A true radiotherapeutic emergency occurs when failure to deliver treatment within a few hours or days could result in death or catastrophic irreversible damage. Severe pain, although distressing to the patient, is not an emergency, but should be treated with great urgency. As RT cannot produce immediate pain relief, pharmacologic measures are essential while RT is being organized and delivered. Table 49.5 lists indications for emergency RT in a large academic cancer center in Canada, the Princess Margaret Hospital, Toronto. In these circumstances, the patient should be seen by a radiation oncologist on the same day the lesion is diagnosed, and appropriate treatment should be started promptly.

Although RT should be administered without delay, relief may not be immediate. The time taken for the benefits of RT to be observed depends on the situation but is rarely less than a few days. With the exception of a few very radiosensitive tissues and cells (e.g., lymphocytes), RT does not cause immediate cell death. Rather, it leads to the failure of cell division, and subsequently cell death at the next scheduled division. As a result, both the beneficial effects and the acute toxicities of RT take several days to manifest. Although not the norm, when treating bone metastases, large-fraction wide-field treatment such as half-body irradiation (HBI) occasionally produces same-day benefits.

There is no threshold of symptom severity that a patient needs to cross to require palliative RT. When treating small or large volume tumors, RT is equally useful whether the disease is producing mild or severe symptoms with little difference in palliative effect, although side effects are usually greater with large volume irradiation. In some instances, as in patients with pain from multiple bone metastases, it may be more appropriate to treat with analgesics as this may give better overall relief with less side effects than RT. Additionally, some patients may become completely pain free if their analgesics are adjusted appropriately. In those circumstances, it may be possible to defer RT.

In a situation where a patient has an incurable cancer that is asymptomatic, treatment may be deferred until symptoms arise, although this should be discussed with the patient. A randomized clinical trial by Falk et al. (4), supports this approach in the management of lung cancer. Two hundred thirty patients with incurable lung cancer and no symptoms requiring immediate RT were randomized for immediate palliative RT (17 Gy in 2 fractions) or observation with RT at the time of symptomatic progression. After a 6-month follow-up, patients who received immediate RT were no more likely to be free of chest symptoms (i.e., cough, dyspnea) or to survive than patients in the observation arm. Additionally, one third of patients in the observation arm never required RT (or chemotherapy). Therefore, the use of RT to prevent potential symptoms (of lung cancer) is not supported by evidence. Many radiation oncologists have admitted the use of palliative RT to “give hope” (5) as many patients are unhappy about a “wait-and-watch” approach and would prefer to receive active treatment. In such cases, the benefits may be minimal and patients may still be exposed to side effects. Despite the lack of evidence, prophylactic palliative RT may be used if the physician feels the patient is at high risk of developing a clinically significant morbidity such as fracture, cord compression, airway obstruction, or superior vena cava compression.

Patients, who have previously received RT, whether palliative or radical, may develop new symptoms related to tumor in the same anatomical area. As palliative RT may provide symptom relief, further reirradiation should be considered although questions frequently arise as to the feasibility of further RT to a previously irradiated area. Due consideration to three key factors helps address this question: what is the residual tolerance of the normal structures? How likely is the disease to respond? How do the risks and benefits of retreatment with RT compare to other symptom management options?

Normal tissue tolerance refers to the relationship between dose levels and the risk of developing significant long-term side effects. Normal tissue tolerances are unique to each anatomic structure. For example, small bowel tolerance is in the order of 45 Gy in 1.8- to 2-Gy fractions, with an expected 5% patient population risk of serious small bowel serious complications (e.g., bowel obstruction). The risk of toxicity escalates with increasing doses. Normal tissue tolerance is further affected by treatment volume and underlying medical conditions. Some normal tissue repairs occur with the passage of time although many of the changes due to high-dose RT, such as fibrosis, vascular changes, and depletion of parenchymal cells, are permanent. Therefore, previous RT doses, even if remote, need to be considered, when assessing the risk of reirradiation.

How the symptom and the disease are likely to respond to reirradiation are important factors in considering reirradiation. Palliative RT provides symptom relief by a complex and poorly understood mechanism that includes, but is not limited to, killing tumor cells, leading to a reduction in tumor volume. Patients who previously responded well to RT are expected to respond again, although possibly with a lower probability and durability of response. At the cellular level, previously irradiated areas may represent an environment with a greater proportion of resistant cancer cells, and regions of hypoxia that may lead to an attenuated response.

Finally, alternative treatment options should always be considered, so as to select the approach with the least side effects and the best likelihood of benefit. Literature describing the effectiveness of reirradiation is typically scant and confined to retrospective reviews. Patients administered reirradiation represent a minority of those initially treated. The selection criteria for reirradiation are generally not well described, making generalization difficult. Altered fractionation (lower dose per fraction) has been used in an attempt to lower the risk of late effects (6), although evidence to support its superiority is limited.

The evidence regarding reirradiation for specific clinical indications (bone metastases, brain metastases, lung cancer) is described in corresponding sections of this chapter. In all of the common indications for palliative RT, only highly specific patients are offered reirradiation. Patient selection is typically based on the feasibility of delivering a reasonable dose and volume, the predictability of acceptable risks of late toxicities and favorable performance status and life expectancy. The low risk of generally observable late effects is likely the combination of a meticulous planning technique, choice of dose fractionation, exclusion of patients at high risk of developing toxicities, and, in cases such as brain metastases, the shorter life expectancy that limits the manifestation of late effects. Despite these limitations, reirradiation has a definitive role in providing symptom relief in selected patients and should be considered where appropriate.

Although individual RT treatments often take only 10–20 minutes to deliver, time spent traveling and waiting for treatment can add up to several hours. A protracted course of RT, especially for patients living some distance from the treatment center, may occupy most of their waking hours. One needs to remember that “time is precious when life is short” (2). For each patient, the benefits of treatment need to be compared with the cost of “lost opportunities” for them to spend their remaining days as they choose (7). In many situations, it appears likely that large single fractions are as efficacious as longer courses (see next section). Even if they were not, it may still be appropriate in patients when the “opportunity cost” of a 2-week treatment would be extremely high. Reduction in palliative benefit would be minimal at most, and concerns about the duration of the effect of single treatments are probably not relevant in patients with extremely limited prognosis.

Lung cancer is the most common cancer in North America and the most common cause of cancer deaths in both men and women. Most patients either present with stage IV (metastatic and incurable) disease or develops metastases some time after the initial diagnosis. Although advances have been made with palliative chemotherapy, palliative RT continues to play an important role in the management of intrathoracic (and extrathoracic) disease, including endobronchial or extrinsic lesions causing atelectasis, postobstructive pneumonia, shortness of breath, cough, hemoptysis, pain, and large airway obstruction. Not surprisingly, RT is not effective in relieving shortness of breath resulting from widespread or parenchymal disease, pleural effusion, or lymphangitic carcinomatosis. Symptoms due to nerve compression (e.g., superior sulcus/Pancoast tumors and intercostal neuropathic pain) are more difficult to palliate and may require high doses of RT aimed at tumor eradication.

The relevant issues in assessing palliation in patients with lung cancer are the following:

Obviously the interplay between these issues is complex, and most research studies only attempt to measure some of these variables.

Numerous palliative RT trials have been performed; the more recent ones are highlighted in Table 49.6 (10, 11, 12, 13, 14). Most of the dose-fractionation schedules demonstrated considerable symptom palliation. Many studies have suggested that less protracted radiation protocols (including 17 Gy in 2 fractions 1 week apart and 10 Gy in a single fraction) (11) provide better palliation (i.e., equivalent symptom control with less toxicity and less burden to the patient and family). In a recent Norwegian study comparing short, intermediate and long schedules of 17 Gy per 2 fractions, 42 Gy per 15 fractions and 50 Gy per 25 fractions, there was no difference in quality of life, symptom response or survival among the three study arms (15). In the shorter treatment protocols, approximately 80–85% of patients reported improvement in hemoptysis while 60% reported improvement in cough and two thirds reported pain improvement. On an average, symptom relief lasted for at least 50% or more of the patient’s survival time. A few studies, on the other hand, have documented a longer duration of symptom control with the more protracted fractionation: in the Dutch trial by Kramer et al. (16), palliation in the 10 × 3 Gy arm was more prolonged than in 2 × 8 Gy. Similarly, a recently published study by Erridge et al. (17) demonstrated superior symptom control with a more protracted course, consisting of 30 Gy per 10 fractions as compared to 10 Gy single fraction. It should be noted, however, that defining and analyzing symptom palliation in lung cancer is complex, as the effectiveness of palliative radiation may be related to initial symptom severity (18). Timing of the assessment is also important (19) as a standard definition of palliation is lacking. These methodological concerns may be contributing factors to some of the disparities seen in various studies.