Deep learning based automated epidermal growth factor receptor and anaplastic lymphoma kinase status prediction of brain metastasis in non-small cell lung cancer

Aim: The aim of this study was to investigate the feasibility of developing a deep learning (DL) algorithm for classifying brain metastases from non-small cell lung cancer (NSCLC) into epidermal growth factor receptor (EGFR) mutation and anaplastic lymphoma kinase (ALK) rearrangement groups and to compare the accuracy with classification based on semantic features on imaging. Methods: Data set of 117 patients was analysed from 2014 to 2018 out of which 33 patients were EGFR positive, 43 patients were ALK positive and 41 patients were negative for either mutation. Convolutional neural network (CNN) architecture efficient net was used to study the accuracy of classification using T1 weighted (T1W) magnetic resonance imaging (MRI) sequence, T2 weighted (T2W) MRI sequence, T1W post contrast (T1post) MRI sequence, fluid attenuated inversion recovery (FLAIR) MRI sequences. The dataset was divided into 80% training and 20% testing. The associations between mutation status and semantic features, specifically sex, smoking history, EGFR mutation and ALK rearrangement status, extracranial metastasis, performance status and imaging variables of brain metastasis were analysed using descriptive analysis [chi-square test (χ2)], univariate and multivariate logistic regression analysis assuming 95% confidence interval (CI). Results: In this study of 117 patients, the analysis by semantic method showed 79.2% of the patients belonged to ALK positive were non-smokers as compared to double negative groups (P = 0.03). There was a 10-fold increase in ALK positivity as compared to EGFR positivity in ring enhancing lesions patients (P = 0.015) and there was also a 6.4-fold increase in ALK positivity as compared to double negative groups in meningeal involvement patients (P = 0.004). Using CNN Efficient Net DL model, the study achieved 76% accuracy in classifying ALK rearrangement and EGFR mutations without manual segmentation of metastatic lesions. Analysis of the manually segmented dataset resulted in improved accuracy of 89% through this model. Conclusions: Both semantic features and DL model showed comparable accuracy in classifying EGFR mutation and ALK rearrangement. Both methods can be clinically used to predict mutation status while biopsy or genetic testing is undertaken

CT-guided radiofrequency ablation in osteoid osteoma: Result from a tertiary cancer centre in India

Aims: The aim of this study is to evaluate the clinical efficacy of computed tomography (CT)-guided radiofrequency (RF) ablation as a minimally invasive therapy for osteoid osteoma. Materials and Methods: This is a retrospective analysis of prospectively maintained data of 43 symptomatic osteoid osteoma patients who were treated by radiofrequency ablation (RFA). Forty out of 43 patients were naive cases and underwent primary treatment for osteoid osteoma with RFA, whereas 3 patients included in the study underwent RFA for local recurrence after having undergone surgical treatment. Diagnosis was based on clinical and characteristic imaging findings, and biopsy was done for cases with atypical presentation. Pre and post procedure Visual Analog Score (VAS) was documented in all cases. Monopolar RFA system was used in all patients, and the electrode was placed within the lesion nidus under CT guidance coaxially through 11G introducer needle. Ablation was performed at 90° C for 5 min. Results: Technical success rate of intranidal placement of electrode was 100%. The primary clinical success in our study was 97.7% (42 of 43), and the secondary clinical success was 100%.Pre and postprocedure VAS score in our study group was 7.8 and 0.4, respectively. Mean follow-up period in our study was 48 months (Range: 4–129 months).One patient had recurrence of pain 4 years after treatment and was treated successfully by a second session. Minor complications were seen in 3 patients with two cases of RF pad burns and one case of skin burn at the treatment site, and these were managed conservatively. No patients developed temporary/permanent neurological deficits, and no procedure-related mortality was seen in our study. Conclusion: CT-guided percutaneous RFA is a simple, safe, minimally invasive, and highly effective treatment option for osteoid osteoma with good long-term pain control and potentially low disease recurrence

Protocol for a phase II randomised controlled trial of TKI alone versus TKI and local consolidative radiation therapy in patients with oncogene driver-mutated oligometastatic non-small cell lung cancer

Introduction Tyrosine kinase inhibitors (TKIs) have significantly improved the progression-free survival (PFS) of metastatic non-small cell lung cancer (NSCLC) with oncogene mutations of epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) compared with systemic therapy alone. However, the majority eventually develop resistance with a median PFS of 8–12 months. The pattern of failure studies showed disease relapse at the original sites of the disease-harbouring resistant tumour cells.Methods and analysis This study is designed as a phase II randomised controlled trial to evaluate the efficacy of local consolidative radiation therapy (LCRT) in addition to TKI in upfront oligometastatic NSCLC. Patients will be screened at presentation for oligometastases (≤5 sites) and will start on TKI after confirmation of EGFR or ALK mutation status. After initial TKI for 2–4 months, eligible patients will be randomised in a 1:1 ratio with stratification of oligometastatic sites (1–3 vs 4–5), performance status of 0–1 versus 2 and brain metastases. The standard arm will continue to receive TKI, and the intervention arm will receive TKI plus LCRT. Stereotactic body radiation therapy will be delivered to all the oligometastatic sites.The primary end point is PFS, and secondary end points are overall survival, local control of oligometastatic sites, toxicity and patient-reported outcomes. The sample size calculation took a median PFS of 10 months in the standard arm. To detect an absolute improvement of 7 months in the interventional arm, with a one-sided alpha of 5% and 80% power, a total of 106 patients will be accrued over a period of 48 months.Ethics and dissemination The study is approved by the Institutional Ethics Committee II of Tata Memorial Centre, Mumbai, and registered with Clinical Trials Registry—India, CTRI/2019/11/021872, dated 5 November 2019. All eligible participants will be provided with a participant information sheet and will be required to provide written informed consent for participation in the study. The study results will be presented at a national/international conference and will be published in a peer-reviewed journal

Standard maintenance therapy versus local consolidative radiation therapy and standard maintenance therapy in 1–5 sites of oligometastatic non-small cell lung cancer: a study protocol of phase III randomised controlled trial

Introduction Two-phase II randomised studies have shown a significant benefit of local consolidation therapy in oligometastatic non-small cell lung cancer (NSCLC). This phase III randomised controlled trial (RCT) will evaluate the efficacy of local consolidation radiation therapy (RT) in oligometastases (OM) NSCLC after completion of initial systemic therapy.Methods and analysis This is a single-centre phase III RCT of OM NSCLC patients. One hundred and ninety patients will undergo 1:1 randomisation to either standard maintenance therapy (control arm) or local consolidation RT and standard maintenance therapy (experimental arm). Patients will be stratified into the number of OM sites (1–2 vs 3–5), nodal metastases (N0–N1 vs N2–N3) and presence or absence of brain metastases. Stereotactic body radiation therapy to all the oligometastatic sites and definitive RT to primary disease will be given in the experimental arm. The primary endpoint is overall survival and secondary endpoints include progression-free survival, local control of OM sites, new distant metastases free survival, objective response rate, toxicity and quality of life. Translation endpoint include circulating tumour cells and radiomics using texture analysis.Ethics and dissemination All patients will be provided with a written informed consent form which needs to be signed before randomisation. The study is approved by the institutional ethics committee-II (project number 3445) and registered with Clinical Trials Registry—India, dated 21 April 2020.Trial registration number CTRI/2020/04/024761; Pre-Results