Retrospective Studies Confirm Survival Benefit of Stereotactic Body Radiotherapy in Early-Stage NSCLC


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Stereotactic body radiation therapy is becoming more widely adopted for the treatment of early-stage non–small cell lung cancer (NSCLC). Along with its increasing uptake, survival has significantly increased over the past decade, according to two large retrospective studies presented at the 58th Annual Meeting of the American Society for Radiation Oncology (ASTRO).1,2

The first study showed a 20% improvement in survival over the past decade in elderly patients with lung cancer treated with stereotactic body radiation therapy,1 and the second study showed about a doubling in 4-year survival rates with the use of stereotactic body radiation therapy in patients with early-stage lung cancer treated at Veterans Health Administration hospitals.2

Primary Treatment in Elderly Patients

In recent years, stereotactic body radiation therapy has become the standard of care for patients with inoperable early-stage NSCLC. Stereotactic body radiation therapy is considered an advance over conventional radiotherapy (ie, small doses of radiation given daily over several weeks), because it delivers a highly targeted, escalated dose of radiation in a single session or as many as five treatments, typically between one and five fractions. Stereotactic body radiation therapy has become widely used in the community as the definitive primary treatment for elderly patients, who often have multiple comorbidities that render them unfit for surgery.


Physicians should feel confident recommending stereotactic body radiation therapy to patients who are too sick to undergo surgery or who choose not to undergo surgery for other reasons.
— Andrew Farach, MD

“With advancing age, radiation replaces surgery as the most appropriate treatment modality for early-stage NSCLC. Our findings indicate that physicians should feel confident recommending stereotactic body radiation therapy to patients who are too sick to undergo surgery or who choose not to undergo surgery for other reasons,” said lead author Andrew Farach, MD, a radiation oncologist at Houston Methodist Hospital, Houston.

Coinciding with widespread adoption of stereotactic body radiation therapy over the past decade, overall survival at 23 months increased by 19% over the study period (2004–2012), and cancer-specific survival increased by 24% in these older patients with early-stage NSCLC.

The study was based on records of 62,213 patients 60 years and older diagnosed with stage I NSCLC between 2004 and 2012 included in the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) database. Patients with squamous, adenocarcinoma, and adenosquamous histologies and those with records defining local therapy were eligible for inclusion.

“The records show that the majority of younger early-stage lung cancer patients aged 60 to 64 get surgery [81%], but with age, there is a dramatic drop-off, until it reaches 21% in patients 90 and older,” Dr. Farach explained. “Radiation replaces surgery in older patients,” he added.

The database showed that among patients of all ages, 41,509 were treated with surgery alone, 11,589 received radiation alone, and 7,373 had no treatment. “The number of patients left untreated is a striking finding. Up to 40% of the oldest population are not being treated,” he emphasized.

Results were analyzed by age in 5-year subsets starting at age 60. From 2004 to 2012, overall survival increased dramatically in this nationally representative population of older patients with stage I NSCLC. In patients treated with stereotactic body radiation therapy, 23-month survival rates rose by nearly 20%: 39% in 2004 to 58% in 2012 (P < .001). Twenty-three month overall survival rates for surgery alone rose only 5% during that time: from 79% to 84%. No survival improvement was reported for untreated patients.

Over the same period, cancer-specific survival increased from 48% to 72% in patients treated with stereotactic body radiation therapy alone (P < .001) and from 87% to 91% in patients receiving surgery alone (P < .001). Cancer-specific survival rates improved slightly for patients who received neither surgery nor radiation.

Overall, survival rates were lower for patients who had radiation therapy compared with surgery. Dr. Farach and colleagues suggested that this could be due partly to a selection bias, where healthier patients were treated with surgery.

Veterans Health Administration Study


At our institution, no one with stage I NSCLC is receiving conventional radiation. Stereotactic body radiation therapy is the standard across the board.
— Matthew Boyer, MD, PhD

Survival rates for early-stage NSCLC doubled from 2001 to 2010 with the use of stereotactic body radiation therapy vs conventional radiation therapy, according to a study of patients treated at Veterans Health Administration hospitals. “When we started this analysis, there were no direct comparisons of these techniques,” stated lead author Matthew Boyer, MD, PhD, a resident at Duke University Medical Center in Durham, North Carolina.

“Outcomes are better with stereotactic body radiation therapy,” he continued. “The increased use of stereotactic body radiation therapy is strongly associated with improved survival. These findings...are generalizable to patients outside the [Veterans Health Administration].”

For the study, the Veterans Affairs Central Cancer Registry was cross-referenced with the Corporate Data Warehouse from 2001 to 2010. Patients had clinical stage I NSCLC and were treated with conventional radiation or stereotactic body radiation therapy. Of 14,177 stage I NSCLC cases, approximately 3,000 patients were treated with radiation: 1,203 with conventional radiation and 468 with stereotactic body radiation therapy.

The median age was 72 years; 89% of patients had a smoking history; 98% of patients were male; and the plurality of patients had squamous histology.

Over time, 4-year overall survival increased by 16%, and 4-year lung cancer–specific survival increased by 17%. Overall survival was 18.8% with conventional radiation vs 37.7% with stereotactic body radiation therapy. Lung cancer–specific survival was 28.3% vs 53.2%.

“The increased survival was linked to increased use of stereotactic body radiation therapy. By 2010, the majority of patients who received radiation were treated with stereotactic body radiation therapy,” Dr. Boyer told listeners.

Stereotactic Body Radiation Therapy for Early-Stage NSCLC

  • Stereotactic body radiation therapy is gaining favor for the treatment of early-stage NSCLC. It has advantages over conventional radiotherapy for this indication, including fewer visits and shorter treatment time.
  • Two large retrospective studies showed that stereotactic body radiation therapy improves survival in early-stage NSCLC, supporting its use as a standard of care.

Over time, improved survival was associated with increased use of stereotactic body radiation therapy. In 2001, the year the study was started, 95% of patients treated with radiation had conventional radiation therapy. By 2010, 60% of patients treated with radiotherapy received stereotactic body radiation therapy.

A multivariate analysis that accounted for age, use of positron-emission tomography (PET), treatment era (2001–2005 vs 2006–2010), histology, stage, and number of comorbidities found that older age, higher Charlson Comorbidity Index Score, and more advanced stage were associated with poorer survival. No significant survival difference was seen among patients who did or did not have staging PET scans or those treated in the second half of the decade. However the benefit of stereotactic body radiation therapy persisted on multivariate analysis with a HR of 0.72 for overall survival. Dr. Boyer emphasized that this indicates the improvement was strongly correlated with the increased use of stereotactic body radiation therapy and not PET scans or other treatments or interventions.

“We were surprised by the magnitude of improvement in our study. Other studies have suggested an improvement with stereotactic body radiation therapy. At our institution, no one with stage I NSCLC is receiving conventional radiation. Stereotactic body radiation therapy is the standard across the board,” said Dr. Boyer. ■

Disclosure: Drs. Farach and Boyer reported no potential conflicts of interest.

References

1. Dalwadi SM, Szeja S, Teh BS, et al: Outcomes in elderly stage I non-small cell lung cancer in the stereotactic body radiation therapy era: A Surveillance, Epidemiology, and End Results analysis. 2016 ASTRO Annual Meeting. Abstract 152. Presented September 26, 2016.

2. Boyer MJ, Williams C, Kelley MJ, et al: Survival with stereotactic body radiation therapy and conventional radiation therapy in stage I non-small cell lung cancer patients in the Veterans Affairs System. 2016 ASTRO Annual Meeting. Abstract 18. Presented September 25, 2016.


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Expert Point of View: Brian Kavanagh, MD


Older patients are healthier in many segments of the population than ever before, and the undertreatment of patients in Dr. Farach’s study might reflect a component of ageism. We wouldn’t want to deny a life-extending therapy to patients who can benefit from it.
— Brian...


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