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Mitigating Frailty and Sarcopenia to Improve Treatment Outcomes in Lung Cancer


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Frailty and sarcopenia are common conditions among patients with lung cancer and are linked with decreased survival as well as increased surgical complications, chemotherapy toxicity, and cost of care. If a survey of oncologists at the 2019 Multidisciplinary Thoracic Cancers Symposium is any indication, however, the assessment of frailty is considerably underutilized, with more than half of attendees indicating that they lack the information needed to properly evaluate this patient population.1 According to Mark K. Ferguson, MD, a thoracic surgeon at the University of Chicago Hospital, although standardization of frailty indices is still a work in progress, screening for frailty and sarcopenia—age-associated loss of skeletal muscle function and mass—prior to starting treatment and instituting a program of exercise can significantly improve outcomes in these patients.


Short-term exercise can decrease complications after lung resection compared with no exercise intervention.
— Mark K. Ferguson, MD

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“A lot of people throw up their hands and say there’s nothing we can do about either condition, but as it turns out, exercise can mitigate some of the adverse effects,” said Dr. Ferguson. “Short-term exercise can decrease complications after lung resection compared to patients who undergo no exercise intervention. High-intensity exercise lasting only a week can demonstrably improve physical function and is associated with decreased complications.”

Screening for Frailty

As Dr. Ferguson reported, current population analyses project that by the year 2050, 80 million to 90 million people in the United States will be aged 65 years or older, and a significant percentage of this population will be frail. Described as the increased vulnerability to physiologic stressors, frailty is associated with a higher risk of falls, disability, and early mortality. In the surgical population of patients with lung cancer, frailty is associated with an increased risk of postoperative complications, prolonged hospital length of stay, discharge to somewhere other than home, and substantially increased costs.

Despite the associated risks, however, frailty rarely enters into the decision-making process, said Dr. Ferguson, unless providers have studied the condition or have mechanisms to evaluate it. He stressed the importance of observation when seeing patients in clinic for the first time or after the first course of chemotherapy—looking for weight loss, exhaustion, weakness, low activity, slow gait, and dementia, although the latter is not an essential component of frailty assessment.

With screening conducted at our clinic, we found that 70% of patients referred for thoracic surgery were either prefrail or frail, and the incidence of frailty or prefrailty increased with age.
— Mark K. Ferguson, MD

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Although the Fried frailty phenotype is often used as an initial screening tool, frailty can also be assessed in relation to the accumulation of deficits with a sum of comorbidities on the 5-factor modified index developed by the National Surgical Quality Improvement Program. In addition, there are a number of anthropometric tests incorporating laboratory and clinical data.

“With screening conducted at our clinic, we found that 70% of patients referred for thoracic surgery were either prefrail or frail, and the incidence of frailty or prefrailty increased with age,” said Dr. Ferguson. He noted that there is no single agreed-upon way to screen for frailty or to define someone as having frailty.

Frailty and Sarcopenia Worsen Outcomes

Testing for frailty may lack standardization, but its impact on patient outcomes has been observed across clinical studies. One study of patients undergoing lung resection found an increase in overall complications and serious complications for patients scoring higher on the Modified Frailty Index.2

What’s more, said Dr. Ferguson, the frailty effect is not limited to surgical patients. A separate study of patients with newly diagnosed non–small cell lung cancer (NSCLC) showed frailty and a cancer-specific geriatric assessment to be independently associated with higher odds of chemotherapy toxicity (odds ratio = 7.0) in the first round of treatment.3 Finally, an association between frailty and survival has been found in patients who underwent stereotactic body radiotherapy for early-stage NSCLC.4 Those who were frail had a much higher incidence of coronary artery disease, peripheral vascular disease, heart failure, and other comorbidities and had significantly shorter overall survival compared to nonfrail patients.

MORE ON FRAILTY AND SARCOPENIA

For more on mitigating frailty and sarcopenia to improve treatment outcomes, see an interview with Mark K. Ferguson, MD, on The ASCO Post Newsreels at ascopost.com/videos.

Often associated with frailty, sarcopenia is also predictive of falls, disability, and mortality, and within the surgical realm, is associated with increased complications, prolonged length of stay, discharge to somewhere other than home, and increased costs as well. A study from Japan showed that sarcopenia, as determined by preoperative computed tomography, could be used to predict postoperative major complications and prognosis in patients with resected NSCLC.5 A separate analysis of stage IV NSCLC found sarcopenia reduced the benefits of immunotherapy.6 Unfortunately, said Dr. Ferguson, definitions of sarcopenia also vary across the board.

“Although some studies look at the whole torso or abdomen, others look at core skeletal muscle, and there are other elements that can be assessed including visceral fat, subcutaneous fat, and bone density,” said Dr. Ferguson. He observed that more than 80% of oncologists in the audience either cannot assess for sarcopenia or lack familiarity with the condition.

“Gait speed is a simple way of defining sarcopenia (< 0.8 meters per second), but a self-completed questionnaire (SARC-F) and/or a grip strength test using a dynamometer are other valid screening tools,” Dr. Ferguson added.

Mitigating Frailty and Sarcopenia With Exercise

Providers already accept that some patients are at higher risk than others, Dr. Ferguson acknowledged, but measuring risk helps with informed decision-making. More importantly, there are new ways of mitigating risks associated with frailty and sarcopenia. Once a patient is identified as being frail or having sarcopenia, said Dr. Ferguson, a comprehensive geriatric assessment is appropriate. Providers should then consider -prehabilitation.

“Every single patient I see in the clinic who may be a surgical candidate is instructed to undergo prehabilitation primarily through vigorous walking exercise, but there’s also evidence that strength training and nutritional repletion with a high-protein diet are beneficial,” said Dr. Ferguson, who noted that exercise has been shown to reduce postoperative length of stay and complication rates. “High-intensity training for only 7 days has demonstrated a substantial improvement in 6-minute walk distance and, in a presurgical lung resection population, reduced complications as well.”

Looking Ahead

In the future, Dr. Ferguson added, there will be increased use of morphomics—linking body factors to outcomes—to define sarcopenia and frailty. In addition, improvements in laboratory data will be used to develop an accumulated deficits scale that will be integrated into the electronic medical record.

“As our patient population gets older, how should we standardize our frailty testing and come up with strategies for curative surgery for early-stage disease?” asked one member of the audience.

“There are reasonable ways of screening for frailty, but nobody has agreed upon a standard definition for frailty,” said Dr. Ferguson. “Ultimately, I think it will be determined by a biochemical evaluation combined with physiologic performance, including assessment of the pituitary-adrenal axis, chronic inflammation, and the immune system, among other factors.”

He added, “Five years from now, we may be a lot closer to standardization of frailty testing, but making patients ready for surgery is another challenge. Prehabilitation, of course, is useful, but it’s not known whether frail patients will respond to that as well as prefrail patients do. I think a general understanding of the development of frailty and mitigation in the general population may be a better approach than waiting until patients are diagnosed with cancer.” 

DISCLOSURE: Dr. Ferguson reported no conflicts of interest.

REFERENCES

1. Ferguson MK: Is my patient frail? 2019 Multidisciplinary Thoracic Cancers Symposium. Presented March 15, 2019.

2. Cairo SB, Ventro G, Sandoval E, et al: Long-term results of cholecystectomy for biliary dyskinesia: Outcomes and resource utilization. J Surg Res 230:40-46, 2018.

3. Ruiz J, Miller AA, Tooze JA, et al: Frailty assessment predicts toxicity during first cycle chemotherapy for advanced lung cancer regardless of chronologic age. J Geriatr Oncol 10:48-54, 2019.

4. Raghavan G, Shaverdian N, Chan S, et al: Comparing outcomes of patients with early-stage non-small-cell lung cancer treated with stereotactic body radiotherapy based on frailty status. Clin Lung Cancer 19:e759-e766, 2018.

5. Nakamura R, Inage Y, Tobita R, et al: Sarcopenia in resected NSCLC: Effect on postoperative outcomes. J Thorac Oncol 13:895-903, 2018.

6. Chen KC, Cheng YJ, Hung MH, et al: Nonintubated thoracoscopic lung resection: A 3-year experience with 285 cases in a single institution. J Thorac Dis 4:347-351, 2012.


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