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.

Computerized tomography-based first order tumor texture features in non-small cell lung carcinoma treated with concurrent chemoradiation: A simplistic and potential surrogate imaging marker for survival.

Objectives: This study examines the role of tumor texture on computed tomography (CT) images as a complement to clinical prognostic factors in predicting survival in patients of non-small cell lung carcinoma (NSCLC) treated with radical chemo-radiation (CRT). Methods: A total of 93 patients with confirmed NSCLC treated with CRT accrued in a study approved by the institutional ethics committee were analyzed for CT-based radiomic features. Pretreatment CT images were used to contour the primary tumor and texture features were computed by the image filtration method to differentially highlight fine to coarse textures. Texture parameters included mean intensity, entropy, kurtosis, standard deviation, and mean positive pixel and skewness. Optimal threshold cut-off values of the above tumor texture features were analyzed. These features were explored as imaging biomarkers to predict survival using Kaplan-Meier and Cox proportional hazard model. Results: Median follow-up of the entire cohort was 23.5 months [Interquartile range, IQR: 14-37] while for alive patients, median follow-up was 31 months (IQR: 23-49), 47 (50.6%) patients had died at the last follow-up. Univariate analysis revealed certain features like age, gender, response to therapy, and texture features like mean and kurtosis in CT images to be significant predictors of survival. In multivariate analysis, age (P = 0.006), gender (P = 0.004), treatment response (P< 0.0001), and two CT texture parameters: mean (P = 0.027) and kurtosis (P= 0.002) were independent prognostic factors of survival. Interpretation and Conclusion: CT-derived tumor heterogeneity (mean and kurtosis) complements clinical factors for predicting survival in NSCLC patients treated with CRT. Tumor radiomics warrants further validation as potential prognostic biomarkers for these patients.

Determining the impact of COVID-19 pandemic on adjuvant therapy for oral cancer - A matched-pair analysis.

Background: The ongoing coronavirus disease 2019 (COVID-19) pandemic has hard-pressed the health care systems beyond their capabilities, causing a lack of appropriate cancer treatment delivery. The aim of this study was to assess the impact of pandemic-related restrictions on adjuvant therapy delivery for oral cancer patients during these demanding times. Materials and Methods: Oral cancer patients who were operated on between February and July 2020 and scheduled to receive prescribed adjuvant therapy during the COVID-19-related restrictions (Group I) were included in the study. The data were matched for the length of hospital stay and type of prescribed adjuvant therapy, with a set of patients who were similarly managed 6 months preceding the restrictions (Group II). Demographic and treatment-specific details, including inconveniences faced in procuring prescribed treatment, were obtained. Factors associated with delay in receiving adjuvant therapy were compared using regression models. Results: A total of 116 oral cancer patients were considered for analysis, comprising 69% (n = 80) adjuvant radiotherapy alone and 31% (n = 36) concurrent chemoradiotherapy. The mean hospital stay was 13 days. In Group I, 29.3% (n = 17) of patients were not able to receive any form of their prescribed adjuvant therapy at all, which was 2.43 times higher than Group II (P = 0.038). None of the disease-related factors significantly predicted delay in receiving adjuvant therapy. Of the delay, 76.47% (n = 13) was present during the initial part of the restrictions, with the most common reason being unavailability of appointments (47.1%, n = 8), followed by inability to reach treatment centers (23.5%, n = 4) and redeem reimbursements (23.5%, n = 4). The number of patients who were delayed the start of radiotherapy beyond 8 weeks after surgery was double in Group I (n = 29) than in Group II (n = 15; P = 0.012). Conclusions: This study highlights a small part of the rippling effect the COVID-19 restrictions have on oral cancer management and pragmatic actions may be needed by policymakers to deal with such challenges.

Definitive radiation therapy with dose escalation is beneficial for patients with squamous cell cancer of the esophagus.

Objective: We report the long term follow-up, toxicity, and outcomes of patients with localized squamous cell carcinoma of the esophagus(ESCC) who underwent definitive chemo-radiotherapy(dCRT) at our institute. Materials and Methods: Patients diagnosed with carcinoma post cricoid, upper cervical and thoracic oesophagus and treated with dCRT between January 2000 and March 2012 were retrospectively analyzed. Radiotherapy was delivered in two phases to a maximum dose of 63Gy in daily fractions of 1.8Gy using conventional or conformal techniques. OS and PFS were defined from date of registration and were calculated by Kaplan-Meier method with comparisons between different subgroups performed using log-rank test. All data were analysed using SPSS Version 22. Results: Three hundred and fourteen patients with ESCC treated with dCRT were included in this analysis. Median age at presentation was 56 years and median KPS at presentation was 70. Two-third of patients were treated with conformal technique. Median dose of radiation delivered was 60Gy(range 30.6Gy-70Gy). Neoadjuvant chemotherapy was administered in about 35% patients and 57% patients received concurrent chemotherapy. About 10% patients required hospitalization during treatment due to complications and 7 patients did not complete treatment. Grade 1/2 dermatitis and mucositis was seen in 77% and 71% patients respectively. Complete response at first follow up was observed in 56% of patients. At a median follow up of 56 months, 77 patients were alive with controlled disease. The 1- and 3-yr OS were 80% and 62% respectively. Median PFS was 28 months; 1- and 3-yr PFS were 66% and 46% respectively. A higher RT dose was found to be a significant predictor for OS and PFS on both uni- and multivariate analysis. Conclusion: Our study highlights that the delivery of higher RT doses (≥63Gy) is feasible in this patient group and that a higher RT dose was associated with significantly better PFS and OS.

Using Artificial Intelligence for Optimization of the Processes and Resource Utilization in Radiotherapy.

The radiotherapy (RT) process from planning to treatment delivery is a multistep, complex operation involving numerous levels of human-machine interaction and requiring high precision. These steps are labor-intensive and time-consuming and require meticulous coordination between professionals with diverse expertise. We reviewed and summarized the current status and prospects of artificial intelligence and machine learning relevant to the various steps in RT treatment planning and delivery workflow specifically in low- and middle-income countries (LMICs). We also searched the PubMed database using the search terms (Artificial Intelligence OR Machine Learning OR Deep Learning OR Automation OR knowledge-based planning AND Radiotherapy) AND (list of Low- and Middle-Income Countries as defined by the World Bank at the time of writing this review). The search yielded a total of 90 results, of which results with first authors from the LMICs were chosen. The reference lists of retrieved articles were also reviewed to search for more studies. No language restrictions were imposed. A total of 20 research items with unique study objectives conducted with the aim of enhancing RT processes were examined in detail. Artificial intelligence and machine learning can improve the overall efficiency of RT processes by reducing human intervention, aiding decision making, and efficiently executing lengthy, repetitive tasks. This improvement could permit the radiation oncologist to redistribute resources and focus on responsibilities such as patient counseling, education, and research, especially in resource-constrained LMICs.

Neoadjuvant Chemoradiotherapy and Surgery for Esophageal Squamous Cell Carcinoma Versus Definitive Chemoradiotherapy With Salvage Surgery as Needed: The Study Protocol for the Randomized Controlled NEEDS Trial.

Background: The globally dominant treatment with curative intent for locally advanced esophageal squamous cell carcinoma (ESCC) is neoadjuvant chemoradiotherapy (nCRT) with subsequent esophagectomy. This multimodal treatment leads to around 60% overall 5-year survival, yet with impaired post-surgical quality of life. Observational studies indicate that curatively intended chemoradiotherapy, so-called definitive chemoradiotherapy (dCRT) followed by surveillance of the primary tumor site and regional lymph node stations and surgery only when needed to ensure local tumor control, may lead to similar survival as nCRT with surgery, but with considerably less impairment of quality of life. This trial aims to demonstrate that dCRT, with selectively performed salvage esophagectomy only when needed to achieve locoregional tumor control, is non-inferior regarding overall survival, and superior regarding health-related quality of life (HRQOL), compared to nCRT followed by mandatory surgery, in patients with operable, locally advanced ESCC. Methods: This is a pragmatic open-label, randomized controlled phase III, multicenter trial with non-inferiority design with regard to the primary endpoint overall survival and a superiority hypothesis for the experimental intervention dCRT with regard to the main secondary endpoint global HRQOL one year after randomization. The control intervention is nCRT followed by preplanned surgery and the experimental intervention is dCRT followed by surveillance and salvage esophagectomy only when needed to secure local tumor control. A target sample size of 1200 randomized patients is planned in order to reach 462 events (deaths) during follow-up. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT04460352.

Outcomes of COVID-19 and risk factors in patients with cancer.

Patients with cancer are at higher risk for adverse coronavirus disease 2019 (COVID-19) outcomes. Here, we studied 1,253 patients with cancer, who were diagnosed with severe acute respiratory syndrome coronavirus 2 at a tertiary referral cancer center in India. Most patients had mild disease; in our settings, recent cancer therapies did not impact COVID-19 outcomes. Advancing age, smoking history, concurrent comorbidities and palliative intent of treatment were independently associated with severe COVID-19 or death. Thus, our study provides useful insights into cancer management during the COVID-19 pandemic.

Tackling brain metastases from lung cancer during the COVID-19 pandemic.

Given the enormous strain the COVID-19 pandemic has put on healthcare worldwide, appropriate allocation of resources according to priority is of immense importance. As brain metastases are a common presentation in lung cancer, during the pandemic, it potentially can pose a major management challenge to clinicians. In this article, we outline a pragmatic approach that oncologists should consider while managing these patients. The overarching principle is to deliver best, evidence-based treatment without compromising patient care while ensuring the safety of healthcare workers.

Incremental value of endoscopic brush cytology in response assessment after chemo-irradiation for Esophageal cancer.

BACKGROUND: Response assessment after chemo-radiotherapy (CTRT) in locally advanced esophageal cancer is usually performed using a PET-CT scan, an upper GI endoscopy (UGIE) and histological correlation with biopsy or cytology. We aim to study the incremental value of brush cytology in addition to PET-CT for response assessment. MATERIALS AND METHODS: In this retrospective analysis, 40 patients with Stage II- IV carcinoma esophagus treated with radical intent between June 2015 and August 2019 were included. Patients were treated with either upfront concurrent CTRT or neo-adjuvant chemotherapy followed by CTRT. All patients underwent PET-CT and UGIE for initial staging and response assessment on follow-up. Patients with esophageal stricture (disease related or treatment induced) had brush cytology done during UGIE. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of brush cytology were calculated considering serial clinical follow-up as gold standard. RESULTS: Twenty-three male (57.5%) and 17 (42.5%) female patients with median age of 57 years (range: 27 - 79 years) were analyzed. Concurrent CTRT was delivered in 52.5%; 75% patients were treated with intensity-modulated radiotherapy (IMRT); median RT dose was 63 Gy (range- 41.4 to 64 Gy). At a median follow-up of 16 months (range 6- 54 months), 20 patients (55.5%) were clinically controlled, 9 (25%) had local recurrence, 5 (13.8%) had loco-regional recurrence and 2 had distant metastasis. Considering clinical follow-up as the gold standard, sensitivity, PPV and NPV of PET-CT combined with brush cytology improved compared to PET-CT alone and was found to be 75%, 90%, 85.7% and 81.8% respectively. CONCLUSION: We found that brush cytology on endoscopy is a simple tool with high specificity which adds value to the findings of response assessment PET-CT scan and thereby can increase the confidence of the treating oncologist in making clinical decisions.

Surgical Management of Parapharyngeal Tumors: Our Experience.

Context Tumors of parapharyngeal space (PPS) are rare and histologically diverse. The management of these tumors requires diligent assessment and planning with due consideration of various anatomical and pathological aspects of the lesion. Aims This retrospective study aims to present our experiences in the clinical and pathological aspects of PPS tumors with a critical evaluation of management. Settings and Design Retrospective analytical study. Methods and Material The electronic medical records of 60 cases of PPS tumors, managed surgically from 2007 to 2017, were reviewed and analyzed using SPSS 22 software. The mean follow-up duration was 44 months. Results The mean age was 45 years with a male-to-female ratio of 1.7 (38:22). The majority of the tumors were benign (71.7%) and the most common presentation being upper neck mass or oropharyngeal mass. Histologically, neurogenic tumors were most common (43.3%) PPS tumors, followed by tumors of salivary gland origin. Magnetic resonance imaging was used as a diagnostic modality in 70% of cases, and computed tomography scan and positron emission tomography/CT were used in 26.7 and 3.3% of cases, respectively. In our study, the diagnostic accuracy of fine-needle aspiration cytology was 71% for benign and 47% for malignant lesions. The most common approach for surgery used was transcervical (72%). Conclusion The study reveals that cranial nerve palsy is the most common complication associated with PPS tumors. Completely resected, malignant tumors originating within PPS have a good prognosis, as compared with tumors extending or metastasized to PPS.

Is Maximum Intensity Projection an Optimal Approach for Internal Target Volume Delineation in Lung Cancer?

PURPOSE: Respiratory-induced tumor motion is a major challenge in lung cancer (LC) radiotherapy. Four-dimensional computed tomography (4D-CT) using a maximum intensity projection (MIP) dataset is a commonly used and time-efficient method to generate internal target volume (ITV). This study compared ITV delineation using MIP or tumor delineation on all phases of the respiratory cycle. MATERIALS AND METHODS: Thirty consecutive patients of LC who underwent 4D-CT from January 2014 to March 2017 were included. ITV delineation was done using MIP (ITVMIP) and all ten phases of the respiratory cycle (ITV10Phases). Both volumes were analyzed using matching index (MI). It is the ratio of the intersection of two volumes to the union of two volumes. A paired sample t-test was used for statistical analysis, and P < 0.05 was considered statistically significant. RESULTS: The mean ± standard deviation volume of ITV10Phases was significantly larger compared to ITVMIP (134 cc ± 39.1 vs. 113 cc ± 124.2, P = 0.000). The mean MI was 0.75 (range 0.57-0.88). The mean volume of ITV10Phases not covered by ITVMIP was 26.33 cc (23.5%) and vice versa was 5.51 cc (6.1%). The mean MI was 0.73 for tumors close to the mediastinum, chest wall, and diaphragm. MI was not different between tumors ≤5 cm and >5 cm. The average time required for delineation was 9 and 96 min, respectively. The center of mass of two ITVs differed by 0.01 cm. CONCLUSION: ITV using MIP is significantly smaller and may miss a tumor compared to ITV delineation in 10 phases of 4D-CT. However, the time required is significantly less with MIP. Caution should be exercised in tumors proximity to the mediastinum, chest wall, and diaphragm.

Outcomes of Palliative Radiotherapy in Metastatic Epidural Spinal Cord Compression in Lung Cancer-A Prospective Observational Study from Tata Memorial Hospital.

Background Metastatic epidural spinal cord compression (MESCC) secondary to lung cancer (LC) is a debilitating complication associated with poor prognosis and is commonly treated with radiotherapy (RT). There is no consensus for RT dose fractionation in spinal cord compression. Methods Forty consecutive patients of LC with radiological evidence of MESCC treated with palliative RT were evaluated for functional outcomes (pain, ambulation, and sphincter function) at 2-, 4-, and 24-week post RT completion. Pain assessment was done using visual analogue scale (VAS) and response was categorized according to international consensus criteria, ambulation status (AS) using Tomita's scale, and sphincter function by the presence or absence of a catheter. Overall survival (OS) was assessed using Kaplan-Meier method and compared using log-rank test. Impact of potential prognostic factors on survival was also analyzed and p -value ≤0.05 was considered significant. Results Sixteen, 22, and two patients received 8 Gy single fraction (SF), 20 Gy in five fractions (20/5), and 30 Gy in 10 fractions (30/10), respectively. At 2 weeks, overall response (OR) rates of pain, ambulation, and sphincter control were 73, 81, and 81%, respectively. At 4 and 24 weeks, 93.7, 84.3, 87.5% and 88, 94, 76.5% had OR, respectively. Median OS was 4 months. Six- and 12-months OS was 50 and 37.5%. Nonsignificant difference in OS was seen between SF and 20/5 fractions (median 2.2 vs. 7.1 months, p = 0.39). Age ≤50 years was the only significant factor ( p <0.05) in univariate analysis for OS. Conclusion Radiotherapy provided equivalent pain control, ambulation, and sphincter function compared with reported literature in MESCC. Nonsignificant difference in OS exists between SF and multifraction RT regimens.

Radiotherapy of brain metastasis from lung cancer in limited resource settings.

Radiotherapy is one of the most commonly used treatment modality for brain metastases from lung cancer. Its use has evolved from conventional whole brain radiation therapy (WBRT) to more sophisticated stereotactic radiosurgery (SRS) and hippocampal sparing radiotherapy. Indications of cranial radiotherapy are also evolving with the advent of targeted therapies directed against molecular markers like epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK). Prognostic criteria such as recursive partitioning analyses and graded prognostic score helps in prognostication of brain metastases patients. Majority of the prospective and randomized studies of brain metastases from lung cancer have come from the developed countries with adequate resources. Efforts have been made to replicate or validate the data in developing countries. In this overview, we intend to discuss the role of radiotherapy for brain metastases in limited resource settings of developing countries. The aim should be to generate a good quality data which is applicable for routine clinical practice in a resource friendly manner. SRS is indicated in guidelines for limited brain metastases, however, it requires a more sophisticated treatment delivery and quality assurance machines which are not available at many centres in majority of the developing countries. Similarly, clinical research should be undertaken considering the demographic, clinical and genetic differences among different populations. Currently, tyrosine kinase inhibitors have dramatically changed the outcomes of metastatic non-small cell lung cancer including brain metastases. The role of WBRT is being questioned in driver mutated patients in developed countries. However, the applicability of this approach should be examined in resource constrained settings as availability of these drugs is limited, its higher cost and frequent use of surveillance brain imaging are the practical challenges.

Optimal Standardized Uptake Value Threshold for Auto contouring of Gross Tumor Volume using Positron Emission Tomography/Computed Tomography in Patients with Operable Nonsmall-Cell Lung Cancer: Comparison with Pathological Tumor Size.

PURPOSE: Incorporating 18F-fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG-PET/CT) for gross tumor volume (GTV) delineation is challenging due to varying tumor edge based on the set threshold of the standardized uptake value (SUV). This study aims to determine an optimal SUV threshold that correlates best with the pathological tumor size. MATERIALS AND METHODS: From January 2013 to July 2014, 25 consecutive patients of operable nonsmall-cell lung cancer (NSCLC) who underwent staging18F-FDG-PET/CT before surgical resection were included in the test cohort and 12 patients in the validation cohort. GTVs were delineated on the staging PET/CT by automatic delineation using various percentage threshold of maximum SUV (SUVmax) and absolute SUV. The maximum pathological tumor diameter was then matched with the maximum auto-delineated tumor diameter with varying SUV thresholds. First-order linear regression and Bland-Altman plots were used to obtain an optimal SUV threshold for each patient. Three radiation oncologists with varying degrees of experiences also delineated GTVs with the visual aid of PET/CT to assess interobserver variation in delineation. RESULTS: In the test set, the mean optimal percentage threshold for GTV was SUVmax of 35.6%±18.6% and absolute SUV of 4.35 ± 1.7. In the validation set, the mean optimal percentage threshold SUV and absolute SUV were 36.9 ± 16.9 and 4.1 ± 1.6, respectively. After a combined analysis of all 37 patients, the mean optimal threshold was 36% ± 17.9% and 4.27 ± 1.7, respectively. Using Bland-Altman plots, auto-contouring with 40% SUVmax and SUV 4 was in greater agreement with the pathological tumor diameter. CONCLUSION: Automatic GTV delineation on PETCT in NSCLC with percentage threshold SUV of 40% and absolute SUV of 4 correlated best with pathological tumor size. Auto-contouring using these thresholds will increase the precision of radiotherapy contouring of GTV and will save time.

Intensity-modulated radiation therapy for nasal cavity and paranasal sinus tumors: Experience from a single institute.

BACKGROUND: To assess the efficacy of intensity-modulated radiation therapy (IMRT) for tumors of the nasal cavity and paranasal sinus (PNS) region. MATERIALS AND METHODS: Two hundred fourteen patients with tumors of the nasal cavity and PNS region treated with curative intent IMRT between 2007 and 2019 were included in this retrospective analysis. RESULTS: Fifty-one (24.1%) received definitive RT/CTRT and 163 (75.9%) received adjuvant RT. Most common histology was squamous cell carcinoma (26.1%) followed by adenoid cystic carcinoma (21.5%). The median follow-up was 43.5 months. The 5-year local control (LC), event-free survival (EFS), and overall survival (OS) for the entire cohort was 66.9%, 59%, and 73.9%, respectively. On univariate analysis treatment with nonsurgical modality, T classification and undifferentiated/poorly differentiated histology were associated with inferior 5-year LC, EFS, and OS. Four patients had late Grade 3/Grade 4 ocular toxicity. CONCLUSIONS: IMRT should be the standard of care for tumors of PNS region across all histologies and treatment setting.

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.

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.

Concurrent chemoradiotherapy for locally advanced unresectable adenoid cystic carcinoma of head and neck: experience from a single institute.

PURPOSE: To analyze the outcome of locally advanced unresectable adenoid cystic carcinoma (ACC) of head and neck treated with radical concurrent chemoradiotherapy (CRT) at a single tertiary care centre. METHODS: Between 2011 and 2018, 23 patients with locally advanced unresectable ACC of head and neck treated with non-surgical radical treatment with concurrent chemoradiotherapy were evaluated for outcome and toxicity. All but one patient received cisplatin-based concurrent chemotherapy and 74% of patients were treated with intensity-modulated radiotherapy. RESULTS: Median follow-up was 53 months (range 3-115 months). Following treatment, 11 patients achieved complete response (47.8%) and of the 12 patients with residual disease, 7 patients additionally had disease stabilization without local progression. Overall 15 patients had disease progression. Median time to progression was 28 months (range 6-67 months). The 3-year and 5-year overall survival, local progression-free survival (LPFS) and distant progression-free survival (DPFS) were 78%, 79.7%, 67.4% and 63%, 50.9%, 48.6%, respectively. Acute grade 3 mucositis was observed in three patients, and one patient additionally developed grade 4 neutropenia with subsequent complete recovery. No grade 3 or higher late toxicity was observed. CONCLUSION: Radical concurrent chemoradiotherapy is a promising treatment option in locally advanced unresectable ACC with acceptable toxicity.

Nodal recurrences after stereotactic body radiotherapy for early stage non-small-cell lung cancer.

Lobectomy is considered the standard of care for early stage non-small-cell lung cancer. However, for those patients who remain unfit to undergo surgery due to advanced age, poor performance status, comorbidities, poor pulmonary reserve or a combination of these are now treated with stereotactic body radiation therapy (SBRT). Due to its noninvasive nature, lower cost, lower toxicity, reduced recovery time and equivalent efficacy, even medically operable patients are attracted to the option of SBRT despite the lack of level I evidence. Thus, studying the incidence and patterns of recurrence after SBRT help in understanding the magnitude of the problem, risk factors associated with the different patterns of recurrence, and aid in devising strategies to prevent them in future. Nodal recurrences are not uncommon after SBRT and can potentially lead to further seeding for distant metastases and ultimately poor survival. This review is aimed at reviewing the published data on the incidence of nodal recurrences after SBRT and compare it to surgery, identify potential risk factors for recurrence, salvage treatment options and prevention strategies.