ATOM: A phase II study to assess efficacy of preemptive local ablative therapy to residual oligometastases of NSCLC after EGFR TKI.

OBJECTIVES: NSCLC patients harboring EGFR mutation invariably developed resistance to EGFR TKI. We postulated that oligoresidual disease (ORD) after initial TKI might harbor resistant clones. This study aimed to test if preemptive local ablative therapy (LAT) can improve progression free survival (PFS) or not compared to historic data. MATERIALS AND METHODS: Patients indicated for EGFR TKI who possessed ORD (≤ 4 PET-avid lesions) after an initial 3-month TKI therapy were enrolled. After screening PET-CT, eligible patients with PET-avid ORDs were treated by LAT, either by stereotactic ablative radiotherapy (SABR) or surgery per clinicians' discretion. TKI was continued after LAT until it was considered ineffective. PET-CT was repeated on the 3rd and 12th month post-LAT (or at progression) apart from regular imaging. Further LAT was allowed in oligoprogressive disease. Primary endpoint was PFS rate at one-year from enrollment. Overall survival (OS), PFS and treatment safety were secondary endpoints. A post hoc comparison with screen failure cohort was performed. RESULTS: Eighteen patients were enrolled from 2014-17. Recruitment was stopped before the planned number (34) due to slow accrual. Two were excluded due to consent withdrawal and significant protocol violation. Median follow up was 39.1 months. Among the 16 analyzed patients, the one-year PFS rate (i.e. 15 month post TKI) was 68.8 %. Median OS was 43.3 months. All LAT were done by SABR, and none experienced ≥ grade 3 SABR related toxicities. Compared with screen failure cohort (n = 48), pre-emptive LAT effectively reduced risk of progression (HR 0.41, p = 0.0097). CONCLUSION: Preemptive LAT in ORD appeared to be safe and feasible. The 1-year PFS rate was encouraging. However, potential biases and the limitations of the study should not be overlooked. Further randomized studies are warranted.

Targeted next-generation sequencing reveals recurrence-associated genomic alterations in early-stage non-small cell lung cancer.

PURPOSE: The identification of genomic alterations related to recurrence in early-stage non-small cell lung cancer (NSCLC) patients may help better stratify high-risk individuals and guide treatment strategies. This study aimed to identify the molecular biomarkers of recurrence in early-stage NSCLC. RESULTS: Of the 42 tumors evaluable for genomic alterations, TP53 and EGFR were the most frequent alterations with population frequency 52.4% and 50.0%, respectively. Fusion genes were detected in four patients, which had lower mutational burden and relatively better genomic stability. EGFR mutation and fusion gene were mutually exclusive in this study. CDKN2A, FAS, SUFU and SMARCA4 genomic alterations were only observed in the relapsed patients. Increased copy number alteration index was observed in early relapsed patients. Among these genomic alterations, early-stage NSCLCs harboring CDKN2A, FAS, SUFU and SMARCA4 genomic alterations were found to be significantly associated with recurrence. Some of these new findings were validated using The Cancer Genome Atlas (TCGA) dataset. CONCLUSIONS: The genomic alterations of CDKN2A, FAS, SUFU and SMARCA4 in early-stage NSCLC are found to be associated with recurrence, but confirmation in a larger independent cohort is required to define the clinical impact. MATERIALS AND METHODS: Paired primary tumor and normal lung tissue samples were collected for targeted next-generation sequencing analysis. A panel targets exons for 440 genes was used to assess the mutational and copy number status of selected genes in three clinically relevant groups of stage I/II NSCLC patients: 1) Early relapse; 2) Late relapse; and 3) No relapse.

Attitudes, knowledge, and actions with regard to organ donation among Hong Kong medical students.

OBJECTIVE: To study attitudes, knowledge, and actions of local medical students with regard to organ donation and self-perceived confidence and competence in approaching potential organ donors. DESIGN: Cross-sectional questionnaire survey. SETTING: Faculty of Medicine, The University of Hong Kong, Hong Kong. PARTICIPANTS: Medical students, years 1-5. MAIN OUTCOME MEASURES: Knowledge on various aspects of organ donation was assessed, and students' self-evaluated competence and confidence about counselling for organ donation was evaluated. Factors influencing attitudes and actions were determined. RESULTS: The response rate was 94% (655/694). A majority (85%) had a 'positive' attitude, but only a small proportion (23%) had signed the organ donation card. Inconvenience and lack of knowledge about organ donor registration, and concerns about premature termination of medical treatment accounted for such discrepancies. Socio-cultural factors such as the traditional Chinese belief in preservation of an intact body after death, unease discussing death-related issues, and family objections to organ donation were significantly associated with a 'negative' attitude. Knowledge and action increased with medical education yet only a small proportion of medical students felt competent and confident in counselling patients on organ donation. CONCLUSIONS: The medical curriculum should increase medical students' awareness of the organ shortage problem. The donor registration system should be made more convenient and public education is recommended to correct misconceptions.