Abstract The place of bevacizumab in the management of advanced non-small cell lung cancer (NSCLC) was reviewed. Particular reference has been made to the recent research on the systemic treatment of ...NSCLC indicating that treatment tailored to specifically identified morphology or genetic profile has recently changed practice. The result of this recent research means that bevacizumab has little, if any, place in the treatment of NSCLC.
Abstract Background Cure of lung cancer is impossible without local tumour control. This can be compromised by accelerated repopulation of tumour cells during radiotherapy and chemotherapy. A ...strategy to minimise accelerated repopulation might improve local control. We investigated whether concurrent chemo-radiotherapy could be given safely over four weeks. Methods We conducted a randomised phase II trial in which patients with inoperable Stage III Non-Small Cell Lung Cancer (NSCLC) received a radical radiation dose over four weeks rather than conventional fractionation. Treatment was given either sequentially or concurrently with three to four cycles of cisplatinum and vinorelbine. 130 patients with inoperable stage III NSCLC and PS 0-1 were randomised to receive cisplatinum and vinorelbine with either sequential or concurrent chemo-radiation using 55 Gy in 20 fractions over four weeks. The primary end-point was treatment related mortality. Secondary end-points were toxicity and survival. Findings Treatment related mortality was: 2.9% (exact 95% confidence interval CI 0.36–10.2%) and 1.7% (exact 95% CI 0.043–9.1%) for the Concurrent and Sequential group respectively; relative risk (RR) 1.25; (95% CI 0.55, 2.84). Toxicity was similar between arms; grade 3 or worse oesophagitis was 8.8% versus 8.5%; RR 1.02 (95% CI 0.58, 1.79). OS HR was 0.92; 95% CI (0.60–1.39; p = 0.682). The 2 year overall survival rates were: 50% versus 46%; RR 1.06 (95% CI 0.77, 1.46) for Concurrent versus Sequential. Interpretation A strategy to minimise the effects of accelerated repopulation using accelerated hypofractionated radiotherapy with chemotherapy is feasible, and reasonably safe for patients with stage III NSCLC. The reported two year survival is promising and suggests that a four week regime of radiotherapy should be compared with conventionally fractionated radiotherapy in an adequately powered randomised controlled phase III trial.
Abstract Lung stereotactic ablative radiotherapy (SABR) is a method of delivering high ‘ablative’ doses of radiotherapy to tumours in the lung. It was developed at the Karolinska Institute in the ...early 1990s using the methods established in cranial radiosurgery with multiple beams prescribed to an isodose and using a custom designed stereotactic body frame for immobilisation. Since then, aligned with the advances in radiotherapy technology and techniques (e.g. four-dimensional computed tomography simulation and image-guided radiotherapy), there has been a rapid increase in the use of lung SABR for both early stage lung cancer and lung metastases. For peripheral primary lung cancers less than 5 cm in diameter, high rates of local control and low levels of acute and late toxicity are consistently reported in the published literature. Compared with historical control rates of stage I lung cancers treated with conventionally fractionated radiotherapy, SABR seems to offer higher rates of local control, lower levels of acute toxicity and a better quality of life after treatment. However, the full results of randomised controlled trials of SABR versus conventionally fractionated are awaited and will provide higher-level evidence. For central lung tumours, very high SABR doses can be associated with significant toxicity. Dose-adapted fractionation schedules seem to have much lower rates of toxicity and prospective trials, including the completed RTOG 0813 study and the on-going EORTC LUNGTEC study, should provide further evidence of safety and establish organ at risk tolerances. SABR can also be used for tumours metastatic to the lung with high rates of local control and is a reasonable alternative to surgery in selected patients. Going forward, prospective trials are underway to establish the safety and efficacy of SABR in oligometastatic disease. Population-based outcomes will be crucial in supporting/establishing SABR as the treatment of choice in medically inoperable patients with peripheral stage I lung cancers. Randomised phase III trials will hopefully extend the evidence base and show the safety and the utility of SABR in early central tumours and oligometastatic disease.
•Large retrospective analysis of patients with brain metastasis who are normally excluded from prospective trials.•Third of patients received active treatment.•Performance status, mutation status ...effects survival.
Lung cancer is the leading cause of cancer death with the majority of cases being non-small cell lung cancer (NSCLC) 1. A common complication of NSCLC is brain metastasis (BM) 2, 3, where the prognosis remains poor despite new treatments. Real world data complements data gained from clinical trials, providing information on patients excluded from prospective research 4. However, information from patient notes may prove incomplete and difficult to extract. We developed an algorithm to identify patients in our clinical database with brain metastasis from the electronic health record (EHR).
We retrospectively extracted data from the EHR of patients managed at a large teaching hospital between 2007 and 2018. Using the ICD-10 code C34, for lung cancer, our algorithm used phrases associated with BMs to search the unstructured text of radiology reports. Summary statistics and univariant analysis was performed for overall survival.
818 patients were identified as potentially having BM and 453 patients were confirmed on clinical review of their records. The median age of patients was 69 years, 50% were female and 66% had a performance status of >2. 12.2% had an identifiable mutation and 11.5% were identified as PD-L1 positive. In the first line setting, 65% of patients received symptomatic treatment, 23% received systemic anticancer therapy (SACT), 6.1% surgery and 10% radiotherapy, of which 6.5% had external beam and 3.5% stereotactic radiosurgery. Regarding those treated with SACT, 35% had an intracranial response to treatment (3% had complete response, 32% had a partial response). Median survival was 2 months (1.9 – 2.4 months 95% CI).
The real-world prognosis for NSCLC patients with BMs is poor. By using an algorithm, we have reported outcomes on a comprehensive cohort of patients which helps identify those for whom an active treatment approach is appropriate.
Abstract Aims To report outcomes for the first UK cohort treated for early stage peripheral lung cancer using stereotactic ablative radiotherapy (SABR). Materials and methods Patients were included ...who received SABR between May 2009 and May 2012. Electronic medical records were reviewed for baseline characteristics, treatment details and outcomes. Patients were treated according to the UK SABR Consortium Guidelines. Univariate and multivariate Cox regression was used to determine factors that influenced overall survival and local control. Results In total, 273 patients received SABR for 288 lesions in the time period examined. The median follow-up was 19.7 months. The median overall survival for all patients was 27.3 months, with 1, 2 and 3 year overall survival of 78.0, 54.9 and 38.6%, respectively. The 1, 2 and 3 year rates of local control were 98.2, 95.7 and 95.7%, respectively. All patients completed the planned course of treatment and rates of Common Toxicity Criteria grade 3+ toxicity were low. On multivariate analysis, patients with Medical Research Council (MRC) breathlessness scores of 3–5 had worse overall survival compared with patients with scores of 1–2 (hazard ratio: 2.10; 95% confidence interval: 1.25–3.59) and the presence of histological diagnosis conferred improved overall survival (hazard ratio: 0.54; 95% confidence interval: 0.31–0.93), probably reflecting that patients who are considered well enough to undergo biopsy are generally fitter overall. No factors were identified that significantly influenced local control. Conclusions SABR is an effective and well-tolerated treatment option for patients with early stage peripheral lung cancer who are not suitable for surgery. No patient cohort was identified in whom SABR was considered inappropriate. This series adds to the existing positive data that support SABR for this patient group.
Stage I non-small cell lung cancer (NSCLC) is potentially curable, and surgery is considered to be the standard of care for patients with good performance status and minimal co-morbidity. However, a ...significant proportion of patients with stage I NSCLC have a poorer performance status and significant medical co-morbidity that make them at higher risk of morbidity and mortality from surgery. Stereotactic ablative radiotherapy (SABR), which uses modern radiotherapeutic techniques to deliver large doses of radiation, has shown superiority over conventional radiotherapy in terms of local control and toxicity and is a standard of care for patients with stage I NSCLC who are at too high risk for surgery. However, it is not known whether surgery or SABR is the most effective in patients with stage I NSCLC who are suitable for surgery but are less fit and at higher risk surgical complications. Previous randomised studies have failed to recruit in this setting, and therefore, a feasibility study is required to see whether a full randomised control trial would be possible.
SABRTooth is a UK-based, multi-centre, open-label, two-group individually (1:1) randomised controlled feasibility study in patients with peripheral stage I NSCLC considered to be at higher risk from surgical resection. The study will assess the feasibility of conducting a definitive large-scale phase III trial. The primary objective is to assess recruitment rates to provide evidence that, when scaled up, recruitment to a large phase III trial would be possible; the target recruitment being 54 patients in total, over a 21-month period. There are multiple secondary and exploratory objectives designed to explore the optimum recruitment and data collection strategies to help optimise the design of a future phase III trial.
To know whether SABR is a better, equivalent or inferior alternative to surgery for higher risk patients is a key question in lung cancer. Other studies comparing SABR to surgery have closed early due to poor recruitment, and therefore, the SABRTooth feasibility study has been designed around the UK National Health Service (NHS) cancer pathway incorporating many design features in order to maximise recruitment for a future definitive phase III trial.
controlled-trials.com ISRCTN13029788.
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