bluuebunny/crossref_metadata_2025 huggingface dataset:
Possible association of postmeiotic segregation increased 2 (PMS 2) gene deletion and myelodysplastic syndrome.
Authors: Shah Trushil , Gerstner Gregory James , Sutaria Jaini
Published: March 2020

e17021

Background: Postmeiotic segregation Increased 2 (PMS2) gene is one of the gene family members found in clusters on chromosome 7 involved in DNA mismatch repair. Mutations in this gene are associated with hereditary nonpolyposis colorectal cancer and Turcot syndrome. PMS-2 defects are not extensively studied and hence there is still considerable potential to detect new hemato-oncological associations with same. Chromosome 7 defects are the most commonly associated genetic abnormalities associated with myelodysplastic syndrome (MDS). Here, we describe a case of a patient with known PMS 2 gene deletion presenting with early onset MDS. Methods: A 52 year old caucasian female came in to our oncology clinic for evaluation after being diagnosed with DCIS of right breast. She underwent surgical resection followed by tamoxifen and surviellance mamograms. She developed gradual onset of fatigue, prompting follow-up laboratory tests which revealed WBC of 8,600, Hgb of 8.5, MCV of 101, and Plt 383,000. B12, folate, and iron studies were normal. Bone marrow biopsy revealed cellularity 80% and cytogenetics with trisomy 8.This lead to diagnosis of myelodysplastic syndrome, refractory cytopenia with multilineage dysplasia and ringed sideroblasts (RCMD-RS). Patient is currently treated with supportive transfusions after lack of benefit of darbopoietin (baseline epo level 67). Family history is pertinent for a son who died at age 21 from colon cancer and a daughter diagnosed at age 22 with colon cancer, who survives. Her daughter subsequently tested positive for G750 PMS-2 from her father and complete deletion of PMS2 from her mother (our patient). Results: PMS2 gene deletion might predispose patients to MDS. Conclusions: Given the common link with chromosome 7 abnormalities, it is therefore possible that there is an associated increased risk of MDS in PMS-2 patients. While our patient did not have any general abnormalities by karyotype, current assays and general karyotyping are of potentially limited value unless specific mutation points are identified. Therefore, additional evaluations may be necessary to better identify at-risk patients.
MicroRNA-137 and microRNA-29a expression in non-small cell lung cancer diagnosis and prognostic.
Authors: Ming Zhao
Published: March 2020

e17501

Background: Current staging methods are inadequate for predicting the outcome of treatment of non–small-cell lung cancer (NSCLC). We investigated whether microRNA expression proﬁles can predict clinical outcome of NSCLC patients. Methods: We studied frozen specimens of lung-cancer tissue from 76 randomly selected patients who underwent surgical resection of NSCLC. Using real-time reverse-transcriptase polymerase chain reaction (RT-PCR) analysis, we chosed U6 as the internal control for real-time RT-PCR because it is invariant in clinical cancer specimens. We obtained microRNA137 and 29a expressions level in 76 NSCLC patients and evaluated diagnoisis value and the association between the level of expression and survival. Results: This microRNA137 is with diagnosis value, microRNA29a expression level signature is an independent predictor of the cancer relapse and survival of NSCLC patients. Conclusions: Our microRNA signature is closely associated with relapse-free and overall survival among patients with NSCLC.
Mediastinal lymph node staging in patients with non-small cell lung cancer (NSCLC) with F18-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT).
Authors: Mendez Miriam , Maximiano Constanza , Huelves Miriam , Doger de Speville Bernard Gaston , Ibeas Patricia , Ruiz-Valdepeñas Andrea , Palka Magda , Diaz Gema , Gomez David , Provencio Mariano
Published: March 2020

e17503

Background: Lung cancer is the leading cause of cancer-related deaths in the Western world. CT and mediastinoscopy are the standard for staging modalities in recent years; PET has emerged as a complement to other techniques. Mediastinal lymph node (MLN) staging is important because it establishes subsequent treatment. The aim of the present study is to analyze the relationship between mediastinal staging by endobronchial ultrasound-guided transbronchial needle aspiration, mediastinoscopy, lymphadenectomy and PET. It also analyzes the patient characteristics like age, sex, histology. Methods: The study prospectively evaluated 42 patients from August 2009 to March 2011. All of them had MLN staging by PET and pathology (tumor resection with systematic lymph node dissection, transbronchial needle aspiration or mediastinoscopy). Univariable date analysis was conducted using Pearson's chi-square test. P values were considered statistically significant if <0.05. Results: The study group comprised 42 patients, 83% men and 17% female, mean age of 66 years. The primary tumor cell type: 45% squamous cell, 33% adenocarcinoma and 19% large cells. 40 patients were smoking. The most frequent location of tumor was upper lobes (58%). The most common stage found after surgery was stage I (42%), stage II (19%), stage III (A: 29%, B: 5%) and stage IV (5%). The kappa statistic for diagnostic agreement between CT and PET was 0.53 (p<0.001). About MLN staging, PET has a sensitivity of 61% and specificity of 53% , positive predictive value 61% and negative 53%. Conclusions: The present study attempts to find the relationship between tumor involvement found in PET and resected tumor specimens obtained from the mediastinum. Our sensitivity and specificity were not concordant with those previously reported; this may be due to the learning curve at our center or the shortness of our series. In contrast we conducted histological examination of all involved MLNs, supporting our data and shows that this confirmation can lead to a change of therapeutic strategy in some cases.
Management of locally advanced non-small cell lung cancer (NSCLC) at a community hospital: A retrospective analysis.
Authors: Spranklin Laura Jane , Heflin Jon Willis , Calvo Alejandro R.
Published: March 2020

e17506

Background: The optimal management of stage IIIA NSCLC has not been clearly defined. Much of this controversy is due to the heterogenity of this group. The current standard for unresectable stage IIIA disease is concurrent chemoradiotherapy. In patients with resectable stage IIIA disease however, neoadjuvant treatment followed by surgery provides better outcomes but not a significant survival benefit. Our study analyzed the management of stage IIIA NSCLC patients diagnosed at Kettering Health Network (KHN) and the observed 5-year survival as compared to the current NCCN guidelines and national 5-year relative and observed survival using the SEER database and National Cancer Database statistics. Methods: This retrospective study included all patients treated at KHN for Stage IIIA NSCLC from January 2004 to December 2009. 117 cases were analyzed, 53% female and 47% male. 42% were squamous cell, 28% adenocarcinoma, and the final 30% accounting for the remaining histology. 20 patients were not candidates for therapy due to poor performance status or comorbidity. 37 of the 97 patients under active treatment underwent resection at some point during treatment and 60 patients were deemed unresectable. Results: 68% of individuals with unresectable NSCLC received definitive concurrent chemoradiation, 32% received chemotherapy alone. In regards to resectable stage IIIA, 25% were treated with neoadjuvant therapy. 54% received postoperative therapy. 21% were treated with surgery alone due to multiple factors. The observed 5-year survival was 12.2% as compared to 10% nationally. The SEER data 5-year relative survival from 2001 to 2007 for stage IIIA NSCLC is 14%. Conclusions: In this heterogenous group of patients, treatment provided at KHN was individualized and followed national trends. The majority of unresectable stage IIIA NSCLC patients at KHN received the standard approach of concurrent chemoradiation. In terms of resectable stage IIIA NSCLC, approximately 25% were treated with either neoadjuvant chemotherapy or chemoradiotherapy. Overall, the 5-year survival rate for stage IIIA NSCLC at KHN is comparable to other community hospitals however slightly lower than the national average.
Epidermal growth factor receptor mutation in small cell lung cancer patients detected by mutant-enriched liquidchip technology from plasma in China.
Authors: Lu Hongyang , Lu Zhen-Yi , Cheng Qiao-Yuan , Cai Ju-Fen , Zhang Yiping , Jia Wang Xiao , Lou CaiJin , Yu Xinmin , Qin Jing , Ye Wei-Wu , Lei Lei , Wang Zeng , Zheng Yong-Qing , Mao Weimin
Published: March 2020

e17512

Background: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) has been widely used in non-small cell lung cancer (NSCLC), and the incidence of EGFR mutation in NSCLC is higher in China than in the United States and European countries. EGFR exons 19 and 21 mutation in NSCLC is related to response of tumors to EGFR TKIs, suggesting its usefulness as a biomarker. Some case studies reported that gefitinib-responsive small cell lung cancer (SCLC) with EGFR mutation. However, there are few large studies which reported the mutation status of SCLC patients. It is difficult to obtain tumor tissues to detect EGFR mutation in SCLC patients especially from surgery. This aim of the study is to know the EGFR mutation status in SCLC patients in China, and evaluate the feasibility of EGFR mutation detection from plasma by mutant-enriched liquidchip (MEL) technology. Methods: From September 2011 to January 2012, 27 cases of SCLC plasmas were collected at our Hospital, China. There are 6 female, 21 male. Age from 46 to 74 years old and median age is 60 years old. The stage (Veterans Administration Lung Study Group, VALSG): limited disease (LD) 6 cases, extensive disease (ED) 21 cases. Smoking history: non-smoker 8 cases, light smoker 0 cases, moderate smoker 3 cases and heavy smoker 16 cases. MEL technology was used to detect EGFR exon 19 and exon 21 mutations from plasma of 27 SCLC patients. Results: One of 27 cases was found with mutation in exon 19 of the EGFR gene. The patient with EGFR exon 19 mutation is a female and non-smoker. Conclusions: EGFR mutation is rare in SCLC patients, and may be more easily occurred in female and non-smokers. It is feasible to detect EGFR mutation for SCLC from plasma by MEL technology.
Adjuvant chemotherapy with cisplatin and gemcitabine in resected non-small cell lung cancer: A single institutional experience.
Authors: Carrera Sergio , Rubio Itziar , Sancho Aintzane , Marrodan Ines , Muñoz Alberto , Iza Estibaliz , Iruarrizaga Eluska , Buque Aitziber , Calvo Begoña , Aresti Unai , Lopez-Vivanco Guillermo
Published: March 2020

e17522

Background: Adjuvant chemotherapy in operable non small cell lung cancer (NSCLC) has been shown to improve overall survival in many meta-analysis. The use of cisplatin and gemcitabine combination is considered one of the standard regimens for first-line treatment of advanced NSCLC, with mild side effects. The aim of the study was to evaluate the clinical feasibility and toxicity of the cisplatin-gemcitabine combination in adjuvant setting. Methods: Resected NSCLC patients who met criteria for recommending adjuvant chemotherapy received treatment with cisplatin 75 mg/m2 on day 1 and gemcitabine 1.200 mg/m2 on days 1 and 8 of each 21 days cycle. A maximum of four cycles were delivered. Main objectives were clinical feasibility, drug delivery, and efficacy. Results: From November-2004 to July-2011 a total of 89 patients (73 male/16 female, median age 57) were included. Surgery: lobectomy 62.9%, pneumonectomy 29.2%, bilobectomy 5.6%, wedge resection 2.2%. Tumor stages: 19.1% IB, 55.1% II, 23.6% III, 2.2% IV; histology: 48.3% squamous, 43.8 % adenocarcinoma, 3.4 % large cell carcinoma and 4.5% NSCLC not otherwise specified. ECOG 0: 62.9%, ECOG 1: 37.1%. Toxicity: grade 3/4 neutropenia 19.1%/6.7 %; grade 3 febrile neutropenia 3.4%; grade 3/4 anaemia 6.7%/1.1%; grade 3/4 thrombocytopenia 6.7%/4.5%; grade 3 ototoxicity 1.1%; no grade 3/4 nephrotoxicity was reported. There was one toxic death. Compliance: 85.4% of the patients received 4 cycles of the combination chemotherapy. Cisplatin dose intensity was 24.6 mg/m2/wk and gemcitabine dose intensity was 773.6 mg/m2/wk. Median overall survival and progression free survival has not yet been reached. With a median follow up of 36 months, 77.5% of the patients are still alive and 61.8% without documented relapse. Reported 3 year overall survival in patients with ECOG 0 was 82%, and in patients with ECOG 1 54%, being this difference statistically significant. Conclusions: Combination chemotherapy with cisplatin and gemcitabine in adjuvant setting is safe and feasible with a good toxicity profile. Those patients with ECOG 0 benefit most. Our data are similar to those obtained in previously reported trials.
Oral vinorelbine and cisplatin with concomitant radiotherapy in stage III non-small cell lung cancer (NSCLC): COVeRT study.
Authors: Singhal Nimit , Pittman Kenneth B. , Karapetis Christos Stelios , Stephens Sonya , Borg Martin
Published: March 2020

e17544

Background: Chemoradiation is standard of care for the treatment of stage III NSCLC. Vinorelbine has been widely used for the treatment in NSCLC and it has been established, either as single agent or in combination with platinum, as one of the standard reference treatments. Oral vinorelbine is a new formulation which has achieved comparable results to the IV vinorelbine. The present trial is evaluating combination of oral vinorelbine, cisplatin with radical radiation for management of stage III NSCLC. Methods: Patients with diagnosis of stage III NSCLC with PS 0-1 and adequate cardio-respiratory function. Primary objective: progression-free survival. Secondary objectives: response rate, overall survival and safety profile. Treatment - chemotherapy (2 cycles q 21 days): vinorelbine oral 50 mg/m2 d1, d8. Cisplatin 100 mg/m2/ cycle (given as either 20mg/m2 D1-5 or 50mg/m2 D1 and D8) - radiotherapy: 60 Gy in 30 fractions at 2 Gy/ fraction to the isocentre, treating all fields daily, 5 days a week over 6 weeks using 10 MV photons and 3-D CRT. Results: Since May 2008, 33 patients have been enrolled with 31 patients having completed treatment so far. The data is presented for these 25 patients. 16 were male with age ranging from 50-89. The median age was 66. 13 patients had stage IIIa. There were 11 squamous cell carcinoma and 10 adenocarcinoma. The side effects were generally mild and included Gr I, II nausea, constipation and esophagitis. Serious adverse events requiring admission included dehydration, fever with grade I neutropenia, atrial fibrillation and UTI in one patient each. One patient had tracheo-esophageal fistula resulting in death within 30 days of completing chemoRT and was attributed to treatment. The confirmed radiological response assessment is available for 22 patients with 1 CR, 13 PR, 7 SD and 1 PD giving a total response rate of 64%. Conclusions: Two cycles of chemotherapy with oral vinorelbine and cisplatin plus radical radiation appears to be well tolerated with significant activity in stage III NSCLC.
Survival benefit from combined chemoradiation (CRT) in elderly patients with unresectable stage III non-small cell lung cancer (NSCLC).
Authors: Domingues Pedro Masson , Zylberberg Ricardo , Matta-Castro Thalita , Baldotto Clarissa Serodio , de Lima Araujo Luiz Henrique
Published: March 2020

e17548

Background: CRT is the standard therapy in locally advanced NSCLC. Nevertheless, the best approach in the elderly population is still poorly defined. Methods: We retrospectively reviewed the charts of elderly (≥ 65 years) patients (pts) with diagnosed stage III (6th AJCC), unresectable, NSCLC, treated at the Brazilian National Cancer Institute (INCA) between 2003 and 2005. Pts with malignant pleural effusion were excluded. The primary outcome was overall survival (OS), measured from diagnosis until death. Prognostic factors were analyzed using log-rank and stepwise Cox model. Palliative therapy (PT) included best supportive care, radiation therapy (RT; ≤ 40 Gy), and palliative chemotherapy. Among pts treated with radical RT, OS was measured from date of treatment beginning until death (OST). Results: One hundred fifteen pts were included. Median age was 71 (range 65-83), 76% were male, 51% had squamous histology, and 82% stage IIIB. Seventy percent had more than 5% weigh loss at diagnosis, 44% had PS 0-1, while 29% and 26% had PS 2 and 3, respectively. Ninety percent were current/former-smokers, and Charlson comorbidity index (CCI) was 0 in 66% and 1-2 in 34%. Thirty-six percent received PT, 32% exclusive RT (>40 Gy), and 32% CRT (concomitant or sequential). Post-radiation surgery was not performed in this cohort. The median OS was 9.9 months (ms; 95% CI, 7.2-12.6). Survival was significantly longer among pts with PS 0-1 (p<0.0001) and no weigh loss (p=0.026), while histology (p=0.15), tumor stage (p=0.51), CCI (p=0.37), and age (p=0.54) were not prognostic factors. Pts treated with exclusive RT and CRT had better OS (median 14.3 ms [95% CI, 11.7-16.9] and 17.0 ms [95% CI, 14.1-19.9], respectively) than PT (median 4.1 ms [95% CI, 3.5-4.8]; p<0.0001). In the multivariate analysis, RT (HR 0.25 [95% CI, 0.15-0.42]; p<0.0001) and CRT (HR 0.16 [95% CI, 0.09-0.27]; p<0.0001) were independently associated with better survival in comparison to PT. Among pts receiving radical RT, the addition of chemotherapy was associated with longer OST (median 14.1 vs 10.7 ms; p=0.025). Conclusions: CRT was independently associated with longer survival in elderly pts with locally advanced NSCLC.
γ-H2AX as a novel prognostic marker in patients with non-small lung cancer.
Authors: Matthaios Dimitrios , Hountis Panagiotis , Trypsianis Grigorios , Zissimopoulos Athanasios , Bouros Demosthenes , Karakitsos Petros , Kakolyris Stylianos
Published: March 2020

e17553

Background: Phosphorylation of the H2AX histone is an early indicator of DNA double-strand breaks and of the resulting DNA damage response. In the present study we assessed the expression of γ-Η2ΑΧ in a cohort of 96 patients with non-small cell lung carcinoma and evaluated its role as a prognostic indicator in resectable NCSLC patients. Methods: 96 parafin-embedded specimens of non-small lung cancer patients were examined. All patients underwent radical thoracic surgery of primary tumor (lobectomy or pneumonectomy) and regional lymph nodes dissection. γ-Η2ΑΧ expression was assessed by standard immunohistochemistry.Multivariate Cox proportional hazards regression analysis, using a backward selection approach, were performed to explore the independent effect of variables on survival. All tests were two tailed and statistical significance was considered for p values <0.05. Results: Follow-up was available for all patients; mean duration of follow-up was 27.50 ± 14.07 months (range 0.2-57 months, median 24 months). Sixty-three patients (65.2%) died during the follow-up period. The mean survival time was 32.2 ± 1.9 months (95% CI = 28.5 to 35.8 months; median 30.0 months); one, two and three-year survival rates were 86.5 ± 3.5%, 57.3 ± 5.1% and 37.1 ± 5.4% respectively. Low γ-H2AX expression was associated with a significant better survival as compared with those having high γ-H2AX expression (23.2 months for high γ-Η2ΑΧ expressin vs 35.3 months for low γ-H2AX expression, p=0.009; HR=1.95, 95% CI=1.15-3.30). Further investigation with multivariate Cox proportional hazards regression analysis revealed that high expression of γ-H2AX remained independent prognostic factors of worse overall survival (HR=2.15, 95% CI=1.22-3.79, p=0.026). Conclusions: Our study is the first study to demonstrate that overexpression of γ-Η2ΑΧ is an independent prognostic indicator of worse overall survival in patients with non-small lung cancer. Further studies are needed to confirm our results.
How safe is surgery in obese lung cancer patients?
Authors: Dhakal Binod , Sukumaran Sunitha , Santana-Davila Rafael , Haasler George , Eastwood Daniel , Tisol William , Gasparri Mario , Choong Nicholas W.
Published: March 2020

e17555

Background: Obesity is a risk factor for increased peri-operative morbidity and mortality in surgery. There have been limited studies to correlate morbidity of lung cancer resection with obesity. Methods: We performed a retrospective study of patients who underwent surgical resection for lung cancer at the Medical College of Wisconsin from 2006 to 2010. Data on patient demographics, weight, pathology findings and hospital course were abstracted after appropriate IRB approval. Peri-operative morbidity was defined as atrial fibrillation, heart failure, respiratory failure, pulmonary embolism or any medical complications arising within 30 days after surgery. Fisher’s exact test was used to test the association between BMI and perioperative morbidities. Results: Between 2006 and 2010, 320 lung resections were performed for lung cancer. Median age was 67 (25-88) years and 185 (57.8%) were females. The body mass index (BMI) distribution was 121 (37.8%) in BMI<25 and 199(62.18%) in BMI≥25. In patients with BMI < 25, surgical procedures consisted 76 (23.75%) lobectomy, 38 (11.8%) wedge resection and 7 (2.18%) pneumonectomy. In patients with BMI ≥ 25, surgical procedures consisted: 131 (40.93%) lobectomy, 61 (19.06%) wedge resection and 7 (2.18%) pneumonectomy. Tumor histology was: adenocarcinoma 138 (42.9%), squamous cell cancer 107 (33.3%), bronchoalveolar 25 (7.7%), large cell 19 (5.9%) and mixed 31 (9.68%). The 30-day mortality rate was 1.8 % (6 patients), out of which only 2 had BMI ≥ 25. Peri-operative morbidity occurred in 28 (23.14%) of normal BMI patients and 47 (23.6%) of BMI ≥ 25 patients (p=0.54). Specific morbidities encountered by patients with normal vs. BMI ≥ 25 were: atrial fibrillation 11(9.09%) vs. 24(12.06%) (p=0.46), pulmonary embolism 1(0.83%) vs. 3(1.51%) (p=1.0), congestive heart failure 2(1.65%) vs. 2(1.01%) (p=0.63), respiratory failure 12(9.92%) vs. 17(8.54%) (p=0.69) and ARDS 2(1.65%) vs. 1(0.50%) (p=0.55).Median hospital stay was 5 days in lower BMI group and 4 days in BMI ≥25 groups (p=0.52). Conclusions: Potential curative surgical resections can be offered to even significantly overweight patients as there is no significant difference in the peri-operative morbidities and length of stay as compared to normal BMI patients.
Cytology- versus histology-based diagnosis in small cell lung cancer: Is there any clinical implication?
Authors: Strimpakos Alexios S , Ramfidis Vassilios , Maragkos Charilaos , Panagiotarakou Meropi , Gkiozos Ioannis , Syrigos Kostas N
Published: March 2020

e17557

Background: Small cell lung cancer (SCLC) is a common disease representing around 15% of all lung cancer patients. Unlike other solid tumours, SCLC is staged as limited or extensive depending on whether the disease can be confined to a radiation field or not. Diagnosis is confirmed either on histology (H) or cytological (C) examination, but it has not been studied yet whether there is a clinically significant difference between them. This study aimed to highlight possible differences and clinical significance of SCLC diagnosis made by H or C. Methods: Medical records of 422 patients (pts) diagnosed with SCLC between 2000 and 2011 were screened. Complete demographic, clinical and treatment data were available for 414 patients. Results: 274/414 pts (66,2%) were diagnosed by histology and 140/414 (33,8%) by cytology. Male:female ratio was 224:50 and 122:18 in H and C groups whereas median age 64 years in both. Limited:extensive stage was established in 89:185 pts in the H group and 41:99 in the C group. Chemotherapy was received by most patients in both groups but radiotherapy only in 110/274 pts (40%) in H and 59/140 pts (42%) in the C group. Median survival (OS) for the H and C groups were 7,7 and 7,3 months respectively. Conclusions: SCLC is a common and aggressive disease with poor prognosis. Early diagnosis offers the best chances for a longer survival and treatment should be commenced promptly. Diagnosis based on histology or cytology shares similar demographic and clinical characteristics without difference in treatment outcomes and survival.
Survival benefit from maintenance therapy after first-line chemotherapy in advanced non-small cell lung cancer: A meta-analysis.
Authors: Chouahnia Kader , Des Guetz Gaetan , Uzzan Bernard , Nicolas Patrick , Morere Jean F.
Published: March 2020

e18003

Background: Maintenance therapy corresponds to a prolonged treatment after induction chemotherapy (CT) for patients with advanced non-small cell lung cancer (NSCLC). Several recent randomized controlled trials (RCTs) showed a survival benefit for maintenance therapy, especially for EGFR tyrosine-kinase inhibitors (TKIs), but conflicting results have been published. We performed a meta-analysis of all RCTs published either as articles or in abstract form. Since its presentation at ESMO 2011, this meta-analysis has been updated with one additional study (AVAPERL) and the preliminary data of PARAMOUNT on Overall Survival (OS). Methods: A PubMed query using several keywords simultaneously (NSCLC, maintenance, RCT, survival) found 79 references. Abstracts from ASCO and ESMO proceedings were also reviewed. References were cross-checked. Outcomes were OS and PFS (Progression Free Survival). We used a fixed-effect model when heterogeneity was absent and a random-effect model when present. We used EasyMA software. Results: Thirteen RCTs were included with IFCT-GFPC trial used twice since it assessed 2 maintenance therapies in parallel, gemcitabine and erlotinib. These 13 RCTs included 5251 patients (median age 61 years, 4261 stage IV, 913 stage III diseases, 2929 adenocarcinomas, 983 squamous cell carcinomas). For OS (14 sub-studies), the overall HR was 0.85 (95 % Confidence Interval or CI 0.80-0.91; fixed effect model). For PFS (13 sub-studies), the overall HR was 0.65 (CI 0.58-0.73; random effect model). Both continuation maintenance (6 RCTs, HR 0.87, CI 0.76-0.99) and switch maintenance (3 RCTs, HR 0.85, CI 0.75-0.98) significantly improved OS. Targeted therapies also significantly increased OS (5 RCTs, HR 0.85, CI 0.77-0.93). Anaemia, thrombocytopenia and neutropenia were significantly more frequent after maintenance chemotherapy, and skin rashes and diarrhoea after biotherapies. Conclusions: Maintenance therapy with either continuation or switch chemotherapy or EGFR TKIs significantly improved OS and PFS. The benefit-to-risks ratios of these 3 types of maintenance should be compared more precisely thanks to additional RCTs.
EGFR variant III expression in Chinese patients with non-small cell lung cancer.
Authors: Wang Jie , Duan Jianchun , Bai Hua , Yang Lu , An Tongtong , Wang Zhijie , Zhuo Minglei
Published: March 2020

e18022

Background: Patients with advanced squamous cell lung carcinoma (SCC), even though harboring the EGFR mutation, showed an inferior response to EGFR-TKI. The aim of this retrospective study was to determine the clinicopathologic characteristics and distribution profiles of EGFRv III in Chinese NSCLC patients, and to explore the likely relationship between EGFRv III mRNA levels and the response to EGFR-TKI. Methods: Frozen tissues were retrospectively obtained from 114 NSCLC patients who received surgery resection and 13 advanced NSCLC patients who received EGFR-TKI treatment in Peking Universuty Cancer Hospital. EGFRv III expression was detected by RT-PCR and EGFR mutation was detected by denaturing high-performance liquid chromatography (DHPLC). The association between EGFRv III and clinicopathologic features was investigated by statistical analysis. Results: frequency of EGFRv III in 114 post-surgery NSCLC patients was 7.02% (8/114), including 11.11% (6/54) in SCC and 3.64% (2/55) in adenocarcinomas (ADC). The frequency of EGFRv III expression was higher in SCC than in ADC, but the difference didn’t reach statistical significance (p = 0.269). In the subgroup of 8 EGFRv III-positive patients, 7 (87.5%) were male, 6 patients (75.0%) were smokers or former smokers,. No EGFR mutation was detected. In 13 advanced SCC patients who received treatment with EGFR-TKI, no patient harboring EGFRv III was found, and 3 patients (23.08%) were tested for EGFR mutation. Conclusions: The frequency of EGFRv III in Chinese NSCLC was low and squamous histology, smokers or former- smokers, and male gender might be related to EGFRv III and have effects exclusive of EGFR mutation.
Retrospective analysis of nanoparticle albumin-bound paclitaxel (nabP) administered as a single agent in the treatment of recurrent stage IV (st4) non-small cell lung cancer (NSCLC).
Authors: Saxena Ashish , Christos Paul J. , Cagney Jennifer M. , Scheff Ronald J.
Published: March 2020

e18029

Background: NabP is a formulation of P designed to reduce toxicity of therapy and increase drug delivery to tumor cells. An established therapy for st4 breast cancer, single-agent nabP has also been shown to produce responses in frontline therapy of st4 NSCLC. Its role in relapsed NSCLC has not been well reported. Methods: We analyzed the records of st4 NSCLC patients (pts) treated with single-agent nabP at our institution. Cases were assessed with regard to age, sex, KPS, histology, line of systemic therapy, prior taxane exposure, # of cycles administered, dose attenuation, and progression-free survival (PFS) estimated by Kaplan-Meier analysis. Standard dosing of nabP was considered to be 260 mg/m2 IV Q 21 days. Disease was considered to have progressed on the date of any clinical assessment (typically CT scan) that led the treating oncologist to conclude that disease had progressed. All pts completed nabP therapy except 1, who was assessed at 427 days of follow up. Results: From Oct 2008 to Jan 2012, 15 st4 NSCLC pts (median age 67, range 48 to 82; 8 F, 7 M; KPS 60-80%; 12 adenocarcinoma, 2 squamous cell, 1 unspecified) received a median of 3 cycles (range 1-17) of single-agent nabP. All pts received at least 1 prior line of systemic therapy in the st4 setting: 6 received nabP as 2nd line therapy, 4 as 3rd line, and 5 as 4th line. 5 pts had also received prior chemotherapy for early stage NSCLC. 9 pts were taxane-naïve; 6 had received prior taxane therapy. 10 pts began nabP at standard dose; 5 began on an attenuated dose or schedule. Subsequent dose reduction occurred in 3 pts due to toxicity (fatigue, myelosuppression). Only 1 patient discontinued treatment due to toxicity (myalgias, arthralgias). Median PFS for all pts was 82 days (95% CI 35 to 205 days). Older age reduced risk of progression [hazard ratio 0.93 per 1-year age increase (95% CI 0.86 to 0.99), P=0.04]. Prior taxane exposure decreased PFS (median 39 vs. 113 days, P=0.07 by log-rank test). PFS did not vary by KPS, histology, or line of therapy. Conclusions: Single-agent nabP administered in relapsed St4 NSCLC is well tolerated and associated with extension of PFS, particularly in older and taxane-naïve pts.
Phase II study of bevacizumab in combination with S-1 plus cisplatin in patients with advanced nonsquamous non-small cell lung cancer.
Authors: Yoshino Reiko , Kaira Kyoichi , Tomizawa Yoshio , Kazama Toshifumi , Yoshii Akihiro , Miura Yousuke , Ishihara Shinichi , Fueki Naoto , Minato Koichi , Sunaga Noriaki
Published: March 2020

e18037

Background: Cisplatin combined with S-1 is an active regimen for patients with advanced non-small cell lung cancer (NSCLC). Although the addition of bevacizumab to platinum based regimens significantly improved outcome, it remains unknown about the safety and efficacy of first-line cisplatin plus S-1 with bevacizumab. Therefore, we conducted a phase II study to evaluate the efficacy and tolerability of bevacizumab in combination with S-1 plus cisplatin regimen in patients with advanced non-squamous NSCLC. Methods: Patient with ages ranging from 20 to 74 years, non-squamous NSCLC, no prior systemic therapy, no brain metastases and ECOG PS 0-1 were enrolled. Patients received cisplatin 60mg/m2 and bevacizumab 15mg/kg on day 1 of each cycle, and S-1 80mg/m2 orally twice daily for 14 days every 21 days. After 4-6 courses, patients were continued on bevacizumab until progression disease (PD). Primary end point was response rate (RR). Secondary end points included overall survival (OS), PFS, time to treatment failure (TTF), and safety. Results: Twenty-nine patients were enrolled in this study. Median age was 67 years (range: 42 to 74); male/female=17(58%)/12(42%); ECOG PS 0/ 1 = 18 (62%) / 11(38%); stageIIIB/IV=3(10%)/26(90%); adeno / NSCLC = 26 (90%) / 3 (10%). The median courses of the induction therapy was 4 (range: 2 to 6), and that of the maintenance therapy was 3 courses (range: 1 to 15). Response rate (RR) was 65.5%, and disease control rate (DCR) was 100%. Median PFS was 5.39 months (95%CI, 125-265 days). Hematological adverse events reaching grade 3 or 4 were leukocytopenia (6.8%), neutropenia (20.9%), anemia (3.4%), thrombocytopenia (6.9%), and febrile neutropenia (3.4%). Nonhematological toxicities of grade3/4 were hypertension (17.2%), appetite loss (3.4%), mucositis oral (3.4%), alkaline phosphatase elvation (3.4%), serum amylase elevation (3.4%), and hyponatremia (3.4%). Seven patients delayed the start of next course because of adverse events. Conclusions: Bevacizumab in combination with S-1 plus cisplatin was effective in disease control and well-tolerated regimen for the treatment of patients with advanced non-squamous NSCLC.
Erlotinib in the “real life”: Retrospective results in NSCLC in two Italian centers.
Authors: Lorusso Vito , Saracino Valeria , Romano Giampiero , Nacci Angelo , Leo Silvana Assunta , Chiuri Vincenzo Emanuele , Pellegrino Antonio , Rizzo Pietro , Giampaglia Marianna , Cinefra Margherita , Cinieri Saverio
Published: March 2020

e18048

Background: Erlotinib is an oral tyrosine kinase inhibitor, approved for treatment of advanced NSCLC after the failure of more than 1 or 2 previous chemotherapy regimens. Its efficacy is comparable to that of chemotherapy, however, some concerns have been raised on its activity in pts with poor PS or in those not harboring EGFR mutation. Methods: Wereviewed the medical records of pts treated with erlotinib in the last 5 years in two Oncologic Centers of South Italy, with the aim to correlate response to pts characteristics. Results: Since January 2006 we have treated with erlotinib 388 pts affected by stage IIIb-IV NSCLC as 2nd, 3rd or 4th line of therapy. Median age was 67 (range 23-90), 300 were males and 88 women. Histology was ADK in 214 (55.2 %), SQM in 129 (33.2%) BAL in 12 (3.1%) and other in 33 (8.5%). Stage IIIb/IV was 66/322 (17%/83%). PS was 0 in 90 (23.5%), 1 in 214 (57.4%), 2 in 60 (15.5%) and 3 in 14 (3.6%) pts, respectively. Smoking status was: never smoker 60 (15.6%), ex smoker 276 (71%), currently smoker 52 (13.4%). With regard to the line of therapy, 250 pts (64%) were treated as 2nd line, 113 (29.1%) as 3rd line and 25 (6.5%) as 4th line. Overall, 117 pts (30%) received only the first drug supply and were lost to follow-up, 131 (33.4%) received 2 or 3 drug supplies, 134 (35.7%%) 4-30 drug supplies and 5 pts (0.9%) > 30 drug supplies, respectively. According to RECIST Criteria, 20/256 evaluable pts (11 too early, 121 not evaluable) achieved PR (7.8%), 74 SD (28.9%) and 162 (63.2%) progressed. The characteristics of the responding pts were as follows: 12 women and 8 men, 15 ADK, 4 SQM and 1 other histology (undifferentiated), 9 never smoker, 10 ex smoker and 1 current smoker, PS 0/1/2 in 8/9/3 pts; line of therapy 2nd/3rd/4th in 16/4/0. The median duration of response was 10 months (range 3 to >30). Median duration of SD was 9 months. Responding pts had a median survival of 28 months (range 3-105). Conclusions: These retrospective data suggest a more cautious usage of the drug, in order to avoid the huge number of pts lost to follow-up. In fact, erlotinib should not be prescribed in pts with poor PS and in lines beyond the 3rd, unless for pts harboring EGFR mutation.
Clinical benefits of sequential administration of docetaxel and intermittent erlotinib as a second-line therapy for advanced non-small cell lung cancer (NSCLC): A phase II randomized study.
Authors: Aparisi Francisco , Sanchez-Hernandez Alfredo , Giner Vicente , Muñoz-Langa José , Esquerdo Gaspar , López Jiménez Antonio , Garde Javier , Garcia Sanchez Jose , Juan Vidal Oscar
Published: March 2020

e18049

Background: Patients (p) with advanced NSCLC have few treatment options after progressing to 1st-line platinum doublet chemotherapy. Several preclinical and phase I studies have suggested that sequential administration of erlotinib (E) and docetaxel could avoid possible negative interactions and optimize the benefit obtained against NSCLC. This randomized phase II was designed to address the clinical benefit obtained with the use of sequential administration of docetaxel and intermittent E. Methods: 70 p with advanced NSCLC progressing to previous PDC for advanced disease were randomized (1:1): Group A (n = 34): Docetaxel 75 mg/m2 day 1 and intermittent E (day 2-16), up to 4 cycles, followed by E in monotherapy; and Group B (n = 36): E in monotherapy. Treatment was administered until unacceptable toxicity or disease progression. Primary endpoint: rate of p free of progression at 6 months; secondary endpoints: progression-free survival (PFS), overall survival (OS), disease control rate (DCR) and safety. The study has completed enrolment. At the date of cut-off for this communication, data of 60 patients were available: 30 in Group A/30 in Group B. Results: Baseline characteristics: non-adenocarcinoma (60.3%), current/former smokers (95%), male (90%) and stage IV (87.9%). 6 months PFS: 13.5% in the sequential arm. PFS: 2.7 months (m) in Group A (95% CI 2.1 – 3.8) and 2 m in Group B (95% CI 1.7 – 2.4) p value 0.08. Median OS: 11.0 m (95% CI 4.5 – 13.4) in group A and 4.7m (95% CI 2.5 – 6.6) in Group B with a p value 0.02. DCR: 44.4% in the experimental group whereas in the E one was 30.8%. Adverse events (AEs), including skin rash and diarrhea, were all generally tolerable. Of interest, the low number of p developing neutropenia in the D + E arm. Conclusions: Although the primary objective has not been met, an encouraging benefit on survival has been shown in the exploratory analysis, with a median overall survival of 11 months for patients treated with the sequential regimen (p value 0.02). Final data will be presented during the meeting.
Quantification of circulating endothelilial cells (CECs) as a predictor of response to chemotherapy with platinum and pemetrexed in patients with nonsquamous non-small cell lung carcinoma.
Authors: Sanchez-Hernandez Alfredo , Garcia Sanchez Jose , Blanco Remei , Maciá Sonia , Esquerdo Gaspar , Aparisi Francisco , Garde Javier , Catot Silvia , Vidal Jose , Garcia-Pinon Francisco , Juan Oscar
Published: March 2020

e18053

Background: CECs play an important role in tumor neovascularisation and may have prognostic value in cancer patients (pts). The objective of this study is to assess the quantification of CECs as a predictor of response to chemotherapy (CT) in non-squamous NSCLC. Methods: 10ml of blood was obtained prior to the first, second and third cycle of CT in pts treated with platinum plus Pemetrexed. The quantification of CECs was undertaken using CellSearch technology in a central laboratory. The basal levels and the evolution of CECs was correlated with response to treatment according to RECIST criteria after 3 cycles of CT using analysis of variance (ANOVA). Results: Between July 2010 and June 2011 67 pts were included: 43 pts (64.2%) received CDDP/PEM and 24 (35.8%) received CBDCA/PEM. Median age: 60 years (range 40-82), 46 male (68,7%). Nine (13,4%) PS 0; 46 (68,7%) PS 1; 11 (16,4%) PS 2; 1 (1,5%) PS 3. Range of basal CECs: 8 - 1171 cel (median of 85 cel). CECs prior to cycle 2: median of 100 cel (range: 10-1388). CECs prior to ciclo 3: median of 94,5 cel (range: 5-1857). Response after 3 cycles was: 25 PR (36%), 17 SD (25%) and 16 PD (23%) and 11 NE (16%). In the analysis of variance, no significant relationship between the basal CEC count and response was found (p-value=0,831). Decrease >50% between the 1st and 2nd cycle is correlated significantly with progression disease (p=0.026). Conclusions: In this homogeneous group of patients with NSCLC there is no correlation between response to treatment and basal levels of CECs. The decrease in CEC numbers after the first cycle could be a negative predictive factor. The correlation between the variations of CECs with PFS and OS will be presented during the conference.
Oral S-1 and carboplatin plus bevacizumab with maintenance S-1 and bevacizumab for chemo-naive patients (Pts) with advanced non-squamous non-small cell lung cancer (NSCLC).
Authors: Kaneda Hiroyasu , Urata Yoshiko , Okamoto Isamu , Hattori Yoshihiro , Okuno Keiko , Shimada Temiko , Takeda Masayuki , Kurata Takayasu , Miyazaki Masaki , Terashima Masaaki , Tanaka Kaoru , Kiyota Hidemi , Hayashi Hidetoshi , Kudo Toshihiro , Okabe Takafumi , Azuma Koichi , Morita Satoshi , Nakagawa Kazuhiko , Negoro Shunichi , Satouchi Miyako
Published: March 2020

e18060

Background: Our previous phase III trial has demonstrated that S-1 in combination with carboplatin has promising activity as well as superior toxicity profile compared with carboplatin/paclitaxel for the first-line treatment of advanced NSCLC (JCO vol28, 2010). This study evaluated the efficacy and safety of new combination of S-1 and carboplatin plus bevasizumab (Cb/S1/Bev) followed by continuation maintenance of S-1 and bevacizumab (S1/Bev) in chemo-naïve Pts with advanced non-squamous NSCLC. Methods: Pts receive carboplatin AUC 5 and bevacizumab 15 mg/kg on day 1 plus oral S-1 (40 mg/m2 b.i.d. ) on days 1 to 14. Treatment is repeated every 21 days up to 6 cycles. For the patients with SD or PR, S-1 combined with bevacizumab are continued every 21 days until disease progression or toxicity. Primary endpoint of this study was overall response rate (ORR). Results: Between April 2010 to October 2011, 48 patients were enrolled. Median age was 65 years (range=F35-77), male/female=33/15, PS 0/1=15/33, adeno/non-adeno=42/6. Median cycles of Cb/S1/Bev treatment were 4 (range=1-6), and 59% (n= 28) of Pts shifted to maintenance therapy. Among Pts who shifted to maintenance phase, median cycles treated with S1/Bev were 3.5 (range=1-10). Grade 3/4 toxicities included: neutropenia (23.4%/4.3%), anemia (4.3%/6.4%), thrombocytopenia (6.4%/6.4%) and hypertension (8.3%/0%). No treatment related death was occurred. Forty-six pts were evaluable for response. ORR was 50 % and disease control rate was 78 %, with a median time to progression of 7.4 months (95% CI: 3.9-10.8). Conclusions: Treatment with S-1 and carboplatin plus bevacizumab with maintenance S-1 and bevacizumab in pts with advanced non-squamous NSCLC is feasible with an acceptable toxicity profile. The encouraging activity justifies further development of this new regimen.
Utility of a novel quantitative EGFR-mutated protein analysis using AQUA system for EGFR-TKI treatment in non-small cell lung cancer.
Authors: Goto Koichi , Ishii Genichiro , Fujimoto-Ouchi Kaori , Shirane Masatoshi , Saito Tatsuro , Nishiwaki Morie , Ohmatsu Hironobu , Niho Seiji , Yoh Kiyotaka , Umemura Shigeki , Yamane Yuki , Shiozawa Toshihiro , Yamaguchi Yoko , Taira Tetsuhiko , Nagai Kanji , Ohe Yuichiro
Published: March 2020

e18064

Background: Lung cancer carrying EGFR mutation (muEGFR) expresses good response to EGFR tyrosine kinase inhibitors (TKIs). However, not all patients (pts) with mutation showed similar clinical benefits from EGFR-TKIs. Heterogeneity of tumor cells is considered to be one plausible reason. MuEGFR was usually genotyped in qualitative manner in present clinical practice. In addition, new technology of AQUA system enables us to measure protein levels objectively with considering expression heterogeneity in tissues. Here we investigated the correlation between AQUA score obtained from each specimen and the response and the response duration by EGFR-TKIs. Methods: Slice sections from genotyped 105 pts with muEGFR and 33 pts with wild-type EGFR were stained by E746-A750 deletion (6B6)- and L858R (43B2)-specific antibodies. Homo- or heterogeneous staining and muEGFR protein levels of these specimens were evaluated with AQUA system. Results: Concordance rate between genotypes and AQUA-based phenotypes (deletion and L858R), with cut-off values based on ROC curve, were 60% and 82%. Low sensitivity of 6B6 was due to lucking of reactivity for other deletion variants. Alternatively, specificities of both antibodies were 96% and 92%, indicating highly selectivity to muEGFR protein. The AQUA score of 27 pts treated with EGFR-TKIs were varied (8.7 – 907.4) but the falls plot analysis indicated that pts with high AQUA score showed better objective response. Specimens of partial response (PR) had significantly higher AQUA score than those of progression disease (136.5 vs 9.8, p=0.014). When divided pts into two groups based on median AQUA score, the pts with high AQUA score showed a tendency of longer treatment duration (21 mo vs 14 mo, p=0.162). These results indicate that AQUA-based analysis can classify pts carrying genotyped muEGFR into susceptible and less susceptible ones to EGFR-TKIs. Conclusions: We observed that pts with high AQUA score were more sensitive to EGFR-TKIs. It is important for predicting sensitivity to EGFR-TKIs to investigate not only genotyping but also muEGFR protein levels by using AQUA system.
The predictive value of clinical variables in patients affected with non-small-cell lung cancer (NSCLC) treated with pemetrexed (PEM) plus platinum-based regimen: A retrospective analysis.
Authors: Fabbri Maria Agnese , Moscetti Luca , Nelli Fabrizio , Gamucci Teresa , Mansueto Giovanni , Narducci Filomena , Quadrini Silvia , Sperduti Isabella , Passaro Antonio , Campenni Giuseppe , Cortesi Enrico , Martelli Olga , Bianchetti Sara , Angelini Francesco , Pellegrino Arianna , Pavese Ida , Signorelli Carlo , Ruggeri Enzo Maria
Published: March 2020

e18065

Background: PEM plus platinum–based regimen is a standard of care in chemonaïve advanced non-squamous NSCLC pts. This retrospective multicenter analysis was performed to evaluate the predictive value of clinical variables for PFS in an unselected population. Methods: Data were obtained by reviewing the clinical data of pts affected with advanced NSCLC treated from 2009 to 2011. 193 pts were retrieved. Main characteristics were: median age: 63 years (range 33-79); male/female (M/F): 67%/33%; ECOG PS 0-1: 97%; weight loss >5%: 34%; current smoker 31%. Stage IV disease: 81% ; ≥ 1 site of metastasis: 79%. Brain metastasis: 28% of pts at diagnosis. Results: All 193 pts are evaluable for analysis. 158 pts (82%) received the cisplatin- and 35 pts (18%) the carboplatin-based regimen. Most pts received at least 2 cycles of therapy and 21% received PEM maintenance treatment. The overall disease control rate observed was 69%. (CR+PR = 44%, SD 25%). At a median follow-up of 6.7 months (range 1-22), the median PFS was 6 months (95%CI 5-7) with a 1 year-PFS rate of 16.8%. In the Cox multivariate analysis, factors found to be associated with a statistically significant longer PFS were: gender (M vs F, HR 1.68, C.I.95% 1.19-2.38; p=0.003); no. of metastatic site (>1 vs 1, HR 1.6, 95%CI 1.07-2.40; p=0.02); type of response (CR/PR vs no response, HR 2.74, 95%CI 1.95-3.86; p<0.0001); and maintenance treatment (no vs yes, HR 2.74, 95%CI 1.95-3.86; p=0.02). The Kaplan-Meyer analysis of 1-year PFS confirmed female gender (F vs M 24.4% vs 12.2%, log-rank p=0.01), objective response (CR/PR vs SD/PD 29.9% vs 5.2%, log-rank p<0.0001), and maintenance therapy (yes vs no 30% vs 17.3%, log-rank p=0.01) as the significant clinical variables predictive of longer survival. Conclusions: According to our data only female gender, responsive disease and subsequent maintenance therapy were independent predictive factors. No difference in term of PFS outcome were found for elderly pts, presence of brain metastases and weight loss at diagnosis. Overall survival data will be presented.