Radiotherapy Dose Escalation Linked To NSCLC Patient QoL Reduction

Patient-reported quality of life measures show a clinically meaningful decline with escalated dose of radiotherapy for inoperable non-small-cell lung cancer

medwireNews: Quality of life (QoL) analysis confirms trial results indicating that patients with stage III unresectable non-small-cell lung cancer (NSCLC) do not benefit from a higher dose of radiation.

The initial Radiation Therapy Oncology Group 0617 results showed that patients given 74 Gy of radiotherapy, alongside chemotherapy alone or with cetuximab , had poorer survival than those given 60 Gy, explain Benjamin Movsas, from Henry Ford Hospital in Detroit, Michigan, USA, and co-workers.

The current QoL analysis, published in JAMA Oncology, found that patients given 74 Gy were significantly more likely than those treated with 60 Gy to experience a clinically meaningful decline (CMD) in QoL after 3 months, at 45% versus 30%.

This CMD, as measured on the Lung Cancer Subscale of the Functional Assessment of Cancer Therapy (FACT)-Trial Outcome Index (TOI), remained significant after adjusting for receipt of cetuximab and other confounding factors.

By contrast, the only clinician measurement of toxicity to differ between the treatment groups was the 3-month rate of severe oesophagitis, the team reports, noting that while just 21% of high-dose patients were affected by this at 3 months, 50% had reported a CMD in FACT-TOI for this time point.

Moreover, multivariate analysis identified several dosimetric markers that were significantly associated with a CMD in QoL, the researchers say.

For example, the percentage of lung receiving at least 20 Gy was significantly associated with FACT-TOI and its physical wellbeing and functional wellbeing measures at the end of treatment, while the percentage of oesophagus receiving at least 60 Gy was associated with CMD in FACT-TOI and physical wellbeing at 3 months.

David Cella, from Northwestern University in Chicago, Illinois, USA, writes in an accompanying comment that such dosimetric findings, “linking dose with patient reports of symptoms and functioning, help plan future studies that aim to determine the acceptability of dose escalation and aggressive combined modality treatments.”

Praising the QoL analysis, he says that the results “affirm a few principles of [QoL] measurement in advanced tumor oncology that can now be considered teachable facts”, summarising that patient QoL at baseline is predictive of survival, that the clinician-rated toxicity underestimates the adverse effect of treatment on patient lives, and that dose escalation has a predictable impact on QoL.

However, the JAMA Oncology editor, Charles Thomas Jr, cautions that the trial is “not the definitive treatise” on radiotherapy dose escalation, noting that future studies could be guided by tumour molecular signatures indicating radiosensitivity or radioresistance.

He also highlights the impact of different types of radiation delivery and dose escalation, and the inability to get a true picture of adverse effects from weekly patient consultations.

“This is fraught with recall bias and other factors that contribute to a diminished appreciation of real-time patient-related outcomes, which should ideally be recorded on a continuous 24/7 basis to assess QOL during treatment”, he suggests.


Movsas B, Hu C, Sloan J, et al. Quality of life analysis of a radiation dose-escalation study of patients with non-small-cell lung cancer. A secondary analysis of the Radiation Therapy Oncology Group 0617 randomized clinical trial. JAMA Oncol 2015; Advance online publication 25 November.doi:10.1001/jamaoncol.2015.3969

Cella D. Dose escalation in stage III non-small-cell lung cancer. Patients agree with the clinical results. JAMA Oncol 2015; Advance online publication 25 November.doi:10.1001/jamaoncol.2015.4683

Thomas Jr, CR. The importance of quality of life assessment.JAMA Oncol 2015; Advance online publication 25 November.doi:10.1001/jamaoncol.2015.4087

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