bluuebunny/crossref_metadata_2025 huggingface dataset:
Multiple uses for a clinical research database
Authors: Greco A. O. , Licavoli C. M. , White L. A. , Eckardt J. R. , Easley K. O. , Sjak-Shie N. N.
Published: March 2020

17037

Background: In Sept 2000, the research staff at The Center for Cancer Care and Research (TCCCR) developed an excel data base to track new consults referred to the practice. It is used to identify pts for participation in Cooperative Group Clinical Trials and to identify gaps in the active protocol list. Several additional uses for the data base have evolved. Methods: Medical records provided by referring physicians for each new consult are evaluated by a Research Coordinator. Information including the pt's name, date of visit, physician, referring physician, diagnosis, protocol for which the pt is evaluated, and eligibility information is entered in the data base. Results: The data base provides a method by which we can follow pts through the protocol selection and informed consent process. Early on, the data base identified a site need for trials in metastatic breast cancer prompting us to search other sources such as the CTSU and industry. Additionally, the percentage of new consults actually enrolled on a clinical trial can be determined as well as tracking eligibility/ineligibility trends. The Pharmaceutical Research Dept can use the information to complete feasibility studies prior to participating in industry trials. The data base can be used to evaluate trends in referral patterns and has helped identify referring physicians who support our research efforts. In 2006, TCCCR had a protocol available for 45% of new consults with a cancer dx. Of those pts, 16% enrolled on a Cooperative Group Clinical Trial. According to published evaluations, 16% is well above the national average of pts who participate in oncology clinical trials. It is our assessment that TCCCR's success is due in part to the data base. Conclusions: It is well known that in order to improve treatment outcomes and diminish treatment toxicity, oncology practices and pts must participate in clinical research. It is also well known that the numbers of pts who participate in oncology clinical trials is dismal. This data base has become a valuable tool providing a method to identify and evaluate some of the reasons why pts do not enroll in clinical trials and given our practice guidance to increase pt participation. Our next goal is to evaluate the differences between the rural and urban population at TCCCR's two sites to identify additional trends in clinical trial participation.

No significant financial relationships to disclose.
Average length of stay in hospice for five types of cancer
Authors: Tanis D. , Kinzbrunner B.
Published: March 2020

17038

Background: Factors which influence average length of stay (ALOS) for cancer patients who choose hospice include patient and family preferences, availability of hospice services, demographics, specialty and experience of referring physician, advances in treatment options, and type of cancer. In this paper, we examine trends in ALOS for the top five cancers in patients who utilized a large, national hospice provider between 2000 and 2006. Methods: We examined 61,457 patients with prostate, colorectal, breast, lung, or pancreatic cancer who were admitted to one of 40 hospice programs and died on service between 1/1/2000 and 11/30/2006. The top five cancers accounted for 58% of all cancer deaths in the Vitas programs. The effect of Type of Cancer and Year on ALOS was evaluated using analysis of variance. Pair-wise differences were compared using the Bonferroni correction. Results: Overall ALOS was 40.6 days. ALOS for prostate, colorectal, breast, lung and pancreas was 47.9, 45.6, 45.5, 37.8 and 31.7 days, respectively. Prostate, colorectal and breast ALOS were not significantly different from one other; lung ALOS was significantly less than the top three (p < .001); and pancreas ALOS was significantly lower than all others (p < .001). There was no evidence of yearly trends in ALOS for different cancers during the study period. Conclusions: ALOS for patients with one of the five leading cancers who elected hospice services prior to death has remained remarkably stable over the last seven years. This stability, combined with an overall ALOS of less than six weeks, suggests that much still needs to be done to maximize cancer patient utilization of hospice services. The somewhat longer ALOS for patients with prostate, colorectal and breast cancer may be related to differences in natural history and effectiveness of anti-neoplastic therapies when compared to cancers of the lung and pancreas.

No significant financial relationships to disclose.
The relation between health systems coverage and clinical outcomes among women with newly diagnosed breast cancer in a region of southeast Brazil
Authors: Guerra M. R. , Bustamante-Teixeira M. T. , Cintra J. R. Duarte , Domenge C. , Mendonça G. A. , Passman L. J.
Published: March 2020

17045

Background: Brazil is a continental size country with a population of 186 million. Breast cancer is the leading cause of death among Brazilian women. There are two principal forms of health systems coverage: a universal government system, Sistema Único de Saúde (SUS), and private health insurance (PHI). We investigated whether clinical outcomes among women with newly diagnosed breast cancer differed according to health system used. Methods: We studied breast cancer patients in the Juiz de Fora metropolitan area of the state of Minas Gerais, where the educational attainment, income and racial composition of the population of approximately 1 million roughly mirror that of the nation. We studied all breast cancer patients newly diagnosed from 1998 to 2000 who were treated with standard consensus guidelines regimens, to compare outcomes in the two Brazilian health systems. Kaplan-Meier method and Cox proportional hazard model were used to calculate overall survival (OS) and to determine the prognostic importance of health systems after adjusting for factors as age, stage, and race. Results: 869 patients were studied with a follow-up of at least 5 years; median 5.3 years. SUS patients presented with more advanced disease than PHI patients (P<0.001). At 5 years, OS was 69% for SUS patients versus 79% for PHI patients (p=0.003); however, when adjusted for age, stage, and race this effect disappeared (p=0.13). The adjusted relative risk of death for SUS compared to PHI patients was 1.3 (95%CI: 0.9 to 1.8). Conclusions: In the two Brazilian health systems, women with breast cancer treated with guideline protocols have similar stage-adjusted clinical outcomes. However, women in the public system are diagnosed at more advanced stages, and thus have significantly poorer outcomes. This suggests that such women would benefit from improved access to screening and referral for evaluation that promotes earlier diagnosis and treatment.

[Table: see text]

No significant financial relationships to disclose.
Nitric oxide and asymmetric dimethylarginine and CD 40 ligand levels in malignancy associated thrombosis and their modulation by anticoagulants
Authors: Hoppensteadt D. , Fareed D. , Iqbal O. , Lale A. , Fareed J.
Published: March 2020

17049

Background: Cancer associated thrombotic complications are primarily due to endothelial dysfunction and upregulation of inflammatory processes. Nitric oxide (NO) represents one of the major endothelial derived vasoactive mediators. Asymmetric dimethylarginine (ADMA) is an endogenous competitive inhibitor of NO synthase which inhibits NO production at pathophysiologic levels. CD 40 ligand (CD 40L) is also upregulated in cancer. Methods: To test the hypothesis that endothelial dysfunction in cancer patients may result in increased ADMA levels, plasma samples were retrospectively analyzed from an open label, multidose, active comparator designed study in which all patients (n=110) were initially treated with low molecular weight heparin, enoxaparin (E) at 1–1.5 mg/kg sc for 5 days and further subdivided into group E which continued to receive E and warfarin (W) group which was given oral anticoagulants for a period of up to 12 weeks. Baseline blood samples (BL), 5 days post E (IPE) and 4–6 week samples from the E and W were analyzed for ADMA and CD 40L levels by ELISA methods. NO levels were measured using a chromogenic method. Results: The baseline levels of NO, ADMA and CD 40L levels were markedly elevated in cancer patients. The E treated group showed a marked decrease in the ADMA and CD 40L levels which persisted throughout the treatment period. However, in the W converted group the ADMA and CD 40L levels rebounded to an increased level indicating that E differentially regulated ADMA in these patients. The down regulation pattern of NO was similar for both E and W. Conclusions: These results suggest that patients with cancer and thrombosis exhibit simultaneous upregulation of ADMA, CD 40L and NO. While E and W show a differential regulation of ADMA and CD 40L, both result in a downregulation of NO. The fact that E regulates ADMA is highly suggestive of its role in iNOS regulation which may be involved in the inflammatory response in cancer patients.

[Table: see text]

No significant financial relationships to disclose.
Evaluation of outcomes before and after electronic medical record (EMR) and computerized physician order entry (CPOE) system implementation in an outpatient oncology setting
Authors: Harshberger C. A. , Brockstein B. , Carro G. , Jiang W. , Spath W. , Lawton J.
Published: March 2020

17058

Background: Computerized physician order entry (CPOE) in electronic medical records (EMR) has been recognized as an important tool in optimal health care provision that can reduce errors and improve safety. The objective of this study is to describe documentation completeness and user satisfaction of medical charts before and after outpatient oncology EMR/CPOE system implementation in a hospital based outpatient cancer center within three treatment sites and with sixteen physicians. Methods: A retrospective chart review was conducted on 32 randomly selected patients to date, who received one of the following regimens: FOLFOX, carboplatin-paclitaxel, CHOP-rituximab, or AC between 1999 and 2006. Charts were case matched with physician and regimen to compare documentation completeness. Completeness scores were assigned to each chart based on the number of documented data points found out of the 33 data points assessed. A user satisfaction survey of the paper chart and EMR/CPOE system was conducted among the physicians (n=16), nurses (n=43), and pharmacists (n=8) who worked with both systems. Results: The mean percentage of identified data points successfully found in the EMR/CPOE charts was 94% vs. 68% in the paper charts (p<0.001). Regimen complexity did not alter the number of data points found. The survey response rate was 64% and the results showed that satisfaction was statistically significant in favor of the EMR/CPOE system. The time required to find the data points will be assessed by having a physician, nurse, and pharmacist review the same charts. Data on 112 charts will be presented. Conclusions: Using EMR/CPOE systems improves completeness of medical record and chemotherapy order documentation and improves user satisfaction with the medical record system.

No significant financial relationships to disclose.
Compliance to National Comprehensive Cancer Network guidelines in patients with newly diagnosed small cell lung cancer at a community cancer center
Authors: Oettel K. R. , Joseph R. , George B. , Lee J. , Mathiason M. , Meyer L. , Go R.
Published: March 2020

17064

Background: The National Comprehensive Cancer Network (NCCN) provides yearly updated guidelines for the management of patients diagnosed with small cell lung cancer (SCLC). Compliance to clinical guidelines may improve patient care and outcome, but this may vary among institutions. In this study, we determined the compliance of our community cancer center to the NCCN guidelines in patients with SCLC. Methods: We identified patients with newly diagnosed SCLC in 2004 and 2005 using our cancer registry database. Using the NCCN guideline for the corresponding years, we determined the compliance rate for the following phases of cancer care: initial evaluation (pathology review, imaging, smoking cessation counseling, mediastinal staging for T1-T2 limited disease), and treatment (chemotherapy, radiation). Results: There were 39 new patients with SCLC, 14 (35.9%) of which had limited stage disease. The overall compliance rates for initial evaluation and treatment were 33.3%, and 92.3%, respectively. A total of 32 deviations were identified: 21 (65.6%) for neglecting smoking cessation counseling, 7 (21.9%) for not performing recommended imaging, 3 (9.4%) for not giving recommended chemotherapy and/or radiation and 1 (3.1%) for not reviewing outside pathology. In all of the imaging and treatment deviations, there were medically appropriate reasons for doing so: 7 patients with limited disease had PET/CT scan instead of CT/bone scan (PET/CT scan now incorporated into the 2006 guidelines); 2 patients with limited disease did not receive concurrent chemoradiotherapy due to poor performance status and co-morbidity; 1 patient with extensive disease refused chemotherapy. Conclusion: Our compliance with NCCN guidelines for SCLC was poor for initial evaluation, but better for treatment. The primary reasons for this outcome were the lack of a perceived benefit in smoking cessation counseling and the use of PET/CT scanning as the initial imaging modality of choice.

No significant financial relationships to disclose.
Development of a novel information technology (IT) system using the electronic medical record (EMR) in daily clinical practice
Authors: Matsumoto S. , Nishimura T. , Kanai M. , Ishiguro H. , Yasuda H. , Yoshikawa K. , Misawa A. , Kitano T. , Yanagihara K. , Fukushima M.
Published: March 2020

17066

Background: The information generated in daily practices is critical to assure safety and efficacy of therapeutic interventions. Clinical investigators are faced with enormous amounts of data and a greater need to organize it in a meaningful and coherent manner than ever before. Computerization could offer many advantages that clinical data systematically accumulated in the course of routine medical care can provide researchers with the clues to resolve many medical questions. Methods: We developed a novel clinical database system, named CyberOncology, integrated in EMR of Kyoto University Hospital. It contained summarized treatment history, national cancer registry and consecutive clinical database. All adverse events according CTCAE ver.3, response to the treatment based on RECIST criteria and survival data were collected. The medical staffs have routinely used the CyberOncology since its starting on October 2003. The CyberOncology directly collected all data concerning oncology management of inpatient and outpatient care from EMR, and simultaneously analyzed clinical outcomes. Results: For three years since October 2003, consecutive 1,516 new cancer patients including 590 GI, 435 lung, 234 breast cancer, and 140 lymphoma with 19,767 chemotherapeutic administrations were registered in the CyberOncology. Main benefits are improvement of the quality of patient care and safety, practice standardization, and the quickness and the reliability of collecting the data. Moreover, it had the capability to serve a cross-sectional approach of cancer and drug-orientated analysis. For example, this system can easily provided with a review of clinical practice in a real time manner. Conclusions: The CyberOncology form integrated EMR successfully meets requirements of electronic case report. It has been useful in monitoring outcomes of care, effectiveness, efficiency and adherence to clinical trial.

No significant financial relationships to disclose.
Economic impact of mortality risk reduction with first-line imatinib (IM) versus interferon-α (IFN) in patients newly diagnosed with chronic phase (CP) chronic myeloid leukemia (CML) under the Brazilian public healthcare system perspective over a 5-year period
Authors: Mataveli F. D. , Calabró A. , Mendes W. , Vianna D. , Dorlhiac-Llacer P. , Bigni R. , Hungria V.
Published: March 2020

17068

Background: Patients receiving imatinib had a significant survival advantage compared with patients receiving IFN therapy (Roy et al. Blood 2006; Kantarjian et al. Blood 2006). Although reimbursed as second line therapy for CP CML patients who did not respond to INF-a, IM was not considered for public reimbursement as first line treatment in Brazil based on drug costs. An economic evaluation considering the mortality risk reduction with first line IM versus INF was performed under the Brazilian Public Healthcare System perspective, comparing the costs to avoid one death of a chronic phase CML patient over a 5-year period. Methods: Risk of death in 5 years was defined by survival rates in the 60 month follow-up of IRIS for IM (Rim= 10%) (Druker et al. JCO 2006), MD Anderson cohort of CML patients treated with INF-a for INF-a (RINF-a= 38%) (Cortes et al. American J. Med 1996) and a population based-survey in Norway for the natural course of the disease (Rnon-treatment= 67%). IRIS INF group survival rate was not used due to high crossover to IM in the trial. Risk of death in the natural course of the disease was the basis for the absolute risk reduction (ARR) calculation (ARRim= 57%; ARRINF-a= 29%). Number need to treat (NNT) was obtained by the inverse of ARR value for each first line treatment (NNT =1/ARR). Costs were estimated based on the Brazilian public healthcare reimbursement payment (APAC-SUS) for chronic phase CML treatment. A base case economic model of 100 patients for each treatment option was constructed focused on drug costs and adverse events (AE) from the IRIS study for both groups. Clinical guidelines from two public hematology centers were used to estimate AE treatment costs. Costs were discounted at a 6% annual rate. Results: The treatment costs and NNTs for a 5-year period are US$ 62,135 and 3.45 for INF-a, and US$ 93,397 and 1.75 for IM, respectively. The costs to avoid one death over a 5-year period are US$ 214,368 for INF-a and US$ 163,445 for IM. Conclusions: The costs for avoiding one death of a chronic phase CML patient over a 5-year period is US$ 50,923 higher with first line INF-a than it would be with first line imatinib.

[Table: see text]
The impact of Australia Asia Pacific Clinical Oncology Research Development (ACORD) on research productivity of participants according to region of origin
Authors: Koczwara B. , Ackland S. , Esterman A. , Marine F. , Stockler M. , Olver I.
Published: March 2020

17074

Background: ACORD is a 1-week, intensive educational workshop designed to increase skills of junior cancer clinical researchers from the Asia Pacific region. Participants come from region of diverse cultures, languages and resources. Methods: We surveyed participants 1 year after the workshop to determine its impact on their research output. Participants were grouped into those from: Australia or New Zealand (ANZ), developed Asian countries (Japan, Korea, Taiwan), and developing Asian countries (India, China, Bangladesh, Philippines, Indonesia, Malaysia). Results: The response rate was higher from developed Asia (10/10, 100%), than ANZ (44/59, 75%) and developing Asia (7/12, 58%). The proportion of respondents spending more than half of their time in research was higher in ANZ (21%), than developing Asia (14%) or developed Asia (10%). The workshop was rated very valuable by more respondents from developing Asia (71%) than from ANZ (59%) and developed Asia (60%). More than half of respondents had submitted their ACORD protocol to an IRB. Progress activating protocols was reported more frequently by respondents from developing Asia (86%) than developed Asia (70%) and ANZ (59%). Involvement in other research was also reported more frequently by respondents from developing Asia (100%) than ANZ (82%) or developed Asia (80%). The most frequently reported barriers to progressing research were: other work commitments (71% for developing Asia, 44% for ANZ, 30% for developed Asia) and lack of funding (71% for developing Asia, 39% for ANZ, and 33% for developed Asia). Continuing contact with faculty and participants was reported more frequently by respondents from ANZ (59%), than developed Asia (43%) or developing Asia (30%). Conclusions: Respondents were highly satisfied with the workshop, perceiving positive effects on their research skills and careers. Participants from developing countries were more likely to take their protocols forward, despite reporting greater barriers to progress, and less continuing contact with faculty and participants. Protected time and support for researchers are worth considering for developing countries wanting to improve their research output.

[Table: see text]
Healthcare (HC) utilization and costs in patients (pts) with newly diagnosed metastatic thyroid cancer (mTC)
Authors: Berger A. , Edelsberg J. , Chung K. , Ngyuyen A. , Stepan D. , Oster G.
Published: March 2020

17082

Background: mTC is relatively rare and little is known about treatment patterns or HC costs in patients with newly diagnosed disease. Methods: Retrospective longitudinal cohort study. Using a large (∼14 million covered lives) US health-insurance claims database, we identified a cohort of pts with diagnoses of thyroid cancer (ICD-9-CM diagnosis codes 193.XX) and distant metastatic disease (197.XX-198.XX) between 1/1/2003 and 12/31/2005 (“study period”); the date of first mention of metastatic disease was designated the “index date”. All pts were required to be =18 years of age as of their index date and to have been continuously enrolled in the database for =6 months prior to this date. Pts were followed from their index date until health plan disenrollment (for any reason) or end of the study period, whichever occurred first. Utilization of HC services and costs (total reimbursed amount including pt liability) were then examined during each quarter of follow-up (eg, first 3 months of follow-up=Q1). Results: 183 pts met all study entry criteria. Mean (±SD) age was 51.5 (11.8) years; mean duration of follow-up was 344 days (median=275 days). Most common management/treatment strategies during Q1 included: imaging [eg, US/CT of the neck (49.7%)], thyroglobulin/thyroglobulin antibody testing (25.7%); radiation therapy (23.0%); I131 therapy (19.1%); thyroid surgery (12.6%); chemotherapy (10.9%); lymphadenectomy (8.7%); and bisphosphonate therapy (3.8%). In addition, during Q1, pts averaged 9.5 office visits (95% CI, 8.2, 10.9) and 0.6 hospitalizations (95% CI, 0.5, 0.7); for pts hospitalized during Q1, average length of stay was 6.6 (95% CI, 4.9, 8.4). Costs during the first 2 years of follow-up are presented in the table ; inpt care represented 43% of total HC costs. Conclusions: Many different treatment modalities are used in pts with newly diagnosed mTC; the cost of such care is substantial.

[Table: see text]

[Table: see text]
Burden of hospitalizations associated with skeletal related events in patients with breast cancer or lung cancer and bone metastases or multiple myeloma
Authors: Lage M. , Harrison D. J. , Barber B. , Jun S.
Published: March 2020

17083

Background: Patients with bone metastases secondary to cancer often experience skeletal related events (SREs) including pathological fracture, spinal cord compression, hypercalcemia, bone surgery or radiotherapy, or initiation of opioid analgesic use. These SREs result in major morbidity and reduced quality of life. This research examines hospitalizations associated with SREs. Methods: Data for this study were obtained from i3 LabRx Database (05/01/2000 to 03/31/2005). Individuals were included in the analyses if they had at least two diagnoses of breast cancer (based upon an ICD-9 code of 174.xx), lung cancer (162.xx), or multiple myeloma (203.0x) and had at least two diagnoses of bone metastases (198.5x) after the first diagnosis of cancer. In addition, individuals were required to have at least one SRE (based upon a previously published algorithm) on or after their initial diagnosis of bone metastases (their index date). Individuals were required to be continuously insured for at least 6 months prior to, and at least one month post their index date. Data were analyzed until 03/31/2005 or until the end of their continuous coverage, whichever occurred first. Descriptive statistics for each of these cohorts are provided. Results: A total of 1,204 individuals with breast cancer, 1,094 with lung cancer, and 258 with multiple myeloma were included in the study. The vast majority of individuals with breast cancer (96.5%), lung cancer (95.9%), or multiple myeloma (96.8%) were hospitalized. All three patient groups were likely to have SRE-related hospitalizations; multiple myeloma 43.4%, breast cancer 36.2% and lung cancer 35.6%. The average number of days per patient year that patients were hospitalized related to a diagnosis or procedure for a SRE was 6.75 days for patients with lung cancer, 6.56 days for patients with multiple myeloma, and 3.75 days for patients with breast cancer. Conclusion: Hospitalizations related to SREs are common and the number of days per year is substantial.

No significant financial relationships to disclose.
Analysis of antioxidant enzymes combined with the detection of MCL-1 and Bax expressions in acute childhood leukemias
Authors: Elbordiny M. , Moawia S. , Elsayed I. , Bassiuony K. , Elshahat M.
Published: March 2020

17522

Background: Occurrence and biological characteristics of tumors are related not only to over-proliferation of carcinoma cells but also to decrease of apoptosis. Investigation of apoptosis helps to disclose the biological characteristics of tumors, and seeks new methods of diagnosis and treatment for tumors. In this study, we analyzed the level of some antioxidant enzymes in various leukemic patients including SOD. Methods: To investigate the involvement of apoptosis regulating proteins in acute leukemias, immunocytochemical examination of Mcl-1 and Bax proteins expression was investigated in two groups of patients, one with acute lymphoblastic leukemia (ALL) and the other with acute myeloid leukemia(AML). Moreover, the free radicals utilizing enzymes were sought including superoxide dismutase (SOD), glutathione peroxidase (GSH-PX), and catalase (CAT), in addition to malonaldhyde (MDH), nitric oxide (NO), and glutathione content (GSH). Results: The obtained results showed a significant difference of SOD, GSH-PX, CAT, MDH, NO, and GSH levels in the leukemia patients (AML, ALL) compared to control group (P<0.001 for each comparison). On the other hand, there was a significant difference of SOD, GSH-PX, MDH, NO, and GSH levels in the AML group compared to ALL patients (P<0.001 for each comparison). In AML patients, a significant positive correlation was existed between SOD and GSH-PX (r=0.684, P<0.001) and a negative correlation was existed between catalase and MDH (r=-0.419, P<0.019). Mcl-1 expression was found positive in ten ALL patients out of 31(32.3%) versus 17 out of 31 (54.8%) in AML patients. Concerning Bax reactivity, only seven cases (22.6%) were positive in ALL patients versus 11 cases (35.5%) in AML patients. In ALL patients, a positive correlation was found between Mcl-1 and Bax expressions (r=0.453, P=0.011). Conclusions: Our results collectively reflect remarkable differences between AML and ALL suggesting different mechanisms underlying their formation and their progression. Mcl-1 and Bax expressions relating to the programmed cell death (PCD) or apoptosis in addition to the anti-oxidant status are deregulated mechanisms that contribute in the pathobiology of ALL differently from AML.

No significant financial relationships to disclose.
Elderly patients with resected stage II, IIIA non-small cell lung cancer, increased referral rate to medical oncologists, 1992-2002
Authors: Wang J. , Kuo Y. , Freeman J. L. , Goodwin J. S.
Published: March 2020

18002

Background: Resectable non-small-cell lung cancer (NSCLC) has been once considered as a surgical disease and therefore managed by surgeons alone, as the primary therapeutic option was surgical resection. However, it is now widely accepted that the optimal care for NSCLC requires a multidisciplinary care approach between surgeons, radiation oncologists and medical oncologists. Methods: Using data from the Surveillance, Epidemiology, and End Results (SEER) Program, we identified 3266 patients over 66 years with Stage II, IIIA NSCLC who underwent resection between 1992 and 2002. We examined the trend of medical oncology referral, indentified the predictors associated with medical oncology referral and subsequent use of adjuvant chemotherapy. Results: From 1992 to 2002, 1562 patients (47.8%) with resected stage II, IIIA NSCLC were referred to the medical oncologists; there was a steady rising trend in the proportion of the patients referral to medical oncology over the ten year period. The medical oncology referral rate increased from 26.9% in 1992 to 60.5% in 2002 (P<0.001). This change has paralleled to a rising trend in use of adjuvant chemotherapy in same population during same period. Among those seen by oncologists, 518 (33.2%) of patients received adjuvant chemotherapy. Female, white race, younger age, advanced tumor stage, adenocarcinoma, later year of diagnosis and being married were strong predictors to be seen by a medical oncologist. Patients older than 70 years of age, African American race and living in certain SEER geographic region were less likely to be referred to medical oncologists. Patients who had a medical oncology consultation were more likely to receive adjuvant chemotherapy (adjusted odds ratio [OR], 5.14; 95% CI, 4.11 to 6.43). Conclusions: The medical oncology referral rate doubled during last decade. Access to medical oncology consultation is linked to the use of adjuvant chemotherapy in the patients with resected Stage II, IIIA NSCLC. The steady increase in referral to medical oncologists paralleled an increase in the use of adjuvant chemotherapy. This changing pattern of medical oncology referral may mirror the changing attitude and perception towards to the benefits of adjuvant chemotherapy in the community.

No significant financial relationships to disclose.
Lymphatic vessel density is not associated with lymph node metastasis or survival in non-small cell lung carcinoma (NSCLC)
Authors: Villaflor V. M. , Faoro L. , Hutto J. , Varalakshmi J. , Suzue K. , Vokes E. , Husein A. , Salgia R.
Published: March 2020

18008

Background: Angiogenesis is accepted as being essential for tumors to grow and metastasize to distant sites. Lymphatic metastasis is also an important means of tumor spread. Vascular endothelial growth factor C (VEGF-C) plays and important role in lymphangiogenesis and activates VEGFR (VEGF receptor)-3. Numerous studies suggest that tumor expression of VEGF-C is a significant prognostic factor in NSCLC. In non-small cell lung carcinoma (NSCLC), the relationship of lymphangiogenesis with lymph node metastasis and patient prognosis is unknown. Methods: A retrospective analysis of 78 patients who were diagnosed with NSCLC from 1987 to 2004 were analyzed for lymphatic vascular density (LVD). LVD was measured by use of D2–40 monoclonal antibody staining. Survival was assessed and Mantel-Cox and Wilcoxon signed rank tests were used for statistical analysis. Results: Intratumoral and peritumoral LVD was significantly higher than in the uninvolved adjacent lung, but showed no significant association with lymph node status at the time of tumor resection. Variables which appeared to affect survival in our study were the presence of lymph node metastasis (median survival 1,425 vs absence 467 days, p=0.002). The presence of VEGF staining inversely affected median survival (present 757 vs absent 1,944 days, p= 0.014). LVD ≤ 53 events per field 895 days vs >53 median survival 1,302 days, p+0.867. Survival appeared to not be affected by LVD. Conclusions: These data suggest that although lymphangiogenesis occurs in association with NSCLC, it may not be an important factor in lymph node metastasis or in survival. In fact, there is a suggestion that the number of lymphatics that a patient inherently has appears to be more important than lymphangiogenesis when it comes to the development of lymph node metastasis.

No significant financial relationships to disclose.
Phase II study of irinotecan and paclitaxel for patients with recurrent small cell lung cancer (SCLC)
Authors: Owonikoko T. K. , Ramalingam S. , Forster J. , Shuai Y. , Evans T. , Gooding W. E. , Sulecki M. , Belani C. P.
Published: March 2020

18011

Background: Recurrent SCLC has a poor prognosis and is devoid of treatment options that improve overall survival. Irinotecan and paclitaxel are both active agents against SCLC, and have synergistic preclinical interactions. We conducted a phase II study to evaluate the efficacy and safety of the combination of irinotecan and paclitaxel for patients with recurrent SCLC. Methods: Patients with SCLC who relapsed following one prior chemotherapy regimen were eligible. Other pertinent inclusion criteria were: ECOG performance status 0–2, adequate bone marrow, hepatic and renal function and willingness to provide informed consent. Patients with untreated brain metastasis were excluded. Paclitaxel (75 mg/m2) and irinotecan (50 mg/m2) were administered on days 1 & 8 of every 3-week cycle. Treatment was continued until progression up to a maximum of 6 cycles or unacceptable toxicity. The primary endpoint was response rate. Toxicity was graded by CTC version 2.0. The simon two-stage design was utilized and the estimated sample size was 55 patients (stage I - 23 patients; stage 2 - 32 patients). The study has a 90% power to detect a response rate of 30%, with an alpha error rate of 10%. Results: 55 patients have been enrolled and complete data are available for 32 patients at the time of this report. Patient baseline characteristics are: male 53%, PS 0–44%; PS 1–47% and PS 2–6%. The median age is 61 years. Fifteen patients received ≥ 4 cycles. Salient grades 3–5 toxicities seen: neutropenia (13%), fatigue (13%); diarrhea (3%), hypersensitivity (3%) and hyponatremia (3%).The objective response rate is 37% (95% CI 19%-55%) with 9 PRs and 1 CR. Additional 8 patients (24%) had stable disease. The median survival is 19.6 weeks (95% CI 15.1–29.4) and the 1-year survival rate is 15%. Conclusions: The combination of irinotecan and paclitaxel is well tolerated and has promising anti-cancer activity in recurrent SCLC. Updated data on all 55 patients will be available at the time of the presentation.

No significant financial relationships to disclose.
Treatment of advanced non-small cell lung cancer in the elderly: Spanish Lung Cancer Group (SLCG) experience
Authors: Provencio M. , Camps C. , Alberola V. , Dómine M. , Isla D. , De las Peñas R. , Etxaniz O. , Cobo M. , Millán I. , Massuti B.
Published: March 2020

18012

Background: The number of elderly patients (p) with cancer continues to increase. Approximately two-thirds of p diagnosed with non-small cel lung cancer are > 65 years (y), and nearly 50% are > 70 y. The aim of our study was to discern whether clinical characteristics, toxicity, response rate, treatment and survival are different in p < 70 y vs p = 70 y. Methods: We reviewed the database of 6 SLCG clinical trials with different doublet combinations from 2000 to 2005 Results: Of 1653 p included, only 280 p (17% ) were = 70 y. No significant differences were found between the two groups with respect to gender, stage, response rate or histology. However, a higher frequency of squamous cell carcinoma was found in p = 70y. No differences were found in median number of cycles administered. The only significant difference was found in the higher frequency of grade 3–4 neutropenia among p = 70 y. (Table) Conclusions: p = 70 y were a small percentage of all p included in these clinical trials. However, outcome and toxicities were similar in p = 70y vs <70 y, and “fit” elderly p can be treated with standard doublets. Further research is warranted on genetic differences for customizing treatment in this population.

[Table: see text]

No significant financial relationships to disclose.
PET response following stereotactic body radiotherapy for non-small cell lung carcinoma correlates with local control
Authors: Feigenberg S. J. , Yu J. Q. , Eade T. , Buyyounouski M. , Wang L. , Langer C. , Scott W. , Movsas B.
Published: March 2020

18013

Background: Given the success of Stereotactic Body Radiotherapy (SBRT) for Non-Small Cell Lung Carcinoma (NSCLC), early surrogates of local failure (LF) are necessary to allow timely surgical salvage. This study tries to determine the utility of PET response as an early surrogate for LF. Methods: Eligible patients(pts) had biopsy proven NSCLC < 5 cm in size who underwent a pre- and post- SBRT PET scans. Pts treated at Fox Chase Cancer Center were either: 1. early stage (10 pts), 2. biopsy-proven local recurrences (4 patients) or 3. oligometastases (3 patients). Eleven of the 17 pts were treated on a prospective phase I dose escalation protocol and received either 40 Gy or 48 Gy in 4 fractions over 8 days. Non-protocol pts generally received 48 Gy in 4 fractions (5 of 6 pts). Treatment volumes were individualized for each pt using either 4 D or multi-phase CT simulation. As part of the prospective study design, PETs scan was obtained pre- and post-SBRT to correlate metabolic response with LF based on the work by MacManus. The post-SBRT PET scan was obtained at a median of 3 months following treatment (range, 2 to 6 months). LF was defined by my an increase in size on CT on serial imaging. Results: With a median follow up of 14 months (range 4 to 31 months), 3 LF have been documented. The median SUV max pre-SBRT was 4.7 (range 1.32 to 18.2) and 1.9 (range 0.9 to 7.0) post-SBRT. Only four pts had a post-SBRT SUV max > 2.5 (2.8, 5.1, 5.3 and 7). Overall, twelve pts had a drop in their SUV max following SBRT, while 1 pt had stabilization and 4 had an increase . Of these last 5 pts, 3 developed LF. The other two have been followed without any intervention and remain free of recurrence for > 2 years, respectively. No pt with an initial drop in post SBRT PET scan SUV has had LF. Conclusions: PET response (defined as a drop in the SUV max by 3 months) correlates with LF, and appears to be a good early surrogate of outcomes following SBRT. Larger studies are required to confirm this finding.

No significant financial relationships to disclose.
Accuracy of CT-guided transthoracic needle biopsy of lung lesions: Results of 612 consecutive procedures
Authors: Ricardi U. , Priola A. M. , Priola S. M. , Novello S. , Cataldi A. , Crida B. , Scagliotti G. V. , Fava C.
Published: March 2020

18022

Background: CT-guided transthoracic needle biopsy (TNB) is commonly used in diagnostic work-up of lung lesions. The availability of a on-site pathologist at the time of the procedure ameliorate its sensitivity, reduce the number of biopsies and false negatives. Methods: 612 procedures (608 patients with a CT-documented central or peripheral pulmonary lesion) performed at S. Luigi Hospital between November 2002 and August 2005 were prospectively analyzed; 66% males, median age was 66 years (range 29–87). Ineligibility criteria for the procedure included severe coagulopathy, previous contralateral pneumonectomy, lesions with a maximum diameter less than 5 mm or the impossibility to understand the procedure or to maintain the clinostatism for the time of the procedure. The on-site pathologist assigned to each specimen a semiquantitative score: 0 for bloody sample without other cells, 1 for aspecific benign or inflammatory cells, 2 for malignant cells without histotype characterization and 3 for well established benign or malignant histotype. Results: Most of the procedures was performed by fine needle aspiration biopsy, while in a minority of cases a tru-cut biopsy was requested. In 57.2% of the cases a single transthoracic access (range 1–4) was used and in 31% the procedure was repeated on the basis of the radiologist/pathologist judgment. In 154 patients a surgical resection was subsequently performed, while 454 were patients non-surgical. A score of 3 was obtained in 71% of cases (88% malignancies), 2 in 12.5%, 1 in 7.5% and 0 in 9%. A definitive diagnosis was made in 83.5% of procedures, while a score of 0–1 was assigned in 101 cases. Among 458 malignancies there were 411 lung cancer, 7 non-epithelial cancers and 40 metastases with only 1 false positive. The diagnostic accuracy for benign and malignant lesions was 67% and 92%, respectively (Pearson’s test p<0.005) with overall diagnostic accuracy of 83.3%. The variables affecting diagnostic accuracy were final diagnosis (benign 67%, malignant 92%, p<0.001) and lesion size (lesion 5 cm 78%, p<0.05). The presence of cavitation or necrotic areas and location of the lesion didn’t affect the diagnostic accuracy. Conclusion: In consecutive cases of CT-guided TNB final diagnosis and lesion size affect diagnostic accuracy.

No significant financial relationships to disclose.
A sensitive method for detection of EGFR gene mutations in plasma
Authors: Sanders H. R. , Qu K. Z. , Sferruzza A. D. , Strom C. M. , Bender R. A.
Published: March 2020

18027

Background: Somatic mutations in the tyrosine kinase (TK) domain of the EGFR gene are associated with clinical response to TK inhibitors in patients with non-small cell lung cancer. An assay that detects such mutations in the plasma would provide a noninvasive technique to assess suitability for TK inhibitor therapy. Here we describe: 1) the development of a sensitive assay to detect the E746-A750 deletion in the TK domain of EGFR in plasma; and 2) optimization of the method for plasma DNA extraction. Methods: Our assay uses Mse I to specifically digest wild-type (WT) genomic DNA (gDNA) to reduce non-specific amplification. After digestion, samples are PCR- amplified using 1 unlabeled primer and 1 FAM-labeled primer spanning the E746-A750 deletion region and fluorescence detected with an automated analyzer. Serial dilution studies were conducted using H1650 gDNA (del E746-A750 cell line) diluted in WT gDNA after Mse I digestion. To assess detection of the deletion in plasma, 3–4 mL whole blood was spiked with 1–37 ng H1650 gDNA; gDNA from the separated plasma was then extracted (silica column/2-propanol precipitation), digested with Mse I, and amplified as above. Several extraction methods were evaluated using pooled plasma samples and PBS spiked with 10–350 ng gDNA: silica column, magnetic bead, phenol:chloroform, and 2-propanol precipitation. Results: Digestion of the WT EGFR allele followed by deletion-specific fluorescent PCR allowed detection of caof ca. 1 copy of the del E746-A750 EGFR gene (10 pg gDNA) diluted to 0.001%. Furthermore, del E746-A750 was successfully detected in 1/5 the final DNA volume (5 μl) in all spiked blood samples. Magnetic bead-based DNA extraction yielded the highest percent recovery of gDNA from PBS (69% recovery of the 10-ng sample). Phenol:chloroform extraction gave the highest yield with pooled plasma samples. Conclusions: The combination of an optimized DNA extraction method, clearing the plasma DNA sample of amplifiable WT DNA by restriction digestion, and mutation-specific fluorescent PCR provides a highly sensitive assay for detection of somatic mutations in plasma.

No significant financial relationships to disclose.
Lipoplatin plus gemcitabine versus cisplatin plus gemcitabine in NSCLC: Preliminary results of a phase III trial
Authors: Boulikas T. , Mylonakis N. , Sarikos G. , Angel J. , Athanasiou A. , Politis G. , Rapti A. , Rassidakis A. , Karabatzaki M. , Anyfantis N.
Published: March 2020

18028

Background: Lipoplatin is a liposomal formulation of cisplatin, designed to reduce its adverse reactions without reducing efficacy. Its nanoparticles evade immune surveillance and extravasate preferentially into tumors inducing tumor cell apoptosis; lipoplatin may also act as antiangiogenesis factor. This is the initial report of a randomized, multicenter, phase III trial comparing the two drugs. Methods: Eligibility criteria included confirmed diagnosis of inoperable/metastatic NSCLC, no previous chemotherapy, WHO PS 0–1, adequate end-organ function. Patients received Lipoplatin 120 mg/m2 D1,8,15 or cisplatin 100 mg/m2 D1, combined with gemcitabine 1,000 mg/m2 D1,8, in 3-week cycles, with disease evaluation after 3 and 6 cycles. Primary endpoints are overall survival and toxicity, with Response Rates, PFS and QOL also being evaluated. Results: 59 patients have been treated, 33 with lipoplatin and 26 with cisplatin; 17 have completed treatment. 2 lipoplatin patients had a hypersensitivity reaction during the first infusion. There were no grade 4 toxicities. Grade 3 toxicities were observed in <5% of the patients and were comparable for the two groups, except neutropenia (3% for lipoplatin, 15% for cisplatin). Main grade 1–2 toxicities were anemia (93% vs 88%), leucopenia (51% vs 38%), neutropenia (45% vs 30%), thrombocytopenia (58% vs 31%), hepatotoxicity (38% vs 46%), nausea/vomiting (13% vs 35%), asthenia (31% vs 30%) and anorexia (32% vs 34%). Concerning nephrotoxicity, grade 2 was reported in only 6% of lipoplatin patients vs 19% in cisplatin, although lipoplatin was administered without pre-hydration as a 6-hour infusion. Neurotoxicity was also markedly less in lipoplatin. So far, 32 patients have been assessed for response, 16 in each group; 4 partial responses have been reported in each group. However, difference has been observed in stable disease (23% in lipoplatin vs 12% in cisplatin) as well as progressive disease (16% vs 35%). Conclusions: Preliminary results show that lipoplatin may have a better safety and therapeutic profile than cisplatin, when combined with gemcitabine, in advanced NSCLC. Particularly important might be its significantly lower neuro- and nephro-toxicity and its administration on an outpatients basis.

No significant financial relationships to disclose.