Palliative Radiotherapy for Lung Cancer

Indications

Palliative thoracic radiotherapy is indicated whenever a patient has disease that is not potentially curable and has troublesome symptoms that can be attributed to growth of the primary tumor and/or mediastinal node disease. These findings need to be integrated into the whole care of the patient and any systemic therapy that is ongoing or being planned. Thoracic palliative radiotherapy is most often used when a patient is unfit for chemotherapy because of poor performance status or comorbidities and there is no appropriate targeted therapy, or when symptoms persist or recur during or after systemic therapy. Additionally, for patients with NSCLC, because the response to radiotherapy is faster and more reliable than to chemotherapy, there are often occasions when local symptoms mean that it is better to treat patients with radiotherapy first and consider systemic treatment later. For patients with SCLC, palliative radiotherapy is probably only indicated as a first-line treatment in emergency situations such as severe stridor or if the patient is considered too unwell to tolerate systemic chemotherapy, but is often useful when there is symptomatic recurrence and resistance to chemotherapy.

Most of the common symptoms from intrathoracic disease are well palliated by radiotherapy. These include cough, hemoptysis, and chest pain. The response rates range from 50% to 90%, with the highest complete response rates seen for hemoptysis. Breathlessness appears to be less well palliated as it may be also caused by a number of other factors, such as obstructive airways disease, cardiac disease, lymphangitis carcinomatosa, or pleural effusion. Moreover, when there is a tumor in an airway causing lung, lobar, or sublobar atelectasis, the lung may not always reexpand even if the tumor shrinks and the airway is opened up, especially if there has been infection or a coexisting pleural effusion. However, any patient who presents with stridor or computed tomography (CT) evidence of a tumor threatening a major airway should be considered for urgent radiotherapy, as even modest shrinkage of a tumor causing obstruction of a large airway can provide considerable symptom relief. Superior vena cava obstruction (when due to tumor compression rather than thrombus) may also be relieved by palliative radiotherapy, although when severe, more rapid improvement may follow a stenting procedure. However, if a patient has both superior vena cava obstruction and airway compromise, the placement of a superior vena cava stent would not palliate the airway compromise, whereas palliative radiotherapy could improve both; thus, the pros and cons regarding placement of a stent followed by radiotherapy rather than palliative radiotherapy alone need to be carefully considered.

Sometimes it may be considered appropriate to treat patients prophylactically before symptoms develop. There no good evidence that this approach improves outcomes. The authors of one randomized clinical trial carried out in the United Kingdom before widespread use of chemotherapy for patients with NSCLC found that in a group of asymptomatic patients randomly assigned to no immediate palliative radiotherapy, 56% died without having had radiotherapy and that there was no substantial difference in symptom control or survival between patients who received immediate or as required palliative radiotherapy, neither at an early time point nor a later 6-month time point.

Palliative radiotherapy may be delivered either by external beam or as intracavitary; i.e., endobronchial brachytherapy.

External-Beam Radiotherapy

Most palliative radiotherapy to the chest can be delivered simply with uncomplicated fields and short courses of mega-voltage radiotherapy. Because this treatment is palliative and the aim is to improve the patient’s symptoms and improve quality of life, unnecessarily complex and prolonged courses of treatment should be avoided, especially in patients with a poor performance status and limited life expectancy.

Radiotherapy Planning

Usually simple parallel opposed anterior/posterior beam arrangements are sufficient, and although recent CT images are useful to assess the extent of disease, complex CT planning should not be needed. The fields should be designed to cover the extent of the tumor causing the troublesome symptoms, but should be kept as small as possible to minimize toxicity ( Fig. 41.1 ), especially as many patients with advanced lung cancer have coexisting chronic obstructive pulmonary disease and therefore already compromised pulmonary function. Widespread sites of disease that are unlikely to be causing symptoms, such as involved but relatively small nodes in the mediastinum, should not necessarily be included. More complex field arrangements may occasionally be needed if there is a risk of overlap with previously treated areas or it is considered essential to minimize the dose to the spinal cord (see later).

Palliative Chemoradiation Therapy

Many patients with symptomatic incurable NSCLC may be candidates for both palliative chemotherapy and radiotherapy; the usual approach is to sequence the therapy, typically starting with palliative radiotherapy for local symptoms, as the expected symptomatic response rates are overall higher than with palliative chemotherapy. This finding has been confirmed in a randomized phase III study of palliative radiotherapy with or without chemotherapy; toxicity was greater and patient outcomes were not better with the addition of concurrent chemotherapy (fluorouracil [5FU]). In 2013, Strøm et al. published the results of a randomized trial that compared chemotherapy alone (cisplatin and vinorelbine) with concomitant chemoradiation in which 45 Gy in 15 fractions was given along with cycle 2, in patients with “poor prognosis” stage III NSCLC. Survival was significantly better in the patients receiving chemoradiation, (1-year survival 53.2% vs. 34.0%; p < 0.01), even those aged over 70 years and with bulky disease, but with increased toxicity. The survival benefit was not, however, seen in those with World Health Organization Performance Status. Although these results are interesting, they come from only one underpowered trial and should be treated with caution. It would certainly not be appropriate to extrapolate them to the management of those with stage IV disease.

International Bone Metastases Consensus End Points

Although many phase III trials assessed the palliative benefit of radiotherapy in patients with painful bone metastases, caution is required when interpreting and generalizing the results of older studies because of variable definitions of response, including what constitutes complete and partial relief. The International Bone Metastases Consensus Working Party has defined a uniform set of eligibility criteria, end point measurements, repeat radiation guidelines, and statistical analysis for clinical trials to increase consistency in reporting.

Indications for External-Beam Radiotherapy: Uncomplicated Bone Metastases

External-beam radiotherapy provides durable and timely symptom relief while minimizing toxicity, resource utilization, and the number of visits to the cancer center, but would not be expected to confer a survival benefit. Tumors do not have to be completely eradicated in order to improve symptoms, and therefore doses lower than that required for lesion ablation are used for palliation. Moreover, the treatment of asymptomatic bone metastases may be deferred unless there is a risk of a serious adverse event such as spinal cord compression.

Authors and investigators of more than 20 randomized controlled trials, two systematic reviews, and four meta-analyses have shown that single-fraction palliative external-beam radiotherapy provides equivalent pain relief to multiple fractions in patients with a variety of tumors (up to 25% in lung cancer). The most recent meta-analysis included 25 studies comprising 2818 patients who were randomly assigned to single-fraction radiotherapy and 2799 to multiple-fraction radiotherapy. The overall response rate to single-fraction radiotherapy was 60%, and the complete response rate was 23% (intent-to-treat), which was comparable to the 61% and 24% rates for patients who received multiple-fraction radiotherapy. There were no differences in acute toxicity, pathologic fracture (3%), or spinal cord compression (2% to 3%). None of the meta-analyses separated out treatment effects by histology, and there is no convincing evidence that outcomes differ by primary site. Single-fraction radiotherapy has been repeatedly recommended as the standard of care for uncomplicated bone metastases ( Table 41.2 ) Fig. 41.2 demonstrates a radiotherapy plan using an anterior and posterior beam to deliver 8 Gy in one fraction to a painful right scapular metastasis.

Despite this strong evidence, there has so far been reluctance to adopt single-fraction schedules as standard practice in many countries. In a large prospective study conducted in the United States, 25 in 1574 patients with lung cancer and metastatic disease who received palliative bone radiotherapy, only 6% received single-fraction radiotherapy. Patients who were younger than age 55 years, had had surgery at a metastatic site, or had received chemotherapy were more likely to receive radiotherapy. Patients treated in integrated networks (e.g., health maintenance organizations) received on average 3.4 fewer fractions ( p = 0.001) and 4 Gy less dose ( p = 0.049), although the overall rates of radiotherapy delivery were similar. Suggested reasons for this reticence include country of training, membership affiliation, institutional structure, available pain management teams, wait times for radiotherapy consultation or delivery, reimbursement levels, and departmental policy.