麻豆传媒

Relatively fit elderly patients with locally advanced non-small cell lung cancer (NSCLC) undergoing intensity-modulated radiation therapy (IMRT) are much less likely than younger patients to benefit from a concurrent chemotherapy and radiation therapy (cCRT) regimen, according to a Dutch research team.

Secondary analysis of a phase II trial cohort of patients age 75 and older with stage 3 NSCLC showed that even though they had a World Health Organization performance score ≤1, the median OS was 15.6 months compared with 19.8 months in younger patients treated with the same standard regimen for lung cancer.

Conversely, in elderly patients given sequential chemotherapy and RT (sCRT) or IMRT alone (RT), OS was comparable to that of younger patients treated with the same regimen, said Judith van Loon, MD, PhD, of the Maastro Clinic in Maastricht, The Netherlands.

The study was presented at the European Society for Radiotherapy & Oncology (ESTRO 37) , April 20 to 24, in Barcelona.

The 5-year OS rate with cCRT was 13.2% in the elderly cohort compared with 24.1% in the younger patients. There was no significant difference in physician-determined toxicity scores between the older and younger patient groups, van Loon said.

"These findings underscore the need for prospective studies including geriatric assessment in this understudied patient population to identify predictive factors for treatment outcome, including quality of life and patient-reported outcome measures. Most importantly, they show that selecting elderly patients for concurrent chemo-radiotherapy on the basis of their performance score is not sufficient. Physicians need to take care when deciding whether or not to administer concurrent chemo-radiotherapy outside the conditions of a study."

Asked for his perspective, George Rodrigues, MD, PhD, a radiation oncologist at the London Health Sciences Centre in Ontario, who was not involved with the study, told 麻豆传媒 that the study authors "should be commended for investigating this important topic of the influence of age on outcomes for locally advanced NSCLC."

However, he also pointed out that the generalizability of the findings might be limited, since the results are based on a trial-specific fractionation schedule "that doesn't represent a broadly accepted standard-of-care regimen."

The median survival for patients in this study was significantly lower than the 28 months reported in the international RTOG 0617 , Rodrigues noted, adding that it is also likely that multiple factors determine the influence of age on survival.

"Until more robust data are available, clinicians should still offer combined radiotherapy and chemotherapy for appropriate locally advanced lung cancer patients after assessing various factors such as performance status, weight loss, and medical co-morbidities," Rodrigues emphasized. "Inappropriate treatment de-intensification in elderly patients may further degrade their survival characteristics for this challenging disease."

Investigation of newer forms of treatment with less toxicity will improve treatment for elderly patients with NSCLC, he predicted. In the meantime, better patient selection based on pretreatment clinical, tumor, and imaging factors will improve treatment tolerability and outcomes, as will improved management of medical co-morbidities, he said.

The phase II trial, which was conducted between April 5, 2009, and April 26, 2012, included 300 patients with stage 3 NSCLC. A total of 76 patients (25.3%) were ≥75 years. The secondary OS analysis was conducted in October 2017.

Patients in the cCRT arm of the study received one cycle of cisplatin-etoposide followed by two cycles of the same chemotherapy with concurrent radiotherapy, which included IMRT, 45 Gy BID followed by 2 Gy daily fractions to the maximal organ at risk constraints. Patients in the sCRT arm received three cycles of cisplatin-etoposide followed by the same RT regimen.

Of the patients 75 and older, 32% underwent cCRT, 29% had sCRT, and 39% had RT. In the group receiving sCRT, the mean total tumor dose was 66.7 ± 5.5. In patients receiving cCRT, the mean total tumor dose was 66.2 ± 27.6 Gy.

Previously, the researchers showed that increasing the RT dose was feasible with an overall treatment time of less than 6 weeks. Since no data were available on the impact of concurrent chemo/RT in elderly patients treated with IMRT, the team hypothesized that radiation customized to tumor dimension might improve OS while decreasing toxicity in this patient population.

A recent retrospective Dutch (CONDOR) in unselected stage 3 NSCLC patients ≥70 years did not show a survival benefit with cCRT compared with sCRT or RT, van Loon noted. "In contrast to the results with 3D conformal RT, isotoxic dose escalation was not feasible with IMRT."

"This analysis demonstrates that one size does not fit all when it comes to treating cancer patients of different ages," ESTRO President Yolande Lievens, MD, PhD, head of the Department of Radiation Oncology at Ghent University Hospital in Belgium, said in a statement issued by the society.

"More research needs to be performed to define the most effective treatment strategies for these [elderly] patients that do not impact on their quality of life without improving survival."

She noted that a new trial that has randomized fit elderly patients with locally advanced lung cancer to either concurrent or sequential chemo-radiotherapy will determine the value of a more intensive treatment strategy, and that results are expected in 2022.

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