bluuebunny/crossref_metadata_2025_split huggingface dataset:
The impact of PET-based staging on survival of patients with stage I lung cancer
Authors: Begum M. , Robinson L. , Sommers E. , Bepler G. 
Published: August 2020

7570 Background: Patients with completely resected stage I lung cancer have the best survival. Stage I, as defined by Mountain in 1997, includes tumors of any size located within one lobe of the lung without involvement of the parietal pleura, a distance of 2 cm or more from the carina, and no evidence for metastatic disease in any pulmonary, hilar, or mediastinal lymph node or distant site. The 5-year survival for such patients is 57–67% (Mountain, 1997). We hypothesized that the introduction of FDG-positron emission tomography (PET) scanning would lead to upstaging of stage I patients with a consequential increase in survival. Methods: To test this hypothesis, we compiled a database of all patients with stage I lung cancer that underwent a complete surgical resection at the Moffitt Cancer Center from 1996 to 2006. Results: During this 11-year period, 1230 patients fulfilled these criteria. Surgery was performed by two thoracic surgeons (LR and ES). Description of pts: 638 women, 592 men; 11 African-American, 1215 Caucasian; 18 Hispanic, 1202 Non-Hispanic; age range 28.1–94.0 y, mean 68.9 y, median 69.9 y; 26 pneumonectomies, 243 segmentectomies or wedge resections; 699 adeno-, 15 adenosquamous, 325 squamous, 25 large cell, 57 neuroendocrine carcinomas; maximum tumor diameter range 0.1–25 cm, mean 2.9 cm, median 2.3 cm; 477 dead (survival 0.0–138.8 months), 753 alive (survival 0.1–144.4 months). The median OS by year of resection was: 88.0 m (1996, N=49), 61.2 m (1997, N=52), 72.1 m (1998, N=73), 58.0 m (1999, N=87), 83.6 m (2000, N=100), 75.0 m (2001, N=114), 70.7 m (2002, N=133), >55.7 m (2003, N=140), >41.5 m (2004, N=158), >33.1 m (2005, N=164), and >17.9 m (2006, N=160). These differences were not statistically significant (log-rank p=0.72). PET scanning was initiated at the beginning of the year 2000. The median OS for the 261 patients treated between 1996 and 1999 was 70.7 m (95% CI: 53.9–84.0), and the median OS for the 969 patients treated between 2000 and 2006 was 75.1 m (95% CI: 66.4–83.7). This difference was not statistically significant (log-rank p=0.34). Conclusions: We conclude that the introduction of PET scanning has not impacted on the survival of patients with stage I lung cancer at our institution. No significant financial relationships to disclose.
Comparison of primary tumor maximal standardized uptake value (SUVmax) on preoperative [18F]fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) and histological subtype in patients with non-small cell lung cancer (NSCLC)
Authors: Davidson J. A. , Wong V. , Fraser R. , Hirsh V. 
Published: August 2020

7571 Background: The routine preoperative use of PET/CT in patients with potentially resectable NSCLC is rapidly expanding. The SUVmax is a semiquantitative measure of metabolic activity that can distinguish benign from malignant tissue but published data are conflicting regarding its ability to discriminate between major histological subtypes. Methods: Pathology and PET/CT reports of 39 NSCLC patients who underwent a preoperative scan and curative resection at the McGill University Health Centre were reviewed. Only patients with Adenocarcinoma (AC), Squamous Cell carcinoma (SC), or Large Cell carcinoma (LC), and definitive pathological staging, were included. The SUVmax values for each histological subtype, along with primary tumor sizes, were compared using F test and t-test analyses. Results: The 15 patients with SC and 5 with LC histology were found to have significantly greater preoperative SUVmax values than the 19 patients with AC (mean 12.7 and 17.2 vs. 9.4, respectively, P < 0.05), despite the fact that no significant differences in tumor size were observed between histological subtypes. Patients with LC histology displayed higher SUVmax values than patients with SC histology, but this was not found to be significant (P = 0.057).Conclusions: These data suggest that SC pulmonary tumors have significantly greater uptake on PET/CT than AC tumors. This finding may be helpful in the future when sufficient tissue cannot be obtained for pathological diagnosis or to identify the predominant pathology of mixed tumors. Larger studies are required to confirm our results. [Table: see text] No significant financial relationships to disclose.
The study of FDG PET-CT on the value in predicting of patient outcome after treatment of stage III non-small cell lung cancer
Authors: Zhang H. , Yu J. 
Published: August 2020

7572 Background: Up to the present study, the value of FDG PET-CT in patients of non-small cell lung cancer (NSCLC) before and after treatment has been approved. However, the significance of FDG PET-CT during the treatment has not been confirmed. The objective of this study was to evaluate 18FDG PET-CT for assessment of therapy response and prediction of patient outcome after concurrent chemo-radiotherapy (CCRT) of NSCLC. Methods: Forty six patients with histologically proven stage III NSCLC had two repeated FDG PET-CT scans either one week before therapy and at the dose of 40∼50Gy, the SUVmax and Changes of the two group after completion of NARCT were compared with (1) the therapy response and (2) treatment results and long-term survival. Results: Of the 46 eligible patients, the pretreatment SUVmax of the responding and nonresponding groups was7.59±3.14 and 14.72±4.67 respectively. The midtreatment SUVmax of the two groups was 2.89±1.39 and 9.82±3.31 respectively. Significantly difference (t= 4.74,P=0.001; t=7.23,P=0.001) in SUVmax were observed either before and during treatment. Furthermore, the percent change of SUVmax of pretreatment and midtreatment was ΔSUVmax=61.91±86.69 and ΔSUVmax=33.56±90.37, difference between the two groups was also significantly (t=2.83, P=0.007). In addition, the 1 year survival rate of the the respond and non-respond group were 73% and 69% respectively, the 2-year survival rate of the two groups were 40% and 37% respectively, significant difference was observed between the two groups (P=0.001; P=0.001). Conclusions: 18FDG PET-CT is highly effective in detecting therapy response in stage III NSCLC patients, the analysis of percent change of SUVmax provides incremental value in early prediction of therapy response and patient outcome. No significant financial relationships to disclose.
Phase I trial of neoadjuvant dasatinib in patients with resectable malignant pleural mesothelioma
Authors: Mehran R. , Gil J. , Rice D. , Swisher S. , Lee J. J. , Lippman S. , Pisters K. , Blumenschein G. , Hong W. K. , Tsao A. S. 
Published: August 2020

7580 Background: The optimal multi-modality treatment for resectable malignant pleural mesothelioma (MPM) remains unknown. We designed a biomarker-based neoadjuvant trial from our preclinical studies showing that dasatinib, a multi-targeted Src kinase inhibitor, has activity against MPM and target specificity to Src Tyr419. Methods: Untreated MPM patients underwent extended surgical staging (ESS) with multiple biopsies to account for tumor heterogeneity, lymph node status and to rule out sarcomatoid features. If deemed a surgical candidate for either pleurectomy/decortication (P/D) or extrapleural pneumonectomy (EPP), patients received 4 weeks of oral dasatinib (70 mg BID) followed by P/D or EPP. If either a radiographic or molecular response (de-phosphorylation of Src Tyr419 in tumor) is achieved, an additional 2 years of dasatinib maintenance after adjuvant radiotherapy and systemic chemotherapy is given. The primary endpoint of this trial was biomarker modulation of Src Tyr419. Secondary endpoints included response, survival, safety/toxicity, and biomarker modulation in tumor/serum/platelets/pleural effusion. The total planned sample size is 24 to detect a 50% reduction in positive p-Src Tyr419 expression with 80% power, one-sided 10% type I error rate, and 10% inevaluable rate. Results: To date, ten patients have registered on the trial (4/08 - 12/08); six have successfully completed the ESS, neoadjuvant dasatinib, and P/D (n=3) or EPP (n=3). Two patients are still receiving neoadjuvant dasatinib; and 2 patients were deemed to not be surgical candidates due to a rapid decline in PS and one was found to have bilateral mesothelioma. The main side effects to dasatinib were grade 1–2: anemia, nausea, vomiting, anorexia, electrolyte abnormalities, fatigue, and anxiety. Grade 3 toxicities included hyperkalemia (1), infection - pneumonia (1), and hypoxia (1). There were no grade 4–5 toxicities. Post-surgical grade 3 toxicity included anemia, electrolyte abnormalities, arrhythmia, HTN, and pleural effusion; one grade 4 episode of hyperglycemia was seen. Conclusions: This study demonstrates that biomarker-based neoadjuvant MPM trials with novel agents are feasible. Updated clinical and translational correlative results will be presented. No significant financial relationships to disclose.
Mesothelin as a marker of response in malignant pleural mesothelioma
Authors: Wheatley-Price P. , Yang B. , Patel D. , Ma C. , Xu W. , Leighl N. , Feld R. , Cho B. , De Perrot M. , Liu G. 
Published: August 2020

7581 Background: Malignant pleural mesothelioma (MPM) is a rare malignancy related to asbestos exposure. Radiological assessment of disease status and treatment response using RECIST criteria is often difficult, therefore blood markers of disease burden may be useful adjunctively. Soluble mesothelin related peptide (sMRP) can distinguish between MPM and benign pleural disease. We performed an exploratory analysis to determine whether sMRP correlates with MPM disease course. Methods: From December 2006 to August 2008 blood samples were collected from MPM patients during clinic visits. Plasma sMRP levels were measured using the MESOMARK assay (Fujirebio diagnostics). Changes in sMRP levels were compared with corresponding radiological tests, scored as progression, stable or disease shrinkage. Results: From 41 patients, 165 samples were collected (median 4/patient; range 2–10). At study entry 34/37 (92%) patients with measurable disease had elevated sMRP (>9ng/ml, range 14–60). In 22 patients receiving chemotherapy or biologic therapy, relative (Fisher's exact test, p=3.2x10–6) and absolute (p=2.6x10–5) changes in sMRP correlated with radiological assessment (Table). All 4 post-surgery surveillance patients, with no evidence of recurrence, had normal sMRP levels (1.8–4.9). Of 8 patients who underwent surgical resection, 7 had elevated pre-operative sMRP that fell to normal post-operatively (Wilcoxon rank (WR) p=0.02). Absolute sMRP rose in all patients with radiological progression (systemic therapy, n=9, WR p=0.004; supportive care, n=10, WR p=0.02). Conclusions: sMRP levels not only correlate with surgical debulking but we report, for the first time, that they also correlate with treatment response and radiological progression in MPM patients undergoing systemic therapy or supportive care. sMRP may be a clinically useful biomarker in MPM clinical trials and in patient management. These findings should be validated prospectively. [Table: see text] [Table: see text]
Intraoperative sentinel lymph node identification using novel receptor binding agent (technetium-99m neomannosyl human serum albumin, 99mTc-MSA) in stage I non-small cell lung cancer
Authors: Kim H. , Kim S. , Kang D. , Yong H. , Lee S. , Jeong J. , Choi Y. 
Published: August 2020

7588 Background: In order to simplify synthesis and labelling procedures and to improve the biological properties, we developed a novel mannose receptor-binding agent, Technetium-99m neomannosyl human serum albumin (99mTc-MSA). This study was designed to test the reliability and feasibility of sentinel nodes identification using this new radioactive agent in stage I non-small cell lung cancer. Methods: A total dose of 1mCi of 99mTc- MSA in 0.2ml was administered in one shot at the peri-tumoral region under the chest CT or bronchoscope guidance 3 hours before surgery in the CT room. Dynamic whole-body SPECT lymphoscintigraphic image was obtained at 30 min after injection and static thoracic SPECT lymphoscintigraphy images were acquired at 1 and 2 hour after injection. During operation, the radioactivity of the lymph nodes was counted with a handheld gamma probe before (in vivo) and after (ex vivo) dissection. Lymph nodes with an ex vivo radioactive count more than 5 times the radioactivity count of the resected lung tissue were identified as sentinel nodes. The correlation between the in vivo and ex vivo results was examined. All harvested lymph nodes were examined histologically. Results: Thirty patients (20 men, 10 women; mean age, 62.6±9.40 years) who were candidates for lobectomy with mediastinal lymph node dissection for stage I non-small cell lung cancer were enrolled consecutively. Sentinel nodes could be detected from 30 minutes to 5 hours after the injection of 99mTc-MSA on lymphoscintigraphy. The mean number of dissected lymph nodes per patients was 20.7±1.30 (8∼41). Among 30 patients, sentinel lymph nodes could be identified in all patients (100%). The mean number of sentinel lymph nodes identified was 2.4±1.04 stations (range, 1∼5) per patient. No false-negative sentinel lymph nodes were detected in any of the 8 patients with N1 or N2 disease (0%). The relationship between in vivo and ex vivo results for mediastinal sentinel lymph nodes showed concurrence in 25 of 30 patients (83.3%). Conclusions: The results of this clinical trial showed that 99mTc-MSA had promising properties for sentinel nodes identification in non-small cell lung cancer. No significant financial relationships to disclose.
Phase II study of the histone deacetylase inhibitor belinostat in thymic malignancies
Authors: Giaccone G. , Rajan A. , Carter C. , Kelly R. , Berman A. , Spittler J. , Espinoza-Delgado I. , Lee M. , Trepel J. , Loehrer P. 
Published: August 2020

7589 Background: Thymic malignancies are rare tumors. Chemotherapy is used for advanced disease. There is no established role of second-line therapy in patients with refractory or recurrent disease. Belinostat is an HDAC inhibitor with activity in cutaneous and peripheral T cell lymphoma and is being investigated in several solid tumors. One prolonged minor response (31 m) was seen in a phase I study of this agent in a patient with thymoma. Methods: Patients with recurrent thymoma or thymic carcinoma, progressing after platinum-based chemotherapy were eligible. They were also required to have measurable disease, PS 0–2 and normal organ functions. Belinostat was given iv at 1.0 g/m2 on days 1–5 of a 21-day cycle until disease progression or intolerable side effects. Correlative markers of activity in blood and tumor were performed. Results: From December 07 to December 08, 22 patients have been accrued from 2 institutions; 12 patients were males, median age 52 (23–72), 14 thymomas and 8 thymic carcinomas, mean number of prior regimens 3.5 (1–10), 16 prior tumor resection and 3 myasthenia gravis. A median of 4 cycles have been given (1–15+). Treatment was well tolerated, with nausea being the most common side effect and well controlled with prophylactic antiemetics. 21 patients are evaluable for response: 2 had a partial response (9+, 9+ m), 13 stable disease (3–11+ m) and 6 progression. No responses were seen in 8 evaluable patients with thymic carcinomas. Acetylated lysine and tubulin were analyzed in lymphocytes and monocytes by multiparameter flow cytometry. An increase of protein acetylation (2–10 fold) over baseline was observed at 1 hour post-infusion on day 3 of the first cycle in all patients analyzed. Other correlative markers are being investigated. Conclusions: The thymoma cohort has been expanded to the second stage of the study. Belinostat has activity in patients with recurrent or refractory thymoma. No significant financial relationships to disclose.
Tumor survivin expression in locally advanced non-small cell lung cancer (NSCLC) patients treated with platinum-based chemoradiation followed by surgical resection
Authors: Fidler M. J. , Seba A. , Farlow E. C. , Basu S. , Kaiser-Walters K. , Steker D. , Coon J. , Kim A. W. , Bonomi P. , Faber L. P. 
Published: August 2020

7595 Background: Recently tumor molecular markers have shown promise as prognostic and predictive indicators for survival in early and advanced stage NSCLC patients (pts.) treated with chemotherapy. The objective of this study was to correlate immunohistochemistry (IHC) markers of pre-treatment biopsies in locally advanced NSCLC patients treated with concurrent platinum based chemoradiation followed by surgical resection. Methods: This is a retrospective study that included stage III NSCLC pts who had adequate pre-treatment tumor specimens and were treated with platinum based chemotherapy regimens and concurrent thoracic radiation (40 Gy). Thirty three pts had sufficient pre-treatment tissue for IHC and were identified from a surgical database. Cells were stained by IHC for frequency (0–4) and intensity (0–4) of ERCC1, PTEN, and survivin and analyzed by log-rank and multivariate Cox PH regression for potential relationships to pathologic complete response (pCR), time to recurrence (TTR), and overall survival (OS). Results: Characteristics of 33 pts: 15 females; median age 61; 17 adenocarcinoma, 10 squamous(sq), 5 undifferentiated, 1 adeno-sq. Median OS was 23 months (mo) (5.9–140), and median TTR was 14.7 mo (3.5–121). Following chemoradiation, 9 patients had pCR. pCR was associated with improved TTR, p < .027. ERCC1 and PTEN were not significantly related to OS, TTR, or pCR. High nuclear survivin frequency (>2) was associated with worse OS, HR 0.4, p< .045 and lower nuclear survivin intensity (<4) was marginally associated with pCR, p< .10. Conclusions: In this exploratory analysis, higher survivin expression was associated with worse prognosis in locally advanced NSCLC patients treated with chemoradiation followed by surgery. These results suggest that additional studies of survivin are warranted in NSCLC and that adding survivin inhibitors to chemoradiation is a reasonable strategy for locally advanced NSCLC with high survivin expression. No significant financial relationships to disclose.
Epidermal growth factor receptor inhibitors as second-line treatment in advanced non-small cell lung cancer: A meta-analysis
Authors: Cruz M. C. , Tan M. 
Published: August 2020

7597 Background: Overall survival in lung cancer remains poor despite availability of chemotherapy, which is limited by its toxicity and drug resistance. Advancement in research resulted to the development of targeted therapies, specifically epidermal growth factor receptor (EGFR) inhibitors. Results of clinical studies on survival benefits of EGFR inhibitors were conflicting although beneficial improvements in the quality of life and adverse effects were consistently demonstrated. The aim of our study is to determine the overall survival benefit of EGFR inhibitors alone or in combination with chemotherapy in second-line treatment of advanced non-small cell lung cancer (NSCLC). Methods: We did a meta-analysis of all randomized controlled trials involving patients with advanced NSCLC who failed at least one prior chemotherapy and were given EGFR inhibitor alone or in combination with chemotherapy compared to placebo or chemotherapy, with overall survival as an outcome. Pre-planned subgroup analysis was done on studies comparing EGFR to placebo and chemotherapy.Results: Five of the six trials included were analyzed for overall survival involving 4482 patients. Treatment with EGFR tyrosine kinase inhibitor (TKI) showed a trend towards significant survival benefit (RR=0.96, 95% CI 0.93–1.00, p=0.04) compared to placebo or chemotherapy. Preplanned subgroup analysis demonstrated significant survival benefit with EGFR-TKI versus placebo (RR=0.92, 95% CI 0.86–0.97, p=0.003) but comparable efficacy with chemotherapy (RR=1, 95% CI 0.96–1.06, p=0.84).Conclusions: Second-line treatment with EGFR-TKI demonstrated significant survival benefit versus placebo and comparable survival effect to chemotherapy. Further research should be done to identify patients’ characteristics associated with good treatment response. [Table: see text]
Diagnostic reproducibility of squamous cell carcinoma (SC) in the era of histology-directed non-small cell lung cancer (NSCLC) chemotherapy: A large prospective study
Authors: Grilley-Olson J. E. , Hayes D. N. , Qaqish B. F. , Moore D. T. , Socinski M. A. , Yin X. , Wilkerson M. D. , Leslie K. O. , Travis W. D. , Funkhouser W. K. 
Published: August 2020

8008 Background: Morphology remains the best biomarker for chemotherapy selection in NSCLC. Both bevacizumab and pemetrexed (in first line) are FDA indicated for non-SC histology only, making precise diagnosis key, although data are few on the reproducibility of their categorization. The standard of care, consensus-based World Health Organization diagnostic classification system, Ed. 4 (WHOC) includes 44 diagnostic categories (DC), does not include immunohistochemical (IHC) data, and is not independently validated. In this study, we estimate the reproducibility of SC versus non-SC classification to be only moderately precise. Methods: Pathologists (P) assigned WHOC diagnoses to virtual H&E slides from an incident surgical cohort of 96 primary lung tumors. At a power of 80% we estimated 24 P reviewing 48 slides each would allow for a reproducibility measure in the clinically useful range kappa=0.7, standard error=0.09. In addition to the 44 DC, we also considered the reproducibility of a simplified 10 category system and a chemotherapy-directed 2 class system. Results: 12 self-identified “lung experts” (E) and 12 community (C) P scored slides based on the 44 possible WHOC DC totaling 222 pathologist-pairs and 7130 slides-pairs. P rated confidence in their choices as: high 53%, somewhat 38%, and not confident 8%. 92% of slides were rated as having sufficient quality. Distribution of DC included SC 30% and adenocarcinoma 36%. Conclusions: To our knowledge this is the largest study ever performed of the WHOC, the only one to consider all 44 DC and to distinguish E vs C P. Although this model tests the reproducibility of the WHOC, not clinical lung cancer diagnoses, it shows that reproducible diagnosis of SC based on H&E morphology alone is inadequate. In the era of histology guided therapy, it highlights the need for strict diagnostic criteria and confirmatory IHC stains in the diagnosis of SC. [Table: see text] No significant financial relationships to disclose.