bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparing prognosis estimates of patients with cancer and their oncologists.
Authors: Gentzler Ryan D. , Kraft Walter K , Leiby Benjamin E , Filicko-O'Hara Joanne E.
Published: March 2020

e16548

Background: Authors have reported a discrepancy between patient (pt) and physician survival estimates in pts with advanced malignancies. Methods: Oncology pts receiving chemotherapy at Thomas Jefferson University Hospital were assessed for their prognosis estimates. Matched surveys were given to their oncologists. The primary outcome was the level of agreement between pt and physician survival estimates. Prognosis estimates were obtained by three categorical responses: < 1 year, 1–5 years, or > 5 years. Pt prognosis estimates were categorized as pessimistic, concordant, or optimistic in relation to physician estimates, and differences between pt and physician estimates were evaluated using a two-sided Stuart-Maxwell test. Secondary outcomes assessed pt perceptions related to prognosis. Results: 51 pts completed surveys, and 29 of 51 matching physician responses were obtained for the primary analysis. 1 pt was deemed ineligible. 14 (48.2%) pts were optimistic, 14 (48.2%) were concordant, and only 1 (3.4%) was pessimistic. These results demonstrate asymmetric responses for the categorical variables, and pts were more likely to be optimistic when compared to physicians’ estimates (p=0.006). Of the 50 pts completing the survey, only 44% (22) based their survival estimate on information received from their oncologist, while others listed themselves (18%, 9) or hope (6%, 3) as the source of information. The majority of pts (86%, 43) use the internet to learn about their cancer, but only 8% (4) identified the internet as their information source for choosing a prognosis estimate. A discrepancy between pts’ beliefs about curability also exists. 5 of the 20 (25%) pts who believed their disease is curable had metastatic lung, breast, or neuroendocrine pancreatic cancer. Conclusions: The findings of this study demonstrate that pts estimate longer survival when compared to physician estimates. Other results of the survey also shed light on where pts obtain information pertaining to their cancer diagnosis and pts’ beliefs about the curability of their disease. This data highlights a need for a multicenter survey to validate these conclusions and the creation of teaching tools to help pts better understand their disease and prognosis.
Delivery of adjuvant chemotherapy (AC) to veterans with resected colon cancer.
Authors: Riggs Heather Dawn , Lane Kathleen A. , Loehrer Patrick J. , Hui Siu , Rawl Susan , Ormerod Anne , Weiner Michael
Published: March 2020

e16557

Background: Patients (pts) with incomplete administration of AC for colon cancer (CC) likely experience inferior survival while oxaliplatin- and capecitabine-containing AC may not improve survival for older pts. The influence on AC completion of age, other baseline patient characteristics, or regimen characteristics is unknown. We evaluated the association of baseline characteristics and planned AC regimen with AC delivery in resected CC pts. Methods: This retrospective cohort study identified stage II and III resected CC pts from our local VA Medical Center tumor registry who initiated AC between 2004 and 2010. AC delivery was measured as percentage of planned cumulative dose (PCD) of 5-fluorouracil or capecitabine delivered. Baseline characteristics were demographics, CC stage, travel distance to the treatment site (TD), Adult Comorbidity Evaluation-27 score, and labs. We classified AC as fluoropyrimidine (oral or IV)-based and as oxaliplatin-containing. Linear regression tested each association with PCD. We recorded occurrence of toxicity and death. Cox regression models were used for survival analysis. Results: Fifty pts (98% male, median age 63) initiated AC for stage II (n=6) or III (n=44) disease with median interval from resection to AC of 7.4 weeks. The median PCD was 75%; median treatment duration was 5 months. Lower PCD was associated with older age (p=0.05), lower GFR (p=0.05), higher TD (p=0.02), lower baseline hemoglobin (p=0.10), and receipt of capecitabine (p<0.01). Receipt of capecitabine (p=0.008) and TD (p=0.04) remained significantly associated with PCD in a multiple linear regression model. Toxicity was noted for 78%, and PCD tended to be lower for reported cardiac events (p=0.07). Pts older than 63 had inferior survival (HR=4.17, p=0.03). Pts receiving less than 80% PCD tended toward inferior survival (HR=4.31, p=0.07). Conclusions: Capecitabine-based AC and travel distance were associated with lower PCD, which may negatively impact survival. Efficacy of shorter courses of oxaliplatin-based chemotherapy is being evaluated elsewhere. Close attention to quality prescribing and monitoring practices for capecitabine are recommended. These findings should be confirmed in a larger cohort.
Cost-utility analysis of maintenance therapy with either gemcitabine or erlotinib versus observation with predefined second-line treatment after cisplatin-gemcitabine induction chemotherapy in advanced NSCLC: IFCT-GFPC 0502-eco phase III study.
Authors: Borget Isabelle , Perol Maurice , Perol David , Lavole Armelle , Greillier Laurent , Bizieux-Thaminy Acya , Westeel Virginie , Berard Henri , Auliac Jean Baptiste , Zalcman Gerard , Dujon Cecile , Robinet Gilles , Fournel Pierre , Thomas Pascal , Margery Jacques , Oster Jean-Philippe , Chabaud Sylvie , Vergnenegre Alain , Chouaid Christos
Published: March 2020

e16560

Background: The IFCT–GFPC 0502 phase III study reported a prolongation of progression-free survival with maintenance with either gemcitabine or erlotinib versus observation after cisplatin-gemcitabine induction chemotherapy in advanced NSCLC. The aim of this analysis is to assess the incremental cost-effectiveness ratio (ICER) of these strategies in the global population and in pre specified sub-groups. Methods: A cost-utility analysis was performed to evaluate ICER of maintenance therapy with either gemcitabine or erlotinib, compared to observation, from randomization until end of follow up. Direct medical costs (including drugs costs, hospitalization, follow-up examinations, second-line treatment and palliative costs) were prospectively collected per patient alongside the trial, until death, from the third party payer perspective. Utility data were extracted from literature. Sensitivity analyses were performed. Results: The ICER for maintenance therapy with gemcitabine and erlotinib were respectively 84,011 and 183,261 euros per quality-adjusted life years (QALY). Gemcitabine maintenance therapy had a favourable ICER in patients with PS = 0 (51,168 €/Qaly), in responders to induction chemotherapy (65,554€/Qaly) and in patients with squamous cell carcinoma (44,884€/Qaly); erlotinib had a favourable ICER in patients with PS = 0 (162,371 €/Qaly) and objective response to induction (101,569 €/Qaly ). Conclusions: Gemcitabine and erlotinib maintenance therapy have acceptable ICER but with a wide variation function of histology, PS and response to the first line chemotherapy.
Overcoming the barriers to early-phase clinical trials (EPCT): Increasing EPCT minority accrual.
Authors: Weitman Steven D. , Ramirez Amelie G. , Chalela Patricia , Munoz Edgar , Pollock Brad H.
Published: March 2020

e16566

Background: Increasing minority accrual is critical to the development of novel cancer therapeutics. Without adequate minority representation in EPCT, researchers cannot assess differential effects among groups nor ensure the generalizability of trial results. Little is known about cultural factors that impact the decision to participate in EPCT among Hispanics. Methods: The goals of this research were to identify cultural, economic and environmental barriers to EPCT accrual and potential interventions to reduce these barriers. Two surveys were conducted. One survey was with 114 oncologists and one with 100 cancer patients (50 who were enrolled in an EPCT and 50 who never participated). Results: The top four logistical barriers stated by oncologists were all related to the extra work and time of recruiting and referring patients: referring patients is extra work (63%), too much paperwork (57%), too complex of procedures (57%) and excessive details of protocols (50%). Significant differences between clinical trial and non-clinical trial participants were found for two barriers in the decision-making process [lack of knowledge about available trials (88% and 94%), and lack of understanding about trial processes and purpose due to medical jargon (82% and 90%)]. Non-clinical trial participants gave higher importance to four barriers related to attitudes and beliefs [fear of being a guinea pig (80%), fear that the experiment is more important than the patient (76%), distrust in the medical system (72%), and fear of sacrificing QoL (72%)]. Non-participants in EPCT tended to have less education, lower income, and were Hispanic. In addition, two-thirds (68%) of non-participants considered language as a major barrier. Conclusions: Oncologists would be more likely to refer patients for EPCT if they are aware of the studies, feel confident with their patients, trust the research team, see benefit for their patients, and have an easy way to refer patients. The results of this study may have implications in terms of message development for groups traditionally underrepresented, which may require language appropriate materials, more visual materials with lower reading levels, and with more precise economic information.
Quality Oncology Practice Initiative (QOPI): Preliminary results from a Brazilian academic public oncology service.
Authors: Cubero Daniel Iracema , Cruz Felipe Melo , Martins Suelen Patricia dos Santos , Glasberg Joao , Rivelli Thomas Giollo , Campos Arinilda Silva , Matos Leandro Luongo , Del Giglio Auro
Published: March 2020

e16568

Background: The Quality Oncology Practice Initiative (QOPI) is a voluntary program developed by ASCO to aid oncology practices in quality self-assessment and continuous improvement of patient records. It consists of a cyclical, semiannual measurement of the adequacy of several care processes pertaining to some important aspects of patient care. Few academic cancer centers have been QOPI participants in the United States and there aren’t reports to our knowledge of any Latin American Cancer Center adopting this strategy. Methods: This study shows the pilot initiative to implement the QOPI at the ABC School of Medicine, Discipline of Oncology, a large public academic cancer center of Santo André, São Paulo, Brazil. Results: From January 2008 to December 2010, we consecutive selected 37 patients with gastric cancer, 40 with breast cancer, 33 with lung cancer and 40 colorectal cancer. The table below shows the first round of the core QOPI. Conclusions: There are several opportunities for improvement such as assessing and recording of pain and analgesic use, documentation patient consent and of the intent of chemotherapy and providing patients with their chemotherapy summaries. Our current electronic record will be modified to reflect the aforementioned needs in order to improve our results in the following rounds of QOPI program. [Table: see text]
Effect of epigenetic modulation on interleukin-6 (IL-6) gene expression with adjuvant selenomethionine (Se-Met) with imatinib mesylate (IM) in remission of chronic myelogenous leukemia (CML-cp) patients.
Authors: McPherson Eugene
Published: March 2020

e17022

Background: Histone deacetylase (HDAC) are enzymes involved remodeling chromatin and epigenetic regulation of gene expression. Histone deacetylase inhibitors (HDACI) can reverse aberrant epigenetic changes in CML stem cells. BCR-abl tyrosine kinase inhibitors IM is effective in inducing remission in CML-cp patients but residual leukemia stem cells (LSC) may give rise to resistance and relapse. Pan-HDACI may arrest this with downregulation of IL-6, and NFkb activation when adjuvant Se-Met is combined with IM. Methods: CML-cp , CML-bc cases were presented with evidence of overexpression of BCR-abl fusion protein reported previously in elderly patients. A 91 YOF with CML-cp , subclinical hypothyroidism with elevated IL-6, CRP, sIL-2R, VEGF, NFkb, and IGF-1 was treated for seven years with adjuvant Se-Met, IM and levothyroxine ith normalization, minmal toxicity and extended trending down of IL-6, CRP,sIL-2R. Results: After seven years of adjuvant therapy with Se-Met, IM, and Levothyroxine a significant reduction of IL-6, CRP of 9.8075 down from 30.783 mg/L. Subsequuent normalization of the other pro-inflammatory cytokines were normalized. Conclusions: HDACI activity expressed in synergism of Se-Met with IM and Levothyroxine may lower the apoptotic threshold in CML-cp stem cells decreasing BCR-abl expression and rescuing quiescent progenitor cells that may prolong remission and decrease disease relapse.
Radiochemotherapy for lung cancer with cisplatin and vinorelbine orally and shrinking field radiotherapy: Effectivity and feasibility in a nonselected patient collective.
Authors: Zagel Miriam , Tobermann Anja , Fischer von Weikersthal Ludwig , Fahrig Antje
Published: March 2020

e17516

Background: To explore the side effects and effectivity of simultaneous radiochemotherapy (sim RCT) with cisplatin (Cis-DDP) and vinorelbine orally (VRBo) in pts. with NSCLC. Methods: From 2009 and 2011, a total of 20 pts. (5 female, 15 male) aged between 46 and 82 yrs. with NSCLC stage IIIA/B were irradiated with a median dose of 66.6 Gy to the primary and 45 Gy to the involved nodes as neoadjuvant or palliative treatment. Treatment volumes were adapted to tumor shrinkage after 19.8, 30.6, 45 and 59.4 Gy. Cis-DDP (20 mg/qm d1-4, d29-32) and VRBo (50 mg/qm d1,8,15,22,36,43) were administered simultaneously. Comorbidity was scored by the Charlson Index and nutritional status was monitored. Results: Toxicity rates: thrombopenia 3° 10%, 4° 0%, leucopenia 3° 15%, 4° 20%, haemoglobin 0% 3°/4°, esophagitis 3° 5%, 4° 0%, pneumonitis 3° 0%, 4° 5%. No reduction of planned RT-dose. Chx reduction was done due to hematologic toxicity in 35%. Response rates: CR 10%, PR 75%, SD 10%, PD 5%. 11pts. (55%) are alive after a median FU of 19 months. Conclusions: Sim RCT with Cis-DDP and VRBo results in good tumor response rates and is feasible with acceptable side effects. Shrinking treatment volumes allow adequate dose escalation without the risk for early locoregional recurrence.
FOXP3+/CD8+ tumor-infiltrating T-cell ratio as a marker for pathologic response to induction therapy of non-small cell lung cancer.
Authors: Tao Hiroyuki , Shien Kazuhiko , Soh Junichi , Sano Fumiho , Hayashi Tatsuro , Yamamoto Hiromasa , Tanaka Toshiki , Matsuda Eisuke , Toyooka Shinichi , Okabe Kazunori , Sugi Kazurou , Miyoshi Shinichiro
Published: March 2020

e17517

Background: Survival benefits of induction therapy followed by surgery for advanced non-small cell lung cancer (NSCLC) have been shown. Anti-cancer agents are suggested to mediate cytotoxic effect not only directly on tumor cells but also through the immune system. We investigated the relationship between the status of T-cell differentiation in tumor stroma and pathologic responses to induction therapy in patients with advanced NSCLC. Methods: A total of 69 patients with c-stage IIA to IIIB NSCLC who underwent induction therapy followed by R0 surgery between January 2002 and July 2011 were enrolled. Tumor-infiltrating T cells expressing CD8 or FOXP3 were detected by immunohistochemical staining from biopsy and surgically removed specimens using anti-CD8 antibody and anti-FOXP3 antibody. Staining-positive T cells were counted in 10 fields at 200× magnification of digital images, and then FOXP3+/CD8+ T cell ratio was determined based on the average counts. Results: The mean values of FOXP3+/CD8+ T cell ratio in operative specimens were 1.11 for the patients with pathological no change (p-NC), 0.32 for those with pathological partial response (p-PR), and 0.21 for those with pathological complete response (p-CR) (p = 0.002). There was no association of FOXP3+/CD8+ T cell ratio with gender, histologic types of tumor, or clinical stages. Patients with p-CR showed better relapse-free survival, though statistically no-significant (p = 0.323). Pre-treatment TBLB specimens were available in 12 patients (3 p-NCs, 7 p-PRs, and 2 p-CRs). FOXP3+/CD8+ T cell ratios in operative specimens after induction therapies were elevated compared with that of biopsy specimens in p-NC patients (p = 0.105), whereas the ratios were decreased in p-PR and p-CR patients (p = 0.021). Conclusions: The status of tumor-infiltrating T cell differentiation indicated by FOXP3+/CD8+ T cell ratio was correlated with pathologic response in patients treated with induction therapy followed by surgery for NSCLC. FOXP3+/CD8+ T cell ratio can be a marker for effectiveness of induction treatment.
Prognostic factors and trends in outcome for small cell lung cancer over 20 years.
Authors: Dawe David , Navaratnam Sri , Pitz Marshall W.
Published: March 2020

e17518

Background: There has been little change in the chemotherapeutic treatment of small cell lung cancer (SCLC) over the last 30 years but changes in radiotherapy have demonstrated a survival benefit in clinical trails. There is substantial disagreement in the literature on whether or not there has been an improvement in survival for SCLC patients and which patient characteristics serve as important prognostic factors. The majority of the data comes from the selective population of patients included in clinical trials, which do not necessarily reflect real world therapeutic effectiveness. Methods: Using the Manitoba Cancer Registry and Manitoba’s physician billing database, we extracted information on all patients receiving a pathologic diagnosis of SCLC in the Canadian province of Manitoba between Jan 1, 1985 and Dec 31, 2004. Linear regression and Cox proportional hazard regression were then used to determine trends in SCLC incidence, survival, sex distribution, treatment, and prognostic factors. Results: Over the course of the study, the number of cases of SCLC diagnosed each year decreased by 1.41 cases/year (p=0.007), due entirely to a decrease in male cases. The proportion of females increased by 1%/year (p<0.001, 95% CI [0.007, 0.013]). In the whole study population, the proportion of patients receiving no antineoplastic treatment increased dramatically with age, from 11.7% in those ≤50 to 50.6% in patients >80 years old (p<0.001). There has been no change in 2 or 5-year survival (p>0.05 at both time points), which is true for both males and females. Two-year survival was 12.7% for females vs 8% for males (p<0.001), and at 5 years 5.3% of females vs 2.6% of males survive (p=0.002). Male sex was a negative prognostic factor with an adjusted hazard ratio of 1.27 (95% CI [1.16, 1.39]). Conclusions: Female sex is a positive prognostic factor in SCLC. In this population based trial, evolution of therapy over 20 years did not translate into improved survival. A further decline solely in the number of male cases may independently improve survival in the future.
Association of decreased expressions of α1,6-fucosyltransferase (α1,6-FT), GDP-mannose-4,6-dehydratase (GMD), and GDP-fucose transporter (GDP-Fuc Tr) with squamous histology in non-small cell lung cancers (NSCLCs).
Authors: Honma Rio , Kinoshita Ichiro , Miyoshi Eiji , Matsuno Yoshihiro , Shimizu Yasushi , Kaga Kichizo , Taniguchi Naoyuki , Akita Hirotoshi
Published: March 2020

e17520

Background: α1,6-FT, a key enzyme for the core fucosylation of N-glycans, has been shown to be needed for the function of EGF and TGF-β1 receptors. α1,6-FT expression is found in human normal bronchial epithelial cells and bronchial gland cells. However, α1,6-FT expression has not been previously examined in NSCLCs. GMD generates GDP-fucose from GDP-mannose, and is imperative for the synthesis of all fucosylated oligosaccharides. GDP-fucose is transported into the Golgi apparatus by GDP-Fuc Tr to serve as a substrate of FTs. Methods: We examined expressions of α1,6-FT, GMD and GDP-Fuc Tr by immunohistochemistry in 156 surgically resected NSCLCs. Results: High, moderate and low expression of α1,6-FT was found in 25 (16.0%), 35 (22.4%) and 96 (61.6%) NSCLCs, respectively. Multivariate logistic regression analysis for the correlation between α1,6-FT expression and various characteristics revealed a significant association between low α1,6-FT expression and squamous cell carcinomas, as compared with non-squamous cell carcinomas (low vs. moderate, p = 0.0005; low vs. high, p = 0.005). High, moderate and low expression of GMD was found in 32 (20.5%), 32 (20.5%) and 92 (59.0%) NSCLCs, respectively. Multivariate logistic regression analysis for the correlation between GMD expression and various characteristics revealed a significant association between low GMD expression and squamous cell carcinomas, as compared with non-squamous cell carcinomas (low vs. moderate, p = 0.005; low vs. high, p = 0.02). Low expression of α1,6-FT was more prevalent in tumors with low GMD expression than in those with moderate or high GMD expression (p = 0.002). High/moderate, low and no expression of GDP-Fuc Tr was found in 7 (4.5%), 23 (14.7%) and 126 (80.8%) NSCLCs, respectively. Low GDP-Fuc Tr expression was significantly more prevalent in squamous cell carcinomas compared with non-squamous cell carcinomas (p = 0.003). Conclusions: These results indicate that α1,6-FT, GMD and GDP-Fuc Tr may be new markers of NSCLCs with specificity for histology.
Stereotactic body radiation therapy for early-stage non-small-cell lung cancer utilizing a helical intensity modulated image-guided approach.
Authors: Rosen Lane R , Fischer-Valuck Benjamin W , Katz Sanford R. , Durci Michael , Wu Terry , Syh Joseph , Patel Bijal , Syh Jarron
Published: March 2020

e17524

Background: To report the techniques and results of a large cohort of patients treated with stereotactic body radiotherapy (SBRT) for early-stage non-small-cell lung cancer (NSCLC) using image-guided helical intensity modulated radiation therapy (IMRT) and FDG-PET assisted targeting. Methods: Between February 2005 and August 2010, 79 patients with stage 1 NSCLC were treated with SBRT. 59 patients had T1 tumors and 20 patients had T2 tumors. 62 patients had biopsy proven malignancies and 17 patients were treated empirically based on strong clinical indications. Central tumor location did not disqualify patients. All patients underwent FDG-PET or FDG-PET/CT scanning in the treatment position for planned fusion with a separate kilovoltage (KV) CT simulation. Rigid immobilization was achieved during CT simulation using a double vacuum cast device with abdominal compression. SBRT was delivered via 12 Gy x 4 or 12 Gy x 5 fractionation scheme (48-60 Gy total). Megavoltage CT images were obtained on the treatment unit prior to therapy and repeated mid-fraction with comparison to the KV CT simulation planning images to assure set-up accuracy. Serial follow-up with FDG-PET or FDG-PET/CT studies were performed at 3 months and every 6 months thereafter on all surviving patients. Results: Median patient age was 73 years. Mean tumor size was 2.3 cm (range 0.5 – 6 cm). Median follow-up was 24 months (range 4-78 months). Overall local control rate (LCR) was 94% (95% confidence interval (CI), 86-97%) based on serial FDG-PET. LCR for T1 tumors was 95% vs. 90% for T2 tumors (p = 0.60). Entire cohort overall survival rate (OSR) was 87% (CI, 78-93%) at 1 year and 58% (CI, 47-68%) at 3 years. T1 patients had a 3-year OSR of 71% vs. 43% OSR for T2 patients (p = 0.04). No patients developed life threatening radiation pneumonitis or pulmonary complications. Chest wall pain or rib fracture was reported in 8 patients (10%; CI, 5-19%). Conclusions: Image-guided SBRT with helical IMRT delivered in 4 or 5 fractions of 12 Gy with rigid immobilization and FDG-PET assisted targeting is an effective treatment for early NSCLC and is associated with excellent local control rates and acceptable treatment-related morbidity.
Concomitant chemoradiotherapy phase II study comparing pemetrexed/carboplatin with paclitaxel/carboplatin in patients with unresectable stage III non-small cell lung cancer.
Authors: Ma Shenglin , Xu Yaping , Ji Yongling , Sun Xiaojiang , Zheng Yuanda
Published: March 2020

e17527

Background: Concomitant chemoradiotherapy is the standard treatment of unresectable stage III non-small cell lung cancer (NSCLC). However, the optimal chemotherapy regimen is still controversial. We have conducted a phase II study to evaluate concomitant treatment using pemetrexed/carboplatin or paclitaxel/carboplatin in these patients. The purpose of this study is to compare the feasibility and activity, and also assess its impact on progression-free survival (PFS). Methods: A total of 37 patients were enrolled between January 2008 and May 2011. Patients received concomitant chemoradiotherapy [thoracic radiotherapy and pemetrexed 500mg/m2, carboplatin AUC 5 every 3 weeks for 2 cycles; or paclitaxel 50mg/m2, carboplatin AUC 2 weekly for 6 weeks. ] Objective response rate according to the RECIST criteria was recorded and toxicity was evaluated using the NCI Common Toxicity Criteria. The Kaplan–Meier method was used to evaluate patient survival. Univariate analysis of patient characteristics and tumor responses was conducted using the Chi-square and Fisher's exact test. Results: The overall response rate for pemetrexed/carboplatin was statistically superior to paclitaxel/carboplatin (P <0.05). In patients with adenocarcinoma, there was a signiﬁcant improvement in PFS with pemetrexed/carboplatin versus paclitaxel/carboplatin (11.6 vs. 9.3 months, respectively). For pemetrexed/carboplatin, rates of grade 3 or 4 neutropenia, anemia, thrombocytopenia, and febrile neutropenia were signiﬁcantly lower (P <0.05), whereas grade 3 or 4 fatigue (P = 0.08) was more common. Conclusions: This data suggests that concomitant chemoradiotherapy with pemetrexed/carboplatin was better tolerability and more efficacy than paclitaxel/carboplatin in a Chinese population with unresectable stage III NSCLC. Better outcomes were observed in patients with adenocarcinoma in pemetrexed/carboplatin. Although the data presented herewith appears more promising in pemetrexed/carboplatin, this study is relatively small, and more data from randomized trials are needed to further validate this regimen.
Outcomes of patients with malignant pleural mesothelioma (MPM) following the approval cisplatin/pemetrexed: Experience of a comprehensive cancer center.
Authors: Jagtap Deepa , Pass Harvey , Baciewicz Frank , Wozniak Antoinette J. , Alvelo-Rivera Miguel , Konski Andre A. , Chen Wei , Smith Daryn W. , Gadgeel Shirish M.
Published: March 2020

e17528

Background: Mesothelioma is a rare cancer that is estimated to occur in about 2,500 people in the United States every year. MPM is the most common type of mesothelioma. Until 2003 there was no chemotherapeutic regimen approved for the treatment of MPM. The combination of cisplatin/pemetrexed was approved based on improved survival in a randomized phase III study. We analyzed the data of all MPM patients treated at our center, since the approval of this combination, to evaluate the outcomes of these patients. Methods: This retrospective analysis included all patients with MPM evaluated at Karmanos Cancer Institute in Detroit, Michigan, between 2005 to 2010. We analyzed the demographic data, history of asbestosis exposure, histology, clinical stage of diagnosis, treatment received and survival. A multiple Cox regression model was built on age, sex, histology, surgery or not and stage (I&IIvs.III&IV). Results: Fifty-four MPM patients were evaluated between 2005-2010. The median age of patients was 65 years, 70% were males, 74% had known history of asbestos exposure, 76% had epitheloid histology and 63% had stage III/IV disease at diagnosis. Seventy eight percent of patients received pemetrexed based therapy, 50% underwent pleural surgery (EPP-30%, Pleurectomy- 20%) and 37% received radiation therapy as part of the initial therapy. Twenty-one patients underwent surgery following neo-adjuvant chemotherapy. Thirty-nine percent of patients went on to receive second line therapy. The median overall survival was 18 months (95% CI 14- 22). COX model analysis showed that patients with epitheloid histology had a HR of 0.40, p= 0.0168) and patients who were stage I/II had a HR of 0.42, p = 0.0282. Surgery resulted in a HR of 0.66, but it was not statistically significant (p=0.2637). Age and sex were not significantly associated with survival. Conclusions: The median survival of MPM patients in this series was 18 months. As expected epitheloid histology and early stage at diagnosis were associated with improved survival. Surgery did improve survival but this improvement was not statistically significant.
A feasibility study of interventions to improve intraoperative lymph node (LN) collection and pathologic examination of lung cancer resection specimens.
Authors: Ramirez Robert A. , Miller Laura Elizabeth , Wang Christopher Gene , O'Brien Thomas , Khandekar Alim , Schoettle Glenn P , Robbins Samuel G , Robbins Edward T , Gibson Jeffrey B , Osarogiagbon Raymond U
Published: March 2020

e17531^

Background: The number of LNs examined following lung cancer resection has prognostic value. The International Association for the Study of Lung Cancer (IASCLC) recommends a minimum of 6 LNs and other series have recommended greater than 11. Most resections in the United States fail to meet these recommendations. We hypothesized that simple interventions could improve on the number of LNs examined. Methods: We used a pre-labeled specimen collection kit to aid in collection of N2 LNs and developed a re-dissection protocol to retrieve discarded N1 LNs. We performed a 3 era case control study: Era 1, routine surgical examination (RSE) + routine pathology examination. Era 2, RSE + special pathology examination (SPE). Era 3, SPE + special surgical examination. The Chi-Square, Fishers Exact, Wilcoxon-Mann-Whitney and Kruskal-Wallis tests were used where appropriate for comparisons. Results: Patient demographic and tumor characteristics were similar across three groups. Significantly more N1 and total LNs were examined in eras 2 and 3 compared to era 1 (Table). Significantly more N2 LNs were examined in era 3 compared to eras 1 and 2. There was a non-significant trend toward detection of metastatic LNs. More cases met both IASLC recommendations and had at least 11 LNs examined LNs in eras 2 and 3 compared to era 1. Conclusions: The interventions were feasible and effective in improving LN examination. The number of LNs examined using these interventions exceeded consensus recommendations. A phase III trial incorporating these interventions is being designed. [Table: see text]
Evaluation of soluble mesothelin-related peptide as a marker additional to cytology for diagnosing malignant pleural mesothelioma effusions.
Authors: Vigani Antonella , Ferro Paola , Canessa Pier Aldo , Battolla Enrico , Dessanti Paolo , Manta Carmen , Aschele Carlo , Franceschini Maria Cristiana , Fontana Vincenzo , Fedeli Franco , Roncella Silvio
Published: March 2020

e17533

Background: Detection of soluble mesothelin-related peptide (SMRP) levels in serum has been proposed to help the diagnosis of malignant pleural mesothelioma (MPM). In this study we evaluated the SMRP levels in pleural effusions of MPM (MPM-PE), the clinical importance and usefulness of SMRP detection in MPM-PE and whether it can have an additional value to cytological analysis (Cyt). Methods: We studied 52 MPM-PE, 129 benign PE (B-PE) and 94 non-MPM pleural metastasis PE (Mts-PE). In all PE samples, both cytology and SMRP detection were performed. SMRP levels were estimated by means of the MesoMark ELISA kit (Fujirebio Diagnostic, Malvern, PA). Diagnostic performance parameters were estimated through the ROC analysis, Youden's index was applied to obtain the best cut-off level and the degree of correlation was estimated by Diagnostic Odds Ratio (DOR) and by P-value (P) with Chi-square test. Results: The median SMRP levels were significantly higher in MPM-PE (28.2 nM) than in B-PE (3.2 nM) or Mts-PE (3.8 nM). MPM-PE vs B-PE yielded an AUC of 84.5 (P<0.001) whereas MPM-PE vs Mts-PE yelded an AUC of 79.6 (P<0.001). The cut off level in MPM-PE was estimated in 9.30 nM at which value we established Se=75%, Sp=93% for MPM-PE vs BPE and SP=81% for MPM-PE vs Mts-PE. We found SMRP positive cases (≥ cut off) in 38/52 (73%) MPM-PE, in 9/129 (7%) B-PE (DOR=40, P<0.001) and in 18/94 (19%) Mts-PE (DOR=13, P< 0.001).Cyt was negative in 29/52 (56%) of MPM-PE, among which SMRP was positive in 20/29 (69%) cases. Cyt was positive in 15/52 (29%) of MPM-PE, among which SMRP was negative in 4/15 (27%) cases. Finally, in 8/52 (15%) MPM-PE Cyt diagnosis was suspicious and SMRP was found positive in 7/8 (88%) cases. Conclusions: Our results demonstrate that SMRP levels in PE are significantly higher in MPM-PE than in PE from other pathologies. However the test cannot be alternative to cyt but it may provide additional diagnostic value to Cyt. SMRP detection in MPM-PE can be applied in the workup of patients with a PE of unknown origin.
Frequency of actionable genomic alterations in early-stage lung adenocarcinoma (LA) detected by next-generation sequencing (NGS).
Authors: Wang Kai , Stephens Philip , Yelensky Roman , Ross Jeffrey S. , Miller Vincent A. , Dracopoli Nicholas J , Cronin Maureen T. , Platero Suso J.
Published: March 2020

e17541

Background: Early stage LA (≤T1N0) has a variable natural history. Although many patients are cured (~2/3) with surgery, many tumors recur and better methods are needed to distinguish these subsets and tailor therapy accordingly. We undertook a pilot study of NGS in such tumors to characterize the frequency and diversity of actionable genomic alterations in this setting. Methods: Formalin-fixed paraffin embedded (FFPE) tissues from 21 archival samples collected from 2007 to 2011 were obtained commercially with accompanying clinical and pathologic data. Clinical characteristics: female (17)/male (4); T1N0 (18), AIS (2), MIA (1). Pathologic LA subtype: acinar (n=8), mucinous (n=4), lepidic (n=4), and mixed (n=2) in addition to AIS (n=2) and MIA (n=1). Targeted NGS performed in a CLIA laboratory (Foundation Medicine) gave evaluable results in all cases. Genomic libraries were captured for 3230 exons in 182 cancer-related genes plus 37 introns from 14 genes often rearranged in cancer and sequenced to average median depth of 640X with 99% of bases covered >100X. Results: Forty-one driver mutations were identified in 17 genes among the 21 patients (avg= 1.9) including 28 base substitutions, 5 indels, 4 amplifications, 3 homozygous deletions and 1 rearrangement. Notably, 90% of cases (19/21) harbored at least one alteration that can be classified as actionable-linked to an approved therapy in LA or another tumor type or a clinical trial. Examples include alterations in EGFR (n=6), NF1 (n=2, PI3K/mTOR inhibitors), CDNK2A (n=1, CDK inhibitors), EML4-ALK (fusion, n=1, ALK inhibitor), ERBB2 (n=1, TKI inhibitors), STK11 (n=1, mTOR inhibitors), and MDM2 (n=1, nutlins). Conclusions: NGSidentified drivergenomic alterations in T1N0 LA, MIA and AIS. On average, two known driver mutations were identified per tumor, many of which are associated with existing or emerging targeted therapies. This provides rationale for future investigation of larger series of T1N0 LA, AIS and MIA, using NGS to evaluate the prognostic value of these changes and could presage adjuvant trials in higher risk patients.
A phase II study of cisplatin (CDDP) and oral vinorelbine (NVBO) concomitantly with radiotherapy (RT) in locally advanced (LA) non-small cell lung cancer (NSCLC) treatment: Interim analysis.
Authors: Juan Vidal Oscar , Vazquez-Estevez Sergio , Giner Vicente , Casal Rubio Joaquin , Firvida Jose-luis , Aparisi Francisco , Muñoz-Langa José , Garcia Sanchez Jose , Girones Regina , Perez Francisco Javier , Sanchez-Hernandez Alfredo
Published: March 2020

e17545

Background: CDDP+NVBO as induction and concomitant regimen with RT has shown good efficacy outcomes and safety profile (Krzakowski, J Thor Oncol. 2008). The objective of this study was to evaluate the effectiveness and toxicities of the combination of CDDP and NVBO given at full doses concomitantly with RT in LA-NSCLC. Methods: Between February 2010 and May 2011, 26 chemo-naive patients (p) with histologically confirmed stage IIIA/IIIB unresectable LA NSCLC were treated. Treatment consisted of 4 cycles (cy) of NVBO 60 mg/m2 on days 1 and 8 and CDDP 80 mg/m2 every 3 weeks plus RT 66 Gy starting on day 1, cy 2. A standard Fleming two stage design is being used. The sample size is calculated with a power of 90% and a two-sided type 1 error allowance of 5%. Stage 1 included 25 pts, with subsequent expansion to a total of 45. Results: Patient’s characteristics were: Median age, 59 years (range 48-71); males, 92%; smokers, 60%; adenocarcinoma, 28% / squamous, 64%; stage IIIA, 54% / IIIB, 46%. 21 p completed the 4 cy treatment as per protocol. We analyzed 92 cy. Hematological toxicities (% cy): grade (g) 3/4 neutropenia, 42.3%; g3 anemia, 3.3%; g3 thrombocytopenia, 2.2%; febrile neutropenia, 1 p. Non-hematological toxicities (% cy): g3 oesophagitis, 6.5%; g4 diarrhea, 1.1%. 21 p were evaluable for response. 1 CR (4.8%), 17 PR (81%) and 1 SD (4.5%) were reported. ORR 85.8%. Survival analysis has not been performed due to short follow-up. Conclusions: The findings of this interim analysis confirm the previously reported outcomes of efficacy and safety with NVBO plus CDDP when administered concurrently with RT in stage IIIA/IIIB p. The trial has met the criteria for continuation into stage 2.
The efficacy of bronchoscopic intratumoral chemotherapy in palliation of inoperable lung cancer.
Authors: El Ghazaly Hesham , Mohammed Tamer , Madkour Ashraf , Koraa Emad
Published: March 2020

e17556

Background: Endobronchial obstruction is a common complication of advanced-stage lung cancer. Patients presenting with severe bronchial obstruction are at a high risk for developing haemoptysis, post-obstructive pneumonia, or respiratory failure, this often leads to death in weeks to months.Tumor debulking and airway re-canalization has a considerable role in increasing survival in patients with inoperable non-small cell lung cancer (NSCLC). Bronchoscopic endobronchial intratumoral chemotherapy (EITC) is a new intervention to treat airway obstruction. This work aims to determine the efficacy of EITC in palliative care for patients with inoperable NSCLC. Methods: Between April 2009 and June 2011, patients with newly diagnosed non metastatic inoperable symptomatic non-life threatening airway obstruction secondary to NSCLC were selected for tumor debulking via EITC through flexible bronchoscopy. EITC of maximum 20mL cisplatin with the concentration of 50 mg/50 mL was injected into the tumor bulk through flexible needle (weekly for 4 sessions). Patients were followed according to the symptoms, performance and functional status and endobronchial lesions changes after EITC. Results: Forteen male and 1 female were studied in which 7 cases had squamous cell carcinoma, 5 cases had adenocarcinoma and 3 cases had unspecified NSCLC. After 4 sessions of EITC, the involved lumen was considerably opened (> 25%) in 80% of cases in which 7 cases >50% and 5 cases showed a 25–50% luminal opening. Significant improvement was found in dyspnea score, Karnofsky performance scale as well as spirometric and arterial blood gases indices after than before the 4 sessions of EITC. Conclusions: EITC was well tolerated by most of the patients with minimal non systemic complications. In conclusion, EITC is a promising, safe, effective and less invasive procedure for palliative treatment of obstructive non-life threatening endobronchial NSCLC lesions.
Quality of life in poor prognosis patients with locally advanced non-small cell lung cancer (LA-NSCLC) undergoing a phase II study of concurrent cetuximab and definitive thoracic radiotherapy followed by docetaxel and cetuximab.
Authors: Thompson Lora , Extermann Martine , Dilling Thomas J. , Kim Jongphil , Yue Binglin , Stevens Craig William , Antonia Scott , Gray Jhanelle Elaine , Williams Charles C. , Haura Eric B. , Pinder Mary Colleen , Tanvetyanon Tawee , Chiappori Alberto
Published: March 2020

e17559

Background: A single institution prospective clinical trial was conducted to examine the safety and efficacy of concurrent cetuximab and definitive thoracic radiotherapy followed by docetaxel plus cetuximab. Quality of life (QOL) was assessed as a secondary endpoint. Survival and toxicity data are presented separately. Methods: Eligible pts with unresectable stage IIA or IIIB LA-NSCLC, who also had ECOG PS 2 OR weight loss ≥5% in 3 months OR age >70, completed QOL measures at baseline, after concurrent cetuximab/radiotherapy (recovery), and after docetaxol/cetuximab (consolidation). Scores were calculated for Activities of Daily Living (ADL), Instrumental Activities of Daily Living (IADL), Fatigue Symptom Inventory (FSI) worst fatigue, FSI fatigue interference, and Functional Assessment of Cancer Therapy – Lung Trial Outcome Index (FACT-L TOI). FACT-L TOI assessed physical (e.g., nausea) and functional (e.g., difficulty sleeping) well-being as well as lung cancer specific symptoms (e.g., shortness of breath, cough). Descriptive and t-test results are presented. Results: Pts (N = 27) were primarily male (67%) and non-Hispanic Caucasian (96%) with mean age of 73 years. High attrition between recovery (N = 22) and consolidation (N = 10) occurred. Compared to baseline, pts reported higher levels of worst fatigue (p < .03) and fatigue interference (p = .01) at recovery. There was a decline in IADLs (p = .01) but no significant difference in ADLs or FACT-L TOI. Further examination of FACT subscales revealed declines in physical (p < .0001) and functional (p = .02) well-being but improvement in lung cancer specific symptoms (p < .0001). A similar pattern is found for comparisons between baseline and consolidation (ps < .05). There were no significant differences between recovery and consolidation. Conclusions: Although pts experienced declines in QOL across most domains after concurrent cetuximab and radiotherapy, there was improvement in lung cancer specific symptoms. Pts were also able to maintain their ability to perform ADLs. High attrition after recovery is a notable limitation.
Rapid identification of PIK3CA-mutations in lung cancer by using pyrosequencing.
Authors: Schildgen Verena , Lusebrink Jessica , Engel-Riedel Walburga , Stoelben Erich , Schildgen Oliver , Brockmann Michael
Published: March 2020

e18000

Background: Phospatidylinositol-3-kinases (PI3K) play an important role in various cell processes. Oncogenic mutations in the PIK3CA gene which codes for the catalytic subunit have been identified in various malignancies and activate the PI3K/AKT/mTOR pathway which is a critical driver of tumorigenesis. Methods: We tested 41 tumor samples with known KRAS, BRAF, and EGFR mutation status for the occurence of mutations in the PIK3CA gene using a new commercial pyrosequencing kit. Results: Pyrosequencing revealed 2 mutations (4.9 %) in the PIK3CA gene, one in exon 9 and one in exon 20. Both mutations have not yet been identified in lung tumor tissue. Conclusions: The screening of our small patient cohort by pyrosequencing identified two mutations (4.8 %) in PIK3CA, on in exon 9 (Q546H) and on in exon 20 (M1043T). Both mutations have not yet been described in lung tumours and seem to be rather uncommon mutations. Future Screening of large patient cohorts with pyrosequencing may contribute to the detection of more mutations in lung cancer due to the low limit of detections of this method and may contribute to a better understanding of the interaction of mutations and tumorigenesis.
Update of a phase III trial of adjuvant vinorelbine plus cisplatin (NP) versus NP plus endostar (NPE) in patients with completely resected stage IB-IIIA non-small cell lung cancer (NSCLC).
Authors: Jie He , Han Baohui , Liu Yongyu , Wu Shi Xiu , Kuang Yukang , Shen Yi , Chen Chun , Wang Qun , Li Qiang , Haitao Ma , Xu Shaofa , Xu Shidong , Wang Ping , Mao Weimin , Pang Zuoliang , Hou Shengcai , Yang Yue
Published: March 2020

e18013

Background: Adjuvant chemotherapy demonstrated a 5-15% benefit in 5-year survival in early-stage NSCLC. Endostar,a recombinant human Endostatin, could inhibit tumor angiogenesis. In a phase III trial, the addition of Endostar to NP regimen resulted in higher response rate, clinical benefit rate and longer median time to progression compared with NP alone in advanced NSCLC patients. Methods: Completely resected patients (stage IB-IIIA) were randomized to receive adjuvant NP plus Endostar (arm A, Vinorelbine 25mg/m2 on d1 and d8 plus Cisplatin 80 mg/m2 intravenously plus Endostar 7.5mg/m2 per day, iv, for 14 consecutive days. 21 days as one cycle(arm A) or NP regimen alone (arm B) for four cycles. The randomization was stratified by gender, stage and histology. The primary endpoint was OS and the secondary endpoints were RFS and safety. Results: 1037 patients (arm A: 520; arm B: 517) from 43 centers in China were enrolled between 9/2007 and 12/2010. Two arms were well-balanced with regard to age, gender, histology, stage, and resection type. 184 patients in arm A and 202 patients in arm B had relapsed disease or died. The median RFS was 34.1 months in arm A and 30.3 months in arm B (p=0.1573). 79.0% of patients in arm A and 76.0% of patients in arm B received 4 cycles of chemotherapy. Median survival time was not available at this time. Grade 3/4 toxicities in arm A included leukopenia (57.4%), neutropenia (75.0%), anemia (12.9%), nausea (11.3%). Grade 3/4 toxicities in arm B included leukopenia (35.0%) neutropenia (60.5%), anemia (8.5%) and nausea (8.5%). It is worth noting that the incidence of cardiac toxicities in arm A (26.3%) was slightly higher than that in arm B (21.4%). Conclusions: The preliminary result showed that patients in arm A experienced a longer median relapse-free survival time than in arm B (34.1 months vs. 30.3 months), although the difference was not statistically significant by far. The toxicity profiles for both arms were tolerable in this study. The patient follow-up is still ongoing.