tbuckley/cabot-search huggingface dataset:
Second malignancy post-chemoradiation in head and neck cancer patients.
Authors: Gunjesh Kumar Singh, Rohit Swami, Vijay Maruti Patil, Vanita Noronha, Amit Joshi, Nandini Sharrel Menon, Kumar Prabhash
Journal: Journal of Clinical Oncology (2020)

e18525 Background: There is limited data available in the literature regarding incidence and treatment of second malignancy post-chemo-radiation (CTRT) in head and neck cancer patients. Hence we planned this analysis to address this lacuna in the current literature. Methods: We have already published a randomized study of 536 head and neck cancer patients, comparing radical CTRT with weekly cisplatin with or without nimotuzumab. The database of this study was used for the current analysis. Data regarding occurrence, site, stage, treatment details and outcomes were extracted from the database. Continuous variables were expressed in terms of the median with range, while non-continuous variables were reported in percentage. Kaplan Meier method was used for estimating the overall survival (OS). Results: Out of 536 patients, 18 (3.35%) patients developed second malignancy. The most common site was head and neck (44.44%) followed by lung (27.77%), prostate, ovary, breast, gallbladder and thyroid. 16/18 (88.88%) patients developed metachronous, while 2/18 (11.11%) had synchronous second malignancy. Most of the patients (55.55%) presented with locally advanced and metastatic disease, while 44.44% of patients had early-stage disease. 8/18 (44.44%) patients received palliative treatment. Of these, 6/18 (33.33%) patients received best supportive care and 2/18 (11.11%) patients were given palliative chemotherapy and palliative radiotherapy. 10/18 (55.55%) patients received radical treatment in the form of radical surgery (22.22%), CTRT (11.11%) and radical radiotherapy (5.55%), while 16.66% patients were kept under observation only. The median OS after the diagnosis of second malignancy was 451 days (95% CI, 301.45-600.59). It was seen that median OS the diagnosis of second malignancy in the aerodigestive and non-aerodigestive system was 446 days (95% CI, 39.10 - 852.89) and 840 days (95% CI, 278.46 - 1401.53), log-rank test P-value = 0.24. Conclusions: Second malignancy is not an uncommon phenomenon in head and neck cancer patients after CTRT and if properly taken care of, the improved outcome can be expected.
Pancreas transplantation
Authors: Dean Patrick G, Kukla Aleksandra, Stegall Mark D, Kudva Yogish C, 王星, 张梅
Journal: BMJ (2017)

糖尿病患者的治疗向医护工作者提出了许多挑战,在全球医疗保健支出中占很大比例。成功的胰腺移植能够使患者的血糖得到持久的控制，并改善患者的生存质量。该领域的进展主要是以大型单中心研究为基础,并累积分析了器官共享联合网络(UNOS)和国际胰腺移植登记处的登记数据。本综述重点关注伴随或不伴随终末期肾病的患者胰腺移植的结局，着重阐述胰腺移植的现状、现有知识的空白和研究前景。目前急需开展胰腺移植多中心随机试验研究，以明确胰腺移植的疗效、风险和长期获益。
Screening of RET gene mutation in a large Chinese pedigree with multiple endocrine neoplasia type 2A
Authors: Rongbiao Ying, Xiaoping Qi, Yan Ding, Renrong Yang, Jun Feng, Zhenguang Chen, Haiyan Zheng
Journal: BMJ (2014)

Objective
To screen the RET gene mutation in a pedigree of multiple endocrine neoplasia type 2A (MEN2A).


Methods
Clinical data of 21 members in a MEN2A family were collected from June 1976 to February 2013. Systemic clinical investigations including biochemical testing, imaging examinations and germline RET screening were performed.


Results
RET screening showed heterozygous missense mutations of cysteine to tyrosine at codon 634 on exon 11 in 10 MEN2A patients (p.C634Y, 10/21) including 8 males and 2 females, which were completely consistent with the clinical manifestations. There were 7 patients with medullary thyroid carcinoma (MTC), including one with concurrent papillary thyroid carcinoma. The mean age at onset was 34.3 years (range: 21-55), and the mean maximum diameter of MTC was 2.8 cm (range: 0.8-3.7). Five patients underwent non-normative thyroidectomy, 2 patients underwent total thyroidectomy with modified bilateral neck dissection. The mean follow-up period for MTC was 172.4 months (range: 10-440), elevating calcitonin level was found in 4 patients, normal calcitonin level in 3 of the 7 patients, 3 were combined with bilateral pheochromocytoma (2 synchronous and 1 metachronous), the mean age at onset was 48.3 years (range: 42-58), the maximum diameter of pheochromocytoma was 7.0 cm (range: 4.4-8.5). All 3 patients underwent bilateral (2 synchronous, 1 metachronous) cortical-sparing adrenalectomy, none of whom needed long-term steroid replacement and developed Addisonian crisis during the observation period (followed for 15, 17 and 120 months, respectively). Three asymptomatic carriers with a mean age of 11.7 (range: 8-15), rejected surgery and were closely monitored (followed for up to 17 months). The carries had a slightly elevated calcitonin and 1 presented bilateral thyroid minimal lesions (0.2 cm).


Conclusions
Screening of RET-mutation in MEN2A pedigree is helpful for early diagnosis, normative treatment, reducing complications and improve the long-term outcome of MEN2A.


Key words: 
Multiple endocrine neoplasia type 2a; Carcinoma, medullary; Thyroid gland; Pheochromocytoma, adrenal glands; Proto-oncogene, RET
急性有机磷中毒中间综合征的早期诊治
Authors: 袁正强, 高建军, 陈微微, 欧阳兴, 邹玉刚
Journal: BMJ (2005)

急性有机磷中毒(AOPP)除引起急性胆碱能危象和迟发性周围神经病外,还可以引起一组以肌无力为突出表现的综合征--中间综合征(IMS),已成为AOPP死亡的重要原因之一[1].现将我院1991年1月至2002年12月收治的34例IMS患者资料报告如下。
Characteristics of diploma course of family medicine in Hong Kong college of family physician and its implication for China mainland general practitioner job-transfer training program
Authors: Chen Qingqi
Journal: BMJ (2016)

近年来，中国内地开展了全科医师转岗培训以在短期内缓解全科医师短缺的情况，但目前的转岗培训存在不少问题。中国香港家庭医师学会每年举办的家庭医学文凭课程在培训目的、招生对象及学习时长上和内地转岗培训接近。本文系统介绍中国香港家庭医学文凭课程的特点，总结该课程中值得内地全科医师转岗培训借鉴的地方，为开展培训提供参考。
Survival prediction in mesothelioma using a scalable Lasso regression model: instructions for use and initial performance using clinical predictors
Authors: Kidd Andrew C, McGettrick Michael, Tsim Selina, Halligan Daniel L, Bylesjo Max, Blyth Kevin G, 王臻, 施焕中
Journal: BMJ (2018)

目的
对恶性胸膜间皮瘤（MPM）进行准确的预后预测具有一定困难。我们研究一套健全的计算模型来量化常规可用临床数据的预后价值，它们构成了已发布的MPM预测模型的基础。


方法
将269名MPM患者分成平衡训练集（n=169）和验证集(n=100)。预测模板(最小长度体现最佳的是多元训练模型)是由总生存期的套索回归模型产生的，总生存期<6个月或总生存期<12个月。总生存期预测值可通过Somers DXY统计方法量化，波动在0~1之间，它可以增加观察指标和预测结果之间的一致性。6个月和12个月的生存率可用曲线下面积（AUC）表示。


结果
总生存期中位数是272天（四分位间距为140~450天）。主要的生存模型分配4个预测因子高权重：年龄、体能状态、白细胞计数和血白蛋白，交叉验证后的结果比预期结果好[中位DXY 0.332（±0.019）]。然而，验证集DXY只有0.221（0.093 5~0.346），相当于生存预测率提高了22%。6个月和12个月生存期特征包括这4项相同的预测指标，除了上皮组织学+血小板和上皮组织学+C反应蛋白[平均AUC分别为0.758（±0.022）和0.737（±0.012）]。<6个月的生存模型显示：敏感度74%，特异度68%。<12个月的生存模型显示：敏感度63%，特异度79%。模型的内容和效能在整体上可与之前的研究相比。


结论
本研究中包含的基本临床信息和先前发表的模型对MPM的预后预测价值是有限的。可拓展使用的新兴预测因子包括肿瘤基因组学和体积分级。
Analysis of Etiology of 142 cases of endocrine hypertension
Authors: Nan-fang Li, Lei Wang, Xin-ling Wang, Fei-ya Zu, De-lian Zhang, Yan-min Zhang, Gui-juan Chang, Nuerguli, Ke-ming Zhou, Meng-hui Wang
Journal: BMJ (2009)

From 1997 to 2005 total 4642 patients with hypertension were admitted in department of hypertension and 142 cases were endocrine hypertension accounting for 3. 06% of all cases. Among 142 cases primary aldosteronism was most prevalent (58. 45% ), next was pheochromocytoma (35.92%). In primary aldosteronism (PA) there were more males than females(P <0. 05), more youth and middle-age cases than elderly(P<0.05); however, for pheochromocytorna there were more female than males(P < 0.05).

Key words: 
Hypertension;  Retrospective studies
Serum testosterone and primary osteoporosis in men beyond 60
Authors: Zhi-ming Zhao, Fu-liang Wang, Zhi-bin Jiang, Yong He, Xiao-ying Yang, Shi-qi Tang
Journal: BMJ (2008)

One hundred and six men aged >60 years were assigned to Group A (60 to 69 years old, n=33), Group B (70 to 79 years old, n=38) or Group C ( >80 years old, n =35), respectively. Serum testosterone, broadband ultrasound attenuation (BUA), speed of sound (SOS) , and stiffness (STI) were determined. Our results showed that as age increased, serum testosterone, BUA, SOS and STI decreased; serum testosterone was positively correlated with BUA ( r=0.62, P<0.05 ) and SOS ( r=0.54, P<0.05 ). We thus suggest that serum testosterone in elderly men might be closely related with bone mineral density.

Key words: 
Testosterone;  Osteoporosis
Management of patients with chronic kidney disease in the community
Authors: Zheng Qi, Shuai Liu, Hongmei Huan, Xia Chen, Weimin Ye, Ping Zhang, Lan Sun, Qi Shen, Weiying Gu, Xianya Wei
Journal: BMJ (2018)

Huacao Community Health Service Center has established an integrated chronic kidney disease (CKD) management system since 2015, which greatly improved CKD management in the community. From September 2016 to August 2017, 4084 residents were screened by the family doctor team, 975 were suspected to have CKD (23.87%), among whom 202 (20.72%) were referred to district CKD treatment center, and 197 (97.52%) were confirmed as CKD. The detection rate of suspected CKD among patients with hypertension and diabetes mellitus was the highest, which was much higher than that among outpatients and those with routine health check up. It is suggested that the integrated management of CKD should be widely implemented to cope with the prevalence of CKD, particularly for those with hypertension and diabetes.


Key words: 
Disease management; Community health services; Chronic kidney disease
General practitioners should be actively involved in prevention and treatment for tumors
Authors: 杨秉辉
Journal: BMJ (2005)

肿瘤,曾被称为20世纪的瘟疫.如今历史的车轮早己驶入21世纪,但肿瘤的肆虐有增无减.据估计,全世界每年新发的癌症患者约1 000万,死亡约700万,我国约占其中的1/4.我国幅员广大,常见于经济欠发达地区的食管癌、胃癌、肝癌等在我国仍然高发,而在经济较发达的沿海地区,肺癌、乳癌、肠癌的发病率又己显著升高,所以,我国肿瘤防治的任务更显艰巨。
CDK4/6 inhibitors and hormone therapy in hormone receptor-positive advanced breast cancer: Real-world data and intrinsic subtypes defined by PAM50.
Authors: Tamara Diaz Redondo, Rocío Lavado-Valenzuela, Maria Emilia Dominguez-Recio, Sofía Ruíz, Encarnación González Flores, Jose Antonio Lopez-Lopez, Vanessa de Luque, Cristina Morales-Estevez, Marta Robles-Lasarte, Jesus Perales-Adan, Enrique Saez Lara, Martina Alvarez, Alfonso Sanchez-Muñoz, Ana Godoy, Ester Villar, Francisco Carabantes, Jose Manuel Baena-Cañada, Jose Manuel Jerez, Nuria Ribelles, Emilio Alba
Journal: Journal of Clinical Oncology (2020)

e13035 Background: CDK 4/6 inhibitors plus hormone therapy(HT) has been approved by FDA and EMA for the treatment of hormone receptor positive HER2 negative advanced breast cancer (HR+/HER2-BC) with improvement in PFS consistently demonstrated in several clinical trials. Benefit in OS has also been demonstrated in Monaleesa3 and Monarch2 clinical trials. To date we don`t have real-world data and no single biomarker has been validated to identify subgroups that would benefit most from this new drugs. Methods: This is a multicenter, real life, observational study. From January 2015 to December 2019 we recruited 98 patients with immunohistochemical(IHC) HR+/HER2-BC treated with CDK4-6 inhibitor plus HT. All patients were classified into intrinsic molecular subtypes based on PAM50 signature done centrally in diagnostic/metastatic biopsies. Results: The clinical and treatment characteristic are in table. In IHC studies all population were classified as luminalA (40%) and LuminalB (60%) but we found HER2 enriched patients (6%) defined by PAM50. The median PFS for all population was 14 months and median PFS for Luminal A subtype was 12 months and 15 months for Luminal B with no statistically significant differences between them. Conclusions: Based on the results obtained, the intrinsic molecular subtype defined by PAM50 does not appear to be associated with differences in PFS in our study group. However, a study with a larger number of patients would be necessary. Inhibitors of CDK4/6, have established a central role in the management of HR+/HER2-BC. There is a clear benefit in PFS and OS but we still don’t know which patients will benefit from this therapy and who will not while the side effects such chronic neutropenia, QTC prolongation and diarrhea could have a negative impact on their quality of life. Its mandatory to explore a good biomarker to direct therapy. [Table: see text]
蛛网膜下腔出血后腰椎穿刺放脑脊液预防脑血管痉挛
Authors: 赵丽宏, 宋仁兴, 刘伟
Journal: BMJ (2004)

脑血管痉挛(cerebral vasospasm,CVS)是蛛网膜下腔出血(subarachnoid heamorrhage,SAH)的严重并发症,发生率高达31.6%～66.0%[1].为降低CVS的发生率,我们在常规用药基础上采取腰穿放脑脊液疗法治疗SAH患者52例。
Quantitative imaging biomarkers of CNS lymphoma and its correlation with genotypic markers.
Authors: Aleksandr Filippov, Feras Ally, Joo Y Song, Jasmine M. Zain, Ammar Chaudhry
Journal: Journal of Clinical Oncology (2020)

e14520 Background: Central nervous system (CNS) lymphoma can be divided into primary CNS lymphoma (PCNS) versus secondary involvement of the CNS in systemic lymphoma. Traditionally radiology-pathology correlation is needed to accurately stage these entities, but the invasive nature of intracranial biopsies can add to patient morbidity. As such, there is an unmet need for noninvasive imaging biomarkers of CNS lymphoma. We aim to assess whether quantitative imaging analysis can characterize improve diagnostic specific and identify underlying genomic alterations in CNS lymphoma. Methods: 42 cases of CNS lymphoma (26 males, 16 females) were reviewed. Inclusion criteria required MRI (1.5Tesla or 3.0Tesla) of the brain and time-concordant histopathologic evaluation (i.e. MRI obtained within 72 hours of histologic evaluation) confirming diagnosis of CNS lymphoma. 19 patients met the inclusion criteria: 16 patients with large B-cell and 3 patients with T-cell lymphoma. All diagnoses were confirmed by evaluating biopsies through morphological and immunohistochemical analysis. MRI studies included T1-weighted pre- and post-contrast images, T2-weighted images and diffusion weighted images. Quantitative analysis included 3D-volumetric and textural analysis. Results: In B-cell lymphoma, mean patient age was 57 (22-91) while in T-cell lymphoma mean age of diagnosis was 43 (20-59). On MRI, all cases of CNS lymphoma (B- and T-cell) demonstrated enhancement. All T-cell lymphoma lesions were intra-axial and demonstrated homogeneous enhancement. Meanwhile, B-cell lymphomas demonstrated variable pattern of enhancement (homogenous; reticulonodular; subcortical U-fiber; peripheral). 80% (4/5) patients tested for MYC alterations demonstrated peripheral enhancement. 70% (7/10) tested for BCL2 expression demonstrated homogenous enhancement; while BCL2 &amp; MYC dual-expression was noted in the remaining 30% (3/10) with MRI showing peripheral enhancement. All CNS lymphomas demonstrated restricted diffusion with variable ADC range: 292-980. 84.2% (16/19) of the cases were intra-axial while 15.2 (3/19) were extra-axial (all of which were B-cell lymphoma). Conclusions: Our study shows all lymphomas enhance and demonstrate variable degree of restricted diffusion. Patients with Myc-alterations or dual-expression of BCL2-MYC showed peripheral enhancement, while isolated BCL2 expressed tumors showed homogeneous enhancement.
A comparison of patients' and physicians' expectations regarding precision oncology tests.
Authors: Navdeep Dehar, Tasnima Abedin, Patricia A. Tang, D. Gwyn Bebb, Winson Y. Cheung
Journal: Journal of Clinical Oncology (2020)

1568 Background: With the increasing number and frequency of biomarker and genetic tests that are offered to patients with cancer, it is important to ensure that they fully understand the implications of these tests. In this survey study, we aimed to compare the attitudes and expectations of patients and cancer physicians about the role of biomarker and genetic testing in clinical decision-making. Methods: Two separate, complimentary, self-administered questionnaires for cancer patients and their physicians, respectively, were collected in Calgary, Alberta, Canada. Survey responses from patients were subsequently matched with those of their corresponding oncologists to form patient–oncologist dyads. We determined the concordance rates between responses of patients and those of their oncologists. Results: A total of 113 patients and 15 physicians participated in the study from July to September 2019. Patients demonstrated good understanding of general cancer biology (79%) and diagnostic processes (91%) associated with precision oncology. About 70% patients were willing to undergo minor procedures, and participate in research involving biomarker or genetic testing; however, this was over-estimated by their physicians in 82% of cases. Many patients felt that their tumor should be tested to guide treatment (70%) and were not bothered by potential delays in treatment due to testing (23%). These views from patients were largely shared by their oncologists (concordance 64%). While only 28% patients thought that they had enough knowledge to make informed decisions, majority (68%) said that they needed more information. Importantly, knowledge and expectations regarding the applications of biomarker or genetic test results on actual diagnosis and prognosis were grossly discrepant between patients and their oncologists (concordance 26% and 36%, respectively). Conclusions: Patients and cancer physicians tend to be aware of the advances in precision oncology and are willing to participate in biomarker and genetic testing and research. However, they do not consistently agree about the roles and applications of these tests, which may result in misplaced expectations. Strategies to improve education and communication are needed to align these expectations and improve the quality of clinical decision-making.
Clinicopathologic characteristics and immunotherapy outcomes in SMARCA4-mutant (mut) non-small cell lung cancer (NSCLC).
Authors: Joao Victor Machado Alessi, Carolyn Glass, Biagio Ricciuti, Liam F. Spurr, Lynette M. Sholl, Mark M. Awad
Journal: Journal of Clinical Oncology (2020)

9577 Background: The catalytic unit of the SWI/SNF chromatin remodeling complex is encoded by the SMARCA4 gene, which is mutated in ~10% of NSCLCs. We sought to characterize the clinicopathologic characteristics and outcomes to immune checkpoint inhibition in SMARCA4-mutant NSCLC. Methods: We collected clinicopathologic and genomic data from patients with NSCLC that had undergone targeted next generation sequencing (NGS) by OncoPanel at the Dana-Farber Cancer Institute. SMARCA4 frameshift, nonsense, and splice-site mutations were considered pathogenic, as were missense mutations if predicted to be pathogenic by Mutation Assessor and Polyphen-2. Clinical outcomes to immune checkpoint inhibition among SMARCA4-mutant NSCLCs were retrospectively assessed. Results: Of 2690 patients with NSCLC, 8% (N = 211) harbored SMARCA4 mutations. Clinicopathological characteristics were balanced between SMARCA4 mut and SMARCA4 wild-type (wt) in terms of age, histology, and PD-L1 expression. We observed a male predominance (P = 0.03), greater use of tobacco (P &lt; 0.001), a higher tumor mutational burden (TMB) (P &lt; 0.001), a higher prevalence of advanced disease (P &lt; 0.001), and a lower prevalence of concurrent targetable driver mutations (P &lt; 0.001) in SMARCA4mut vs SMARCA4wt NSCLCs. Among 513 patients with nonsquamous NSCLC who received immune checkpoint inhibitors, 11% (N = 57) harbored SMARCA4 mutations. From the start of immunotherapy, we observed no difference in overall response rate (ORR 21.5% vs 19.3%; P = 0.3), median progression free survival (mPFS 3.2 months vs 2.1 months; P = 0.4), or median overall survival (mOS 12.0 months vs 8.2 months; P = 0.09) in SMARCA4wt vs SMARCA4mut NSCLC, respectively. However, among KRASmut NSCLC, a concurrent SMARCA4 mut conferred a significantly lower ORR (23.1% vs 0.0%; P = 0.02), a significantly shorter mPFS (4.8 months vs 1.7 month; HR: 0.31 [95% CI: 0.15-0.61]; P &lt; 0.001), and a significantly shorter mOS (15.6 months vs 2.7 months; HR: 0.25 [95%CI: 0.12-0.49]; P &lt; 0.001). The deleterious effect of SMARCA4 mut on immunotherapy outcomes in KRAS mut NSCLC was maintained when controlling for concurrent STK11 mut. Conclusions: SMARCA4 mutations define a genomic subset of NSCLC with unique clinicopathologic characteristics, and confer worse outcomes to immunotherapy in KRAS mut NSCLC.
复杂动脉导管未闭的经导管封堵治疗临床分析
Authors: 张峰, 葛均波, 周达新, 陈灏珠
Journal: BMJ (2005)

分析在我院接受经导管封堵术的43例复杂动脉导管未闭病例,结果显示43例中40例经导管封堵成功(成功率为93.0%),无一例发生严重手术并发症,封堵后肺动脉收缩压峰值较封堵前明显下降(P＜0.05).术后3～6个月复查超声心动图,40例患者封堵器均无明显移位,39例无残余分流,1例残存少量分流.提示对于合并有其他解剖或血流动力学异常的复杂动脉导管未闭,经导管封堵是一种安全而有效的治疗方法。
Poziotinib shows activity and durability of responses in subgroups of previously treated EGFR exon 20 NSCLC patients.
Authors: Xiuning Le, Jonathan Wade Goldman, Jeffrey Melson Clarke, Nishan Tchekmedyian, Zofia Piotrowska, David Chu, Gajanan Bhat, Francois M. Lebel, Mark A. Socinski
Journal: Journal of Clinical Oncology (2020)

9514 Background: Treatment of non-small cell lung cancer (NSCLC) with EGFR exon 20 mutations is an unmet medical need. Poziotinib is a potent tyrosine kinase inhibitor (TKI) of EGFR and HER2 exon 20 insertion mutants. We evaluated the efficacy and safety of poziotinib in previously treated NSCLC patients with EGFR exon 20 insertion mutations in an independent cohort of a multi-cohort, multi-center Phase 2 study ( ZENITH20-1). Methods: ZENITH20-1 study enrolled pts with advanced NSCLC with an EGFR exon 20 insertion identified on local tissue testing who had received at least one prior line of therapy. Poziotinib (16 mg) was administered orally QD, allowing dose reductions for AEs, with follow up for 24 months. The primary endpoint was objective response rate (ORR), evaluated centrally by RECIST v1.1. Secondary endpoints included disease control rate (DCR), duration of response (DOR), progression-free survival (PFS) and safety. Efficacy was also evaluated by specific exon 20 insertions and prior lines of therapy. Results: 115 patients with a median age of 61 years (33-83) were enrolled. Patients had a median of 2 prior lines of therapy (range, 1-9.) The median relative dose intensity was 72% (7-100%) with 65% having dose reductions. The ORR in the as-treated population was 14.8% (95% CI 8.9 - 22.6%), and the DCR was 68.7% (95% CI 59.4 - 77.0%) with a median DoR of 7.4 months. 65% patients had tumor size reductions and the median PFS was 4.2 months. In the evaluable population (n = 88), the ORR was 19.3% and the unconfirmed ORR was 25%. Responses were predominantly observed in insertions between residues M766 to D770 of exon 20 (8/44; 18.2%). Responses were observed in patients with 2 lines (14%); ≥3 lines of therapy (16.2%). The most common treatment-related Grade ≥3 AEs were rash (28%), diarrhea (26%), stomatitis (9%) and paronychia (6%). The incidence of treatment-related pneumonitis was 4%, however some cases may have been confounded by prior checkpoint inhibitors as first line treatment. Conclusions: Although the ORR primary endpoint was not met, poziotinib induced tumor reduction in the majority of patients with durable responses, including the heavily pre-treated population. Responses were more common in patients with insertions between M766 to D770 of EGFR exon 20. The safety profile was overall consistent with other 2 nd generation EGFR TKIs. Evaluation of these subgroups with refined dosing and improved toxicity management to maintain continuous treatment is warranted to assess the potential of poziotinib in Exon20 related tumors. Clinical trial information: NCT03318939 .