bluuebunny/crossref_metadata_2025_split huggingface dataset:
EGFR gene mutation is not a significant prognostic factor in patients with EGFR mutated non-small cell lung cancer who receive best supportive care alone.
Authors: Masuda Takeshi , Wakabayashi Yu , Shimoji Kiyofumi , Yamaguchi Kakuhiro , Sakamoto Shinjiro , Nishimura Yoshihumi , Horimasu Yasushi , Nakashima Taku , Miyamoto Shintaro , Senoo Tadashi , Iwamoto Hiroshi , Iwamoto Hiroshi , Ohshimo Shinichiro , Fujitaka Kazunori , Hamada Hironobu , Hattori Noboru 
Published: May 2020

e21736 Background: Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), are less toxic than conventional chemotherapy drugs, and benefit patients with EGFR-mutated non-small cell lung (NSCLC) cancer. However, there are a few patients who are not able to receive EGFR-TKI due to poor performance status, older age, or sever comorbidities. Here, we aimed to determine the prognostic significance of EGFR mutation in NSCLC patients who received best supportive care (BSC) alone, and compare the anti-tumor outcomes of only EGFR-TKI-treated patients vs. BSC patients. Methods: We retrospectively reviewed the medical records of patients diagnosed with NSCLC at Higashihiroshima Medical Center during April 1991–January 2019 and Hiroshima University Hospital during April 2008–August 2018. Results: A total of 1163 patients diagnosed with unresectable NSCLC were included in this analysis. Of these 1163 patients, 234 patients received BSC alone.Among 196 patients who underwent EGFR mutation analysis, 38 and 158 did and did not harbor an EGFR mutation, respectively, and the mean survival times (MST) did not differ significantly between these groups (121 vs. 85 days, p = 0.789). Consistent with the survival analysis, the multivariate Cox regression analyses showed EGFR mutation was not an independent prognostic factor. After propensity score matching, a comparison of only EGFR-TKI-treated (n = 35) and BSC patients (n = 35) with EGFR mutation revealed that the former had a significantly longer MST than the latter (372 vs. 121, p < 0.001). Conclusions: EGFR mutation itself was not a significant prognostic factor in untreated NSCLC patients. The patients who received EGFR-TKI had a significantly longer MST than their untreated counterparts. Our results may help to explain the benefit of EGFR-TKI, particularly for patients who would be directed towards treatment with BSC.
Costs of extended immune check point inhibitors treatment in advanced/metastatic lung cancer: Bundling of costs proposal.
Authors: Guirgis Helmy M. 
Published: May 2020

e21738 Background: Pembrolizumab (Pembro) demonstrated remarkable 5-year overall survival (OS) and hazard ratios (HR) in 1st-line advanced/metastatic lung cancer (amLC) lacking EGFR and ALK alterations. After 35 cycles or 2 years, there is no consensus on whether to continue or stop the immune check point inhibitors (ICI). In contrast to ICI receiving no cost adjustment, CAR T-cell were contained at $375,000-$400,000. Probability of survival (PoS) was previously expressed as (1.0- HR) and used as surrogates of outcome. Our objective was to weigh ICI costs at one year and beyond vs PoS. Methods: Costs of Durvalumab (Durv) 10mg/Kg iv were calculated in US dollars q2 weeks. Pemetrexed (Peme) 500 mg/m2, Atezolizumab (Atezo) 1200 mg and Pembro 200 mg were computed q3 weeks. HR at the 95% confidence levels were quoted and PoS calculated. Results: The average ICI yearly-costs were $153,053, increasing annually by 2-4%. Peme were $108.108 and PoS 0.22. One-year adjuvant Durv in unresectable stage III were $145,808 at PoS 0.47. Pembro were $157,213 and PoS 0.40 in PD-L1 > 50%. Pembro costs beyond 5-years exceeded $786,065. Pembro- Peme-carboplatin in non-squamous histology were $265,321. PoS was 0.41 in PD-L1 < 1% and 0.58 in > 50%. Atezo+Bev 4-drug-costs were higher at $389,134 with modest 0.22 PoS. Setting mono-theray ICI yearly-costs at $160,000, one patient treated for 3 years would pay $480,000. Bundling costs at $400,000-$450,00 would save $30,000-$80,000. Savings would multiply with further years of extension. Conclusions: At 0.47 PoS, the one-year cost of adjuvant Durv was worth the dollars spent. The runaway ICI costs beyond 2 years would support the cost bundling proposal.
TP53 fusions with next-generation sequencing (NGS) in Chinese non-small cell lung cancer (NSCLC): A multicenter study.
Authors: Chen Huafei , Wang Wen xian , Xu Chunwei , Zhu You-cai , Zhuang Wu , Huang Yun-jian , Fang Yong , Wang Hong , Zhang Yinbin , Wang Yafei , Chen Meifang , Li Jinluan , Wang Liping , Cai Shangli , Fang Meiyu , Chen Gang , Lv Tangfeng , Song Yong 
Published: May 2020

e21742 Background: Currently, with the advances in detection techniques, such as next generation sequencing (NGS), more and more rare or atypical TP53 fusions had been identified. Such as TP53-PSMD14, the importance of EGFR signaling in the pathogenesis of lung cancer and the efficacy of EGFR-TKI treatment had been demonstrated. The aim of this study was to evaluate the prevalence of TP53 fusions in Chinese NSCLC populations, which had not been reported earlier, and to describe targeting potential in Chinese NSCLC populations. Methods: A multicenter study in China was initiated from February 2014, and NSCLC patients have been enrolled as of December 2018. A total of 2743 patients with NSCLC were screened by using next-generation sequencing (NGS)-based 381 genes panel assay for detecting TP53 fusions. Results: Of this entire cohort, just four (0.15%) patients were identified with a TP53 fusion, including DNAH2-TP53 (1), TP53-MPDU1 (1), TP53-FXR2 (1), TP53-VEZF1 (1). Of the TP53 fusion NSCLC patients, 50.00% were detected in female patients. Biopsies were obtained from primary lung tumor (25.00%) and metastatic sites (75.00%). Overall TMB in the TP53 fusion was high, which had more than 20 mut/Mb. Of the TP53 fusion NSCLC, two cases (50.00%) featured EGFR SV alterations. Conclusions: The frequency of TP53 fusions in Chinese populations with NSCLC is extremely rare (0.17%). TP53 fusions may reduce responsiveness to TKIs and worsen prognosis in EGFR-mutated NSCLC patients, mainly those carrying exon 19 deletions or exon 21 L858R.
Clinical characteristics and treatment outcomes of 65 patients with BRAF-mutated non-small cell lung cancer (NSCLC).
Authors: Mu Yuxin , Yang Ke , Hao Xuezhi , Wang Yan , Wang Lin , Liu Yutao , Lin Lin , Junling Li , Xing Puyuan 
Published: May 2020

e21745 Background: BRAF mutations are infrequently seen in non-small cell lung cancer (NSCLC) in Chinese population. We aimed to investigate the clinicopathologic characteristics and treatment outcomes of Chinese patients with NSCLC harboring BRAF mutations. Methods: We conducted a retrospective multicenter study in China of patients with NSCLC harboring BRAF mutations between Jan 2017 and Jul 2019. Results: A total of 65 patients treated in 22 centers were included, 54 harbored BRAF-V600E mutation and 11 had non-V600E mutations, including K601E, G469S, G469V, G469A, G596R, G466R and T599dup. No significant difference in age or gender was found between BRAF-V600E and non-V600E cases, while the majority of patients with non-V600E mutations were smokers (81.8%). Of the 18 patients with early-stage disease at diagnosis and underwent a resection, the median disease-free survival (DFS) was 43.2 months, 18.7 months and 10.1 months of stage I, II and IIIA patients (P = 0.07), respectively. In 46 patients with advanced-stage disease at data cutoff, disease control rate (DCR) and progression-free survival (PFS) of first-line anti-BRAF targeted therapy was superior than chemotherapy in patients harboring BRAF-V600E mutation (DCR, 100.0% vs. 70.0%, P = 0.027; median PFS, 9.8 months vs. 5.4 months, P = 0.149). Of 30 V600E-mutated patients who received anti-BRAF therapy during the course of disease, the median PFS of vemurafenib, dabrafenib, and dabrafenib plus trametinib was 7.8 months, 5.8 months and 6.0 months, respectively (P = 0.970). Median PFS were similar between V600E and non-V600E patients (5.4 months vs. 5.4 months, P = 0.825) to first-line chemotherapy. Nine patients were treated with checkpoint inhibitors, DCR and median PFS were 62.5% and 3.0 months (95%CI 2.9, 3.1), respectively. Conclusions: Our data demonstrated the clinical benefit of anti-BRAF targeted therapy in Chinese NSCLC patients harboring BRAF-V600E mutation. The value of immunotherapy and treatment selection among non-V600E population needs further study.[Table: see text]
The efficacy of anti-PD-1 combined with temozolomide in unresectable, advanced melanoma from one center.
Authors: Hu Tu , Sun Wei , Xu Yu , Luo Zhi-Guo , Chen Yong 
Published: May 2020

e22007 Background: Anti-PD1/PDL-1 immunotherapy has led to a new era of the unresectable, advanced melanoma treatment. However, there are still a significant part of patients suffer from primary or secondary drug resistance to immunotherapy. We sought to explore the efficacy and safety of anti-PD-1 plus Temozolomide in unresectable, advanced melanoma patients. Methods: Patients with unresectable, advanced melanoma were treated with anti-PD-1 plus Temozolomide, Temozolomide/DTIC based chemotherapy, or anti-PD-1 alone between 1 May, 2018 and 31 January, 2020. Data were retrospectively reviewed and statistically analyzed for best ORR and progression free survival, as well as toxicities. Results: Seventy-seven individuals were identified, including 37 (48.1%) with acral melanoma, 20 (26.0%) with cutaneous melanoma, 16 (20.8%) with mucosal melanoma and 4 (5.2%) with melanoma of unknown primary. Thirty-three (46.8%) patients had received postoperative adjuvant treatment before progression, and none of them had received anti-PD-1 treatment. The objective response rate of anti-PD-1 plus Temozolomide (n = 5, 41.7%) was higher than Temozolomide/DTIC (n = 1, 5%) or anti-PD-1 alone (n = 6, 20.7%) in the front-line therapy and second-line therapy (42.9%, 0%, 23.5%, respectively). Similar results were found in the third-line therapy. Although no significant difference was detected among these groups in the front-line therapy, the progression free survival of anti-PD-1 plus Temozolomide (median, 7 months) was higher than Temozolomide/DTIC (median, 2.5 months) (p = 0.009), while showing no significant difference with anti-PD-1 (median, 4.5 months) (p = 0.267) in the second-line therapy. The incidence of grade 3/4 toxicity was 8% (anti-PD-1 plus Temozolomide), 20.7% ( Temozolomide/DTIC) and 23.8% (anti-PD-1) respectively, mainly immunogenic pneumonia (0%, 0%, 10.3%) and hepatotoxicity (0%, 4.8%, 6.9%), and no significant difference was found among these groups. Conclusions: The efficacy of combination of anti-PD-1 and Temozolomide is better than Temozolomide/DTIC or anti-PD-1 alone in advanced melanoma and does not increase the toxicity. Therefore, Anti-PD-1 combined with Temozolomide may be used as front-line regimen in advanced melanoma.
Clinical experience with the targeted therapy in melanoma patients with brain metastases.
Authors: Zhukova Natalia V. , Orlova Rashida , Antimonik Nina , Beliak Natalia P. , Kutukova Svetlana , Vasyusina Olga , Popova Natalia V. 
Published: May 2020

e22009 Background: According to the clinical studies, the frequency of melanoma brains metastasis reaches 43%, and according to autopsy data, this percentage is even higher - up to 75%. New drugs in clinical practice has significantly improved the prognosis of the metastatic melanoma, however, patients with metastases in the brain are often excluded from large clinical studies, which limits the evidence base of the effectiveness of new therapy methods in this category of patients. Methods: 44 patients with advanced melanoma were treated in SPb Clinical Oncology Dispensary from 2012 till now: 19 male and 25 female, median age is 54y.o. (from 26 to 81). 31 (70%) patients received combination of BRAF and MEK inhibitors, 13 (30%) patients received only BRAF inhibitors. 26 (59%) of patients received target therapy (TT) as 1st line of therapy. Initial performance status (PS) assessed by ECOG scale was following; 8 patient had PS = 0 by ECOG, 29 patients – PS = 1 by ECOG and 6 patients had PS = 2/3 status by ECOG. 8 (18%) patients with brain metastasis has radiation before the TT: 6 patients received at least 1 session of stereotactic radiotherapy and 2 patients underwent radiation of the entire brain. Results: Group of patients without brain metastases: median PFS is 10.0 month (95% CI: 6.0;15.0). The average PFS is 16,90 ± 3,19 month (95% CI:10,64;23,16). Median OS is 15.0 months (95% CI: 11.0;64.0). The average OS is 33,16 ± 5,89 month (95% CI: 21,62 – 44,70). Group of patients with brain metastases: median PFS and OS is not reached. The average PFS is 17,86 +/- 3,3 month (95% CI: 11,42-24,33). The average OS is 20,31 ±2,86 month (95% CI: 14,71 - 25,92). Only 3 from 8 patients have PD after TT on the time of analysis. 5 patients are still alive. Conclusions: Our clinical experience demonstrates comparable efficacy of TT (PFS and OS) in patients with melanoma, regardless of the presence of metastatic brain disease. In the treatment of this category of patients, an integrated approach is very important, including both the use of targeted drugs and the conduct of surgical and radiotherapy. An equally important factor is the rapid onset of treatment.
Safety and efficacy of checkpoint inhibitors in solid organ transplant recipients with cutaneous squamous cell carcinoma.
Authors: Tsung Irene , Worden Francis P. , Fontana Robert J. 
Published: May 2020

e22014 Background: Immune checkpoint inhibitors (ICI) are increasingly used in solid organ malignancies. However, data are limited regarding their safety and efficacy in solid organ transplant (SOT) recipients at risk for allograft rejection. The aim of this study was to review our experience with ICIs in SOT recipients at a large transplant center. Methods: A retrospective review of ICIs used in SOT recipients from April 2011 to September 2019 was undertaken. Patient clinical and demographic features, ICI regimen, immunosuppression, allograft function, and efficacy were reviewed. Results: There were 8 SOT recipients (3 kidney, 4 liver, 1 lung) with 7 diagnosed with metastatic head and neck (H&N) cutaneous squamous cell carcinoma (cSCC) and 1 with Merkel cell carcinoma. At a median of 150 months [79-219] post-transplant, 6 were treated with cemiplimab and 2 with pembrolizumab after minimizing calcineurin inhibitors (CNI). Overall tumor response was 37.5% at a median of 3.8 months [0-8] of follow-up. However, 3 died of tumor progression and 2 of other causes at a median of 55 days [8-214] after starting ICI. The only irAE reported was severe pneumonitis in one patient requiring intubation and ICI discontinuation but responded to steroids. Two patients received prophylactic steroids and have preserved allograft function and ongoing tumor response at month 6. Conclusions: Our data suggest that minimization of CNI along with judicious use of prophylactic steroids may allow for the safe use of ICIs in SOT recipients with advanced H&N cSCC. Short-term efficacy appears promising and prospective studies are warranted. [Table: see text]
Influence of age and cancer history on prevalence of autoimmunity in patients with metastatic melanoma: A large retrospective study.
Authors: Holmes Aaron N. , Wang Xiaoyang , Swede Helen , Hegde Upendra P. 
Published: May 2020

e22016 Background: While immune checkpoint inhibitors (ICIs) have improved the survival rates of metastatic melanoma in recent years, immune-related adverse events (irAEs) remain a major toxicity. Studies have established that pre-existing autoimmunity increases the risk of severe irAEs following ICI therapy (1). Melanoma is common cancer in older patients, and older age is believed to be a risk factor of autoimmunity. However, there is controversy concerning the influence of age increasing the risk of irAEs between clinical trials, which exclude patients with confirmed or suspected autoimmunity, and less-selective but lower-power case reports (2). In order to understand potential irAE risk following ICI treatment, we measured the prevalence of pre-existing autoimmune disease by age and cancer type. Methods: We studied 293,938 patients aged 18-106 years old who were treated at the University of Connecticut Health Center between 2000 and 2018 using GE Centricity’s IDX database. Patients were organized into four study groups based on International Classifications of Diseases codes (ICD-9 and ICD-10), specifically primary melanoma and three comparisons groups: non-cutaneous neoplasms alone, melanoma with non-cutaneous neoplasms, and patients without cancer history. A list of 340 ICD codes corresponding to 105 autoimmune conditions were queried. Results: Non-cutaneous cancer, in the absence or presence of melanoma, was associated with a higher prevalence of autoimmunity (27.0%, 29.4%, respectively) compared to the rates in patients with melanoma alone and those without cancer history (11.1%, 8.7%, respectively, p < 0.05). In patients with both melanoma and non-cutaneous cancers, those with metastases had an 11.7% increase in autoimmune prevalence compared to patients without metastases (p < 0.0001), the largest metastasis-associated increase observed across all cancer groups. Lastly, a logistic regression demonstrated that age is weakly correlated with autoimmunity (r = 0.01, p < 0.0001). Conclusions: The findings suggest that a history of metastasis, non-cutaneous cancer, and advanced age are associated with a higher prevalence of pre-existing autoimmunity in melanoma patients. As ICIs are indicated for metastatic melanoma, our findings warrant future studies and careful risk assessment of autoimmunity in senior patients.
Vitiligo is correlated with clinical benefits in patients with advanced cutaneous melanoma treated with immune checkpoint inhibitors (ICI).
Authors: Martin Reinas Gaston , Muino Marcelo , Abal Mariana , Garcia Gerardi Carlos , Tognelli Flavio , Gil Deza Ernesto , Gonzalez Cesar , Gonzalez Liliana D , Nunell Marcelo Andres , Marin Ordoñez Alba , Morgenfeld Eduardo L. , Rivarola Edgardo G. J. , Gercovich Felipe G. 
Published: May 2020

e22023 Background: Use of ICI changed the treatment of Advanced Cutaneous Melanoma Patients (ACMP). This paper analyzes the evolution of ACMP who develop vitiligo during ICI treatment at Instituto Oncológico Henry Moore (IOHM). Methods: We selected all ACMP that received ICI between August 2015 and December 2019. We collected clinical data and compared Group A (ACMP with vitiligo) with Group B (ACMP without vitiligo) on: response rate (RR), time from ICI treatment initiation to progression (TTP) and overall survival (OS), defined as time from ICI treatment initiation to death. Outcomes were assessed using table tests and Kaplan-Meier curves with log-rank test. Results: Out of 32 ACMP treated with ICI, 12 Pt (37%) were in Group A and 20 Pt (63%) were in Group B. Table shows group characteristics and outcomes. Conclusions: 1) During treatment with ICI, 12 out of 32 (37%) advanced cutaneous melanoma patients were afflicted with vitiligo. 2) Two out of three patients who responded to ICI treatment developed vitiligo and obtained better TTP and OS than those without vitiligo. 3) According to these results, vitiligo is the consequence of the immune system reactivation responsible for considerable clinical benefits. Further studies should analyze if it is feasible to reduce ICI doses in patients who develop this adverse effect. 4) In this small and retrospective series, Nivolumab was more frequently correlated with vitiligo and clinical benefits, but we need prospective studies to decide which ICI treatment is the most effective. [Table: see text]
Retrospective analysis of retreatment with Ipilimumab in patients with metastatic melanoma.
Authors: Formozo André Alexandre , Gomes Jessica Ribeiro 
Published: May 2020

e22032 Background: The checkpoint inhibitors are effective in the treatment of many types of neoplasia, either being used separately or in combination. Ipilimumab pioneered the treatment of metastatic melanoma and nowadays it has being used in combination with anti-PD1. Retreatment with Ipilimumab has rarely been reported, but it may be an important strategy for the current treatment of metastatic melanoma. In this study we analyzed the patients with metastatic melanoma who were retreated with Ipilimumab. Methods: We evaluated patients with metastatic melanoma who had benefited from the first treatment with Ipilimumab, but eventually had progression of disease. They received Ipilimumab at the same dose as the first treatment (3 mg/kg every 3 weeks for four cycles). The effect was evaluated for progression free survival and clinical benefit. Results: Twenty–two patients were retreated with Ipilimumab in our Oncology Center. Most of them retreated six months or more, after the prior treatment. The progression free survival of the first treatment with Ipilimumab was 9.9 months. The median progression free survival of the retreatment was 6.3 months. Fourteen patients were reported to have clinical benefit (63%). Conclusions: This is a retrospective evaluation about the retreatment with Ipilimumab in patients with metastatic melanoma. It has been rarely reported in the medical literature, especially Ipilimumab at doses of 3 mg/kg. Maybe the next step might be the combined retreatment with Ipilimumab and anti-PD1.
Real-world treatment patterns and clinical outcomes of advanced melanoma patients following disease progression on anti-PD-1-based therapy.
Authors: Hernandez-Aya Leonel Fernando , Burke Matthew , Collins Jenna M , Earle Dennis , Hamilton Melissa , Nordstrom Beth L , Zhang Ying , Srivastava Shivani 
Published: May 2020

e22036 Background: Despite the success of anti-programmed cell death-1 (PD-1) based therapies that prolong survival in advanced melanoma, some patients experience disease progression. Real-world treatment patterns and outcomes after progression on anti-PD-1 based regimens are unknown. Methods: Adults with advanced melanoma and a record of disease progression on anti-PD-1 treatment (alone or in combination) between 1 Sept 2014–31 Jan 2019 were selected from the Flatiron Health Oncology electronic medical record (EMR) database for this retrospective study. Index progression date was defined as an event where the treating clinician concluded in the patient record that there had been disease progression. The first subsequent therapy received was identified. Kaplan-Meier methods estimated overall survival (OS) with 95% confidence interval (CI) after the progression date. Analyses were run separately for BRAF mutant (mt) and wild type (wt). Results: Among 2,169 patients with advanced melanoma treated with an anti-PD-1, 213 BRAFmt and 302 BRAFwt had a record of progression following anti-PD-1 initiation and were included; an additional 82 BRAFmt and 138 BRAFwt were excluded due to death without a record of progression. Median age was 64 and 71 years, respectively; 27.7% and 9.9% had >1 line of therapy prior to the anti-PD-1. Among the BRAFmt patients who progressed on anti-PD-1, 94 (44.1%) received no subsequent therapy, 80 (37.6%) BRAF±MEK (± IO), and 16 (7.5%) anti-CTLA4 alone or with anti-PD-1 after progression on the initial anti-PD-1; 11% received other treatments with no clear pattern of care. Median (95% CI) OS from the index progression date for BRAFmt was 11.9 (8.2–16.9) months. In a subgroup of these BRAFmt patients with BRAF treatment prior to or during the first anti-PD-1 line (N = 65), 52.3% had no subsequent therapy and a median OS of 4.0 (2.7–7.5) months. Among the BRAFwt patients who progressed on anti-PD-1, 186 (61.6%) received no subsequent therapy, 46 (15.2%) received anti-CTLA4 alone or with anti-PD-1, 26 (8.6%) switched anti-PD-1s, and 15% received other treatments. Median (95% CI) OS for BRAFwt was 10.1 (8.8–12.5) months. Conclusions: In this real-world retrospective study, > 40% of BRAFmt and > 60% of BRAFwt patients did not initiate a new regimen after progression on anti-PD-1 therapy. Median OS after progression was < 1 year. This may be overestimated, as it excluded patients who died before progression was recorded in the EMR. These findings highlight a need for more effective treatments for advanced melanoma.