bluuebunny/crossref_metadata_2025 huggingface dataset:
The effects of multidisciplinary clinics on the variability in timeliness of care for lung cancer patients.
Authors: Blaseg Karyl , Schallenkamp John M , Stephens Catherine L , Needham Charles Scott , Nieva Jorge J.
Published: March 2020

e17533

Background: Implementation of multi-disciplinary clinics (MDC) has the potential to improve the care of cancer patients. Little data presently exists on the impact of MDC based care on cancer patient populations. Methods: A multi-disciplinary lung cancer clinic was implemented at a large, rural, multispecialty medical center in 2009. A retrospective analysis of the impact of MDC implementation on patient care was accomplished from 2009-2010 and was compared to care of patients from a reference period consisting of all patients treated in 2007. Patient survival, time to first appointment, time to treatment, use of clinical trials, and selection of palliative therapy only were analyzed using descriptive statistics. Two sided students t-test was performed to compare results from each cohort. Results: A new diagnosis of lung cancer was identified in 290 patients from 2009-2010. A total of 175 patients received care within the MDC and 115 patients were treated outside of the MDC. One hundred and forty-two patients were analyzed from the pre-MDC period of 2007. Seventy-seven percent of patients had NSCLC in 2007 and 81% of patients had NSCLC in 2009-2010. The time from referral to first appointment, and diagnosis to treatment are shown in the Table. There was a significant improvement in the mean time to initiation of cancer therapy with the introduction of the MDC clinic with patients starting therapy at a mean of 22 days instead of 28 days, however, the median time to treatment increased to 17 days from 5 days. MDC was associated with improvement in clinical trial accrual to 15% from 10%. Conclusions: The implementation of MDC was associated with greater homogeneity in timeliness of care, with fewer patients being outliers with long delays in time to care, hence improvements in mean time to care, with a detriment in median time to care owning to the increased complexity of scheduling. MDC also resulted in improvements in clinical trial accrual. [Table: see text]
Hospital characteristics and breast cancer patients’ evaluation of care.
Authors: Pfaff Holger , Kowalski Christoph , Ansmann Lena , Ingendahl Julia
Published: March 2020

e17550

Background: There is a large body of research on patient evaluations of care and its associations with patient characteristics, such as the sociodemographics or the severity of diseases. A number of studies have recently been published that consider the characteristics of various hospitals in order to explain the differences in patient evaluations between hospitals in non-oncological patient populations. This study investigates the relationship between13 dimensions of satisfaction and breast center hospital characteristics which account for the patient case mix. Methods: The cross-sectional survey data of 3,601 newly-diagnosed breast cancer patients (response rate: 88% of consenting patients) who were treated in 85 out of 91 breast center hospitals in the German state of North Rhine-Westphalia in 2010 were combined with structural data from a key informant survey from the same hospitals. Multilevel linear regression models were calculated in order to investigate patients’ evaluations of the care differences between hospitals and their associations with hospital characteristics (i.e. teaching status, volume, network size, clinical studies, case manager employed) accounting for patient characteristics (self-rated health, mother language, insurance status, age, education, cancer stage, type of surgery). Results: Patients evaluated non-teaching hospitals as being statistically significantly better in 8 out of 13 satisfaction dimensions. None of the other hospital characteristics were significantly associated with any of the satisfaction dimensions. Overall, the differences between hospitals were small to moderate, with null model ICCs ranging from 0.02 to 0.09 for the different dimensions. Conclusions: Teaching breast cancer hospitals face substantial difficulties in achieving patient evaluations that are as good as those from non-teaching hospitals in Germany. The question of extra staffing for the additional teaching tasks needs to be discussed.
Targeted agents (TA) for advanced solid tumors (AST): What is the likelihood of being helped or harmed (LHH)? Assessing the clinical impact of therapies with FDA/EMEA approval.
Authors: Bria Emilio , Pilotto Sara , Bonomi Maria , Milella Michele , Massari Francesco , Fojo Antonio Tito , Sperduti Isabella , Giannarelli Diana , Tortora Giampaolo
Published: March 2020

e17555

Background: Health care agencies adopt systems to inform patients and health care providers about relative risks and benefits using Evidence Based Medicine (EBM) measures, such as the number of patients needed to be treated/harmed (NNT/NNH), and LHH. This analysis was undertaken to provide an overview of the LHH provided by TA for AST. Methods: Randomized clinical trials (RCTs) supporting FDA/EMEA approval for TA (tyrosine kinase inhibitors, TKI, and monoclonal antibodies, MoAb) were evaluated provided efficacy (PFS, OS), and safety (grade 3-4 specific toxicities) data were available. NNT/NNH were calculated from absolute differences determined for PFS/OS rates (reported/extracted from Kaplan-Meier (K-M) curves and for the worst drug-specific toxicities. LHH was calculated for PFS or OS. A sensitivity analysis according to the randomized comparison (placebo controlled [P] or accepted standard [STD] vs add-on) was performed. Results: Thirty-five separate approvals were identified (23/12 for PFS/OS advantage, respectively). Results are shown in the Table. Hypertension and rash were most frequent drug specific toxicities. LHH >1 may be interpreted as "number of times drug is more likely to provide a benefit than to harm." Conclusions: Despite limitations (estimation from K-M curves and differences in drug toxicities) the data demonstrate the greatest benefit as measured by LHH was achieved with TKI against P or STD with PFS as the endpoint. Marginal benefits were achieved in the majority of OS analyses, and with add-on design. The latter may reflect difficulty of the OS endpoint, marginal benefits of the TA added (bevacizumab and cetuximab) or may indicate TAs combine only poorly with conventional regimens. These data should be complemented with a cost-analysis and put in the context of the general health care system. [Table: see text]
Oncology phase II clinical trials in 2011: Summary description and comparison to phase II trials in other subspecialties.
Authors: Chia Yee Hong
Published: March 2020

e17568

Background: Phase II clinical trials in oncology have previously been reported to differ significantly in design compared to trials in other subspecialties. The purpose of this study is to provide a summary description of Phase II oncology clinical trials published in 2011, and to identify persistent major cross-specialty differences in clinical trial design. Methods: Records identified through a computerized literature search on PUBMED were reviewed manually using pre-defined criteria to identify abstracts of Phase II clinical trials published in 2011. The abstracts were classified according to variables including subspecialty, use of control group (active and/or placebo), randomization, blinding, and study conclusions. Trials with positive outcomes were defined as those in which the conclusion indicated that the intervention was safe and effective/worthy of further investigation. Statistical analysis was performed using the chi-squared test. Results: A total of 1,500 abstracts of Phase II clinical trials were identified, of which the majority (75%) describe trials on interventions for neoplastic diseases. Among oncology trials, the largest proportion of abstracts described trials evaluating intervention for hematologic neoplasms (16%), followed by upper and lower gastrointestinal (15%), lung (13%) and breast (11%) cancers. Compared to trials in other subspecialties, oncology trials are significantly less likely to include the use of randomization (17% vs 66%, p < 0.0001), blinding (3% vs 44%, p < 0.0001), and control (13% vs 70%, p < 0.0001). The majority of the abstracts reported positive outcomes (66% for oncology; 74% for the other subspecialties). Among oncology trials, trials utilizing a control group are less likely to report positive outcomes than those without a control group (53% vs 67%, p = 0.002). Conclusions: Major differences in design still exist between Phase II trials in oncology and other subspecialties. Only a minority of oncology trials report the use of randomization, blinding, or control groups. Whether the growing interest in randomized Phase II oncology trials will translate into a larger proportion of such trials in the future remains to be seen.
Factors affecting the offering and enrollment of patients on clinical trials in radiation oncology.
Authors: Rich Shayna Eliana , Mendenhall Nancy Price
Published: March 2020

e17571

Background: Improvements in cancer treatment require significant patient involvement in research, which may be particularly limited for new technologies such as proton radiation therapy. Studies with biased referrals or enrollment may not be generalizable to a general population. This study examines the reasons why patients were not offered or refused enrollment in clinical trials at the University of Florida Proton Therapy Institute (UFPTI). Methods: All patients seen at UFPTI between April-October 2012 for proton therapy for tumor sites with a clinical trial available (N=463) had information collected prospectively regarding whether they were offered enrollment and consented for clinical trials, and the reasons for each decision. The majority of patients had already secured funding for proton therapy. Results: Seven percent (34/463) of patients were ineligible for an available clinical trial, due to study exclusion criteria, concerns for patient safety based on comorbidity, or concerns for data integrity (e.g., other non-skin cancer within five years). Only 3% (9/275) of eligible patients were not offered a clinical trial. Forty-four percent (99/226) of patients offered a clinical trial refused. The most common reasons for refusal included: discomfort with lack of mature data, dislike of protocol, fear that protocol is not best option for disease control, and fear of side effects. Although UFPTI treats a variety of malignancies, the overwhelming majority of those who refused consent were prostate adenocarcinoma patients, who often self-referred for proton therapy. Conclusions: Despite near universal availability of clinical trials at UFPTI, less than half of patients enroll in clinical trials. The greatest factor for non-enrollment appears to be patient acceptance. Despite the availability of non-randomized trials with fairly standard treatment approaches, 44% refused to enroll on clinical trials, suggesting discomfort for less well documented treatment approaches. Further studies should examine whether findings are similar among all US cancer patients, as patients seeking proton therapy may not resemble the general population.
Prospective clinical experience with research biopsies in breast cancer patients.
Authors: Zeghibe Catherine A. , Luis Ines Maria Vaz Duarte , Frank Elizabeth S. , Sohl Jessica , Washington Kimberly E. , Silverman Stuart G. , Fonte Joseph M. , Mayer Erica L. , Overmoyer Beth , Richardson Andrea L. , Krop Ian E. , Winer Eric P. , Lin Nancy U.
Published: March 2020

e17574

Background: There is active debate concerning the ethics and risks of non-clinically indicated biopsies (bxs) in patients (pts) with cancer. In this analysis we examined our single institution experience regarding acceptance, safety, and success rate with research biopsies in pts with breast cancer (BC). Methods: An IRB-approved ongoing prospective study at the Dana-Farber Cancer Institute collects research bxs from pts with BC. Research bxs are performed as additional passes at the time of a clinical bx (cohort 1) or as a separate procedure for banking purposes only (cohort 2) on known tumor or suspicious lesions. Bxs are not linked to a specific therapeutic or correlative trial. Bx-site related risks are pre-specified in consent forms. Grade 2-5 adverse events (AEs) associated with the procedure are prospectively collected. Chart review for bxs between 2005-2013 was performed in this analysis. Results: As of January 2013, 158 pts had consented to the study; 3 pts withdrew consent and 4 pts did not have bxs. 151 pts are in the analytic cohort (total bxs performed= 161); 82% in cohort 1, 18% in cohort 2. Most pts were white (89%) with a performance status of 0-1 (98%). A majority of pts (96%) underwent a bx in the setting of known or suspected metastatic disease. 39% of bxs were performed at time of diagnosis or first recurrence. The most common sites for bx were liver (38%, n=61), skin (24%, n=39) and breast (18%, n=29). Lung was uncommon (3%, n=4). Research biopsies were successfully performed in 114 (92%) pts in cohort 1 and 27 (100%) pts in cohort 2. In cohort 1, research biopsies were not successful in 10 pts. In 9 pts the clinical samples had insufficient material, leading to the forfeit of the banked research sample for clinical purposes; in 1 pt the bx was suspended for severe pain. Only 3 (1.9%) pts had AEs ≥ grade 2: 1 with grade 2 pain; 1 with grade 2 pneumothorax; and 1 with grade 3 pain. Conclusions: Our experience in an academic medical center suggests that pts with BC are willing to undergo research bxs outside the context of a therapeutic or translational trial. These procedures can be performed safely with a high rate of successful tissue collection. Additional data are needed to fully quantify the risks and to demonstrate the value of these procedures.
Analysis of survival in patients with chronic myelogenous leukemia in pre- and post-imatinib era involving comparison of large academic medical center versus national data: The Beaumont experience.
Authors: Aller Cynthia Barbara , Rigo Paul , Jaiyesimi Ishmael A.
Published: March 2020

e18007

Background: Imatinib mesylate is first-line therapy for chronic myeloid leukemia (CML) since its introduction in May, 2001. Once deadly, CML is now a chronic disorder due to this medication.We sought to analyze the impact on survival in our patient population at Beaumont Health System, a tertiary care facility, versus all hospitals in the United States. Methods: Patients with CML were identified and categorized as pre- or post-2001 when first seen. Analysis of survival in intervals of 12 months in the two groups was done with the Elekta’s National Oncology Data Alliance Database (NODA): 1990-2000 and 2001-2010. Overall 5-year survival results are reported. Results: Analysis of survival was performed on pre- and post-2001 populations in Beaumont patients versus their national counterparts. In the pre-2001 population, 580 patients nationwide and 34 patients from Beaumont were analyzed for a total of 614 patients. In the post-2001 population 1,602 patients nationwide and 122 patients from the Beaumont were analyzed for a total of 1,724 patients. The pre-2001 group nationally showed a survival probability of 28% ± 1.8%, patients in the Beaumont group showed a survival probability of 26% ± 8%. Patients in the post-2001 nationwide group showed a survival probability of 56% ±1.4%, the Beaumont group showed a survival probability of 48% ±5.0%. Both groups showed a significant survival advantage after 2001 in the era of imatinib as first-line therapy for CML. Patients in the national analysis showed a survival advantage of 28% and patients in the Beaumont analysis showed a survival advantage of 22%. Conclusions: This analysis provides evidence for a survival advantage in the post-2001 era of imatinib mesylate therapy a first-line therapy for CML on both a national and our institution level. Differences in numbers of patients analyzed, drug availability, and implementation of molecular monitoring could account for variability of the results. This data supports the revolutionary nature of this medication in the treatment of CML in the United States since 2001.
Myelodysplastic syndrome (MDS) and autoimmune diseases (AD): Hypomethylating agents to treat both.
Authors: Al Ustwani Omar , Ford Laurie Ann , Sait Sheila N. J. , Block Anne Marie W. , Barcos Maurice P. , Griffiths Elizabeth A. , Thompson James E. , Wang Eunice S. , Ambrus Julian L. , Wetzler Meir
Published: March 2020

e18018

Background: AD occurring in the setting of MDS is challenging to recognize and incorporate into the treatment plan. We assessed the clinical presentations, laboratory abnormalities and outcome of patients with MDS and AD. Methods: Records of MDS patients treated at Roswell Park Cancer Institute between 2007 and 2010 were reviewed (n=123). Results: AD was identified in 10 MDS patients (8.1%): 70% were males, median age was 60.6 years (41-75). AD manifested as seronegative polyarthritis in 2, bronchiolitis obliterans in 2, Hashimoto’s thyroiditis in 2, and 1 (10%) for each of rheumatoid arthritis, systemic lupus, polymyalgia rheumatica, Sjogren syndrome and relapsing polychondritis. Laboratory autoimmune markers were: anti nuclear antibodies in 2, rheumatoid factor in 2, anti-double stranded DNA in 1 and anti phospholipid syndrome with thrombosis in 1. Corticosteroids were the most common used treatment for AD (60%). Regarding the MDS diagnosis; 50% had refractory anemia with excess of blasts-1 and -2, 20% refractory anemia with ring sideroblasts, 10% for each of chronic myelomonocytic leukemia, refractory anemia and MDS/myeloproliferative neoplasm. Normal cytogenetics were noted in 70% of patients, 20% with complex karyotype and 10% had monosomy 7. Hypomethylating agents were used to treat MDS in 80% of patients and in one case were associated with concomitant improvement of AD. Overall survival from diagnosis with MDS was 54 months (6-127). Conclusions: Our experience with one patient and review of the literature suggest that both AD and MDS could benefit from treatment with hypomethylating agents. This warrants a prospective clinical trial.
A National Cancer Data Base report on mesothelioma.
Authors: Brin Lauren , Warlaumont Mary , Fuller Timothy , Silberstein Peter T.
Published: March 2020

e18501

Background: This is the first report on mesothelioma using Commission on Cancer National Cancer Database information and this is the largest study on mesothelioma to date. Methods: Using the National Cancer Database (NCDB) 26,605 patients diagnosed with mesothelioma between 2000 and 2010 were identified and analyzed. The NCDB contains data from more than 70% of all new cancers diagnosed in the U.S. each year. Results: The majority of mesothelioma patients are Caucasian (89%), males (78%), over the age of 70 (60%), and are diagnosed with stage IV disease (41%). The majority of patients (41%) received no first course treatment. The patients that were most likely to have surgery include patients <70 years old, at academic centers, with stage I-III disease, and of these only 37% received surgery and 15% received no first course treatment. The youngest patients <50 years received the most surgical therapy (36%) and the oldest patients >80 received the least (12%). Patients with private insurance received more surgical treatment (28%) than patients with Medicaid (22%), Medicare (18%), and VHA (12%)(p<0.009). Private insurance holders also received no first course treatment less often (29.6%) than Medicaid (37%), Medicare (46%), VHA (52%), and uninsured patients (37%)(p<0.002). Conclusions: The majority of patients with mesothelioma are elderly, Caucasian males and many of which do not receive treatment. The standard of care for resectable stage I-III mesothelioma includes surgery and chemotherapy. The results from this study indicate that 41% of all patients received no first course treatment and only 21% of patients received surgical treatment. Of patients most likely to receive surgery, only 37% of patients received surgical treatment and 15% of these patients did not receive any first course treatment. Age and insurance status also affect treatment as the youngest patients and private insurance holders received the most surgical treatment. [Table: see text]
En bloc resection of pulmonary sulcus non-small cell lung cancer invading the spine: A systematic review and pooled analysis.
Authors: Collaud Stephane , Fadel Elie , Schirren Joachim , Yokomise Hiroyasu , Bolukbas Servet , Dartevelle Philippe , Keshavjee Shaf , Waddell Thomas K. , de Perrot Marc
Published: March 2020

e18503

Background: Treatment of locally advanced NSCLC is debated. While survival for inoperable disease ranges between 3-17%, carefully selected patients can be cured when treated surgically in a multimodality concept. Here, we conducted a systematic literature review and pooled data analysis of patients after en bloc resection for pulmonary sulcus NSCLC invading the spine. Outcome and prognostic factors were described. Methods: The MEDLINE database was searched using the PubMed engine to retrieve all relevant articles related to en bloc resection for pulmonary sulcus NSCLC invading the spine. All articles’ corresponding authors were contacted to share their most updated anonymized patient’s data. Data were pooled and analyzed, focusing on outcome and prognostic factors. Results: Search strategy yielded a total of 134 articles. Out of these, only 6 were relevant and non-duplicative. Four out of 6 authors were able to share updated data for a total of 135 patients. All tumors were resected en bloc with the lung, chest wall and spine. Induction treatment was administered in 87 (64%) patients and consisted of chemotherapy (n=32), radiation (n=1) or concurrent chemoradiation (n=54). Spine resections included total (n=23), hemi- (n=94) and partial (n=18) vertebrectomies. Complete resection was achieved in 120 (89%) patients. Five patients died in the postoperative period (4%). Adjuvant treatment was administered in 70 (52%) patients and included chemotherapy (n=16), radiotherapy (n=22) or chemoradiation (n=32). Median follow-up was 26 months. Overall 3-, 5- and 10-year survivals were 57%, 43% and 27%, respectively. Results of the univariate analysis (Cox, Breslow tests) identified incomplete surgical resection (R0 vs R1/2, p<0.001) as the only significant prognostic factors among the variables tested (age, histology, pN stage, type of induction/adjuvant treatment, type of lung resection). Conclusions: Multimodality therapy including en bloc resection for pulmonary sulcus NSCLC invading the spine provides excellent long-term survival. Complete surgical resection is the only determinant for survival. No difference was shown for patients treated with induction vs adjuvant therapy.
Irinotecan in combination with platinum in refractory or relapsed small cell lung cancer.
Authors: Yu Shufei , Wang Yan
Published: March 2020

e18504

Background: To evaluate the efficacy and safety of irinotecan in combination with platinum against refractory or relapsed small cell lung cancer. Methods: In this retrospective study, we analyzed the data of 1,140 patients who diagnosed small cell lung cancer at our hospital between 2009 and 2012. Of all the patients, 34 were treated with irinotecan and nedaplatin (irinotecan 60mg/m2 on days 1,8 nedaplatin 85mg/m2 day 1,every 3 weeks), and 20 patients were treated with irinotecan and cisplatin (irinotecan 60mg/m2 on days 1,8 cisplatin 75mg/m2day 1,every 3 weeks ) as the second line treatment. Prognostic factors of overall survival (OS) were estimated by Kaplan-Meier and Cox's Regression-proportional hazards model. Results: Of 54 eligible patients, median progression free survival (PFS) was 21weeks, and median OS was 58 weeks. Median PFS was 23 weeks for irinotecan plus nedaplatin and 19 weeks for irinotecan plus cisplatin (P=0.410). Median OS was 62 weeks and 58 weeks, respectively (P=0.714).The response rate (RR) was 29% and 33.3%, respectively (HR 0.818,95%CI 0.234to2.855; P=0.753). In multivariate analysis, younger age, extensive stage while diagnosed, brain metastasis, treated with 3 cycles of irinotecan in combination with platinum or less, and PS≥1 were all associated with a statistically significant increase in the mortality harzard. Toxicity profile was slightly different for each of the arms: hematologic toxicity was higher with nedaplatin, and diarrhea was higher with cisplatin. Conclusions: Irinotecan plus platinum is effective and tolerable for refractory and relapsed small cell lung cancer. [Table: see text]
Analysis of the p38MAPK pathway in the prognosis of patients with surgically resected stage I-II NSCLC.
Authors: Pardo-Coto Pablo , Esteban Emilio , Astudillo Aurora , Gracia Jose Manuel , Corral Norberto , Izquierdo Manuel Marta , Lopez Carolina Muriel , Sanmamed Miguel F. , Gutierrez Restrepo Eduardo , Valle Pereda Miguel , Alvarez Fernandez Carlos , Pérez Arnillas Quionia , Berros Fombella Jose Pablo , Jiménez Paula , Vieitez de Prado Jose Maria , Fra Joaquin
Published: March 2020

e18513

Background: TNM staging is the most important prognostic factor in Non-Small Cell Lung Cancer (NSCLC). The MAPK pathway, including p38, JNK and ERK, has been slightly studied in NSCLC, with controversial prognostic significance. Methods: The records of 211 patients with stage I-II NSCLC, surgically resected at Asturias University Hospital between 2000 and 2004 were retrospectively reviewed. Formalin-fixed, paraffin-embedded histological tumour specimens were used to construct tissue microarrays. The nuclear level of phosphorilated p38alpha (nP-p38), JNK (nP-JNK) and ERK (nP-ERK) was assessed using inmunohistochemistry (IHC). Phosphorilated protein expression was considered positive if the staining was present in at least 100% of the nucleus studied. EGFR was also analyzed with IHC following previous studies and was considered positive (EGFR+) if staining was observed in >10% of the cells. Clinicopahological data and outcome differences in terms of overall survival (OS) were compared between positive and negative patients. Results: Patients with nP+ for p38, JNK or ERK had a trend to better OS than those respectively negative for each protein (HR=0.68, p=0.14; HR= 0.75, p=0.16; HR=0.64, p=0.14), and the difference was significative for nP-p38+ in adenocarcinoma histology (p=0.012). EGFR+ patients had worse OS than EGFR- (HR=1.59, p=0.02), but in nP-p38+ patients, those with EGFR+ tumors had similar survival than EGFR- (p=0.9). Fifteen patients were positive for the three MAPK (MAPK “Triple Positive”, MTP), and had better OS than the rest not MTP (HR=0.20, p=0.01). In the univariant analysis, stage, histologic grade, surgery (pneumonectomy vs lobectomy), EGFR status and MTP had significant influence on OS. Multivariant analysis only confirmed the stage as an independent factor (p=0.01). Conclusions: TNM staging remains the most important factor in the prognosis of NSCLC. The activation of the MAPK pathway, its interaction with EGFR, and the MTP feature might have prognostic influence in this tumor and warrant confirmation in a large prospective trial. The potential therapeutic implications of pharmacological manipulation of the MAPK pathway highlight the importance of this study.
Ultrasound Elastography Pattern of lung squamous cell carcinoma: Preliminary report on a possible adjunctive tool for noninvasive imaging.
Authors: Sperandeo Marco , Trovato Guglielmo M. , Dimitri Lucia , Martines Giuseppe Fabio , Simeone Anna , Trovato Francesca M. , Piscitelli Angela Pamela , Catalano Daniela
Published: March 2020

e18518

Background: Trans-Thoracic Ultrasound (TUS) guided Fine Needle Aspiration Biopsy (FNAB) provides a rapid and affordable method of diagnosing and staging lung cancer. It allows safe and easy access to sub-pleural masses. A total of 70% of pleural surface is accessible by TUS, and pulmonary processes, including masses, are visualized when they come up to pleura or are accessible via a sound window (e.g. pleural effusion or atelectasis), provided that no subcutaneous emphysema or pneumothorax is present. US Elastography is a novel approach useful to estimate the stiffness/elasticity of tissues. It is already a valuable tool for the definition of nodules (thyroid, breast, prostate cancer). The aim of our study was to assess if TUS Elastography of concurrent FNAB-proven lung cancer could be of help for a preliminary histological diagnosis. Methods: TUS with Elastography and FNAB after chest x-ray and CT-scan were performed in 57 patients (m 44, f 13; years 64,63±5,96). Tissue stiffness of the subpleural masses was scored from 1 (greatest elasticity) to 5 (no elasticity) using a convex 2-8 mHz probe and a MyLab-ElaXto Esaote-Biomedica equipment. Results: By TUS, subpleural solid masses (cm. 2-5) were detected and assessed by FNAB. Histological diagnosis were: small cell lung cancer (4/57), Adenocarcinoma (29/57), Squamous Cell Carcinoma (12/57, SCC) and poorly differentiated lung carcinoma (12/57). Patients' age and mass dimension are not significantly associated with any histotype. A significant lower elasticity of SCC (4,67±0,492) is observed vs. any of the other three histotypes of cancer (P<0.005). A score of 5 at Elastography is observed in 8/12 SCC and only in 7/45 of the other histotypes (χ2 p<0.0004 vs. any of the other histotypes; OR 10.857; 95% CI 2,557-46,093). By a MLR model, age, TNM and tumor dimension were not significant predictors of the Elastography score. Conclusions: TUS Elastography seems a novel imaging adjunctive tool reasonably suitable to help in the non-invasive diagnosis of Lung Squamous Cell Carcinoma.
The prognostic role of XRCC1, ERCC1, ERCC2, and TP53 single nucleotide polymorphisms (SNPs) in resected non-small cell lung cancer (NSCLC).
Authors: Geredeli Caglayan , Artac Mehmet , Yildirim Selman , Dede Isa , Inal Ali , Guler Tunc , Boruban Melih Cem , Zamani Ayse Gul , Bozcuk Hakan , Demirkazik Ahmet
Published: March 2020

e18521

Background: Identification of biomarkers that can be used for the prognostic evaluation of NSCLC patients is important. The aim of this study was to evaluate the potential prognostic value of XRCC1, ERCC1, ERCC2 and, TP53 SNPs in completely resected NSCLC patients. Methods: In total 130 patients, who had been surgically treated for NSCLC between 2000 and 2012, were included in this study. Analysis of SNPs from peripheral blood cells was performed by polymerase chain reaction. XRCC1 Arg399Gln, ERCC1 Asn118Asn, ERCC2 Lys751Gln and, TP53 Arg72Pro polymorphisms were evaluated in conjunction with clinical and pathological parameters and survival. Kaplan-Meier method and Cox regression analysis were used. Results: In the univariate analysis for disease free survival (DFS) post operative stage (HR,0.50; 95%CI, 0.26-0.96; P=0.03), ERCC2 genotype (HR, 2.47; 95%CI, 1.28-4.78; P=0.007) and PET-CT staging (HR, 0.27;95%CI, 0.14-0.52; P<0.001) were significant parameters. Adjuvant chemotherapy, age and the other SNPs were not significant. In the multivariate analysis post operative stage (HR, 0.40;95%CI, 0.20-0.81; P=0.01), ERCC2 genotype (HR, 2.66;95%CI, 1.35-5.27; P=0.005), PET-CT staging (HR, 0.24;95%CI, 0.12-0.47; P<0.001) retained their significance. The median DFS was 56.5 months (95%CI, 24.6-88.4 months) for the ERCC2 mutant (TT) and heterozygote (GT) genotypes, and 28.3 months (95%CI, 20.8-35.8 months) for the ERCC2 normal (GG) genotype (P=0.005). Conclusions: In addition to stage and PET-CT staging, ERCC2 genotype independently predicted DFS in resected NSCLC patients. Future prospective studies are needed for the further evaluation of potential prognostic SNPs in resected NSCLC.
Optimisation of EGFR TKI efficiency in the therapeutic scheme of EGFR wild-type lung cancer.
Authors: Cabart Mathilde , Raimbourg Judith , Lalier Lisenn , Bennouna Jaafar , Vallette Francois
Published: March 2020

e18532

Background: EGFR tyrosine kinase inhibitors (EGFR TKI) have improved the therapeutic care of lung cancer patients but only a small sub-population of patients, namely those harboring EGFR-mutated tumors, benefit from this therapy. The observation that EGFR TKI enhance prognosis and quality of life in all patients when used as second line or maintenance treatment impelled us into the search of potential markers of the optimal introduction kinetics of EGFR TKI in the therapeutic scheme. Methods: We used lung cancer cell lines harboring either wild-type or mutated EGFR (NCI-H1650, NCI-H1975) to study the consequences of cisplatin treatment in vitro on the consecutive sensitivity to erlotinib. Results: Sub-lethal cisplatin pretreatment (3µM) enhances erlotinib toxicity in EGFR wild-type, but not EGFR mutated cells (A549 IC50 drops from 28 to 15µM for short-term or 12µM for long-term exposure). This correlates with EGFR activation following short-term or prolonged cisplatin treatment through the secretion of EGFR ligands. This activation of EGFR is concomitant to the decrease in other receptor tyrosine kinases phosphorylation including Met. Conclusions: The sensitivity of EGFR wild-type lung cancer cells to erlotinib in vitro is enhanced by cisplatin pretreatment. We identified potential markers of this sensitization, namely EGFR ligands, which serum level might be predicitive of the optimal efficiency of EGFR TKI. In vivo validation of these markers is under investigation. The concomitant decrease in other receptor tyrosine kinases phosphorylation suggests that the targeting of other receptor tyrosine kinases might potentiate EGFR TKI efficiency.
Maintenance chemotherapy with pemetrexed in epiteliomorfe malignant pleural mesothelioma.
Authors: Nacci Angelo , Lotesoriere Claudio , Montrone Michele , Pisconti Salvatore , Orlando Laura , Fedele Palma , Rizzo Pietro , Calvani Nicola , Mazzoni Enrica , Cinefra Margherita , Marino Antonella , Sponziello Francesco , Cinieri Saverio
Published: March 2020

e18545

Background: Maintenance chemotherapy with pemetrexed is not the standard treatment of choice in patients with locally advanced or metastatic epiteliomorfe malignant pleural mesothelioma (EMPM). We would assess the safety and efficacy of a treatment with pemetrexed until progression disease after 4 or 6 cycles of induction therapy with or without platin. Methods: From July 2008 to September 2012, 21 patients (18 males and 3 females with a median age of 67 years range 58-84) with locally advanced or metastatic epiteliomorfe malignant pleural mesothelioma (EMPM) were enrolled. In all patients histology was epiteliomorfe malignant mesothelioma. Only 15 patients (71,4%) had a PS 0 whereas 6 (28,6%) had a PS 1. All patients received an induction therapy with or without platin. Each patient received an average of 5,6 cycles of induction chemotherapy. Then all patients received a maintenance chemotherapy with pemetrexed 500 mg/mq intavenously over 10 minutes every 3 weeks. Each patient received an average of 7,3 cycles of maintenance chemotherapy. All patients received folic acid and vitamin B12 supplementation to improve safety. Results: At the time of analysis all patients were evaluable for response. Fourteen patients (66,6 %) had a partial response and two of these underwent surgery and obtained a complete response. Six patients (28,5%) had a stable disease. The median overall survival was 13 months, while median progression-free survival was 11 months. Grade 2-3 of WHO haematological toxicities (anemia and neutropenia) occurred in 4 patient (19%). We also observed grade 2-3 of WHO gastrointestinal toxicities (diarrhea, nausea and vomiting) in 2 patient (9.5%). Grade 2 of lack of appetite and asthenia occurred in 3 patients (14.3%). Conclusions: Our data show that a maintenance chemotherapy with pemetrexed in EMPM resulted in a moderate overall survival (13 months). These results indicate that patients with EMPM could benefit from a maintenance treatment with pemetrexed.
Concordance between formalin-fixed paraffin-embedded biopsy samples and surgically resected snap-frozen samples in multiplexed molecular profiling of lung cancers.
Authors: Kenmotsu Hirotsugu , Serizawa Masakuni , Koh Yasuhiro , Isaka Mitsuhiro , Takahashi Toshiaki , Murakami Haruyasu , Naito Tateaki , Taira Tetsuhiko , Shukuya Takehito , Ono Akira , Akamatsu Hiroaki , Imai Hisao , Mori Keita , Endo Masahiro , Nakajima Takashi , Ohde Yasuhisa , Yamamoto Nobuyuki
Published: March 2020

e18556

Background: The results of comprehensive genome-wide characterization of lung cancer have recently been reported. However, the concordance of driver mutations between formalin-fixed paraffin-embedded (FFPE) and surgically resected snap-frozen samples is unclear. We conducted the Shizuoka Lung Cancer Mutation Study to analyze driver mutations in patients with lung cancer. Methods: Based on the biobanking system in conjunction with the clinic including the pathology lab, we developed a multiplexed mutational panel designed to assess 23 mutations in 9 genes (EGFR, KRAS, BRAF, PIK3CA, NRAS, MEK1, AKT1, PTEN and HER2), EGFR, MET, PIK3CA, FGFR1 and FGFR2 amplifications, and EML4-ALK translocations, using pyrosequencing plus capillary electrophoresis, qRT-PCR, and RT-PCR, respectively.DNA concentration in FFPE samples was analyzed by measuring absorbance at 260 nm (A260) in a spectrophotometer. Results: Between July 2011 and July 2012, sixty-five lung cancer patients with both FFPE and snap-frozen samples were included in this study. Patient characteristics were as follows: median age (range) 70 (38-92) years; female 68%; never-smoker 34%; histology adenocarcinoma/squamous cell carcinoma/small cell carcinoma/other 52/29/6/13 %. FFPE samples included 64 transbronchial biopsies and one pleural biopsy. We detected driver mutations in 58% of all cases. Mutations found: EGFR 28%, KRAS 12%, PIK3CA 6%, NRAS 2%, HER2 5%, EGFR amplification 5%, PIK3CA amplification 12%, FGFR1amplification 2%. Complete concordance of driver mutations between FFPE and snap-frozen samples was shown in 65%. Median DNA concentration in FFPE samples was 72.7 ng/ul (range; 2.4 - 472.4 ng/ul). Exploratory analyses using an ROC curve, done to evaluate the useful cutoff of DNA concentration in FFPE samples, showed low AUC (AUC; 0.5326). Conclusions: These results suggest that the rate of complete concordance of driver mutations between FFPE and snap-frozen samples might be acceptable, and DNA concentration in FFPE samples might not be correlated with concordance.
The effect of front-line chemotherapy on overall survival in patients with malignant pleural mesothelioma.
Authors: Elkiran Emin Tamer , Sevinc Alper , Harputluoglu Hakan
Published: March 2020

e18560

Background: Malignant pleural mesothelioma (MPM) is a relatively rare, but aggressive tumor that causes high mortality. The major risk factor involved in the etiology is environmental and occupational exposure to asbestos. The optimal modality of therapy is controversial. Methods: The present study retrospectively evaluated the 141 patients from the database. Results: There were 80 males and 61 females with a mean age of 56 ± 1.07 years. The median survival in patients who were administered front-line chemotherapy was 17 months (95% CI: 13.19-20.81). 106 patients were administered pemetrexed-platinum combination and 35 patients were administered gemcitabine-platinum combination as front-line chemotherapy. For the patients who received pemetrexed-platinum regimen, a median of 6 cycles of chemotherapy was administered and 50 patients (47.2%) were able to receive all 6 cycles as planned. For the patients who received gemcitabine-platinum regimen, a median of 6 cycles of chemotherapy was administered and 19 patients (54.3%) were able to receive all 6 cycles. Median survival was found 16 months in the pemetrexed-platinum regimen and 26 months in the gemcitabine- platinum regimen. There was no statistically significant difference between the patients who received pemetrexed-platinum and gemcitabine-platinum regimens in terms of the median overall survival (p = 0.15). Conclusions: Results of our study suggest that chemotherapy prolongs overall survival. Survival rates in patients who received combining platinum analogues with pemetrexed or gemcitabine as front-line chemotherapy were found to be similar.
A clinical prognostic model to predict survival and efficacy in advanced or metastatic non-small cell lung cancer patients who received first-line chemotherapy: A retrospective analysis of 236 patients in northeast China.
Authors: Qu Xiujuan , Gong Jing , Hu Xuejun , Jin Bo , Zhao Mingfang , Yu Ping , Liu Yunpeng
Published: March 2020

e19004

Background: This study was aimed to build a prognostic model for survival and predict efficacy in patients undergoing first-line chemotherapy in advanced or metastatic non-small cell lung cancer. Methods: Sixteen pretreatment clinical and biological variables were analyzed in 236 NSCLC patients who received first-line chemotherapy in our hospital. The prognostic model was calculated according to the results of multivariate Cox model, and the survival in different score groups were estimated by the Kaplan-Meier method and Long-rank tests. Results: Sixteen factors (smoking history, performance status, gender, disease stage, histological type, LDH, fibrinogen, WBC count, granulocyte count, lymphocyte count, hemoglobin, albumin, FBG, PLT, TP, β2-MG) were analyzed in univariate model for overall survival. The result showed PS=1 (HR=1.85, p<0.001), elevated fibrinogen (HR=1.63, p=0.008), elevated LDH (HR=1.78, p=0.002), granulocyte count >4.85×109/L (median) (HR=1.65, p=0.004) and increased PLT (HR=1.78, p=0.004) were poor prognostic factors. Then these five factors were enrolled in multivariate analysis. The result showed that PS=1 (HR=1.93, p<0.001), elevated LDH (HR=2.22, p<0.001) and increased PLT (HR=1.71, p=0.04) were independent prognostic factors. The patients were separated to low risk group (no adverse factor), intermediate risk group (1 adverse factor) and high risk group (2-3 adverse factors) according to the number of adverse factors. Median overall survival for these groups were 22.7, 14.5, and 7.5 months at a p value of <0.001. Kruskal-Wallis analysis revealed that the differences of efficacy in these three groups were statistically significant different (p=0.016). Conclusions: Prognostic model using PS=1, elevated LDH and increased PLT might be applied to predict survival and efficacy in advanced or metastatic NSCLC patients undergoing first-line chemotherapy. The model constituted by these three economic and easily acquired parameters may provide a tool in clinical decision making and therapy selection.
Early use of home health care on health care utilization for patients with advanced lung cancer.
Authors: Rousey Steven , Lassi Kiran Krishan , Wieczorek Jodi , Essler James , Brown Marie , Haroldson Sylvia , Sheppard Sue , Olson Kari , O'Brien Michelle , Wang Yunfei
Published: March 2020

e19015

Background: Patients with advanced lung cancer historically have required significant use of health care resources including hospitalizations, ICU admissions and emergency room visits which are often related to inadequately controlled symptoms. Most patients with advanced lung cancer prefer to remain in their own home as much as possible and are willing to work with home nursing resources, if available. The purpose of this pilot study was to determine the effect of early use of home health care on health care utilization for patients with advanced lung cancer. Methods: Betweem May 2011 and May 2012, 18 patients were enrolled in a pilot program to explore early use of home care for individuals with advanced lung cancer. Inclusion criteria consisted of a diagnosis of stage III/IV lung cancer (any histology) and home care eligibility using Medicare criteria. The endpoints were hospitalization rate, number of ICU admissions and emergency room visits. The results were compared to an historical control group (562 patients with advanced lung cancer diagnosed between 2006 and 2011). Binomial confidence interval (CI) was used to estimate the 95% CIs and Fisher's exact test was used to assess the p-values. Results: Results at one year showed the hospitalization rates for the pilot group and the control group were 44% (95% CI, 22-69) and 78% (95% CI, 74-81), respectively (p<0.01) and the ER visit rate was 17% (95% CI, 4-41) and 41% (95% CI, 37-45), respectively (p=0.049). The ICU admission rates were 0% and 11% in the two groups, respectively, and this difference was not statistically significant. Home care visits ranged from 1-77 with an average of 12 visits per patient. The estimated cost of the home care program for the duration of enrollment was $2,330 per patient. Conclusions: Early use of home health care for patients with advanced lung cancer appears to reduce the rates of hospitalization and emergency room visits when compared with historical controls, and though the results were not statistically significant, none of the 18 patients in the pilot group were admitted to the ICU. A larger multi-institutional study will examine the potential of this simple intervention for cost saving, enhanced care quality and improved patient satisfaction.
Clinical results of recombinant adenoviral human p53 gene in treatment of malignant pleural effusions caused by advanced lung cancers.
Authors: He Yong
Published: March 2020

e19026

Background: Management of the malignant pleural effusion caused by advanced or recurrent lung cancer is a big challenge for clinicians due to multiple reasons: patients’ poor conditions, resistance to chemo- or radio-therapy, intolerance to an aggressive treatment, et al. This report presents a new safe treatment for controlling this type of tough conditions. Methods: Fifty-six patients, 39 males and 17 females with an average age of 64.2 years old were included in this study. All these patients had either a lung cancer in advanced stage or a recurrent cancer after a radical tumorectomy, with malignant pleural effusion. After draining most of the effusion fluid, the patients received intra-cavity infusion of rAed-p53 once per week for 4 weeks, at dose of 2×1012 viral particles (VP) diluted into 300 ml of saline solution. The complete response is defined as the complete disappearance of pleural or peritoneal fluid and negative cytologic findings for >4 weeks, and the partial response is defined as a decrease over 50% of the fluid without the need of drainage and negative cytologic findings for >4 weeks. Results: Participants were followed up for a median time of 15 month. Fifty patients (26.8%) achieved a complete response (CR) and 23 (41.1%) achieved a partial response (PR). The overall response rate is 67.9%. Patients’ quality of life, assessed by using Karnofsky performance scale (KPS) scores, was improved by an average of 27.2. The one-year of overall survival rate was 48.2% with a median survival time of 11.0 months. There were no serious side effects observed except for self-limited fever found in 82.6% of the cases. Conclusions: Intra-cavity infusion of rAd-p53 is a safe and effective method for controlling the malignant pleural effusion for patients with advanced lung cancer and in a poor condition, especially for those who can’t tolerate the standard treatments.