1. Goodwin, Peter M.

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BARCELONA-It is essential to conduct a comprehensive geriatric assessment of patients over 74 with lung cancer before deciding to escalate treatment dose by switching to concurrent chemo-radiotherapy in an attempt to improve outcomes. This was the conclusion of a phase II study reported at the European Society for Radiotherapy & Oncology (ESTRO 37) conference (Abstract E37-2327).

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"You could do more harm with this treatment when you don't take into account other factors," said principal investigator Judith van Loon, MD, PhD, a radiation oncologist at MAASTRO Clinic in Maastricht, The Netherlands. She told Oncology Times this held true despite the fact that only patients who had excellent performance status were selected for such escalation.


"We found that elderly patients who were treated with concurrent chemo-radiotherapy had worse survival than younger patients. They also did worse than elderly patients treated with sequential chemo-radiotherapy or with radiotherapy alone. It was not possible to increase the dose to the tumor without increasing the chance of side effects," van Loon said.


The group had previously showed that for patients with non-small cell lung cancer (NSCLC) increasing the radiotherapy (RT) dose in an overall treatment time of less than 6 weeks was feasible and-according to randomized study data-was thought to have the potential to prolong overall survival (OS) without increasing toxicity. No previous data had been available for patients treated with intensity-modulated radiation therapy (IMRT) and the Netherlands study reported data on patients 75 years old and overtreated with IMRT. Van Loon pointed out that these were comparable with patients in typical clinical settings.


In the overall study, 300 patients with stage III NSCLC (about a quarter of whom were over 74) were treated with RT alone or with a combination of either sequential or concurrent chemo-RT (sCRT or cCRT). The primary endpoint of the study was OS. Toxicity was a secondary endpoint.


Patients treated with cCRT had an initial cycle of cisplatin-etoposide followed by two more cycles of the same chemotherapy together with concurrent radiotherapy (IMRT in fractions of 45 Gray (Gy) twice daily followed by 2.0 Gy daily up to the maximum dose calculated to be tolerable to organs at risk). Patients who had sequential therapy were treated with three cycles of cisplatin-etoposide followed by the same RT regimen as patients in the rest of the study.


Of patients aged 75 or older, 32 percent were treated with cCRT, 29 percent had sCRT, and the remaining 39 percent had RT. The total dose of radiation delivered in the concurrent arm of the study was a median of 66.2 Gy-and the dose was roughly the same (66.7 Gy average) in the sCRT arm.


Mortality from any cause was significantly worse in the older patients who had concurrent therapy, even though most of them (96%) were assessed at the beginning of the study as having World Health Organization performance score of 1 or less-meaning that they were fully active and able to carry on normal life.


Van Loon said that a "real good performance status" did not protect these patients from the increased toxicity of concurrent therapy. "Even when we select patients on the basis of our feeling of which patients will benefit from this intensive treatment (very fit patients), we showed that the overall survival was worse when we compared the whole group to the younger population. And when we looked at subgroups of patients treated with concurrent, sequential, or radiotherapy alone, only the group treated concurrently had a worse overall survival than the younger population," she said.


There was an important message for cancer doctors. "When we don't have other tools to assess, we are just not able to assess the fitness on the basis of just seeing a patient and asking some questions."


Van Loon suggested that clinicians should not choose cCRT for older patients without an extensive assessment. "We need more tools like geriatric assessment-that takes about an hour-where you also take into account comorbidities and what a patient can do in daily life. We can [then] predict better which patients will benefit from intensive treatments."


And she said there was a clear clinical message from the study findings. "Outside of trials-without selection-you shouldn't offer patients concurrent chemo-radiotherapy. We think you should incorporate a geriatric assessment: Take [the patient] to a geriatrician for treatment decisions. And, on the basis of that, you can better select the patient and individually decide which treatment the individual patient will benefit most from," she said.


Need for More Trials

Commenting on the study findings, Yolande Lievens, MD, PhD, President of ESTRO and Head of the Department of Radiation Oncology at Ghent University Hospital in Belgium, implied that clinicians needed to think outside the box.


"The evidence that we have in lung cancer is typically restricted to randomized controlled trials that limit the age of the patients. And, therefore, we look at fit, younger patients. In these patients, we have proven that indeed concurrent chemo-radiotherapy is superior," she said.


But she drew attention to the fact that the study populations do not necessarily reflect the typical patient in clinical practice. "Unfortunately, in daily practice, a lot of our patients are elderly and are in less optimal condition. So we are very often struggling [to ask]: Is the evidence that we have from randomized trials valid for the patients that we have in our daily clinic?"


The way forward, she suggested, was to analyze data from the real world. "What I make of this [Netherlands] study is that we do not only need randomized trials, but we also need very close follow-up of our patients and go to a big dataset of patients treated in daily practice-"phase IV-type" studies-where we can evaluate from daily clinical practice what we have and try to learn from that."


Van Loon's study concluded, that although relatively fit elderly patients had been assigned to cCRT, survival had been worse compared to the younger patient population and also worse compared to patients of at least 75 years treated with sCRT.


The researchers added: "These findings underscore the need for prospective studies, including geriatric assessment in this under-studied patient population, to identify predictive factors for treatment outcome including quality-of-life and patient-reported outcome measures."


Peter M. Goodwin is a contributing writer.