bluuebunny/crossref_metadata_2025_split huggingface dataset:
Concurrent chemoradiation (CChRT) with bi-weekly docetaxel and cisplatin and thoracic radiotherapy for stage III non-small cell lung cancer (NSCLC): A phase II study from the Galician Lung Cancer Group.
Authors: Casal Rubio Joaquin , Brozos EM , Lázaro Quintela Martin , Vazquez-Estevez Sergio , Firvida Jl , Taboada MB , Caeiro M , Castro JE , Vieito Villar Maria , Senin Estor Clara , Villanueva MJ , Varela Ferreiro Silvia , Areses MC , Pena C , Calvo P , Hernandez E. , Martinez N. , Anido Urbano , Huidobro Gerardo 
Published: March 2020

7549 Background: CChRT is recommended as the evidence-based approach for the management of patients (p) with locally advanced stage III NSCLC and a good performance status, although a clearly superior regimen has not been identified. The aim of our study was to evaluate the effectiveness and toxicities of CChRT with bi-weekly docetaxel (D) and cisplatin (C) and thoracic radiotherapy. Methods: 50 p with histologically confirmed inoperable locally advanced NSCLC, stage IIIAN2/IIIB (no pleural T4), PS 0-1 and adequate lung function (FEV1 > 1.1, V20 < 25%) were included: one cycle of D 75 mg/m2 on day 1 and C 40 mg/m2 days 1-2 followed at 21 days by CChRT with bi-weekly D 40 mg/m2 and C 40 mg/m2 for four courses, during conformal thoracic radiotherapy (66 Gys, 180 cGy/day). The primary objective was overall survival (OS); secondary objectives were progression free survival (PFS), response rate (RR) and toxicity. Median follow-up: 14,5 months. Results: The p characteristics were: mean age 59,1 years (34-75); male/female 44/6; squamous/adeno/large cell carcinoma: 52%/34%/14%; stage IIIAN2 14 p (28%) and stage IIIB 36 p (72%). All p were evaluable for response and toxicity. RR: 4 CR, 36 PR (RR 80%; 95% CI:69-91), 4 SD (8%) and 6 PD (12%). The median PFS was 13 months (95% CI:8-18) and median OS was 19 months (95% CI:14-24). The PFS and OS at 1/2 years were 52%/30% and 79%/40% respectively. A total of 50 cycles of D-C induction chemotherapy were given; main toxicities (NCI-CTC 3.0) per p Grade (g) 1-2/3-4 (%) were as follows: neutropenia 2/16; anemia 12/0; nausea/vomiting 28/2; diarrhea 22/4; there were two episodes of febrile neutropenia. Main toxicities per p in CChRT (D-C doses: 192, 3.8 per p; mean doses RT: 64,6 Gys) were g1-2/3 (%): neutropenia 28/6; anemia 60/0; esophagitis 52/4 and pneumonitis 34/0; there were four episodes of hospitalization: febrile neutropenia, 2 p and g3 esophagitis, 2 p. Conclusions: CChRT with bi-weekly docetaxel and cisplatin and thoracic radiotherapy is a feasible treatment option for inoperable locally advanced stage III NSCLC, showing good clinical efficacy and tolerability with acceptable long-term survival.
Fibroblast growth factor receptor 1 (FGFR1) gene copy number gain in adenocarcinoma and squamous cell carcinoma of the lung.
Authors: Tang Ximing , Xue Yuwen , Su Xinying , Harun Nusrat , Cai Yiran , Behrens Carmen , Papadimitrakopoulou Vassiliki , Blowers David , Moran Cesar , Kalhor Neda , Rice David C. , Beran Garry , Lee J. Jack , Kilgour Elaine , Wistuba Ignacio Ivan 
Published: March 2020

7552 Background: FGFR-1 is a novel target for therapy in non-small cell lung carcinoma (NSCLC). FGFR1 gene has been shown to be amplified in ~20% of squamous cell carcinomas (SCC) of the lung. The frequency of FGFR1 copy number gain (CNG) and gene amplification (GA) in lung adenocarcinoma (AC) is unknown, and the clinicopathological and molecular characteristics of the NSCLC tumors with FGFR1gene increase have not been fully described. Methods: We examined FGFR1 gene copy number (GCN) by fluorescent in-situ hybridization (FISH) and FGFR1 protein expression by immunohistochemistry in 475 surgically resected NSCLCs (162 SCCs, and 313 ACs) stages I-III in tissue microarrays. Three FGFR1 FISH categories were identified: a) no CNG; b) CNG, defined as ≥4 gene copies in ≥40% of cells; c) GA, defined as ratio of copies of FGFR1:CEP8 ≥2 or presence of tight gene clusters in ≥10% of cells. FGFR1 protein expression in the cytoplasm and membrane of tumor cells was quantified using H score. Results: FGFR1 GA was detected only in SCCs (14 cases, 9%). CNG was detected in both SCC (39 cases, 24%) and AC (80 cases, 26%). In AC, significantly higher frequency of CNG was detected in patients with smoking history (P=0.008) and in tumors with low differentiated histology (P=0.0005). No correlation was detected between FGFR1 CNG and mutation of KRAS and EGFR in AC. In SCC, tumors with FGFR1 CNG/GA had higher cytoplasmic FGFR1 protein expression than those with no copy changes (49±39 vs. 26±21, P<0.001), and the protein expression correlated with GCN (R=0.55; P<0.001). In multivariate analysis, patients with stage I/II SCCs having FGFR1 gene copy ≥6 or GA showed a significantly better overall survival (HR=0.26; 95% CI: 0.08-0.84, P=0.02) than patients with <6 gene copy, after adjusting for smoking, gender and tumor size. An increase on FGFR1copy number was detected in 8/45 (18%) brain metastasis compared with primary tumors. Conclusions: In NSCLC, FGFR1 GA occurs only is a small subset of SCCs (9%), whereas CNG is a relatively frequent phenomenon in both SCC (24%) and ACs (25%). FGFR1 copies ≥6 or GA is associated with better outcome in patients with surgically resected stages I/II SCCs of the lung.
The role of lymphatic vascular invasion in the prognosis and determination of therapy in surgically resected non-small cell carcinoma of the lung.
Authors: DeCamp Malcolm M. , Andrei Adin-Cristian , Ramakrishna Satvik , Medford-Davis Laura Nyshel , Shelkey Julia , McClean Megan , Recht Abram , Varlotto John M. 
Published: March 2020

7554 Background: Lymphatic-vascular invasion (LVI) is not currently considered in staging of non-small cell lung cancer (NSCLC). We assessed the impact of LVI on overall survival (OS), local/distant recurrence (LR/DR) and patterns of recurrence. Methods: 869 consecutive patients who underwent a definitive surgical resection ± adjuvant chemotherapy for NSCLC from 2000–2008 were qualified for analysis if they did not receive any adjuvant/neo-adjuvant radiotherapy, had at least three months of follow-up, and did not have a history of other cancers within 5 years. Tumors with LVI (N = 160) were compared to tumors without LVI (N = 705). LR/DR rates at 2,3, and 5 years were calculated by the methods of Kaplan-Meier. Association between LVI and OS and LR/DR were compared in the total population and in a propensity matched population (PS) by factors affecting OS and LR/DR (n=160 matched pairs). Results: OS, LR, and DR were significantly worse in patients with LVI in the total population and in the subset of patients matched by propensity score (Table). In the PS-matched pairs, LVI was associated with a greater number of N1 nodes involved, a longer length of stay, higher histologic grade, and higher T-stage. Patterns of local failure (P<.001) but not distant failure (P=.11) differed between patients with and without LVI. Tumors with LVI were 3-fold more likely to recur in ipsilateral mediastinal nodes. In a subset analysis of tumors < 4cm (n=121 PS matched pairs), LVI was also associated with higher LR, DR, a lower OS and a 4-fold risk of mediastinal nodal recurrence. Conclusions: Detection of LVI in resected NSCLC predicts aggressive biologic behavior and provides important prognostic information. LVI may help identify high-risk cohorts within discreet TNM stages who could benefit from adjuvant therapies. [Table: see text]
The role of molecular profiling to differentiate multiple lung primary adenocarcinomas from intrapulmonary metastases from a lung primary.
Authors: Mino-Kenudson Mari , Miyamoto Atsushi , Dias-Santagata Dora , Morales-Oyarvide Vicente , Bernardo Lindsay Ann , Pawlak Amanda , Han Jae Young , Davies Diane L. , Lanuti Michael , Mark Eugene J. , Iafrate Anthony John 
Published: March 2020

7555 Background: In the case of patients with multiple lung adenocarcinomas (ADCs) (whether synchronous or metachronous), the distinction of intrapulmonary metastases from independent primaries is clinically important as it impacts staging and thus therapeutic strategy. Currently the distinction is made based principally on histology of the tumor. Molecular profiling is becoming a routine diagnostic procedure for lung cancer to help treatment decision-making. Thus, we sought the role of mutation assays to differentiate multiple primaries from metastases. Methods: 45 synchronous and 37 metachronous cases of multiple tumors were obtained at 103 surgeries in 68 patients. Each of the resultant 156 tumors was tested with the SNaPshot multiplex PCR genotyping assay and each case, based on molecular profiling, was classified as synchronous multiple primaries (SP), metachronous primaries (MP), synchronous intrapulmonary metastases (SM), or metachronous metastases (MM). Each case was also classified into 4 groups by a comprehensive histologic analysis. Clinical outcomes were compared between multiple primaries (SP and MP) and metastases (SM and MM) in the molecular and histologic analyses using Log-rank test. Results: Based on histology alone, SP were present in 37 cases, MP in 32, SM in 8 and MM in 5. The molecular results were interpreted as SP in 25, MP in 21, SM in 10 and MM in 11. 15 of the 82 cases were non-informative, since no mutations were identified in any lesions. Of the 67 cases harboring mutations, 21 (31%) showed discordant results consisting of 16 with SP or MP by histology and SM or MM by molecular profiling. 5 cases showed the opposite results. Molecular profiling showed a trend toward the 5-year survival of the patients with metastases being shorter than those with multiple primaries (57 months vs. 87 months, P=0.068), which was not observed by histology (P=0.84). Conclusions: Although its performance is limited by non-informative results in 18% of cases of multiple ADCs, SNaPshot profiling for clinical use appears to be useful in determining whether multiple ADCs are primaries or metastases. Thus, it may allow for more accurate staging and optimal therapeutic management.
Human papillomavirus (HPV)-associated early stage non-small cell lung cancer (NSCLC).
Authors: Pillai Rathi Narayana , Ragin Camille , Sica Gabriel , Behera Madhusmita , Chen Zhengjia , Kim Sungjin , Mayfield William , Hermann Robert C. , Saba Nabil F. , Gal Anthony A , Khuri Fadlo Raja , Ramalingam Suresh S. , Owonikoko Taofeek Kunle 
Published: March 2020

7560 Background: HPV is an established risk factor for cervical and oropharyngeal cancer. It has been suggested as a potential risk factor for lung cancer based on studies conducted mostly in Asian patients with advanced NSCLC. We characterize potential role of HPV in a North American patient population with early stage NSCLC. Methods: We analyzed surgically resected samples of NSCLC patients diagnosed between 2002-2007. HPV status was determined by polymerase chain reaction (PCR) using the INNO-LiPA genotyping Extra Amplification and Genotyping Extra kits, followed by reverse hybridization line probe assay to identify specific HPV serotypes. Differences between HPV+ and HPV- patients were assessed by Chi-square, Fisher’s exact, and Wilcoxon rank-sum tests. Survival was estimated by the Kaplan-Meier method and differences between HPV+ and HPV- patients were assessed by Log-rank test. Multivariable logistic regression modeling was employed to select predictors of HPV+ NSCLC. The significance levels were set at 0.05 for all tests. Results: Paraffin-embedded tumor samples from 208 patients were analyzed; M/F (49%/51%); stage I: 80%; II: 11%; III: 9%; IV: <1%; Caucasians 95.6% and African-Americans (AA) 4.4%. There were 32 (14.9%) HPV+ cases including 10 cases with HPV 16/18. Ethnicity was significantly associated with HPV status (p-value=0.033). AA patients are more likely to be HPV+ (OR: 7.373; p=0.01) and more likely to harbor high risk serotypes 16/18 (OR: 10.8; p=0.05). Regression modeling identified AA ethnicity, adenocarcinoma (ADC) histology and current smoking (parameter estimates of 2.04, -2.34 and -2.82 respectively) as predictors of HPV+ NSCLC. Smoking status and histology showed significant interaction in predicting HPV+ tumors: OR: 0.06; p=0.0023 for smokers with squamous cancer; 2.52; p=0.24 for smokers with ADC and 10.339; p=0.0293 for smokers with adenosquamous cancer. Median disease free survival (NR; p=0.42) and median overall survival (71 months; vs. 55 months) were not significantly different between HPV+ and HPV- patients. Conclusions: HPV positivity is observed in 15% of early stage NSCLC with strong association with AA ethnicity, adenosquamous histology and non-smoking status.
Identification of actionable mutations in surgically resected tumor specimens from Japanese patients with non-small cell lung cancer by ultra-deep targeted sequencing.
Authors: Koh Yasuhiro , Kenmotsu Hirotsugu , Serizawa Masakuni , Isaka Mitsuhiro , Mori Keita , Imai Hisao , Akamatsu Hiroaki , Ono Akira , Naito Tateaki , Taira Tetsuhiko , Murakami Haruyasu , Takahashi Toshiaki , Endo Masahiro , Nakajima Takashi , Ohde Yasuhisa , Yamamoto Nobuyuki 
Published: March 2020

7572 Background: Detection of tumor genetic alterations is critically needed for lung cancer clinic as well as for the development of molecular targeted therapeutics. Here we report the results of a broad spectrum of genetic alterations identified in Japanese non-small cell lung cancer (NSCLC) patients by ultra-deep targeted sequencing. Methods: Highly multiplexed amplicon sequencing was performed using genomic DNA extracted from snap-frozen tumor specimens. TruSeq amplicon cancer panel was used for the detection of somatic mutations in 48 cancer related genes followed by ultra-deep sequencing (Illumina) at an average coverage of approximately 2800x. ALK, ROS1 and RET traslocations and EGFR, MET, PIK3CA, FGFR1 and FGFR2 amplifications were also detected by multiplex RT-PCR and quantitative PCR, respectively. Results: The demographics of 204 consecutive patients enrolled in this prospective study at Shizuoka Cancer Center between July 2011 and November 2012: median age 69 years (range: 38-92); male 66%; never smoker 25.5%; histology: adenocarcinoma 68.6%, squamous cell carcinoma (SQ) 27.0%, others 4.4%; tumor stage: I 53.9%, II 28.4%, III 12.7%, IV 4.9%. TP53 mutation was most frequently detected (44.4%) in all patients, particularly in SQ (67.9%). Mutations in genes such as MLH1 (4.9%), STK11 (6.3%), CTNNB1 (5.6%), SMAD4 (1.4%), VHL1 (1.4%), PTPN11 (0.7%) and GNAS (0.7%) were detected besides major mutations in genes such as EGFR (43.0%), KRAS (17.6%) and PIK3CA (14.1%) in adenocarcinoma. PIK3CA (21.4%), MLH1 (5.4%), APC (3.6%), STK11 (3.6%), FGFR2 (1.8%) and VHL (1.8%) mutations were identified in SQ and notably, 48.2% of SQ patients harbored simultaneous gene mutations, suggesting the genetic complexity of this histology. FGFR1 amplification was found in 8.9 % of SQ, suggesting lower frequency in Asian population than in Caucasian population. Conclusions: We managed to detect a wide range of genetic alterations and identified additional actionable mutations besides popular driver mutations. This approach may facilitate elucidation of detailed molecular characteristics of NSCLC, thereby implementing personalized cancer medicine.
Has the paradigm changed away from lobectomy for stage I non-small cell lung cancer (NSCLC)? Anatomic segmentectomy: Surgery’s answer to image-guided ablation/radiation therapy for the small peripheral lung lesion.
Authors: Schuchert Matthew J. , Wizorek Joseph J. , Normolle Daniel Paul , Wilson David O , Siegfried Jill , Awais Omar , Abbas Ghulam , Luketich James D. , Landreneau Rodney Jerome 
Published: March 2020

7577 Background: Lobectomy has been the “gold standard” for stage I NSCLC management. Image guided ablation/radiation therapy approaches are now being touted as alternatives to surgery despite concerns regarding diagnosis, pathologic staging, local control, and delayed toxicities. We evaluated the diagnostic utility and oncologic efficacy of lung sparing, anatomic segmentectomy for indeterminate pulmonary nodules and clinical stage I NSCLC. Methods: Retrospective review of 1,005 anatomic segmentectomies from 2002-2012 for indeterminate pulmonary nodules and clinical stage I NSCLC. Outcome variables included perioperative data, morbidity and mortality. Survival was assessed with the Kaplan-Maier method. Results: Mean age was 66.7 years. Median lesion size was 1.9 cm. VATS was employed in 62.8% of cases. Median operative time and blood loss was 112 minutes and 80 ml, respectively. Median hospital stay was 5 days. Major complications occurred in 12.7%. Thirty-day mortality was 1.0%. Of these, NSCLC was identified in 71.6%, metastases in 8.7%, and other benign conditions in 19.7%. Among patients with clinical stage I NSCLC, clinical: pathological upstaging was seen in 34.5%. Local recurrence rate was 5.2% and five-year freedom from any recurrence was 69%, equivalent to lobectomy in our experience. Conclusions: Anatomic segmentectomy is a valuable primary surgical approach today. In this era of competing image-guided ablation modalities, anatomic segmentectomy provides safety, diagnostic accuracy and adherence to oncologic surgical principles including completeness of resection with adequate surgical margins, systematic nodal staging improving pathologic accuracy, and tissue for pharmacogenomic assessment to guide individualized adjuvant therapy.
Multi-institutional study of reirradiation with proton beam radiotherapy for non-small cell lung cancer.
Authors: Berman Abigail T. , Martin Christine Agnes , Lin Haibo , Both Stefan , Langer Corey J. , Varillo Kristi , Rengan Ramesh , Hahn Stephen M. , Fagundes Marcio , Hartsell William F. , Simone Charles B. , Plastaras John Peter 
Published: March 2020

7578 Background: The management of recurrent non-small cell lung cancer (NSCLC) in the setting of prior radiation (RT) is complex. Proton radiotherapy (PRT) is ideally suited to minimize toxicity by sparing dose to previously-irradiated organs. Herein we report the safety and feasibility of PRT for NSCLC reirradiation. Methods: Patients (pts) with recurrent NSCLC in or near their prior RT field were identified in three proton centers. An interval of 3 months was required between original RT course and PRT start. Pts were classified as low volume (LV, clinical target volume [CTV] ≤250 cc) or high volume (HV, CTV >250 cc). PRT was deemed infeasible if pts were unable to tolerate 15% of fractions or complete all treatments in <10 days of estimated end date and without a break ≥5 days. Results: Between 10/2010-11/2012, 24 pts were reirradiated, with 12 on a prospective trial of PRT for reirradiation. Median age was 69 (51-89). Histologies included squamous cell carcinoma (50%), adenocarcinoma (39%), and other (13%). Stage at initial diagnosis was I (8.3%), II (20.8%), III (50%), IV (12.5%), and unknown (8.3%). All pts were ECOG PS 0-2. Median prior dose was 62.4 Gy (30.6-80); 1 pt had 2 prior RT courses. The majority of pts (63%) were LV (median CTV 75.3, 11.9-236) and 38% were HV (359, 297.8-695.7). Concurrent systemic therapy (platinum-based or erlotinib) was given in 63%. Median PRT dose was 66.6 Gy (36-74). Average mean lung dose was 7.6 and 10.8 Gy and lung volume receiving 5 and 20 Gy was 16 and 24% and 26 and 33% in LV and HV pts, respectively. Follow up was >60 days in 17 pts. Overall, 46% of pts were hospitalized. PRT was infeasible in 3/9 HV and 1/15 LV pts. In HV pts, there were 2 grade 5 toxicities (hemoptysis and neutropenic fever). There was 1 in-field and 4 other thoracic recurrences, and 5 and 4 deaths in LV and HV pts, respectively. Conclusions: Preliminary results show promising early outcomes and acceptable toxicity in LV pts; due to the toxicity seen in HV pts, additional exclusion criteria were added for NSCLC pts in the ongoing trial. NSCLC reirradiation should continue to be studied in prospective trials to identify pts that may derive clinical benefit. Mature follow up is needed prior to standardizing NSCLC reirradiation with PRT.
Multiplexed genetic analysis of malignant pleural mesothelioma and the relationship to clinical outcome.
Authors: Shukuya Takehito , Serizawa Masakuni , Abe Masato , Akamatsu Hiroaki , Tokito Takaaki , Imai Hisao , Ono Akira , Taira Tetsuhiko , Kenmotsu Hirotsugu , Naito Tateaki , Murakami Haruyasu , Takahashi Toshiaki , Endo Masahiro , Nakajima Takashi , Koh Yasuhiro , Yamamoto Nobuyuki 
Published: March 2020

7582 Background: Genotype-based stratification is essential to improve cancer treatment. We have developed a multiplexed tumor genotyping panel for detecting gene alterations relevant to molecular targeted therapies. We applied this genotyping panel to malignant pleural mesothelioma (MPM) and evaluate the relationship between clinical outcome and gene alterations. Methods: Surgical specimens and tumor biopsies from 40 patients with MPM were collected from 2003 to 2012. Pathological diagnoses were confirmed by immunohistochemistry in addition to HE stain. 37 patients were genotyped with multiplexed tumor genotyping panel developed to assess 9 gene mutations (EGFR, KRAS, BRAF, PIK3CA, NRAS, MEK1, AKT1, PTEN and HER2) and 5 genes amplifications (EGFR, MET, PIK3CA, FGFR1 and FGFR2) using pyrosequencing plus capillary electrophoresis, and qRT-PCR, respectively. Other 3 patients were analyzed by ultra-deep targeted sequencing with next generation sequencer. 5 fusion genes (EML4-ALK, CD74-ROS1, SLC34A2-ROS1, KIF5B-RET and CCDC6-RET) were tested in 2 patients with fresh frozen specimens. Results: Gene alterations were detected in 6 patients (Table shown below). These patients harboring gene alterations showed poorer survival than the patients in whom gene alterations were not detected (median survival time (MST): 583 vs 164 days, log-lank: p=0.009). Moreover, the patients with PIK3CA amplification/mutation showed poorer survival than the patients without PIK3CA amplification/mutation (MST: 583 vs 103 days, log-lank: p=0.031). Conclusions: Gene alterations which could be a target for molecular targeted therapy were detected in MPM. Especially, PIK3CA pathway is a potential target. [Table: see text]