ABSTRACT
Lung cancer is the leading cause of cancer mortality worldwide and most patients are unsuitable for 'gold standard' treatment, which is concurrent chemoradiotherapy. CONCORDE is a platform study seeking to establish the toxicity profiles of multiple novel radiosensitisers targeting DNA repair proteins in patients treated with sequential chemoradiotherapy. Time-to-event continual reassessment will facilitate efficient dose-finding.
ABSTRACT
INTRODUCTION: Lung cancer is the most common cause of cancer mortality in the UK, and non-small-cell lung cancer (NSCLC) accounts for approximately 85% of all lung cancers. Most patients present with inoperable disease; therefore, radiotherapy plays a major role in treatment. However, the majority of patients are not suitable for the gold standard treatment (concurrent chemoradiotherapy) due to performance status and comorbidities. Novel strategies integrating radiotherapy advances and radiobiological knowledge need to be evaluated in patients treated with sequential chemoradiotherapy. Four separate dose escalation accelerated radiotherapy schedules have been completed in UK (CHART-ED, IDEAL-CRT, I-START and Isotoxic IMRT). This study will compare these schedules with a UK standard sequential chemoradiotherapy schedule of 55 Gy in 20 fractions over 4 weeks. As it would be impossible to test all schedules in a phase III study, the aim is to use a combined randomised phase II screening/'pick the winner' approach to identify the best schedule to take into a randomised phase III study against conventionally fractionated radiotherapy. METHODS AND ANALYSIS: Suitable patients will have histologically/cytologically confirmed, stage III NSCLC and are able to undergo chemoradiotherapy treatment. The study will recruit 360 patients; 120 on the standard arm and 60 on each experimental arm. Patients will complete 2-4 cycles of platinum-based chemotherapy before being randomised to one of the radiotherapy schedules. The primary endpoint is progression-free survival, with overall survival, time to local-regional failure, toxicity and cost-effectiveness as secondary objectives. ETHICS AND DISSEMINATION: The study has received ethical approval (research ethics committee (REC) reference: 16/WS/0165) from the West of Scotland REC 1. The trial is conducted in accordance with the Declaration of Helsinki and Good Clinical Practice. Trial results will be published in a peer-reviewed journal and presented internationally. TRIAL REGISTRATION NUMBER: ISRCTN47674500.
Subject(s)
Carcinoma, Non-Small-Cell Lung/therapy , Chemoradiotherapy/methods , Dose Fractionation, Radiation , Lung Neoplasms/therapy , Carcinoma, Non-Small-Cell Lung/mortality , Carcinoma, Non-Small-Cell Lung/pathology , Clinical Trials, Phase II as Topic , Dose-Response Relationship, Radiation , Humans , Lung Neoplasms/mortality , Lung Neoplasms/pathology , Multicenter Studies as Topic , Randomized Controlled Trials as Topic , Survival Analysis , Treatment Outcome , United KingdomABSTRACT
In lung cancer, outcome measurement has been mostly limited to survival. Proper assessment of the value of lung cancer treatments, and the performance of institutions delivering care, requires more comprehensive measurement of standardised outcomes.The International Consortium for Health Outcomes Measurement convened an international, multidisciplinary working group of patient representatives, medical oncologists, surgeons, radiation oncologists, pulmonologists, palliative care specialists, registry experts and specialist nurses to review existing data and practices. Using a modified Delphi method, the group developed a consensus recommendation ("the set") on the outcomes most essential to track for patients with lung cancer, along with baseline demographic, clinical and tumour characteristics (case-mix variables) for risk adjustment.The set applies to patients diagnosed with nonsmall cell lung cancer and small cell lung cancer. Our working group recommends the collection of the following outcomes: survival, complications during or within 6â months of treatment and patient-reported domains of health-related quality of life including pain, fatigue, cough and dyspnoea. Case-mix variables were defined to improve interpretation of comparisons.We defined an international consensus recommendation of the most important outcomes for lung cancer patients, along with relevant case-mix variables, and are working to support adoption and reporting of these measures globally.
Subject(s)
Carcinoma, Non-Small-Cell Lung/therapy , Lung Neoplasms/therapy , Medical Oncology/standards , Pulmonary Medicine/standards , Carcinoma, Non-Small-Cell Lung/psychology , Consensus , Cough/diagnosis , Dyspnea/diagnosis , Fatigue/diagnosis , Humans , Interdisciplinary Communication , International Cooperation , Lung Neoplasms/psychology , Medical Oncology/organization & administration , Outcome Assessment, Health Care , Pain Measurement , Patient-Centered Care , Pulmonary Medicine/organization & administration , Quality of Life , Registries , Treatment OutcomeABSTRACT
In countries with the best cancer outcomes, approximately 60% of patients receive radiotherapy as part of their treatment, which is one of the most cost-effective cancer treatments. Notably, around 40% of cancer cures include the use of radiotherapy, either as a single modality or combined with other treatments. Radiotherapy can provide enormous benefit to patients with cancer. In the past decade, significant technical advances, such as image-guided radiotherapy, intensity-modulated radiotherapy, stereotactic radiotherapy, and proton therapy enable higher doses of radiotherapy to be delivered to the tumour with significantly lower doses to normal surrounding tissues. However, apart from the combination of traditional cytotoxic chemotherapy with radiotherapy, little progress has been made in identifying and defining optimal targeted therapy and radiotherapy combinations to improve the efficacy of cancer treatment. The National Cancer Research Institute Clinical and Translational Radiotherapy Research Working Group (CTRad) formed a Joint Working Group with representatives from academia, industry, patient groups and regulatory bodies to address this lack of progress and to publish recommendations for future clinical research. Herein, we highlight the Working Group's consensus recommendations to increase the number of novel drugs being successfully registered in combination with radiotherapy to improve clinical outcomes for patients with cancer.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Neoplasms/radiotherapy , Cell Hypoxia/radiation effects , Clinical Trials as Topic/methods , Combined Modality Therapy , Drug Approval , Humans , Neoplasms/drug therapy , Patient Education as Topic , Patient Participation , Quality Assurance, Health Care , Quality of Health Care , Radiation Dosage , Radiation Tolerance/radiation effects , Treatment OutcomeABSTRACT
The importance of intratumour genetic and functional heterogeneity is increasingly recognised as a driver of cancer progression and survival outcome. Understanding how tumour clonal heterogeneity impacts upon therapeutic outcome, however, is still an area of unmet clinical and scientific need. TRACERx (TRAcking non-small cell lung Cancer Evolution through therapy [Rx]), a prospective study of patients with primary non-small cell lung cancer (NSCLC), aims to define the evolutionary trajectories of lung cancer in both space and time through multiregion and longitudinal tumour sampling and genetic analysis. By following cancers from diagnosis to relapse, tracking the evolutionary trajectories of tumours in relation to therapeutic interventions, and determining the impact of clonal heterogeneity on clinical outcomes, TRACERx may help to identify novel therapeutic targets for NSCLC and may also serve as a model applicable to other cancer types.
