N0 neck trial: Does intensification of follow-up (Ultrasound + Physical Examination) influence outcomes in early-stage oral cancer?

AIM OF THE STUDY: We previously reported a survival benefit of elective neck dissection (END) over therapeutic neck dissection (TND) in patients with clinically node-negative early-stage oral cancer. We now report the results of the second question in the same study addressing the impact of adding neck ultrasound to physical examination during follow-up on outcomes. METHODS: Patients with lateralized T1/T2 oral squamous cell carcinoma (SCC) were randomized to END or TND and to follow-up with physical-examination plus neck ultrasound (PE+US) versus physical-examination (PE). The primary endpoint was overall survival (OS). RESULTS: Between January 2004 and June 2014, 596 patients were enrolled. This is an intention to treat analysis of 592 analysable patients, of whom 295 were allocated to PE+US and 297 to PE with a median follow-up of 77.47 months (interquartile range (IQR) 54.51-126.48). There was no significant difference (unadjusted hazard ratio [HR], 0.92, 95% CI, 0.71-1.20, p = 0.54) in 5-year OS between PE+US (70.8%, 95% CI, 65.51-76.09) and PE (67.3%, 95% CI, 61.81-72.79). Among 131 patients with neck node relapse as the first event, the median time to relapse detection was 4.85 (IQR 2.33-9.60) and 7.62 (IQR 3.22-9.86) months in PE+US and PE arms, respectively. The N stage in the PE+US arm was N1 33.8%, N2a 7.4%, N2b/c 44.1% and N3 14.7% while in PE was N1 28.6%, N2a 9.5%, N2b/c 39.7%, N3 20.6% and unknown 1.6%. CONCLUSION: Adding neck ultrasound to physical examination during follow-up detects nodal relapses earlier but does not improve overall survival.

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.

Challenges in the Sustainability of Brachytherapy Service in Contemporary Radiotherapy.

Brachytherapy has a long history of delivering a highly conformal radiation dose to the target volume with sparing of adjacent normal tissue and has an irreplaceable role in certain cancers, such as cervical and prostate cancers. There have been futile attempts to replace brachytherapy with other radiation techniques. Despite that there are multifaceted challenges in preserving this dying art, from establishment, to a trained workforce, to maintenance of the equipment and source replacement costs. Here we focus on the challenges to access brachytherapy, the availability and distribution of care across the globe and appropriate training leading to proper implementation of the procedure. Brachytherapy holds a significant place in the treatment armamentarium of most common cancers, such as cervical, prostate, head and neck and skin cancers. However, there is an uneven distribution of brachytherapy facilities, not only across the globe, but also at a national level, with a larger proportion of facilities concentrated in certain regions, more so in low and low-middle income countries. The regions with the highest incidence of cervical cancer have the least access to brachytherapy facilities. Attempts to bridge the gap are essential and should be focused on uniform distribution and access to care, improving training of the workforce through specialised training programmes, reducing the cost of care, planning to reduce the recurring cost, generating evidence and research guidelines, renewing interest in brachytherapy through rebranding, use of social media and building an attainable long-term roadmap.

Quality and Safety With Technological Advancements in Radiotherapy: An Overview and Journey Narrative From a Low- and Middle-Income Country Institution.

PURPOSE: To present an overview of quality and safety in radiotherapy from the context of low- and middle-income countries on the basis of a recently conducted annual meeting of our institution and our experience of implementing an error management system at our center. METHODS: The minutes of recently concluded annual Evidence-Based Medicine (EBM-2021) meeting on the basis of technology in radiation oncology were reviewed. The session on quality and safety, which had international experts as speakers, was reviewed. Along with this, we reviewed the literature for preventive and reactive measures proposed to manage errors including error reporting and learning systems (ILSs). Concise summary for the same was prepared for this article. RESULTS: We also reviewed the journey of development of our institutional ILS and present here a summary of achievements, challenges, and future vision. CONCLUSION: Preventive and reactive measures must be followed to achieve high-quality and safe radiotherapy. Despite resource constraints, a successful ILS program can be developed in a low- and middle-income country center by first understanding the patterns of error and developing one that suits the working ecosystem.

Oral metronomic chemotherapy after definitive chemoradiation in esophageal squamous cell carcinoma: a randomized clinical trial.

BACKGROUND: Improving outcomes in locally advanced esophageal/GEJ squamous cell cancer (SCC) is an unmet need. We investigated the addition of oral metronomic chemotherapy (OMC) following definitive chemoradiotherapy (CRT). MATERIALS AND METHODS: This was a randomized open-label integrated phase II/III study in patients with SCC of esophagus/GEJ following definitive CRT who had no radiologic evidence of progression, and no endoscopically detected disease. Randomization was 1:1 to OMC (celecoxib 200 mg twice daily and methotrexate 15 mg/m2 weekly) for 12 months or observation. The primary endpoint for the phase II portion was progression-free survival (PFS); secondary endpoints were overall survival (OS) and toxicity. P ≤ 0.2 for PFS was required to proceed to phase III. RESULTS: Between Jan 2016 and Dec 2019, we enrolled 151 patients for the phase II portion, 75 to OMC and 76 to observation. The tumor originated in the upper thoracic esophagus in 79% patients. Concurrent CRT consisted of median 63 Gy in a median of 35 fractions; concurrent chemotherapy was weekly paclitaxel + carboplatin in 91%. OMC was started at a median of 2.6 months (IQR 2.3-2.8) from CRT completion. Grade 3 or higher toxicities occurred in 18 patients (24%) in the OMC arm and 9 (12%) in the observation arm; P = 0.071. Median PFS was 25 months (95% CI, 17-58) in the OMC arm and was not attained [NA] (95% CI, 25-NA) in the observation arm; HR, 1.51, 95% CI, 1-2; P = 0.073. Median OS was 36 months (95% CI, 23-NA) in the OMC arm, and not attained (95% CI, NA-NA) in the observation arm; HR, 1.77; 95% CI, 1-2.9; P = 0.023. CONCLUSION: Oral metronomic methotrexate and celecoxib in patients who have not progressed radiologically and have no endoscopic evidence of disease following radical CRT for locally advanced esophageal/GEJ SCC does not improve outcomes and may lower survival. [Funded by the TMC-Research Administration Council (TRAC); CHROME study (CHemoRadiotherapy followed by Oral Metronomic therapy in Esophageal cancer); ctri.nic.in number: CTRI/2015/09/006204]. TRIAL REGISTRATION NUMBER: CTRI/2015/09/006204.

Concurrent Cetuximab-based bioradiotherapy versus Cisplatin-based Chemoradiotherapy in the Definitive Management of Favourable Biology Human Papillomavirus-associated Oropharyngeal Squamous Cell Carcinoma: Systematic Review and Meta-analysis.

Replacing cisplatin with cetuximab concurrently during radiotherapy has been one of the strategies of treatment de-escalation in human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC). However, until recently, there were limited data on the efficacy and safety of such an approach. A systematic search of the literature was carried out to identify prospective randomised controlled trials comparing definitive cisplatin-based chemoradiotherapy (CT-RT) versus cetuximab-based bioradiotherapy (BRT) in HPV-positive OPSCC. Overall survival and locoregional control were primary outcomes of interest; rates of acute and late toxicities (≥grade 3) were secondary end points. Outcome data were aggregated using a random-effects model as per Cochrane methodology including risk of bias assessment and expressed as hazard ratio or risk ratio as appropriate with respective 95% confidence intervals. Data from five randomised controlled trials involving 1560 patients with HPV-positive OPSCC were aggregated in the meta-analysis. Cetuximab-based BRT was associated with a significantly increased risk of death (hazard ratio = 2.83, 95% confidence interval 1.22-6.57; P = 0.02) and locoregional relapse (hazard ratio = 2.78, 95% confidence interval 1.77-4.39; P < 0.0001) compared with cisplatin-based CT-RT. Cisplatin was associated with higher rates of acute ≥grade 3 toxicity in terms of acute kidney injury, dry mouth, febrile neutropenia, hearing impairment, nausea and vomiting, whereas dermatitis and acneiform rash were more common with cetuximab. There were no significant differences in overall rates of late ≥grade 3 toxicity (risk ratio = 0.63, 95% confidence interval = 0.36-1.10; P = 0.10). In conclusion, there is moderate-certainty evidence that cetuximab-based BRT leads to inferior efficacy outcomes compared with cisplatin-based CT-RT in the definitive curative-intent management of HPV-associated OPSCC.

Post-cricoid and Upper Oesophagus Cancers Treated with Organ Preservation Using Intensity-modulated Image-guided Radiotherapy: a Phase II Prospective Study of Outcomes, Toxicity and Quality of Life.

AIMS: To prospectively examine the outcomes, toxicity and quality of life (QoL) of patients with post-cricoid and upper oesophagus (PCUE) cancers treated with an organ-preservation approach of (chemo)-radiotherapy using intensity-modulated image-guided radiotherapy (IM-IGRT). MATERIALS AND METHODS: This phase II prospective study was conducted at a tertiary cancer centre from February 2017 to January 2020. Forty patients with squamous cell carcinoma of PCUE of stage T1-3, N0-2, M0 were accrued. Gross exolaryngeal extension/dysfunctional larynx were major exclusion criteria. Patients received 63-66 Gy in once-daily fractions using volumetric modulated arc therapy with daily IGRT. Outcome measures included disease-related outcomes, patterns of failure, Radiation Therapy Oncology Group toxicities, feeding tube dependency and QoL. RESULTS: The median follow-up was 22 months. Twenty-six (87.5%) patients had locoregionally advanced disease and 34 (85%) patients received (chemo)-radiotherapy. A complete response was observed in 26 (65%) patients. The 2-year locoregional control, event-free survival and cause-specific survival were 59.6%, 40.2% and 44.8%, respectively. The volume of primary tumour (GTVPvol) exceeding 28 cm3 had inferior overall survival (P = 0.005) on univariate analysis. Multivariable analysis showed GTVPvol and positron emission tomography-computed tomography maximum standardised uptake value to be independently predictive for event-free and overall survival. A feeding tube requirement at presentation was seen in 11 (27.5%) patients, whereas long-term feeding tube dependency at 6 months was seen in 10 (37%) patients. For QoL, a statistical improvement in pain, appetite loss and swallowing was observed over time. CONCLUSION: Although the outcomes of PCUE cancers remain dismal, the use of state of the art diagnostic modalities, careful case selection and modern radiotherapy techniques improved outcomes as compared with before in this exclusive analysis of PCUE cancers.

Salvage radiotherapy for postoperative locoregional failure in esophageal cancer: a systematic review and meta-analysis.

Locoregional recurrences following surgery for esophageal cancers represent a significant clinical problem with no standard recommendations for management. We conducted this systematic review and meta-analysis with the objective of studying safety and efficacy of salvage radiotherapy in this setting. All prospective and retrospective cohort studies, which studied patients who developed locoregional recurrence following initial radical surgery for esophageal cancer and subsequently received salvage radiation therapy (RT)/chemoradiation with all relevant information regarding survival outcome and toxicity available, were included. The quality of eligible individual studies was assessed using the Newcastle-Ottawa Scale score for risk of bias. R package MetaSurv was used to obtain a summary survival curve from survival probabilities and numbers of at-risk patients collected at various time points and to test the overall heterogeneity using the I2 statistic. Thirty studies (27 retrospective, 3 prospective) published from 1995 to 2020 with 1553 patients were included. The median interval between surgery and disease recurrence was 12.5 months. The median radiation dose used was 60 Gy and 57% received concurrent chemotherapy. The overall incidence of acute grade 3/4 mucositis and dermatitis were 8 and 4%, respectively; grade 3/4 acute pneumonitis was reported in 5%. The overall median follow-up of all studies included was 27 months. The 1-, 2- and 3-year overall survival (OS) probabilities were 67.9, 35.9 and 30.6%, respectively. Factors which predicted better survival on multivariate analysis were good PS, lower group stage, node negativity at index surgery, longer disease-free interval, nodal recurrence (as compared to anastomotic site recurrence), smaller disease volume, single site of recurrence, RT dose >50 Gy, conformal RT, use of concomitant chemotherapy and good radiological response after radiotherapy. Salvage radiotherapy with or without concomitant chemotherapy for locoregional recurrences after surgery for esophageal cancer is safe and effective. Modern radiotherapy techniques may improve outcomes and reduce treatment-related morbidity.

South Asian Declaration-Consensus Guidelines for COVID-19 Vaccination in Cancer Patients.

We provide the South Asian Declaration, containing the consensus guidelines for coronavirus disease 2019 (COVID-19) vaccination in cancer patients.

Primary mediastinal germ cell tumours with high prevalence of somatic malignancy: An experience from a single tertiary care oncology centre.

BACKGROUND: Primary mediastinal germ tumours (PMGCT) constitute, a mere 3-4% of all germ cell tumours (GCT). Although they account for approximately 16% of mediastinal tumours in adults and 19-25% in children as per western literature, there is hardly any large series on PMGCT reported from the Indian subcontinent. DESIGN: We have retrospectively analysed clinicopathological features of 98 cases of PMGCT diagnosed over 10 years (2010-2019) from a tertiary-care oncology centre. RESULTS: The study group (n = 98) comprised predominantly of males (n = 92) (M:F ratio-15:1), with an age range between 3 months to 57 years (median: 25 years). The tumours were predominantly located in the anterior mediastinum (n = 96). Broadly, Non-seminomatous germ cell tumours (NSGCT) were more common (n = 73, 74%) compared to pure seminoma (n = 25, 26%). Mixed NSGCT was the most common histological subtype (n = 30) followed by pure mature teratoma (n = 18), pure Yolk sac tumour (n = 13), mixed seminoma and NSGCT (n = 5), pure immature teratoma (n = 3) and GCT; NOS (n = 4). Interestingly, all female patients had exclusive teratomas. Nine cases revealed secondary somatic malignancy (5 carcinomas and 4 sarcomas). The majority of patients received neoadjuvant chemotherapy (n = 71). Surgical excision was performed in 60 patients. Follow up was available in 68 patients. NSGCT showed a poor prognosis as compared to seminoma (p value = 0.03) and tumours with somatic malignancies had a more aggressive clinical course. CONCLUSION: PMGCT was seen predominantly in young adult males and somatic malignancies were noted in as high as 9% of cases. Patient with somatic malignancy have aggressive clinical course, hence, extensive sampling and careful histopathological evaluation are recommended for the identification and definitive characterization.

Evolving multidisciplinary treatment of squamous cell carcinoma of the head and neck in India✰.

In this article, we highlight the evolution of a multimodal approach in the overall management of squamous cell carcinoma of the head and neck (SCCHN) in India; present advances in technology (newer surgical techniques), novel medical and radiotherapy (RT) approaches; review their roles for an integrated approach for treating SCCHN and discuss the current role of immunotherapy in SCCHN. For locally advanced (LA) SCCHN, the multidisciplinary approach includes surgery followed by RT, with or without chemotherapy (CT) or concurrent chemoradiotherapy. Improved surgical techniques of reconstruction and voice-preservation are being implemented. Advanced forms of high-precision conformal techniques like intensity-modulated radiotherapy are used to deliver highly conformal doses to tumors, sparing the surrounding normal tissue. Compared with RT alone, novel CT regimens and targeted therapeutic agents have the potential to improve locoregional control and survival and reduce treatment-induced toxicities. Several clinical trials have demonstrated efficacy, safety, and quality of life benefits of adding cetuximab to RT regimens in LASCCHN. Studies have also suggested a cetuximab-related laryngeal preservation benefit. At progression, platinum-based CT combined with cetuximab (a monoclonal anti-epidermal growth factor receptor antibody) is the only validated option available as the first-line therapy. Thus, an integrated multidisciplinary approach plays a key role in maximizing patient outcomes, reduction in treatment related morbidities that consequently impact quality of life of survivors.

Treatment planning comparison of volumetric modulated arc therapy employing a dual-layer stacked multi-leaf collimator and helical tomotherapy for cervix uteri.

PURPOSE: To ascertain the dosimetric performance of a new delivery system (the Halcyon system, H) equipped with dual-layer stacked multi-leaf collimator (MLC) for risk-adapted targets in cervix uteri cancer patients compared to another ring-based system in clinical operation (Helical Tomotherapy, HT). METHODS: Twenty patients were retrospectively included in a treatment planning study (10 with positive lymph nodes and 10 without). The dose prescription (45Gy to the primary tumour volume and a simultaneously integrated boost up to 55Gy for the positive patients) and the clinical planning objectives were defined consistently as recommended by an ongoing multicentric clinical trial. Halcyon plans were optimised for the volumetric modulated arc therapy. The plan comparison was performed employing the quantitative analysis of the dose-volume histograms. RESULTS: The coverage of the primary and nodal target volumes was comparable for both techniques and both subsets of patients. The primary planning target volume (PTV) receiving at least 95% of the prescription isodose ranged from 97.2 ± 1.1% (node-negative) to 99.1 ± 1.2% (node-positive) for H and from 96.5 ± 1.9% (node-negative) to 98.3 ± 0.9% (node-positive) for HT. The uncertainty is expressed at one standard deviation from the cohort of patient per each group. For the nodal clinical target volumes, the dose received by 98% of the planning target volume ranged 55.5 ± 0.1 to 56.0 ± 0.8Gy for H and HT, respectively. The only significant and potentially relevant differences were observed for the bowels. In this case, V40Gy resulted 226.3 ± 35.9 and 186.9 ± 115.9 cm3 for the node-positive and node-negative patients respectively for Halcyon. The corresponding findings for HT were: 258.9 ± 60.5 and 224.9 ± 102.2 cm3. On the contrary, V15Gy resulted 1279.7 ± 296.5 and 1557.2 ± 359.9 cm3 for HT and H respectively for node-positive and 1010.8 ± 320.9 versus 1203.8 ± 332.8 cm3 for node-negative. CONCLUSION: This retrospective treatment planning study, based on the dose constraints derived from the Embrace II study protocol, suggested the essential equivalence between Halcyon based and Helical Tomotherapy based plans for the intensity-modulated rotational treatment of cervix uteri cancer. Different levels of sparing were observed for the bowels with H better protecting in the high-dose region and HT in the mid-low dose regions. The clinical impact of these differences should be further addressed.

Taxane-based Induction Chemotherapy Plus Concurrent Chemoradiotherapy in Nasopharyngeal Carcinoma: Prospective Results from a Non-endemic Cohort.

AIMS: To report the outcomes of induction chemotherapy (ICT) followed by chemoradiotherapy (CTRT) for a large cohort of locoregionally advanced nasopharyngeal cancer (LA-NPC) from a non-endemic region. MATERIALS AND METHODS: Between January 2008 and July 2015, 201 patients with histologically proven, non-metastatic NPC were treated with ICT followed by CTRT at our institute. All the patients received two to three cycles of a taxane-based ICT regimen. Radiotherapy was delivered using an intensity-modulated radiotherapy (IMRT) technique in all patients. RESULTS: After a median follow-up of 37 months (range: 7-110 months), the 3-year disease-free survival (DFS), locoregional relapse-free survival (LRFS), distant metastasis-free survival (DMFS) and overall survival of the entire cohort was 72, 85, 83 and 87.4%, respectively. On multivariate analysis, histology was an independent predictor of DFS, LRFS and overall survival, with keratinising squamous cell carcinoma histologies predicting a worse outcome. The nodal stage was an independent predictor of DFS, DMFS and overall survival. Age, gender, ethnicity, tumour stage and response to ICT did not significantly affect any of the outcomes. Grade 2 or worse subcutaneous fibrosis was seen in 19% of patients at last follow-up and grade 2 or worse xerostomia was seen in 24% of patients. Thirty-nine per cent of patients developed clinical hypothyroidism at last follow-up. CONCLUSION: ICT followed by concurrent CTRT in the IMRT era provides excellent locoregional control, distant control and overall survival rates in patients with LA-NPC. However, distant failure continues to be a problem and may require further systemic intensification.

Oral Cavity Cancer in the Indian Subcontinent - Challenges and Opportunities.

Oral cavity cancer (OCC) poses a global challenge that plagues both the Orient and the Occident, accounting for an estimated 350 000 new cases and 177 000 deaths in 2018. OCC is a major public health problem in the Indian subcontinent, where it ranks among the top three cancer types in both incidence and mortality. Major risk factors are the use of tobacco, betel quid and alcohol consumption. OCC is a heterogeneous group of multiple histologies that affects multiple subsites. The oral cavity includes the lips, buccal mucosa, teeth, gingiva, anterior two-thirds of the tongue, floor of the mouth and hard palate. OCC is defined as cancer of lips, mouth and tongue as defined by the International Classification of Diseases coding scheme. The epidemiology, aetio-pathogenesis and treatment philosophy are similar within this group. Although salivary gland malignancies, sarcomas, mucosal melanomas and lymphomas can also arise within the oral cavity, this review will focus on squamous cell cancer, which is the predominant histology in OCC. We review and contrast data from developing and developed countries. We also highlight the unique regional challenges that countries in the East face; citing India as an example, we elaborate on the opportunities and scope for improvement in the management of OCC.

An Audit for Radiotherapy Planning and Treatment Errors From a Low-Middle-Income Country Centre.

AIMS: To report the findings of an audit for radiotherapy errors from a low-middle-income country (LMICs) centre. This would serve as baseline data for radiotherapy error rates, their severity and causes, in such centres where modern error reporting and learning processes still do not exist. MATERIALS AND METHODS: A planned cross-sectional weekly audit of electronic radiotherapy charts at the radiotherapy planning and delivery step for all patients treated with curative intent was conducted. Detailed analysis was carried out to determine the step of origin of error, time and contributing factors. They were graded as per indigenous institutional (TMC) radiotherapy error grading (TREG) system and the contributing factors identified were prioritised using the product of frequency, severity and ease of detection. RESULTS: In total, 1005 consecutive radically treated patients' charts were audited, 67 radiotherapy errors affecting 60 patients, including 42 incidents and 25 near-misses were identified. Transcriptional errors (29%) were the most common type. Most errors occurred at the time of treatment planning (59.7%), with "plan information transfer to the radiation oncology information system" being the most frequently affected sub-step of the radiotherapy process (47.8%). More errors were noted at cobalt units (52/67; 77.6%) than at linear accelerators. Trend analysis showed an increased number of radiotherapy incidents on Fridays and near-misses on Mondays. Trend for increased radiotherapy errors noted in the evening over other shifts. On severity grading, most of the errors (54/60; 90%) were clinically insignificant (grade I/II). Inadequacies and non-adherence towards standard operating procedures, poor documentation and lack of continuing education were the three most prominent causes. CONCLUSION: Preliminary data suggest a vulnerability of LMIC set-up to radiotherapy errors and emphasises the need for the development of longitudinal prospective processes, such as voluntary reporting and a continued education system, to ensure robust and comprehensive safe practises on par with centres in developed countries.

Applying the QUARTZ Trial Results in Clinical Practice: Development of a Prognostic Model Predicting Poor Outcomes for Non-small Cell Lung Cancers with Brain Metastases.

AIMS: The role of whole brain radiotherapy (WBRT) in patients with brain metastases from non-small cell lung cancers (NSCLC) has been questioned. However, no reliable criteria exist to identify patients who do not benefit from WBRT. The objective of the current study was to develop a prognostic model to identify such patients whose survival matches that of the Quality of Life after Treatment for Brain Metastases (QUARTZ) study. MATERIALS AND METHODS: Outcome data of patients with NSCLC with brain metastases undergoing WBRT enrolled in a prospective observational study in a tertiary cancer centre were used to develop a prognostic model. Baseline clinico-radiological factors were used for development of the model. The model was internally validated and calibration accuracy was checked for prediction of 70 day mortality. The generated prognostic model was presented as a nomogram. RESULTS: The median overall survival of 140 patients enrolled in the study was 166 days (95% confidence interval 108-242 days). The prognostic model identified gender, Karnofsky performance status and epidermal growth factor receptor activating mutation status as significant factors influencing overall survival. The model showed a modest discriminative ability with an optimism-corrected C-index of 0.64. However, model calibration error did reveal a moderate degree of calibration error. The high-risk subgroup identified by the model had a median overall survival of 67 days (95% confidence interval 56-101 days), which was similar to that observed in the QUARTZ trial. CONCLUSION: This prognostic model derived from traditional clinico-radiological features had a modest ability to identify patients with poor prognosis who may not benefit from WBRT. However, the high-risk subgroup identified using this prognostic model had a survival similar to that observed for patients in the QUARTZ trial.