In this survey of geographically diverse radiation oncologists, we found that nearly all of them would recommend CRT for a 55-year-old man with stage III NSCLC and only a remote smoking history. However, there was less agreement regarding recommendations for patients who were older and/or had moderate to severe COPD. In the three scenarios with the greatest variability, the only physician variable that was significantly associated with treatment recommendations was the volume of lung-cancer patients treated. Prospective randomized trials comparing CRT with RT alone for unresectable, locally advanced NSCLC have clearly demonstrated improved overall survival with the addition of chemotherapy to radiation.1–3
As a result, treatment guidelines from a number of different expert panels recommend CRT with curative intent for patients with unresectable NSCLC.4–7
Thus, it is not surprising that there was essentially unanimous agreement on recommending CRT for the young, otherwise healthy patient. Our findings confirm that a strong consensus is achievable with high-quality, randomized data.
However, in the scenarios which are likely to be more representative of typical lung-cancer patients, who are older and have some degree of COPD, the decreasing consensus likely reflects the uncertainty in the literature regarding optimal treatment for patients who are not ideal candidates for CRT. The trials establishing the superiority of CRT over RT generally included only patients with good performance status (Zubrod 0–1) and minimal weight loss (<5%), and the published treatment guidelines are firm in recommending CRT only for such patients. For patients who do not meet these criteria, recommendations vary from offering CRT to patients with borderline performance status only after careful consideration to offering only palliative therapy for symptomatic patients with poor performance status or greater than 10% weight loss.
Notably, treatment guidelines generally do not recommend offering less aggressive therapy on the basis of advanced age alone. Randomized data on the importance of age are limited since some trials excluded or included relatively few patients who were over 70 years-old.2,21
Retrospective analyses specifically examining the benefit of adding chemotherapy in the elderly have yielded mixed results, depending in part on the outcome of interest. For instance, a quality-adjusted survival analysis showed that RT alone yielded the best quality-adjusted survival in patients over 70 years-old.22
More recently, a randomized trial of concurrent versus sequential CRT showed a similar benefit to concurrent CRT between patients older than 70 and younger than 70.23
Based on currently available data, most experts advocate treating “fit” (performance status 0–1) elderly patients in a fashion similar to their younger counterparts.6,7
Consistent with this recommendation, most (85%) radiation oncologists in our cohort reported they would treat an 80-year-old man without COPD similarly to the 55-year-old, although 13% of physicians would recommend RT alone for such men.
Differences in recommendations based on patient age were amplified in the setting of moderate or severe COPD, with radiation oncologists tending to recommend less aggressive therapy overall for older patients. This finding is consistent with findings of the Patterns of Care Study, which showed that patients younger than 70 were more likely than those older than 70 to receive chemotherapy in addition to radiation for stage III NSCLC.10
This difference may reflect concern about the potential increased risk of toxicity among older patients receiving chemotherapy in addition to radiation therapy.8,9
The question of whether such concern is justified would ideally be addressed in a randomized trial of CRT versus RT alone designed specifically for older patients, who were under-represented in prior trials.
Because the Patterns of Care Study10
included only patients who received radiation as a component of their treatment, it does not provide information on the proportion of patients treated with either chemotherapy alone or best supportive care. Our study suggests that most radiation oncologists would not recommend any radiation in patients with severe COPD, regardless of age. The sharp decrease in the frequency of radiation being recommended is likely related to concern that patients with severe COPD may not tolerate the potential pulmonary toxicity associated with radiation. It is also consistent with the statement in the ACCP guidelines that a patient with FEV1 <1L/s is unlikely to withstand definitive therapy.4
However, there are no good prospective data demonstrating that an attempt at definitive RT would indeed be detrimental in patients with severe COPD.
Potential reasons for the lack of consensus in the three most variable scenarios include a shortage of evidence to guide therapy in non-ideal candidates for CRT or physician factors that could lead to treatment recommendations in the absence of strong data. Among the radiation oncologists studied, we found that variability in responses was influenced only by the number of lung-cancer patients treated per month. Overall, however, the variability we observed in the scenarios with “non-ideal” patients was not well-explained by physician characteristics. Thus, our data suggest that the variability we observed for older and sicker patients is unlikely to be significantly reduced by addressing any particular subset of physicians.
The reluctance of “low volume” physicians in this study to offer radiation in the scenarios involving patients with severe COPD suggests that those with less experience may be more concerned about the reported increase risk of pulmonary toxicity in those with pre-existing lung disease.14
Prior studies have shown that higher patient volume may improve outcomes for cancer patients, particularly for patients undergoing surgery.24
Radiation oncologists who treat fewer patients with lung cancer may be less comfortable managing radiation-induced lung toxicity in part because of their own lack of experience and in part because their colleagues (within the same institution but in other specialties) may also have less experience managing the side effects of lung radiation. It has been reported that increased volume at the institutional level is associated with improved survival for locally advanced lung cancer.25
Although the recommendations of the lower-volume physicians in this study may be appropriate, our data suggest that, in general, the impact of patient volume on outcomes may be related not only to technical factors but also to differences in the overall approach to therapy.
A limitation of this study is our use of clinical vignettes and our reliance on physicians’ self-reports to assess care. Although others have demonstrated that vignettes can provide a valid measure of clinical care,26
physicians might overestimate their propensity to provide guideline-concordant care. Moreover, the lack of detail in each scenario may have contributed to the variability in physician response. Furthermore, the vignette patients represented only 2 ages and 3 levels of severity of a single medical condition, and responses may have been different had we used an illness other than COPD. Also, although the vignettes describe the patients’ symptoms, there was no specific information about performance status or degree of weight loss, which some recommendations suggest should be used to guide care.
In addition, the response options were limited to CRT, RT alone, chemotherapy alone, or neither and did not distinguish between sequential and concurrent CRT, or between definitive and palliative RT; nor did they allow physicians to provide reasons for their recommendations. Recent data show concurrent CRT offers superior cancer control in comparison to sequential therapy but is also more toxic.27,28
In practice, patients who are suboptimal candidates for concurrent CRT may be offered sequential therapy, so it is likely that increasing the number of possible responses would have increased the variability we observed, particularly in the 55-year-old with moderate COPD or the 80-year-old with no COPD. Similarly, it is possible that those who recommended RT alone would have been divided with regard to whether the RT was given with curative or palliative intent.
Finally, only radiation oncologists were questioned about recommendations for treatment of patients with unresectable lung cancer; medical oncologists may have had differing views. Moreover, our survey is subject to non-response bias and patients’ reports may not have identified all radiation oncologists in an area, so we cannot be certain that the radiation oncologists in our sample were representative of those caring for cancer patients in the regions studied or nationally. However, the correlation between our results and those of the Patterns of Care Study suggest that our data do provide a reasonable sample of physicians in the United States.
In conclusion, nearly all radiation oncologists recommended CRT for stage III NSCLC for a young, otherwise healthy patient, demonstrating that radiation oncologists are willing to follow strong, randomized data. However, they differ widely on recommendations for patients who are older or have significant lung disease, suggesting that radiation oncologists are less willing to extrapolate the results of randomized trials to patients who were not actually included on the trials. Thus, additional clinical trial data are needed to guide recommendations for older patients and those with moderate to severe COPD, populations that have been largely excluded from previous trials. Although such trials are challenging to conduct given heterogeneity in patients’ baseline pulmonary function, tumor characteristics, and other comorbidities, given that these patients, in fact, comprise the majority of “real world” patients, such trials would likely optimize care for these patients by decreasing variations due to poorly substantiated, individual or regional beliefs about the likely benefits and risks of available treatments in different types of patients.