A recent review article published in the British Journal of Cancer provides comprehensive guidance on optimization of concurrent chemotherapy and radiation therapy (cCRT) for patients with stage III non-small cell lung cancer (NSCLC). The review also highlights best practice approaches to patient evaluation and supportive care.
While the authors acknowledge that better overall survival is achieved when patients are treated with cCRT rather than sequential chemotherapy and radiation, they note that patient selection for these treatments varies widely.
“Stage III lung cancer is a significant proportion of our patient population, around 25%, with an average age of 71. This population is potentially curable, but their cancer is already very advanced… and difficult to treat,” said lead author Alistair Greystoke, MB, PhD, a consultant oncologist at the Newcastle upon Tyne Hospitals NHS Foundation Trust and Clinical Lecturer at Newcastle University in the United Kingdom.
In their review, Dr Greystoke and colleagues highlight the differences in approaches to treating patients with stage III NSCLC around the world, between centers in the same country, and within a given cancer treatment center.
“We were very aware that the treatment that patients received varied [widely] from place to place, even in the UK where we have a national health service and various guidelines,” said Dr Greystoke. “Even within the same center, treatment might vary [from] clinician to clinician … based a lot on people’s expertise, their comfort in looking after these patients, [and] the input from the multidisciplinary team.”
Because the majority of stage III NSCLC patients are current or ex-smokers, they have a high prevalence of comorbidities, including those affecting cardiac and renal function. In their review, Dr Greystoke and colleagues note that one of the main barriers to use of cCRT in stage III NSCLC is patients’ fear of treatment toxicity and a lack of supportive care professionals at some centers to guide patients through their treatment. Physicians at smaller treatment centers, they add, also may be more reluctant to offer their patients cCRT due to limited access to advanced tools and equipment for diagnostics and treatment.
To help physicians optimize treatment of stage III NSCLC in different cancer care settings, the authors offer practical guidance on evaluation of cardiac and renal function; smoking cessation, nutrition, and supportive care; optimized delivery of chemotherapy and radiation therapy; and considerations for chemoradiotherapy with immune checkpoint inhibitors. The review includes a comparison of intensity-modulated vs volumetric arc radiotherapy and an intent-to-cure treatment algorithm, for patients with stage III NSCLC.
“What we wanted to do was highlight some areas of uncertainty, highlight what might be regarded as best practice, and just give some very simple ideas as to how clinicians can try to bring their practice up to a higher level — to what the best centers are achieving,” said Dr Greystoke.
Importantly, the review discusses ways to ensure that physicians and other health care team members have access to a full diagnostic workup, including imaging, patient history, and lung function tests. The authors say that this information can be used to help predict not only how patients are likely to respond to treatment, but also how well they will tolerate cCRT.
“People in the bigger academic centers are used to dealing with more complicated patients. We do this type of treatment [cCRT] so often that we know how to predict things [and] support patients through [their treatment process], and [so] there is [only] a very low level of discomfort,” said medical oncologist Victoria Villaflor, MD, a professor and Head and Neck Section chief in the Department of Medical Oncology and Therapeutics Research at City of Hope Cancer Center in Duarte, California.
The 2 main toxicity concerns that can limit treatment delivery are radiation pneumonitis and acute esophagitis; the review discusses risk factors that can influence the likelihood of these toxicities occurring, including smoking status, respiratory function prior to treatment, and age.
“At smaller sites, they may put just a few patients under cCRT every year, so there’s a bit more hesitation and a bit more concern regarding side effects and the uncertainty of how to deal with them,” said Dr Villaflor.
The review advises clinicians on how to select patients for cCRT based on thorough disease staging and evaluation of patient physiological fitness, and discusses how to optimize the delivery of different treatment modalities and manage associated toxicities.
“I think [the review] is helpful in getting physicians to think about cCRT,” said Dr Villaflor. However, physicians who are uncomfortable with the prospect of administering cCRT should send their patients to centers with experience in the treatment of advanced NSCLC, she emphasized. “[I’m] not saying that we’re any smarter,” she said. It’s just that at centers like City of Hope, where staff routinely treat many patients with cCRT, “it’s easier for us to … deal with a lot of the complications that may arise.”
Supportive care services to optimize patient fitness and reduce the impact of treatment toxicities are clearly beneficial — but how easy is it, for example, to get patients with advanced NSCLC to reduce or quit smoking, given that they may have smoked for most of their lives and are now facing the stress and uncertainty of cancer treatment?
“We can tell them that the chance of their cancer coming back or [of] developing other cancers will reduce,” said Dr Greystoke, “but actually what is quite persuasive is pointing out to [patients] that we are going to put them through some difficult treatment and it’s likely they will get fewer side effects if they can stop or cut back on smoking.”
The 5-year survival rate for stage III NSCLC is typically around 20% with a cCRT approach. However, the potential for improved survival outcomes in this setting is suggested by interim analyses of the phase 3, placebo-controlled PACIFIC trial (ClinicalTrials.gov Identifier: NCT02125461), in which patients received the programmed death ligand 1 (PD-L1) blocker durvalumab after cCRT. “The 4-year survival was just presented from PACIFIC and showed an increase of 10% to 15%, so maybe we will be looking at around 40% ultimately with the best possible treatments available,” said Dr Greystoke.
Treatment of patients with late-stage lung cancer has been revolutionized recently with greater use of small-molecule inhibitors and immunotherapies. However, these gains have been most acute in younger patients who have never smoked or only minimally smoked.
“When I first started treating lung cancer, [very few] patients made it beyond 10 to 12 months,” said Dr Villaflor. “Now they’re living years and we are starting to use more targeted therapies such as [epidermal growth factor receptor] inhibitors and immunotherapies in earlier-stage patients, [so] the future is promising for better outcomes for these patients.”
Disclosures: The referenced study was sponsored by AstraZeneca, and Dr Villaflor reports serving as an advisor/consultant to AstraZeneca.
Storey CL, Hanna GG, Greystoke A, AstraZeneca UK Limited. Practical implications to contemplate when considering radical therapy for stage III non-small-cell lung cancer. Br J Cancer. Published online December 8, 2020. doi:10.1038/s41416-020-01072-4