during 2001-2009 compared to 1992-2000. Conclusions: The relative survival in AML has increased significantly during 2001-2009 compared to 1992-2000. This may be secondary to improvement in supportive care.
Outcomes of invasive fungal infections in hematopoietic stem cell transplant patients.
Authors: Shaheen Shagufta , Upadhyay Shivanck , Marak Creticus Petrov , Kumar Gagan , Guddati Achuta Kumar
Published: March 2020

e18008

Background: Invasive fungal infections are associated with higher mortality in hematopoietic stem cell transplant (HSCT) recipients despite the use of broad spectrum antifungal agents. With the increase in the number of patients undergoing HSCT and a newer array of immunosuppressants, it is necessary to examine the incidence and outcomes of fungal infection in this population. Methods: We used Nationwide Inpatient Sample from years 2000 to 2008 to examine the trends and outcomes of fungal infections in patients admitted for HSCT. We used ICD-9-CM codes to identify those with HSCT. Similarly we identified invasive fungal infection using ICD-9-CM codes. The engraftment period and subsequent admissions were examined separately. Outcomes studied were in-hospital mortality and length of hospital stay. Logistic regression analysis was used to identify independent association of fungal infection with mortality. The model was adjusted for demographic and hospital characteristics, Charlson's co-morbidity index and severity of sepsis using number of organ failures. Results: There were 291,182 admissions with HSCT from 2000 to 2008. Of these, 3.4% patients had invasive fungal infections. They were more frequent in allogenic transplant during the engraftment period (4.2%) and in those with graft versus host disease (GVHD) in subsequent admission (7.1%). The unadjusted in-hospital mortality was significantly higher in those with invasive fungal infection (28% vs. 7%, p<0.001). On adjusted analysis, the odds of mortality were highest for those with mucor (OR 4.3;95%CI 2.5-7.5) and aspergillus (OR 3.7; 95%CI 3.1-4.5) infections while the results did not reach significance for candidemia. The length of hospital stay was significantly longer in those with invasive fungal infections (median 19 days vs. 7 days, p<0.001). Conclusions: Fungal infections are common in HSCT recipients - especially in those with allografts and with GVHD. Mortality is high and is mostly associated with aspergillus and mucor. A higher index of suspicion for fungal infections in HSCT patients, strict isolation precautions and increased surveillance for aspergillus and mucor in HSCT patients may help decrease the length of hospital stay and mortality.
Transforming growth factor-beta gene polymorphisms and acute graft-versus-host disease.
Authors: Kanangat Sivadasan , Basu Sanjib , Kurbecovic Ina , Prod Michele , Maciejewski John Joseph , Nathan Sunita , Fung Henry C. , Rich Elizabeth Shima
Published: March 2020

e18013

Background: Despite allele level HLA matching, graft-versus-host disease (GVHD) remains a major complication of allogeneic hematopoietic cell transplantation (HCT). Differences in minor histocompatibility antigens impact GVHD and HCT outcome via activation of donor T cells that also mediate a graft-versus-leukemia (GVL) effect. Non-HLA determinants, such as immunomodulatory cytokines can promote or protect against GVHD. Certain cytokine gene polymorphisms have been associated with acute GVHD in related and unrelated donor HCT. Methods: 17 patients (pts) who underwent related or unrelated donor HCT for hematologic malignancies and their donors were retrospectively analyzed for polymorphisms in gene sequences for interleukin (IL)-6, IL-10, tumor necrosis factor-alpha (TNF-α), transforming growth factor-beta (TGF-β) and interferon gamma (IFN-γ) using SSP-PCR reagents from One Lambda Inc. (Canaga Park, CA, USA). Pts and donors were categorized into low, intermediate or high producers of respective cytokines based on single nucleotide polymorphisms (SNPs) identified by sequence specific primers as per manufacturer’s instructions. Conditioning regimens included tacrolimus/sirolimus or alemtuzumab/cyclosporine. Results: A marginal association was found between development of acute GVHD and donor intermediate producers of TGF-β (p=0.056). None of the other cytokine gene polymorphisms tested showed significant relationships to either acute or chronic GVHD. Of seven pts tested who received alemtuzumab conditioning, only one pt developed GVHD; both pt and donor were high producers of all five cytokine genes tested. Conclusions: These results suggest that TGF-β gene polymorphisms may affect risk of developing acute GVHD following allogeneic HCT. Further study is warranted in larger cohorts with measurement of low, intermediate, and high cytokine producers, as well as evaluation of the interplay of cytokines and alemtuzumab in GVHD.
Impact of antithymocyte globulin on new HLA groups for unrelated donor allogeneic stem cell transplantation.
Authors: Lee Yoo Jin , Kim Jong Gwang , Lee Soo Jung , Kang Byung Woog , Chae Yee Soo , Moon Joon Ho , Sohn Sang Kyun
Published: March 2020

e18017

Background: The outcomes of unrelated donor transplantation have improved with refinements in HLA testing. Recently, grouping of HLA matching for unrelated donor was suggested, defining by well-matched, partially-matched, and mismatched. In the current study, the role of anti-thymocyte globulin (ATG) for each group was evaluated. Methods: A total of 120 patients diagnosed as hematologic diseases and received allogeneic stem cell transplantation (SCT) from unrelated donor were retrospectively analyzed. Results: 28 patients were classified as well-matched, 52 as partially-matched, and 40 as mismatched. Among them, 73 patients received ATG as graft-versus-host disease (GVHD) prophylaxis. The overall survival (OS) rate was higher for well-matched group (82%) compared to partially-matched (53%) and mismatched (34%, p=0.076). For partially-matched group, the OS was significantly improved with ATG (83.3% vs. 38.6%, p=0.018). But, the OS was not different between groups with or without ATG for well-matched (87.5% vs. 66.7%, p=0.487) and mismatched (32.4% vs. 41.7%, p=0.215). ATG decreased the cumulative incidence of grade 3-4 acute GVHD (10% vs. 40.2%, p=0.068) and severe chronic GVHD (21.2% vs. 52.2%, p=0.037). The use of ATG (HR=0.248, p=0.029) was related with favorable OS for partially-matched group. However, the favorable effect of ATG was not observed in well-matched and mismatched groups. Conclusions: ATG effectively improved survival rate for partially-matched group in unrelated donor transplantation. However, the positive effect of ATG was not observed in well-matched and mismatched group.
Evaluation of elderly patients with extended disease small-cell lung cancer.
Authors: Montella Tatiane Caldas , Vasco Marina Mendes , Silva Ana Licia Maia , Rossi Morgana Stelzer , Sena Carla Valéria Santos , Oliveira Leandro Nascimento , Baldotto Clarissa Serodio , Ferreira Carlos Gil Moreira
Published: March 2020

e18515

Background: At diagnosis approximately 25-40% of patients with small cell lung cancer (SCLC) are over age 65 and more than 60% of them have extended disease (ED). There is a scarcity of data on this subpopulation. The aim of this study was to report clinical characteristics of this subpopulation, highlighting some challenges in their clinical management. Methods: In this retrospective cohort, data from 96 patients aged >65 years with SCLC diagnosed between 1997 and 2007 at a single institution were analyzed. Results: At diagnosis median age at presentation was 71, and most patients (n=65; 67.7%) had ED_SCLC and became the focus of our analysis. In this particular population the median survival time was 5 compared to 9 months for limited disease patients. Further, 63% of these patients had performance status (PS)≥2 and that was correlated with worse survival (PS0-1=9 months, PS2=4 months and PS3-4=3months; p=0.05). Additionally, 70% of this group with ED had at least one comorbidity and 30% had more than one. Of note, chemotherapy (CT) or radiotherapy (RT) were not administered in 23% of those patients, due to the lack of clinical conditions. CT was administered in 49 patients (75%), being carboplatin and etoposide the preferred regimen in contrast to cisplatin and etoposide (71 vs 28%). However, 44% of patients received less than 4 cycles of CT and 34% received only one cycle. Number of CT cycles were correlated with survival (1 cycle 1.5 months and 2-4cycles 8.7 months). Conclusions: Our data show that elderly patients with ED-SCLC constitutes a frail subpopulation, with poor PS and associated comorbidities, leading to suboptimal treatment and a dismal prognosis. Moreover, most of those patients were considered unfit for current treatment. These results highlight the urgent need for an individualized approach and clinical trials focused on elderly patients, in order to provide them an optimal care and improve their outcomes.
Analysis of surgical strategy of treating thymomas: A single center experience.
Authors: Yu Lei , Ma Shan
Published: March 2020

e18519

Background: Thymomas are epithelial thymic tumors, generally considered to have an indolent growth pattern but are malignant. 20-40% of patients with thymomas have paraneoplastic syndromes,including myasthenia gravis(MG). The objective of this study is to evaluate outcome of surgical treatment to thymoma and determine whether the different pathological and clinical characteristics of thymomas influences the prognosis in thymoma patients. Methods: We retrospectively studied data from 228 consecutive patients operated on from1992 to 2007. All thymic epithelial tumors were reclassified according to the WHO histologic classification, and the Masaoka clinical staging system. Patients with type A and stage I thymoma had no adjuvant therapy. Most patients with types AB and B1 thymomas had radiotherapy postoperatively. Patients (stageII, III) were treated with adjuvant mediastinal radiation therapy, and both adjuvant radiation therapy and chemotherapy was administered to stage IV and type C one month after operation. For patients with tumor nodules found on the pleural surface, cytoreductive surgery was performed. After that, patients had both adjuvant radiation therapy and chemotherapy. Results: There were no peri-operative deaths. 19 cases were inoperable. 16.2% patients had postoperative complications: The proportions of type A, AB, B1, B2, B3, and C thymoma in this data were 0%, 22.4%, 26.4%, 30.4%, 20.8%, and 0% respectively in patients with MG. Microthymoma was identified in the paraneoplastic thymus of 3 patients. There were 198 patients followed up. There was no recurrence in patients with type A and a few patients with type AB, B1, B2, B3 and C recurred. The actuarial 5- and 10-year survival rates were 89.6% and 80.5% respectively. Within 5 years postoperatively, 6 of 16 deaths died of myasthenia crisis, 6 were attributable to inoperable tumors (stageIV) and type C thymoma. Conclusions: Surgical treatment to thymoma has a sound prognosis. Multimodality treatment of stage III or IV thymomas may be critical to improve the 5-year survival rate. MG seldom occurs in type A and C thymoma. The main cause of death is myasthenia crisis for thymoma patients with MG and stage IV and /or type C for thymoma patients without MG.
The therapeutic effects of vitamin C on lung cancer cells.
Authors: Mahenthiran Ashorne Krithiesh , Sittampalam Gurusingham Sitta , Somasundaram Raj , Nirmalanandhan Sanjit
Published: March 2020

e18523

Background: In this in-vitro study, we determined the effects of vitamin C (Ascorbic acid), an essential vitamin, on two different lung cancer cell lines (H358 – Bronchioalveolar Carcinoma and A549 – Epithelial Lung carcinoma) and two normal lung cell lines as control groups (MRC5 – Human lung fibroblast tissue and NL20 – Lung epithelial cells). Methods: In the study, the four cell lines were treated with Vitamin C starting from 0.005 molar concentrations and serially diluted down 1:3 ratios to low nM concentrations. All experiments were carried out in a period of 4 weeks. The viability of the cell lines after the drug treatment was measured using a MTS cell proliferation assay. Results: The study was inconclusive since the viability of both normal and lung cells were equally affected under the experimental conditions except that the dosage of vitamin C that killed 50% of H358 was at a slightly lower concentration than the dosage of vitamin C that killed 50% of the normal lung cells. These results show that there is a possibility of an optimal dosage that will only harm cancerous cells in specific cancers and not on all cancers. Conclusions: These results were inconclusive; probably due to the fact that experimental conditions in this in-vitro study may not be appropriate to show the effects of Vitamin C on lung cancer cells. It is possible that lower dosages of vitamin C may still kill cancer cells selectively, and may also be more effective in cancers in ther tissues. Despite these drawbacks, in-vivo experiments in animal models with lung cancer may show the benefits of Vitamin C in combination with standard of care cancer drugs. Future experiments will examine combinations experiments in vitro and in animals to study the beneficial effects of Vitamin C.
Selective expression of the Sp17/AKAP4/PTTG1 in NSCLC for detection and therapy.
Authors: Radhi Saba , Saadeh Charles , Wade Raymond , Mer Jesse , Yu Yuefei , Mirandola Leonardo , Konala Venu , Aulakh Amardeep , Chiaramonte Raffaella , Platonova Natalia , Zepeda Kristopher , Colombo Michela , Jenkins Marjorie , Figueroa Jose A. , Cobos Everardo , Jumper Cynthia A. , Alalawi Raed , Chiriva-Internati Maurizio
Published: March 2020

e18527

Background: Cancer testis antigens (CTA) are a class of tumor associated antigens, showing a restricted expression in cancer, strong immunogenicity, and weak expression in normal tissues. Sp17/AKAP4/PTTG1 have been previously investigated, showing promising results as a target antigens. Our aim was to investigate the expression of Sp17/AKAP4/PTTG1 in lung cancer patients. Methods: We analyzed two lung cancer cell lines, one normal bronchus cell line, a panel of normal tissues and patient’s cells by RT-PCR, flow-cytometry, immunocytochemistry (ICC), and immunofluorescence (IF). CTA immunogenicity was investigated by measuring circulating specific antibodies in the sera of lung cancer patients. Results: ELISA analyses show the presence of circulating CTA-specific antibodies in the sera of lung cancer patients, indicating the immunogenicity of Sp17, AKAP-4 and PTTG-1. We showed that CTA, Sp17, AKAP-4 and PTTG-1 can be detected in both sera and tissue of patients with NSCLC. Furthermore, CTA can elicit an immunogenic response in patients affected with this disease. Conclusions: Our results provide the first evidence that the CTAs SP17/AKAP4/PTTG1 are expressed in both non-small cell lung cancer cell lines and primary tumor tissues and can elicit an immunogenic response in patients afflicted with this disease. Based on our findings we believe further studies are warranted to explore the feasibility of developing CTA-tailored immunotherapeutic strategies for non-small cell lung cancer.
Outcomes of North American, Japanese, and European extensive-disease small cell lung cancer (ED-SCLC) patients under irinotecan-platinum or etoposide-platinum therapy: Systematic review and meta-analysis.
Authors: Lima Joao Paulo Da S.N. , Sasse Andre Deeke , Sasse Emma C. , dos Santos Lucas Vieira
Published: March 2020

e18534

Background: Superiority of irinotecan-platinum (IP) regimens over etoposide-platinum (EP) in ED-SCLC has been extensively debated, with ethnic and pharmacogenomics issues hypothesized as causes of the divergent findings. We undertook a systematic review to scrutinize the data according to geographic origin. Methods: Randomized controlled trials comparing first-line EP doublets versus IP in ED-SCLC patients were searched in major meeting proceedings and databases. The outcomes were overall survival (OS), one-year survival, two-year survival, and safety. Meta-analyses were performed using random-effects model. Subgroup analyses and meta-regression were undertaken to compare and measure the impact of geographical origin of study over the estimated effect size. Results: Seven studies (2,029 patients) were included. IP improved OS worldwide (HR = 0.83; 95% CI 0.76-0.92; P>0.001; I²=0%). However, the impact of IP on OS was different according to geographic origin, with relevant benefit for Japanese, little benefit for North American/Australian and intermediate for European patients (P for interaction = 0.029, table 1). One year survival was homogenously improved from 34% with EP to 40% with IP (P=0.006). IP improved two year survival just for Japanese and European patients but not to North American ones (Table). Toxicity was not impacted by trial origin. Conclusions: IP improved survival for both Western and Eastern patients, but seems to exist a gradient of benefit according to geographic origins, with maximal benefit for Japanese, some relevant for European ones and little, if any, for North American/Australian patients. These findings should be taken in account when considering IP or EP as first-line therapy for ED-SCLC patients worldwide. [Table: see text]
Preclinical and clinical impact of the GLI2 transcription factor in non-small cell lung cancer (NSCLC).
Authors: Leal Ticiana A.B. , Spiegelman Vladimir S. , Goswami Srikanta , Oettel Kurt R. , Weigel Tracey L. , Huang Wei , Choi Sangbum , Kim KyungMann , Larson Martha M. , Hoang Tien , Campbell Toby Christopher , Traynor Anne M.
Published: March 2020

e18537

Background: Components of the Hedgehog (Hh) signaling pathway are over-expressed in NSCLC. Hh signaling contributes to tumorigenesis in lung cancer and is under investigation as a therapeutic target. We assessed in vitro characteristics of the GLI2 transcription factor, a primary mediator of Hh signaling, in NSCLC tumorigenesis, and its prognostic impact in early stage NSCLC. Methods: Colony formation, growth in soft agar, and measurement of GLI2 RNA were assayed in A549 NSCLC cells. Changes in tumor growth and proliferation were evaluated using a two-sample t-test. The automated quantitative analysis system (AQUA) was used to assess protein expression of GLI2 in NSCLC specimens from 88 deceased patients (pts) with resected stages I and II NSCLC. Pts did not receive additional pre- or post-operative anti-cancer therapies. Pt age, sex, smoking history, histology, TNM stage, and type of resection were also collected. Progression-free survival (PFS) and overall survival (OS) were estimated per Kaplan-Meier; multivariate Cox proportional hazard analyses were used to determine if the GLI2 AQUA score was an independent prognostic factor. Results: GLI2 knockdown in A549 NSCLC cells using GLI2 shRNA resulted in inhibition of colony formation and in the anchorage-independent growth, compared to A549 cells with intact GLI2 function. Characteristics of our population included median age 73 (43-96), males 62.5%, smokers 96%, adenocarcinoma 46.6%, squamous cell histology 40.9%, and stage I 62.5%. GLI2 AQUA score was not associated with any clinical variable per Wilcoxon analyses. High GLI2 AQUA score was associated with shorter PFS (median PFS 8.6 mo [95% CI 7.0-10.7 mo]) compared to low GLI2 AQUA score (median PFS 17.2 mo [95% CI 15.8-22.6 mo], p=0.001), and with shorter OS (median OS 14.8 mo [95% CI 10.5-23.0 mo]), compared to low GLI2 score (median 25.9 mo [95% CI 20.2-35.7 mo], p<0.001), independent of clinical variables. Conclusions: The GLI2 transcription factor of Hh signaling impacts in vitro models of NSCLC tumorigenicity and is an independent negative prognostic factor in early stage disease. Hh signaling remains a worthwhile investigational therapeutic target in NSCLC.