bluuebunny/crossref_metadata_2025 huggingface dataset:
Antiemetic prescribing practices using a computerized physician order entry system.
Authors: Kadakia Kunal C. , Leal Alexis D. , Seisler Drew K. , Qin Rui , Fee-Schroeder Kelliann C. , Grendahl Darryl , Sorgatz Kristine , Loprinzi Charles L.
Published: March 2020

e17538

Background: Adherence to guideline-consistent chemotherapy-induced nausea and vomiting (CINV) prophylaxis is suboptimal. The primary aim of this study was to evaluate the magnitude of compliance to institutional guideline-directed antiemetic prophylaxis using a computerized physician order entry system at a single tertiary care institution. A nurse survey was also performed to evaluate how oncology practices, within a cooperative group, manage clinician orders for the prevention of CINV. Methods: The electronic medical records of 100 consecutive patients were evaluated. The primary endpoint was the incidence of compliance to provide all aspects of institutional guideline-directed antiemetic prophylaxis for acute (Day 1) and delayed (Days 2-4) CINV for patients receiving high, moderate, low, and minimally-emetogenic chemotherapy (HEC/MEC/LEC/MinEC). Noncompliance was declared if a recommended antiemetic was not prescribed per the guidelines or if additional antiemetics were prescribed. Descriptive analyses were performed on the convenience sample. Logistic regression was applied to determine the association of potential factors with noncompliance. Results: The incidence of compliance on Days 1-4 was 94%. Half of the noncompliant events occurred on Day 1 alone and involved the omission of pre-chemotherapy prochlorperazine in patients receiving LEC (3 of 6, 50%). There was a high-degree of compliance to institutional guidelines for delayed CINV (97%). Patients receiving doxorubicin/cyclophosphamide were numerically less likely to receive institutional guideline-directed antiemetic prophylaxis, compared to patients receiving other chemotherapy regimens (OR: 0.24 (0.04, 1.36), p-value: 0.05). No other factors were significantly predictive for compliance. The nurse survey demonstrated significant variability amongst the involved institutions, with regards to antiemetic prescribing practices. Conclusions: Computerized physician order entry is associated with impressive adherence to clinician prescribing practices, according to institutional guideline-directed antiemetic prophylaxis, for preventing acute and delayed CINV.
A national treatment survey on the chemotherapy (CTX) treatment for patients (Pts) with metastatic breast cancer (MBC) in Germany.
Authors: Jackisch Christian , Untch Michael , Dall Peter , Thomssen Christoph , Albert Ute-Susann , Lueck Hans-Joachim , Bauerfeind Ingo , Scharl Anton J. ,   on behalf of AGO Organkommission Mamma
Published: March 2020

e17544

Background: The optimal CTX regimens and their sequence is the subject of ongoing debates esp. on the use of anthracycline/taxane (AT)-based adjuvant therapy (tx). Methods: Since 2004 a biennial survey is performed to evaluate routine CTX practice in MBC A total of 1,966 German sites were contacted. From 515 (26.2%) patient data were used for evaluation in order to achieve a representative sample for a chart review between June and August 2012. The current analysis is based on data from 291 sites on characteristics and tx of 741 pts undergoing first (1L), second (2L) or third (3L) line CTX for MBC in May 2012. Results: Data from 417 pts in 1L, 203 pts in 2L, and 121 pts in 3L were evaluated. Median age was 60 years (yrs). Patient characteristics were: 74% hormone receptor positive, 24% HER2-positive at primary diagnosis, 67% premenopausal, 60% had metastases in ≥ 2 organs, 66% had visceral disease. Prior tx (excluding M1 pts) was: no systemic tx 10%, endocrine tx only 13%, adjuvant CTX 58% (40% A and 44% AT-based), neoadjuvant CTX 20% (12% A and 75% AT-based). Median time from primary diagnosis to start of any treatment for MBC was 4.5 yrs for node-negative and 2.1 yrs for node-positive disease. Median time from primary diagnosis to current CTX was 4.9 yrs in 1L, 5.1 yrs in 2L and 5.8 yrs in 3L. Combination CTX was given in 21% of 1L, 12% of 2L and 9% of 3L pts, and its use decreased with increasing age. Agents used most frequently in 1L were taxanes in 61% (paclitaxel (P) 52%, docetaxel (D) 6%, nab-paclitaxel (Nab) 3%), capecitabine (X) 21%, vinorelbin (V) 19%, Epirubicin 6%, carboplatin 5%. 1L taxane tx was given to 73% of pts with prior A-based and 46% of pts with prior AT-based (neo-)adjuvant tx. Agents used most frequently in 2L were X 31%, P 20%, V 20%, gemcitabine (G) 7%, Nab 6% and in 3L V 27%, X 22%, eribulin 15%, Nab 12% P 7%, G 5%. Targeted tx was given in 54% of pts (20% trastuzumab, 4% lapatinib, and 30% bevacizumab), additional tx were bisphosphonates in 58%, and radiotherapy in 20%. Conclusions: The survey showed a high concordance of routine treatment and the existing national guidelines regarding CTX. Taxanes still dominate CTX in MBC including a significant amount of taxane rechallenge after their use in (neo-)adjuvant tx.
Hispanic race and outcome of metastatic (MET) colorectal cancer (CRC): Biology or health care (HC) setting?
Authors: Shabihkhani Maryam , Yu Steven , Yang Dongyun , Lenz Heinz-Josef , Barzi Afsaneh
Published: March 2020

e17559

Background: Hispanics (H) have lower CRC related mortality compared to Whites (W). However, over the past decade H have appreciated less improvement in CRC mortality. Given that treatments (TX) for early stage CRC is unchanged we speculate that the gap is due to poorer outcome in the MET setting. Delivery of HC is identified as one of the factor for poor outcomes. We examined the relationship between HC delivery (public or private hospital) and TX as the drivers of poorer outcome in H. Methods: We identified CRC patients (pts) with at least one cycle of chemotherapy (CT) in the first line MET setting at Los Angeles County Hospital (LAC-public hospital) and Norris Cancer Center (NCC-Private hospital) between 2004-2011. Demographics; tumor and TX related factors were collected. Primary endpoint was TTP (time from first day to progression on first line CT). Descriptive statistics were used to describe the population and where appropriate chi-square, Wilcoxon, and log-rank tests were used for comparison between the groups. Results: 251 pts, 45%H, 26%W, 20% Asian (A) and 9%Black (B) were included. The median age of the population was 55 (21-82) years. 55% of pts were male.74 % of pts had de-novo MET disease. 48% of pts had left sided, 27% right sided and 25% rectal cancer. 71% of pts treated at LAC and 29% at NCC. 46% of pts at LAC and 56% at NCC received bevacizumab (BEV) as part of their TX (p= 0.26). Median TTP in H was 10.2 months (m) (95% CI: 8.1-11.8), and in W was 16.8 m (95% CI: 11.2-27.2; P<0.05). Hispanics who were TX at LAC had longer TTP in comparison to H at NCC (p= 0.01). In multivariate analysis, race remained a significant predictor of TTP (p=0.001). Conclusions: H are the largest and fastest growing minority in the US, identification of factors of disparate outcome is crucial. This study revealed a significant association between race and TTP. Use of BEV for MET CRC became a standard TX in 2004 and since then TX is mostly unchanged. Our cohort received homogenous TX with regards to use of BEV. The results show that H regardless of HC setting have shorter TTP than W suggesting an inherent biological difference in the tumor or response to TX. Future biomarker studies will shed light on the cause.
Does faster rituximab infusion for patients with NHL lower cancer care costs?
Authors: Reyes Carolina , Dai Minghan , Goertz Hans-Peter , Dawson Keith L , Hornberger John C.
Published: March 2020

e17561

Background: Rituximab in combination with chemotherapy is recommended for non-Hodgkin’s lymphoma. A faster (90-minute) infusion schedule for rituximab has been found to be safe and feasible in NHL patients who tolerate their first infusion administered at the standard rate (Phase III study RATE trial; NCT00719472). This study’s objective was to assess the economic impact of adopting the 90-minute rituximab infusion from a US societal perspective. Methods: The analysis complied with the jointly published Good Research Practice guidelines of the International Society of Pharmacoeconomic and Outcome Research and the Society of Medical Decision Making. The target population was US patients in 2013 with previously untreated diffuse large B-cell lymphoma (DLBCL) or follicular lymphoma (FL) who were scheduled to receive rituximab plus CHOP or CVP. Costs included direct medical costs (drug and administration cost, pre-medication cost, cost of adverse events) and indirect costs (income foregone by patients and informal caregivers due to visit duration for infusion). Data sources included RATE trial, Medicare Fee Schedules, and US Labor Department statistics. Results: Of the 23,519 newly diagnosed DLBCL and FL patients in the target population, the estimated direct medical costs and foregone (patient and caregiver) income for conventional infusion totaled $825,005,088 and $9,293,180 respectively. The 90-minute infusion reduced direct medical costs by $2,205,689 (0.3%) and foregone patient income by $3,628,185 (39%). The average cost savings for each patient was $42 per infusion and $248 per course. The factors that most influenced savings included cost to treat adverse events, administration costs, and patient wage rates. As a result from a shorter infusion duration, the increased center capacity may lead to a larger saving as the fixed center costs can be distributed across more patients. Conclusions: In the context of tremendous focus on affordably improving population health, this study confirms that compared with conventional rituximab infusion regimen, a novel, validated regimen that is 3-4 fold faster to administer and is as safe results in direct medical savings and reduces productivity loss for patients and caregivers.
Medical oncologists’ clinical experiences and comfort levels with 20 recently approved agents.
Authors: Love Neil , Anderson Kenneth Carl , Flaherty Keith , Kantarjian Hagop M. , Lynch Thomas James , O'Shaughnessy Joyce , Sartor A. Oliver , Venook Alan Paul , Zelenetz Andrew David , Moss Jonathan , Kelly Gloria , Ziel Kathryn
Published: March 2020

e17570

Background: The rapid pace of current oncology drug development has provided medical oncologists (MO) and patients with many additional treatment options, but minimal publicly accessible information exists on how new agents are incorporated into practice. Methods: From 12/15/2012 to 1/21/2013,100 US-based MO were recruited to complete a survey assessing the diseases they treat and their prescribing experiences with 20 oncologic drugs approved between 9/2009 and 11/2012. MO who manage related cancers were asked to self-report on a 3-point scale their comfort level using these agents. A modest honorarium was provided. Results: See Table. MO generally had limited clinical experience, even with drugs used in common cancers. Multiple clinical and logistical factors were cited for not using agents. For only 4 of the drugs did more than half of MO self-rate their prescribing confidence as 3 (very confident). Conclusions: Variation in MO use of recently approved drugs is multifactorial, and the suboptimal comfort levels reported here may reflect the natural evolution of clinical experience over time. Further research is needed to determine if an improved information infrastructure would better and more rapidly prepare MO to incorporate these and other soon-to-be-approved agents into practice. [Table: see text]
Correlation of insurance status, ethnicity, and race with pathologic risk in retinoblastoma: A Children's Oncology Group (COG) study.
Authors: Green Adam L. , Langholz Bryan , Chintagumpala Murali M. , Cockburn Myles , Chevez-Barrios Patricia , Albert Daniel , Eagle Ralph , Rodriguez-Galindo Carlos
Published: March 2020

e17573

Background: Insurance status affects cancer diagnosis and outcome in adults, but the impact has not been well studied in pediatric cancer. In children with retinoblastoma, time to diagnosis correlates with tumor invasiveness and patient survival, and therefore the disease can be a model to study the effect of demographic variables on delays in diagnosis. Methods: Our patient population consisted of all 203 patients from the United States enrolled on Children’s Oncology Group ARET0332, a study of patients with unilateral retinoblastoma requiring enucleation. All surgical specimens underwent central review by three pathologists to determine the presence of well-defined histopathologic features that correlate with a higher risk of disease progression. Data on insurance status, ethnicity, and race were collected for each patient. For variables not collected, including English proficiency, income, and educational attainment, analyses were conducted indirectly by matching patient zip code with census data for each variable. Results: On univariate analysis, a higher rate of high-risk pathologic findings was found in patients of Hispanic ethnicity (p=0.021) and non-white race (p=0.037), and in those with Medicaid or no insurance (p=0.035). On multivariate analysis, although no one variable correlated with high-risk features independently from the others, Hispanic ethnicity had the greatest impact on risk. Zip code-based analysis did not show significant differences in rates of high-risk findings based on English proficiency, income, or education. Conclusions: Hispanic ethnicity, non-white race, and Medicaid or no insurance all correlated with high-risk pathologic features in a large group of retinoblastoma patients who had central pathology review, and we believe these findings are due to delays in diagnosis for these groups. Future work should use direct methods to study the impact of other variables, including English proficiency, since indirect, zip code-based analysis may be inadequately powered to do so. Further effort should also focus on where in the diagnostic process delays exist, so that interventions can be designed to overcome barriers to care for these groups.
Disparities between high-impact clinical trials in oncology and disease burden.
Authors: Pfanzelter Nicklas , Jeurkar Neha , Finkelman Brian S. , Mamtani Ronac
Published: March 2020

e17591

Background: Recent research has identified a discrepancy between NIH funding in oncology and various measures of disease burden by tumor type. We sought to identify whether this disparity exists in recent high impact publications. Methods: 833 clinical trials published in five high impact general medicine and clinical oncology journals between January, 2009 and October, 2012 were reviewed. 692 trials were included in this analysis after excluding those that studied >1 tumor type. Disease burden was measured as person-years of life lost (YLLs), reported in the Surveillance, Epidemiology, and End Results database, and disability adjusted life years (DALYs), reported by the World Health Organization. We used a chi square goodness of fit test to compare the overall distribution of trials by tumor type to the distribution of annual YLLs and DALYs. Results: Breast cancer was the most published tumor, accounting for 14% of all trials, followed by lung (13%) and colorectal (7%) cancers. More than half of the trials (56%) were for patients with metastatic disease, and most (81%) were phase 2 and 3 clinical trials. Nearly half of all publications studied targeted therapies (45%), and the majority received industry support (61%). 67% of trials with a comparator arm met their primary endpoint. The distribution of trials by cancer site differed significantly from the distribution of both measures of disease burden (YLLs and DALYs) (both p<0.001). The findings were unchanged in analyses that accounted for the total number of subjects enrolled in the trials (both p<0.001). The most underrepresented malignancies based on burden of disease were lung and pancreatic cancers, while the most overrepresented were breast cancer, leukemia, and melanoma. Conclusions: The number of trials published by tumor type does not directly reflect the burden of these diseases in the population as assessed by YLL or DALY. Future studies examining potential confounders such as funding availability by cancer type or number of unpublished clinical trials may further clarify the observed disparities.
Managing health care in a universal bed model system to improve patient outcomes and cost savings after lobectomy procedures.
Authors: Sales V L , Nam Brian T. , Abi Jaoude Wassim , Key Jamie M , Horton Wendy M , Weigel Tracey L.
Published: March 2020

e17595

Background: We measured our outcomes before and after thoracic universal bed (UB) model implementation for patients undergoing lobectomy for primary lung cancer. Methods: 630 patients with primary lung cancer underwent lobectomy: 198 open thoracotomy (OL) patients before (1/2001-12/2005) and 432 patients (1/2006-12/2011) either via OL (n= 258) or via video-assisted thoracoscopy (VATS) (n=174) after transitioning to the thoracic UB model. Results: Discharge mortality was zero post-UB implementation (vs. 2% pre-UB; p<0.05). 30-day mortality was equivalent (pre-UB 4% vs. UB: OL1%, VATS 0%; p=0.2). Postoperative complications were lower in the UB model (Pre-UB 41% vs. UB: OL 26%, VATS 20%; p <0.001), and similar for OL vs. VATS post-UB (p=0.2). Median length of ICU stay was 0 days (pre-UB IQR 29 vs. UB: OL IQR 14, VATS IQR 3; p <0.001; UB: OL vs. VATS; p=0.2). Median length of stay (LOS) was decreased in the UB model and in VATS post-UB (pre UB 5 days vs. UB: OL 3, VATS 2 days; p < 0.001; UB OL vs. VATS, p < 0.001, respectively) with no difference in readmissions (8% vs. 7%, 8%; p=0.9; UB: OL vs. VATS, p=1.0 respectively). Mean total hospital costs fell 37% from $ 24,423 per patient to $ 15,434 post- UB (p<0.05), and similar for OL vs. VATS in the UB model (OL $ 15, 711 vs. VATS $15,022; p=0.2). Home-discharge was more common in UB patients (pre-UB 91% vs. UB: OL 98%, VATS 94%; p <0.05), and similar for OL vs. VATS post-UB (p=0.1). Postoperative chemotherapy and or radiotherapy treatment were similar (pre-UB 31% vs. UB: OL 37%, VATS 22%; p=0.9). Survival rates were similar at 1, 3, 5 years (pre-UB 89%, 72%, 62% vs. UB: OL 89%,69%, 63%, VATS 92%, 81% and 69%, p=0.6). Complications, LOS and chest tube duration were independent predictors of higher cost in the multivariable analysis in favor of the UB model. Non-home discharge and absence of initial postoperative follow-up within or ≥ 4 months were independent predictors of perioperative mortality and poor survival, respectively, in favor of the UB model. Conclusions: The thoracic UB care model is patient-centered, outcomes-driven, value-based approach focused on safety of patients and efficiency of postoperative care.
Utility of the baseline cardiac imaging in the treatment decision for young patients with acute leukemia.
Authors: El Sayed Ali , Dillon Patrick Michael , Densmore John , Patrie James , Sanoff Hanna Kelly
Published: March 2020

e18005

Background: Anthracyclines, the backbone of acute leukemia induction regimens, are associated with risk of cardiotoxicity. Routine cardiac imaging is routinely performed before induction treatment with anthracycline based regimens (ABR).There is no standard guideline on the optimal method of LVEF assessment, nor consensus for the treatment implication of a borderline LVEF finding. The NCCN recommends cardiac imaging for patients with prior heart disease, prior anthracycline use, or clinical symptoms of cardiac dysfunction. We examine the role of routine pre-induction cardiac imaging in young adults diagnosed with acute leukemia. Methods: A database search at the University of Virginia identified patients newly diagnosed with ALL and AML (including APML), between the ages of 18 and 49 from 2000 to 2011. Baseline demographics, pre-treatment cardiac imaging, and the induction chemotherapy regimen chosen were abstracted. Results: A total of 71 patients with ALL or AML were identified. Thirty-three patients (46.5%) were female, and the average age was 36.1 (SD=9.9 years, range 18 to 49 ). Median baseline LVEF was 62.5 (range 54-74). Out of 71 patients, 25 had a borderline LVEF between 50% and 60%.The lowest baseline EF was 54%. Among 25 patients with borderline LVEF, all received ABR for induction. Conclusions: In patients under age 50 with newly diagnosed acute leukemias, pre-treatment cardiac imaging did not alter standard induction therapy with ABR. This suggests that induction therapy should not be delayed to await baseline LVEF assessment. A potential cost saving may be achieved in this population. Routine cardiac imaging may be more helpful in older adults or patients with prior cardiac history or anticipated need for consolidation with an ABR (ie APML).
Hepa systems in hematology clinic to ameliorate the increased fungal infection risk owing to environmental changing.
Authors: Gurman Gunhan , Ozen Mehmet , Yilmaz Gulden , Coskun Belgin , Topcuoglu Pervin , Ozturk Bengi , Ozcan Muhit , Arslan Onder , Ilhan Osman , Beksac Meral , Ismail Balik , Akan Hamdi
Published: March 2020

e18009

Background: Building constructions around Hematology inpatient clinics are always a major concern for Aspergillus infections in immunocompromised patients. The use of HEPA (High Efficiency Particulate Arresting) filters can be helpful in reducing fungal infections. This quasi-experimental study was designed to measure the efficacy of HEPA filters in such a construction period. Methods: In May 2011, Portable HEPA filters have been placed in patient rooms where hematological malignancies were treated, because of the massive construction 10 meters from the clinic. Infection rates and survival 6 months before and after the installment were compared to see the effect of HEPA filters. A total of 413 patients were treated in the department during this 1-year period. Results: There were no statistical differences between antifungal prophylaxis or treatment regimens in groups. After HEPA filter installation the rates of fungal or non-fungal derived infection and pneumonia and length of hospital stay did not deteriorate in AML and ALL patients. Also, infection rates and infection-related mortality did not increase in AML group, moreover these rates decreased in ALL patients in the construction period. These findings were shown in Table. Conclusions: Despite the construction and the summer months, which environmental Aspergillus contamination is more frequently seen, there was no increase in fungal infections during Post-HEPA period. That may reflect a positive effect of HEPA usage even in AML patients. HEPA filters may be used as a protective system in hematology departments, in such a construction period. [Table: see text]
Tumor necrosis factor inhibitors and acute leukemia in two cases.
Authors: Ozen Mehmet , Keskin Onur , Kucuksahin Orhan , Ilgen Ufuk , Topcuoglu Pervin , Turgay Murat , Toruner Murat , Gurman Gunhan
Published: March 2020

e18010

Background: Inhibitors of tumor necrosis factor alpha (anti-TNF agents) are commonly used in Crohn’s disease and rheumatoid arthritis. Relationship between TNF inhibitors and development of malignancy, e.g., lymphoma and solid tumors, is defined recently. However, a few authors reported leukemia. Crohn’s disease and also azothioprine may also be associated with leukemia. Here, we are presenting two acute myeloid leukemia (AML) cases using azothioprine and anti-TNF inhibitors for Crohn’s disease. Methods: Observational case report. Results: Case 1: A 56-year-old male patient with active Crohn’s disease for 4 years was refractory to first line mesalazine, corticosteroid and azothioprine treatment. So, anti-TNF monoclonal antibody (moAb) (Adalimumab) had been given. After second dose of adalimumab treatment AML (AML-M2 as FAB) developed. Case 2: A 38-year-old male had been diagnosed with ankylosing spondylitis for 7 years and Crohn’s disease for 2 years. He had been treated with salazopyrin and indomethacin. Anti-TNF etanercept (50 mg/wk) was started 30 months ago due to severe active pulmonary disease. After 1 year, he developed active Crohn’s disease. So, the treatment changed to infliximab. Also, mesalazine and azothioprine were added to treatment. On the 18th month of the infliximab t(15;17) positive acute promyelocytic leukemia were developed in the patient. Conclusions: Blocking TNF with anti TNF agents may cause blocking apoptosis and inhibit natural killer activity. So, antitumoral activity of natural killer cells is blocked by these agents. TNF alpha gene mutation has been associated with CLL, lymphoma, myelodysplastic syndrome and secondary AML. Azothioprine may also increase leukemia, lymphoma and solid tumors risk at patient on anti TNF treatment. Following the diagnosis of Crohn’s disease without immunomodulator treatment a case had developed acute leukemia in the literature. In our patients, anti-TNF, azothioprine and inflammatory bowel disease may be cause acute leukemia cumulatively. Physicians should be careful and regularly check the patients using anti-TNF agents in considering of malignancy development. In conclusion, the pathogenesis of leukemia development after TNF blockage should be clarified.
Induction chemotherapy with docetaxel plus carboplatin followed by concomitant chemoradiotherapy (CRT) in locally advanced non-small cell lung cancer (NSCLC).
Authors: Abdel Halim Inas Ibraheim , El-Sadda Wael , El Ashry Mohamed , Elmashad Nehal Mohammed
Published: March 2020

e18505

Background: Lung cancer remains the leading cause of cancer death in both men and women. One third of patients with NSCLC presents with localized unresectable disease. With the adavance in the diagnostic and therapeutic procedures, the median survival has shown substantial improvement. The aim of the study was to evaluate the efficacy of induction chemotherapy with docetaxel and carboplatin followed by chemo-radiotherapy in locally advanced NSCLC. Methods: A total of 30 patients (25 males and 5 females) aged between 49–60 years (mean age 51 years) with NSCLC stage III A (10 pts) stage III B (20 pts) were enrolled in the study. Patients received docetaxel 75 mg/m2 IV plus carboplatin AUC 5 on day 1 every 21 days for 4 cycles in combination with G-CSF. Patients then received radiotherapy (RT) at a dose 40-45 Gy depending on patients' tolerability combined with a low dose of carboplatin AUC 2 on the 1st day of each week during RT. Patients underwent CT chest and bronchoscopy before treatment and after completion of treatment to assess response and time to progression, patients with PR and SD received further 2 cycles of DC. Results: Of all patients received 4 cycles of IC were enrolled, 3 pts (10%) demonstrated CR, 9 pts (30%) had PR, 15 pts (50%) had SD and 3pts (10%) had PD. Twenty seven pts underwent CRT, 25 of these pts have completed CRT, five pts had CR, 15 pts had PR and 5pts had SD. No grade 4 toxicities were detected. The most common grade 3 toxicities were mucositis (6%), neutropenia (12%) and alopecia 50%. The median time to progression and median survival were 7 months and 9 months, respectively. Conclusions: IC with docetaxel and carboplatin followed by CRT with weekly carboplatin is feasible effective therapeutic strategy with manageable toxicity in patients with locally advanced NSCLC.
A retrospective evaluation of locally advanced thymoma and thymic carcinoma: Factors influencing the prognosis after local treatment modalities.
Authors: Yalçintas Arslan Ülkü , Geredeli Caglayan , Özdemir Nuriye , Ciltas Aydin , Sonmez Ozlem , Kucukoner Mehmet , Karaca Halit , Gok Durnali Ayse , Boruban Melih Cem , Zengin Nurullah , Buyukberber Suleyman , Suner Ali , Seker Mesut , Alkis Necati , Oksuzoglu Omur Berna
Published: March 2020

e18510

Background: Aim of the study was to determine the relationship between clinicopathologic characteristics and treatment modalities for locally advanced thymic malignancies(TM). Methods: We retrospectively reviewed medical records of 107 patients(pts) who treated from 1992 to 2012 in medical oncology service of 7 tertiary hospital. 21 pts who presented metastatic disease and 31 pts who had early stage at the time of diagnosis were excluded. Results: A total of 55 patient’s data were analyzed. Median age was 46(17-73) years. Median follow-up was 33(1-103) months(mts). 65% of pts was male. Histopathologic diagnosis were as follows: thymoma type A-B2 ( TA-B2) 29 , thymoma type B3 (TB3) 10 and thymic carcinoma (TC) 16. 42 of pts underwent surgery, but total resection of the tumor have been achieved at only 28 pts(6 TC and 22 TA-B2 or TB3).30 pts have stage III diasease (mostly thymoma 23/30). 43 pts treated with mediastinal radiotherapy ( 21 adjuvant, 22 primary). A cisplatin containing regimen has been received 23 pts in the adjuvant setting. 31 pts were given as primary chemotherapy (ADOC, PAC and EP). Overall response rate was 81.6% with first-line chemotherapy. There was no apparent response in 3 pts(3/23) with thymoma and 4 pts(4/8) with TC. 20 pts have experienced a disease progression and 27 pts died ( 8 of these cases died from other unrelated causes). Median progression free survival was 45 (30-59)mts. Kaplan-Meier survival analysis estimated that overall survival of the pts with stage III disease were relatively longer than stage IVA ones, but it can not reach statistical significance (median 78 vs 45 mts,p=.11). Prognosis of TC pts were considerably worse than TB3 and TA-B2 (median 17 vs 45 vs 76 mts respectively,p=.01). Although there was no a statistical difference between pts who underwent total tumor removal and who did not, we have seen a trend toward better survival in pts who were suitable to triple modality therapy(median 79 vs 45 mts,p=.27). Conclusions: Cisplatin based chemo plus mediastinal radiotherapy may provide a chance of achieving a long-lasting remission in locally advanced TM. But, complete surgical removal of the tumor are still the mainstay of treatment.
ERCC1 as a predictor of response to induction therapy for stage III non-small cell lung cancer.
Authors: Marra Alessandro , Kemming Dirk , Krueer Thomas , Bosse Ulrich , Netchaeva Maria , Wagner Wolfgang , Koch Olaf M. , Vogt Ulf , Hillejan Ludger
Published: March 2020

e18511

Background: Neoadjuvant platinum-based chemotherapy in stage III NSCLC offers the chance to eradicate occult metastases and decrease tumor volume, thus improving curative surgical resection rates. A remission after induction therapy is correlated with prolonged survival. However, only 40-50% of patients respond to therapy since there is still no validated predictor for the benefit of platinum based chemotherapy. As DNA repair mechanisms are related with resistance of lung cancer cells to platinum-based chemotherapy, aim of the study was to compare ERCC1 level in lymph node metastases with the degree of pathologic tumor regression after induction treatment and surgery. Methods: From July 2004 to June 2009, 46 NSCLC patients with clinically staged IIIA (N = 32) or IIIB (N = 14) NSCLC underwent at least two cycles of platinum-based induction chemotherapy and combined radio-chemotherapy. After restaging radical surgery was performed. ERCC1 was determined from pretreatment samples of metastatic nodes taken on mediastinoscopy. Real time RT-PCR assays were performed to determine ERCC1 mRNA expression. Tumor regression has been classified on surgical specimen using an score system ranging from grade I (pCR) to grade VI (non-responder). The samples were categorized into three groups according to their ERCC1 expression values and in two groups according to their chemotherapy response (either pCR or non-pCR). Results: A significant correlation between the ERCC1 expression level and the chance to achieve a pCR during a platinum-based chemotherapy could be demonstrated in our samples (P<0.05). Furthermore, the median overall survival in the pCR group was 44 vs. 29 month in the non-pCR group (HR 0.33 [95%-CI: 0.02-1.15]; P=0.06). However, no direct correlation between ERCC1 expression and local or distant metastasis formation could be found. Conclusions: Assessment of ERCC1 mRNA expression in pretreatment tumor tissue is feasible in the clinical setting and predicts response to platinum-based induction therapy. Additional studies are warranted to optimize methodologies for ERCC1 analysis in small tumor samples and to redefine induction protocols on an individual basis, thus enhancing response rates and perhaps outcome.
The relation between neutrophil lymphocyte ratio and survival in patients with small cell lung cancer.
Authors: Inanc Mevlude , Bozkurt Oktay , Kiziltepe Melih , Karaca Halit , Berk Veli , Duran Ayse Ocak , Ozkan Metin
Published: March 2020

e18516

Background: Neutrophil-lymphocyte ratio (NLR) is not an only inflammation marker, but also used as a prognostic index of various malignancies. Small cell lung cancer (SCLC) is considered metastatic at time of diagnosis, and survival is quite short. There is no any study evaluating the relationship between NLR and survival in SCLC. In this study, we aimed to determine the effect of NLR on overall survival. Methods: The study included 200 patients with SCLC. Survival times of patients, clinicopathological data and the results of a complete blood count at diagnosis were evaluated from patient archive files retrospectively. Patients were randomized into two groups according to NLR 5< or 5≥. Results: The median age of patients was 56 (36-80) years. One hundred and eighty one (90.5%) patients were male and 19 (9.5%) were males. Sixty-eight (34%) patients had dyspnea, 36 (18%) of cases had cough, 22 (11%) patients had back pain, and 14 (7%) of the cases had chest pain. While the duration of symptoms longer than 3 months in 90 (45%) patients, 110 (55%) patients had symptoms shorter than 3 months. Seventy-two (36%) patients had limited disease, 128 (64%) patients had extensive disease at the time of diagnosis. Twenty-one (10.5%) patients had brain metastasis initially. The median neutrophil count was 5.46 (1.02-20.2) 103 µl, and the median lymphocyte 1.69 (0.27 to 21.9) 103 µl, and median NLR was 3.19 (0.04 to 37.63) respectively. NLR overall survival rate was lowering in patients with greater than or equal to 5 group (5 ≥ group=7 months, 5< group=10 months) (p = 0.004). Conclusions: NLR is an important prognostic index that emphasis on the relationship between cancer and host in SCLC. However, a blood test is cheap and easy to use. This study was concluded that survival was shorter in patients with NLR ≥ 5 in SCLC.
Preoperative serum CA125 as an independent predictor for recurrence and death in operable patients with non-small cell lung cancer.
Authors: Feng Jianguo , Xu Haiyan , Wu Hanmo , Luo Min , Mao Weimin , Su Dan
Published: March 2020

e18520

Background: The role of serum CA125 in the prognosis of non-small cell lung cancer (NSCLC) remains controversial, especially in early stage patients. The aim of this study is to analyze the prognostic value of CA125 in operable NSCLC. Methods: We retrospectively analyzed 645 patients with non-small cell lung cancer (NSCLC) who underwent curative surgical resection for lung cancer at Zhejiang Cancer Hospital of China from 2006 to 2011. Micropartical enzyme immunoassay was used to measure preoperative serum CA125. Pearson’s chi test was used in univariate analyses and a multivariable proportional hazard Cox regression model was applied to assess the prognostic significance of the different covariates. Kaplan-Meier was used to analyze survival curve. Results: The positive rate of preoperative serum CA125 was 18.9% (126/667) in all patients, and elevated CA125 concentration was associated to poorly differentiated tumor and advanced clinical stage. Moreover, CA125 was closely related to patient outcomes. The Kaplan-Meier survival curves were shown patient with normal CA125 concentration had significantly longer DFS (median DFS, not reach vs 21 months, p=0.000) and OS (median OS, 61 vs 29 months, p=0.000) than those with positive CA125. Multivariate Cox analysis indicated patients with positive CA125 had an elevated risk of disease recurrence or death compared with those who had negative one. The adjusted hazard ratio (HR) was 1.74 for replase (95% confidence interval [CI], 1.25-2.41, p=0.001) and 1.79 for death (95% CI, 1.34-2.41, p=0.000) after adjusted by age, gender, grade, stage, histology and smoking status. Conclusions: CA125 seems to play an important role in disease progression and it may be an independent predictive marker for prognosis in patients with NSCLC. [Table: see text]
Effect of the load versus capacity unbalance on the sensitivity of malignant pleural mesothelioma cells to proteasome inhibitors.
Authors: Jocolle' Genny , Numico Gianmauro , Cerutti Fulvia , Laura Oliva , Cenci Simone , Donati Giovanni , Cascio Paolo
Published: March 2020

e18522

Background: Malignant Pleural Mesothelioma (MPM) is an aggressive cancer that originates from the mesothelium of the pleural cavities. Due to its resistance to all chemotherapies available, news therapies against MPM are urgently needed. Bortezomib is a potent Proteasome Inhibitors (PI) that induces apoptosis in different cancers and it was recently approved for treatment of Multiple Myeloma (MM). Since in MM an unbalance between a reduced proteasomal activity (capacity) and an increased proteins degradation (load) was shown to determine apoptotic sensitivity to PI, we challenged this paradigm also in MPM. Methods: Four different MPM (MM98, REN, MMB, MSTO) and a normal (TERT) pleural lines were treated with increasing doses (from 1 to 1000 nM) of Bortezomib and after 24h apoptosis was assessed by flow cytometric analysis of AnnexinV and propidium iodide positive cells. Levels of polyubiquitinated proteins were evaluated by immunofluorescence microscopy and western blotting with the specific monoclonal Ab Fk2 (BIOMOL International). The three main proteasome activities were measured in continuoin cellular extracts at 37°C with a Carry Eclipse spectrofluorometer (Varian, Palo Alto) by means of specific fluorogenic substrates (Suc-LLVY-amc, Bz-VGR-amc, Suc-YVAD-amc). Results: The sensitivity towards Bortezomib greatly differs between the 5 pleural lines analyzed. Specifically the EC50value was higher for the TERT line (130 nM) while for MPM lines ranged between 17 nM (MM98) and 71 nM (MSTO). Importantly, for all the 5 lines analyzed enhanced sensitivity to Bortezomib perfectly correlates with increased levels of ubiquitinated proteins and reduced proteasome specific activity. Conclusions: Our results prove that MPM lines are significantly more sensitive towards the pro-apoptotic effect of Bortezomib than normal pleural cells. Moreover, as in MM, also in MPM PI-sensitivity stems from an unbalance of the load/capacity ratio. Our data, therefore, establish a rationale for the use of Bortezomib (and new second generation PI) in MPM and indicate that combinatorial therapies with other drugs active on the proteostasis network (like HSP inhibitors) might be highly effective against this cancer.
Prognostic factors affecting survival in malignant pleural mesothelioma.
Authors: Komurcuoglu Berna Eren
Published: March 2020

e18535

Background: Determining the pre-treatment prognostic factors in malignant pleural mesothelioma (MPM) is of importance in terms of both estimating the course of disease and determining the patients who are candidate to multimodal therapy. Aim of the current study was to determine the prognostic factors affecting survival in the patients with MPM. Methods: One hundred and twenty five patients who had been diagnosed histologically as having MPM over the past 5 years were evaluated retrospectively. Relationships of survival of the patients with their age, gender, exposure to asbestos, smoking history, platelet, hemoglobin, leukocyte (WBC), serum lactate dehydrogenase (LDH) values, their histology, performance scores and stage of disease were examined. Results: Advanced clinical stage, N2 nodal involvement and presence of distant metastasis were found to be related to survival. Sarcomatous histology was found to be poor prognostic factor independently of other factors. Conclusions: We showed that histological subtype and stage of disease were the most important parameters in planning the treatment, especially in determining the patients who were candidate multimodal treatment and estimating the prognosis.
Prediction of skip mediastinal lymph node metastasis in surgical patients with clinical N0 non-small-cell lung cancer.
Authors: Nakahara Rie , Suzuki Haruko , Matsuguma Haruhisa , Igarashi Seiji
Published: March 2020

e18554

Background: It has been reported that the prognosis of surgical non-small-cell lung cancer (NSCLC) patients with skip-N2 metastasis (without hilar lymph node metastasis) is generally more favorable than that of those with pathological N2 disease. Therefore, when a surgeon determines whether to perform mediastinal lymph node dissection, it is important to accurately predict skip-N2 metastasis in surgical patients without hilar lymph node metastasis. Methods: Of the patients who had undergone complete resection for NSCLC in our hospital between October 1986 and December 2010, 741 with cN0 NSCLC who had undergone mediastinal lymph node dissection were analyzed. The relationship between the lymph node metastasis status and clinicopathological parameters (age, gender, and serum CEA level, histological type, primary tumor location, tumor diameter, pleural invasion(pl), lymphatic invasion(ly), vascular invasion(v)) was analyzed, and factors that predict differences between pN0 and skip-N2 patients were identified. Results: Of the 741 patients, 609 had pN0 disease, 62 pN1 disease, and 70 pN2 disease. Of the pN2 patients, 23 had skip metastases to the mediastinal nodes alone. No significant difference was observed in the gender, age, or histological type between the N0 and skip N2 groups. However, the serum CEA level, tumor diameter, and pl(+) rate were significantly higher (p=0.0028), larger (mean, 3.7 cm, p=0.012), and higher (p=0.0064), respectively, in the skip-N2 group. Also, the ly(+) and v(+) rates were significantly higher in the skip-N2 group. Skip-N2 appeared more frequently with primary tumors in the lower lobes than with those in the upper lobes. Conclusions: Even if no hilar lymph node metastasis is found during surgery in patients with a high serum CEA level, large tumor diameter or lower lobe location, they may have skip-N2 lymph node metastasis. Although the p factor status becomes clear after surgery, patients with pleural indentation so marked as to raise the suspicion of pl(+) have a high probability of skip-N2 metastasis. Mediastinal lymph node dissection is preferable in these patients.
Significance of EGFR and KRAS gene mutation in small cell lung cancer.
Authors: Kurokawa Koji , Matsui Tomoharu , Ikeda Hideko , Nishikawa Shingo , Sone Takashi , Kasahara Kazuo
Published: March 2020

e18564

Background: In non-small cell lung cancer, epidermal growth factor receptor (EGFR) and KRAS are known as driver mutations. However the association between these gene alteration and small cell lung cancer (SCLC) has been unclear. The aim of this study is to investigate the gene status of EGFR and Kras in SCLC. Methods: This retrospective study included 66 SCLC patients with available tumor tissue from primary lung tumor or metastatic and clinical data including survival. We evaluated for the presence of EGFR and KRAS mutation those patients using Scorpion-ARMS method. This study was approved by IRB. Results: Sixty-six patients (52 male,14 female median age 68 range 49-89, LD/ED 34/32, PS0-1/2-3 57/9, smoker/never smoker 64/2) were evaluated. Their median overall survival (OS) were 484 days, progression-free survival (PFS) were 217 days. Sixty-six samples were evaluated EGFR mutation test and 61 were evaluated KRAS mutation test by Scorpion-ARMs methods. SCLC patients with EGFR mutation were the only one patients (1.5%,1/66). KRAS mutation were also the only one patients (1.6%,1/61). A 54 years-old nevere-smoker female was already treated with EGFR tyrosine kinase inhibitor for non-small cell lung cancer, the patients with EGFR mutation had a transformation into SCLC. The KRAS mutation patient was combined SCLC with adenocarcinoma. Conclusions: This study suggested that EGFR and KRAS patients associated with SCLC is poor, these driver mutation is unnecessary for common SCLC.
Potential impact of different methodologies for detecting EGFR mutations in selecting chemotherapy for patients with lung cancer.
Authors: Bender Ryan P. , Ghazalpour Anatole , Tan Zheng , Gatalica Zoran , Paul Les , Reddy Sandeep K. , Castro Michael
Published: March 2020

e19006

Background: Mutation analysis of the kinase domain of EGFR (exons 18-21) is a standard recommended procedure for patients diagnosed with non-small cell lung cancer (NSCLC). NSCLC patients whose tumor harbors certain EGFR mutations have notable responses to EGFR inhibitors. Several different methodologies are available as published assays or commercially available kits and include Sanger Sequencing, allele specific PCR (ASP) and restriction fragment length polymorphism (RFLP). Differences in the design of these three assays dictate which clinically relevant mutations will be detected. Methods: Sanger Sequencing of EGFR found 518 potentially clinically actionable mutations and 45 variants of unknown significance of the 4307 samples tested. To assess which clinically relevant EGFR mutations will be detected by the ASP and RFLP, we performed an in silico analysis of all observed mutations against the design specification of the ASP and RFLP assays. The RFLP assay used in this assessment was developed in our laboratory and is designed to detect all G719 mutations, all exon 19 deletions, all exon 20 insertions and the specific mutations T790M, L858R, L861R and L861Q. A commercially available ASP kit designed to detect 29 mutations in the kinase domain was also analyzed in this study. Results: Based on the performance characteristics assumed by the RFLP and ASP assays, the analytical sensitivities for detecting clinically actionable mutations of the two methodologies are 98.8% and 86.7% respectively, when compared to Sanger Sequencing. It is notable that the RFLP assay missed the S768I mutation (0% detected) whereas the assay did not detect some G719 mutations, exon 19 deletions, and exon 20 insertions (76.3, 86.6 and 35.3% detected respectively). Conclusions: Sequencing is still the preferred method of mutation detection in EGFR for NSCLC as it is the most comprehensive. However, if tumor nuclei are limited a more sensitive method than sequencing is required; EGFR mutation detection by RFLP would identify more of the potentially clinically relevant mutations than ASP. The ASP method would produce false negative results in 13.3% of patients expected to respond to EGFR inhibitors.