bluuebunny/crossref_metadata_2025_split huggingface dataset:
Is EGFR gene sequencing useful in squamous cell lung cancer?
Authors: Antunes Ana , Barroso Ana , Conde Sara , Neves Sofia , Parente Barbara 
Published: March 2020

e18111 Background: NCCN guidelines for NSCLC, currently do not recommend EGFR gene mutation study in squamous cell carcinoma (SLC), based on its low frequency of mutation (only 3% of SLC) and on the assumed low predictive value of these mutations in this population. Aim: To evaluate EGFR mutation rate in SLC, as well as response to treatment with erlotinib (disease control and survival) of patients with SLC, according to the mutational status of the EGFR gene. Methods: Revision of clinical and pathological features of patients with SLC for which we had performed EGFR sequencing. In the group of SLC patients with stage IIIB//IV at diagnosis treated with erlotinib 150 mg/day after at least one line of chemotherapy, comparison of response to erlotinib – disease control, overall survival (OS) and survival after the introduction of erlotinib (SE) – among the mutated and wild-type EGFR was performed. Results: Between January 2006 and December 2011, 98 patients with SLC were subject to EGFR sequencing – 89 males, 9 females; mean age 66.2 ±11.1 years; 82 smokers or former smokers. EGFR mutation was found in 11 patients (11.2%), 10 of which were male. Of these 98 patients, 22 were treated with erlotinib. 18 patients were in stage IIIB/IV at diagnosis and 5 had mutated EGFR. Of these 18 patients, median OS was 21.52 months and median SE was 5.5 months. Disease control was achieved in 6 (33%) patients. Median OS was 27.45 months in EGFR mutated SLC, against 19.5 in wild-type (p<0.05). Median SE was 13.5 months in mutated EGFR against 4.3 months in the wild-type (p<0.05). EGFR mutation was related with disease control – OR 22 (95% CI 1.53-314.3). Conclusions: In spite of the small sample size, this study shows that EGFR mutation rate of SLC in a Caucasian population is not insignificant and its presence is associated to a greater disease control and longer survival, as it has been described to lung adenocarcinoma.
Outcomes in Latin American NSCLC patients harboring wild-type or activating mutations of EGFR (CLICaP Registry).
Authors: Cardona Zorrilla Andres Felipe , Arrieta Oscar , Bramuglia Guillermo Federico , Campos-Parra Alma Delia , Becerra Ramirez Henry Alberto , Claudio Martin MARCELO , Richardet Eduardo , Serrano Silvia J , Archila Pilar , Rosell Rafael 
Published: March 2020

e18114 Background: Previous exploratory analysis of EGFR status in tumor samples from five LATAM countries suggested that frequency of mutations lies between that of Asian and Caucasian populations and therefore support the genetic heterogeneity of NSCLC around the world. Methods: We analyzed the EGFR sequence of tumor samples from advanced stage NSCLC patients previously participated in the CLICaP registry. We compared the outcomes (overall and progression free survival) of 175 patients (from Argentina, Colombia and México) with an activating EGFR mutation with 414 subjects without this condition. Results: Mutations were more frequent in women (57,1%), in patients who had never smoked (67,4%), and in those with adenocarcinomas (89,4%) (P<0,002 for all comparisons). The mutations were deletions in exon 19 (58,3%) and L858R (36%). Median progression-free survival and overall survival for 175 patients who received tyrosine-kinase inhibitors (TKIs) were 13-mo (95%CI 11,2-14,8) months and 36-mo (95%CI 25,4-46,5), respectively. TKIs produced higher response rates (used as first or second line therapy) in the EGFR mutation-positive patients (70,8% vs. 29,2%; P<0,001), as well as improved PFS (13,0 vs. 3,0; P<0,001). OS is significantly different between treatment groups (36 vs. 14; P<0,001). Conclusions: The analysis of a large comparative registry of Latin-American EGFR mutated and wild type patients confirms the results of individual clinical trials previously published.
Correlation of single nucleotide polymorphisms in NER pathway genes with toxicity in advanced non-small cell lung cancer patients treated with chemotherapy.
Authors: Zhang Ling 
Published: March 2020

e18115 Background: New therapeutic approaches are being developed based on the findings that several genetic abnormalities underlying NSCLC could influence chemosensitivity. We assessed whether polymorphisms in genes of NER pathway, such as ERCC5, ERCC6, MMS19L, CCNH, XPC, RRM1, can affect the tolerability of platinum-based chemotherapy in advanced NSCLC pts. Methods: Eligible pts had histological or cytological confirmed stage IV or IIIB (with malignant pleural effusion) chemo-naïve NSCLC, ECOG PS of 0 to 2 and adequate organ function. Pts received vinorelbine 25 mg/m2 or gemcitabine 1000 mg/m2 on day 1 and 8, or docetaxel 75 mg/m2 or taxel 175 mg/m2 on day 1 plus cisplatin 75 mg/m2 or carboplatin AUC=5 on day 1, every 21 days per cycle, for a maximum of six cycles, unless disease progression or unacceptable toxicity occurred. Hematology and biochemistry analyses were repeated every cycle or before chemotherapy for d8 treatment. Toxicity was classified according to CTC AE 3.0. Venous blood was collected and genomic DNA was isolated. Polymorphisms were assessed. SNPs in ERCC6 (A/G 1413, A/G 1213 and A/G 1097), XPC (T/C 500 and A/C 940), ERCC5 (G/C 1104), RRM1 (−37C/A), CCNH (T/C 270) and MMS19L (G811A) were assessed. Results: Totally 388 pts were included prospectively from Oct 2005 to Mar 2009. Median age was 61 years; 68.8% were male, 36.2% were ECOG PS 1, 33.2% had stage IIIB. The median follow-up time was 18 months (range 8–66 months). Hematological toxicity was the most common AE. SNPs of MMS19L and ERCC6 can predict the AE of chemotherapy in NSCLC,leucopenia (P=0.020), jaundice (P=0.039) by MMS19L. In terms of grade 3-4 AE, SNPs of MMS19L and RRM1 -37C/A have much more predictive effect. SNPs of MMS19L were good at total AE (P=0.042), thrombopenia (P=0.035), SNPs of RRM1 -37C/A were for vomiting (P=0.046) and jaundice (P=0.014). Conclusions: Polymorphisms in ERCC6, MMS19L, RRM1, can predict the tolerability of platinum-based chemotherapy in advanced NSCLC patients. Polymorphisms in other genes of NER pathway, such as ERCC5, CCNH, XPC, have no predictive effect.
Phase II trial of carboplatin, pemetrexed, and bevacizumab in metastatic nonsquamous (NSC) lung cancer.
Authors: Guarino Michael J. , Masters Gregory A. , Biggs David , Schneider Charles , Misleh Jamal Ghazi , Simpson Pamela S. , Suppiah Kathiresan , Wozniak Timothy F. , Grubbs Stephen S. 
Published: March 2020

e18122 Background: The trial was designed to examine PFS, OS and toxicities of a novel 3 drug combination in advanced NSC lung cancer. The first patient was entered 3/08 and the last in 5/11. Methods: Treatment consisted of Carboplatin AUC 5,Pemetrexed %00mg/m2, Bevacizumab 15mg/kg q21d x 6 cycles; then Bev maintenaince q3wk for up to one year. Eligibile pts. had metastatic non-squamous NSC lung ca, EGOG 0-1, first line Rx. Fifty patients were entered, all available for response and toxicity analysis: 26 M, median age 64, 45 white. Results: 52% RR by RECIST (2% CR, 50% PR); 26% SD. Median PFS 24 wks; median overall survival will be in excess of 49 weeks. 62% of patients received all planned 6 cycles and went on to maintenance. Treatment was out-patient and well tolerated with modest toxicities, including 2 DVT's, one PE, one TIA and one episode of F+N Conclusions: The 3 drug combination of Carboplatin, Pemetrxed and Bevacizumab for met NSC lung cancer is effective and well tolerated; and is a resonable choice of Rx for patients with non-squamous tumors hoping to avoid more neurotoxic or myelotoxic options.
Human papillomavirus in non-small cell lung cancer in never smokers in east Asia: A systematic review of the literature.
Authors: Hasegawa Yoshikazu , Ando Masahiko , Kubo Akihito , Isa Shunichi , Yamamoto Satomi , Tsujino Kazuyuki , Kurata Takayasu , Ou Sai-Hong Ignatius , Takada Minoru , Koshiol Jill , Kawaguchi Tomoya 
Published: March 2020

e18128 Background: Non-small cell lung cancer (NSCLC) in never-smokers has emerged as a global health concern, but its cause is undetermined. Epidemiological studies have shown that the disease is frequently observed in East Asia. Human papillomavirus (HPV) infection has been widely investigated in NSCLC, particularly in Asia. However, few studies have focused on regional differences in the prevalence of HPV in NSCLC tissue from never smokers. Methods: We performed a systematic search of PubMed for articles of HPV infection in human subjects with NSCLC between Jan. 1993 and Dec. 2011. We included studies that used polymerase chain reaction (PCR) as the primary HPV detection method. Because smoking status was not fully reported in all studies, we contacted the authors by e-mail to supplement this information. Differences in the distribution of patients with and without HPV infection were tested with the Chi squared test. Results: We identified 42 eligible articles, including 21 from Asian countries (N=2095 NSCLC cases), 17 from European countries (N=1430) and 4 from North and South America (N=160). The HPV prevalence was 28.0% (95% confidence interval (CI): 26.1-30.0%), 8.7% (95% CI: 7.3-10.3%) and 21.2% (95% CI: 15.2-28.4%), respectively. Seven studies from East Asia (N=939) and 4 from Europe (N=569) provided information on smoking status. The number of never smoker was 314 patients (33.4%) in East Asia and 54 patients (9.5%) in Europe. The HPV prevalence in East Asian countries was similar between never and ever smokers (38.2% vs 39.5%, P=0.94) and was significantly higher compared with European countries, where the prevalence was14.8% in never smokers (P<0.001) and 2.9% in ever smokers (P<0.001). In East Asia, the HPV prevalence was particularly high in Taiwan, the central part of China and Okinawa, south of mainland Japan. Conclusions: The prevalence of HPV is high in NSCLC tumor tissues from East Asia. Although the numbers of never smokers from European studies are very small, the different patterns of HPV prevalence from Asian and European countries is intriguing and deserves further study.
High mRNA expression of LMO4, a BRCA1 downregulator, correlates with better prognosis in erlotinib-treated non-small cell lung cancer (NSCLC) patients (p) with EGFR mutations.
Authors: Viteri Ramirez Santiago , Costa Carlota , Gimenez Capitan Ana , Benlloch Susana , Taron Miquel , Sanchez Jose Javier , Gasco Amaya , Martinez-Bueno Alejandro , Karachaliou Niki , Camps Carlos , Moran Teresa , Carcereny Costa Enric , Massuti Bartomeu , Cardenal Felipe , Porta Rut , Bosch Joaquim , Palmero Ramon , Buges Cristina , Rosell Rafael 
Published: March 2020

e18137 Background: Advanced NSCLC p with EGFR activating mutations show an impressive progression-free survival (PFS) to erlotinib. The co-existence of the EGFR T790M mutation, in conjunction with high BRCA1 mRNA levels, affected PFS to erlotinib (Rosell et al. CCR 2011). LMO4 is a negative regulator of BRCA1 function in sporadic breast cancers, and CtIP can bind to BRCA1 and LMO4. We have assessed the expression of CtIP, LMO4 and BRCA1 and examined the impact of CtIP and LMO4 levels on outcome. Methods: mRNA expression of LMO4 and CtIP was examined by RT-PCR in the original pretreatment tumor biopsies of 81 NSCLC p with sensitive EGFR mutations. Results: Expression of BRCA1 and LMO4 was successfully assessed in 55 p: median age, 68; 61.8% female; 98.2% Caucasian; 63.6% never-smokers; 81.8% ECOG PS <2; 80% adenocarcinoma; 14.5% BAC; 4.5% LCC; 94.5% stage IV; 63.6% exon 19 deletion; 36.4% L858R mutation; 36.4% T790M; 83.1% showed clinical benefit to erlotinib (CR/PR/SD). BRCA1 expression was correlated with that of CtIP (r=0.31; P=0.01) and LMO4 (r=0.32; P=0.02). There was no correlation between CtIP and LMO4 (r=0.09; P=0.49). PFS for p with high LMO4 levels was not reached while it was 13 months (m) for p with low levels (P=0.006). Overall survival (OS) was not reached for p with high levels of LMO4 and was 31 m for p with low levels (P=0.17). No differences in PFS or OS were observed according to CtIP levels. When BRCA1 and LMO4 expression was analyzed together, PFS was not reached for p with low BRCA1 and high LMO4 levels and was 19 m for p with low levels of both genes (P=0.04). PFS was 8 m for p with high BRCA1 and low LMO4 levels and 18 m for p with high levels of both genes (P=0.03). In the multivariate analysis, BRCA1 and LMO4 expression emerged as markers of PFS (Table). Conclusions: BRCA1 and LMO4 mRNA expression can predict PFS to erlotinib in p with EGFR mutations and could be useful in the development of new therapeutic strategies. [Table: see text]
Should crizotinib be dosed to sinus bradycardia (SB) (HR < 55)? A single institution, retrospective analysis of heart rate (HR) changes and tumor response in crizotinib treated NSCLC patients.
Authors: Tong Wilson P. , Azada Michele , Ou Sai-Hong Ignatius 
Published: March 2020

e18140 Background: Crizotinib can result in SB as a part of its dose-dependent pharmacodynamic property. We analyzed the correlation between SB and tumor response in ALK or MET+ NSCLC patients (pts). Methods: Single institution retrospectively analysis of SB incidence (HR < 55) of ALK or MET+ NSCLC patients enrolled in 2 phase II crizotinib trials. Comparison performed between pt characteristics, HR changes, treatment duration, tumor response and shrinkage according to SB status. Results: 42 ALK or MET+ NSCLC pts (30 from A8081001, 12 from PROFILE1005) rx’d with crizotinib 250 mg po bid were analyzed. 90% of pts had a HR decrease of > 10 beats per minutes (bpm). 19 (45%) patients developed at least 1 SB episode at anytime during crizotinib treatment including 8 (19%) pts with profound SB (HR =< 45). All pts with SB were asymptomatic. There was no difference in the median age of diagnosis between pts (57.6 yrs [SB] vs. 49.7 yrs [no SB]; p = 0.073) by SB status. Median time to SB was 3 wks (mean: 7.2 wks, range 2-32 wks). There was significant difference in the mean pre-Rx baseline HR by SB status (74.5 bpm [SB] vs. 92.6 bpm [no SB]; p = 0.005), Rx duration (57.3 wks [SB] vs. 33.3 wks [no SB]; p = 0.021). The average maximum HR decrease (MHRD) from baseline for all pts were 26.3 bpm. There was no significant difference in the mean MHRD from baseline according to SB status (28.2 bpm [SB] vs. 24.7 bpm [no SB]; p = 0.598). 68% (13/19) of SB pts compared to 35% (8/23) of pts without SB achieved a CR/PR (p = 0.030). The mean maximum decrease in tumor measurements (MDTM) (RECIST) was 46.2% for pts with SB compared to 32.0% for pts without SB (p = 0.095). There was no difference in the mean MDTM in pts who achieved CR/PR without SB (62.5%) and with SB (63.5%) (p = 0.913) nor the mean response duration (RD) in CR/PR pts by SB status (43.3 wks [SB] vs. 51.5 wks [no SB]; p = 0.426). Conclusions: HR decrease is common in pts treated with crizotinib. Pts who developed asymptomatic SB had significantly lower pre-Rx baseline HR, longer Rx duration, higher response rates. However there was no difference in the mean MDTM or RD between pts who achieved CR/PR by SB status.
Phase II tailored S-1 regimen study of first-line chemotherapy in elderly patients with advanced and recurrent non-small cell lung cancer.
Authors: Shiroyama Takayuki , Kijima Takashi , Komuta Kiyoshi , Yamamoto Suguru , Minami Seigo , Ogata Yoshitaka , Okafuji Kouhei , Imamura Fumio , Hirashima Tomonori , Tachibana Isao , Kawase Ichiro , Kumanogoh Atsushi 
Published: March 2020

e18141 Background: The aim of this study was to evaluate the efficacy and toxicity of a novel oral 5-fluorouracil (5-FU) formulation (S-1), administered according to a tailored dose regimen based on body surface area (BSA) and creatinine clearance (Ccr), in patients with advanced non-small-cell lung cancer who were 75 years or older. Pharmacokinetic analysis was also performed to evaluate the adequacy of the tailored S-1 dose. Methods: S-1 was administered orally for 28 days, followed by 14 days, in 23 patients who received a tailored dose of S-1, adjusted on the basis of individual creatinine clearance (Ccr) and body surface area (BSA). In 8 of the patients pharmacokinetic study were performed on the 5 times points on seventh day after S-1 administration. Results: Of the 23 patients enrolled in this study, 2 (8.7%) had a partial response and 14 (60.9%) had stable disease. The disease control rate was 69.6% (16/23) (95% confidence interval, 50.8-88.4%). Grade 3/4 hematologic and non-hematologic toxicities were minor. In the pharmacokinetic study group the maximum plasma concentration (Cmax) and the area under the plasma concentration curve (AUC) of 5-FU at all 5 times points after administration of the tailored S-1 dose regimen were similar to the values reported in a previous study describing cancer patients with normal renal function who received a standard dose of S-1 (80 mg/m2/day). Conclusions: Our results suggest that tailored S-1 monotherapy is safe and therapeutically useful as first-line treatment for elderly patients with advanced and recurrent non-small-cell lung cancer.
Survival among advanced non-small cell lung cancer patients with poor performance status after first-line chemotherapy.
Authors: Salloum Ramzi George , Smith Thomas J , Jensen Gail , Elston-Lafata Jennifer 
Published: March 2020

e18144 Background: Evidence-based guidelines recommend chemotherapy for medically fit patients with advanced stage non-small cell lung cancer (NSCLC). Performance status (PS) is a commonly used factor in determining the appropriateness for chemotherapy for this group of patients.The prevalence of poor PS and impact of chemotherapy on survival among NSCLC patients has not been studied in community populations. Methods: Insured patients, aged 50+ years, diagnosed with advanced stage NSCLC between 2000 and 2007 were identified via tumor registry (n=292) and linked to medical record abstracted PS, automated medical claims, and Census tract information. A multivariate Cox proportional hazards model was used to determine the factors associated with survival. Tests of statistical significance were two sided. We defined PS 3 or 4 as “poor” since the NCCN and ASCO guidelines agree that those patients should not routinely receive chemotherapy. Results: Of 292 stage IIIB-IV patients, 82 (28%) had PS 3 or 4, and 39% of PS 3-4 patients received first line chemotherapy. Those who received chemotherapy lived 4.8 months compared to 2.4 months for those who did not. Factors associated with a reduced likelihood of death included receipt of chemotherapy (hazard ratio [HR], 0.67) and surgery (HR, 0.27), and female gender (HR, 0.69). Conclusions: In advanced stage NSCLC, poor PS is common, and oncologists are treating about 40% of those patients with the same drugs as for PS 0-2. Modern chemotherapy is associated with positive effects on survival for poor PS patients, as for good PS patients, but we cannot tell if this is due to chemotherapy or some other factor. Further trials, especially randomized trials, in this common but neglected subgroup are indicated.
Treatment for frail elderly patients with diffuse large B-cell lymphoma (DLBCL): A single center experience.
Authors: Chaïbi Pascal , Chebib Amale , Baudry Elodie , Cotto Elise , Piette Francois , Berigaud Sylvie , Siriwardana Melany , Mitha Nathalie , Koenig Nelly , Spano Jean-Philippe 
Published: March 2020

e18505 Background: DLBCL occurs frequently in elderly pts and recent studies demonstrated that immunochemotherapy with R-mini-CHOP could be a safe and effective treatment for selected pts over 80 years Methods: Since 2008, R-mini-CHOP has been the treatment proposed for elderly pts with DLBCL referred to our oncogeriatric unit, irrespectively of their performance status (PS). We reviewed data of elderly pts treated for DLBCL at our institution from January 2008 to June 2011. Results: 74 pts (50 women, 24 men) were treated for DLBCL. Median age was 85 years (range 71–97), 84 % of pts ≥ 80 years and 16 % of pts ≥ 90 years. 68 pts (92%) had at least one comorbidity. Median number of daily medicines was 4 (range 0 – 12), irrespectively of treatments for DLBCL. Malnutrition was diagnosed in 49 pts. 50 pts (67,5 %) had a poor PS (> 2). Age-adjusted International Pronostic Index (aaIPI) was 0-1 in 9 pts, 2 in 28 pts and 3 in 35 pts. 61 pts were treated with mini-CHOP (cyclophosphamide: 400 mg/m2 D1; doxorubicine: 25 mg/m2 D1; vincristine: 1 mg total dose D1 and prednisolone 40 mg/m2 by oral route from D1 to D5) plus rituximab (375 mg/m2 D1) every 21 days for 6 cycles. Doxorubicine was replaced by etoposide (150 mg/m2 D1) for 5 pts because of cardiac dysfunction. 8 pts received reduced dose intensity chemotherapy ( without doxorubicine) for the 2 first cycles because of high risk toxicity. Prophylaxis of neutropenia with GCSF was systematic. Median survival was 11 months. 21 pts died during treatment, because of progressive disease (13) or treatment toxicity (6). Complete response (CR) was observed in 44 pts (59,5 %). With a median follow-up of 18 months, 11 relapses were observed. In our population study, aaIPI appears highly predictive of CR, with a CR Rate of 87,5 %, 75 % and 43% respectively for pts with aaIPI 0 - 1, 2 and 3.Hematological toxicity was the most common side effect. Grade 3–4 neutropenia was observed in 28% of the pts and grade 3–4 thrombocytopenia in 12%. 14 pts (19%) experienced at least one episode of febrile neutropenia. Conclusions: In unselected elderly pts with DLBCL, immunochemotherapy with R-mini-CHOP can be effective, but with significant toxicity, even using systematic G-CSF prophylaxis. Prognosis remains poor for pts with aaIPI 3
Long-term follow-up and secondary malignancy in mycosis fungoides patients treated by electron beam irradiation.
Authors: Lutsyk Miroslav , Kaidar-Person Orit , Bar-Hanna Micha , Cohen Yoram , Kuten Abraham 
Published: March 2020

e18511 Background: Mycosis fungoides (MF) and Sezary's syndrome are the most common subgroup of cutaneous T-cell lymphoma. Total or partial skin electron beam irradiation (TSEI, PSEI) is an accepted treatment option in cases of disease that is limited to the skin and as palliative treatment in advanced disease. Consequently, long term follow-up of these patients and detection of secondary malignancies after TSEI/PSEI is crucial. The aim of this study was to summarize long term follow-up of MF patients treated by TSEI or PSEI and to evaluate the rates of secondary malignancies. Methods: A retrospective review of the medical charts of all consecutive patients diagnosed with MF who was treated from January 1960 to June 2010 at our hospital was conducted. Data collected included demographics, date of diagnosis, staging, treatment, and secondary malignancies. Results: One hundred ninety six patients were included (132 M, 64 F). The median age at diagnosis was 67.3 years. The mean follow-up was 109.4±89.4 months (range 1-566). One hundred patients received TSEI, 45 patients received PSEI, and one patient was treated by low dose total body photon irradiation combined with TSEI. Fifty patients (50/196, 25.5%) developed a second malignancy, 16 patients (16/196, 8%) had a third malignancy, and 4 (2%) patients developed a fourth malignancy. Conclusions: MF is associated with development of sequential malignancies. The contribution of TSEI or PSEI to the development of secondary malignancies is yet to be determined. Long term follow-up in this group of patients is essential.