3.2.3 Palliative External Beam Thoracic Radiotherapy

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3.2.3 Palliative External Beam Thoracic Radiotherapy

Jason Lester and Fergus Macbeth

J. Lester FRCR

Velindre Hospital, Whitchurch, Cardiff, CF14 2TL, UK F. Macbeth FRCR

Velindre Hospital, Whitchurch, Cardiff, CF14 2TL, UK CONTENTS

3.2.3.1 Introduction 247

3.2.3.2 Treatment Effectiveness 247

3.2.3.2.1 How Effective Is Radiotherapy at Palliating Thoracic Symptoms Related to NSCLC? 247 3.2.3.2.2 What Are the Most Effective Dose Regimens? 248 3.2.3.2.3 Treatment-Related Toxicity 250

3.2.3.3 The Asymptomatic Patient 251

3.2.3.4 Radiotherapy, Chemotherapy or Both? 252 3.2.3.5 Appropriate Treatment Strategies 252 3.2.3.6 Conclusion 253

References 253

3.2.3.1 Introduction

Non-small cell lung cancer (NSCLC) continues to be a major health problem in many countries. Despite advances in diagnosis and treatment, 90% of patients are incurable at presentation, and the overwhelming majority will die of their disease. Most of these patients will develop thoracic symptoms at some point during their illness, and the challenge facing heath professionals is to provide effective palliation while avoiding unacceptable toxicity. Management deci- sions involve balancing possible treatment benefi ts against side effects, and this is often diffi cult to do because many lung cancer patients are advanced in age and also have signifi cant co-morbidity.

Palliative thoracic radiotherapy can be deﬁ ned as radiotherapy given in less than radical doses to control symptoms from intrathoracic disease. It has long been used in the management of NSCLC patients;

fractionation schedules and indications for their use have evolved over time, based on empirical obser- vations rather than clinical evidence. Comparative studies of clinical practice have shown that policies

about when to employ palliative radiotherapy and about the fractionation schedules thought appropriate differ between health care systems (Priestman et al. 1989; Maher et al. 1992). A survey of practice from one American radiotherapy centre (Lutz et al.

1997) reported that only 12% of lung cancer patients received low dose palliative radiotherapy, whereas a typical British centre would treat a greater proportion of patients in this way (Macbeth, unpublished observation). Despite the increasing use of chemotherapy over the last decade, radiotherapy continues to play an important role in palliating NSCLC patients, particularly those with symptoms predomi- nantly from intrathoracic disease.

In this chapter, we will discuss the clinical evidence available to guide us on when and how to use palliative thoracic radiotherapy in NSCLC. The studies referred to in this chapter were identiﬁ ed through a search of MEDLINE up to September 2003, and through hand-searching of relevant journals and conference abstracts.

3.2.3.2

Treatment Eﬀ ectiveness 3.2.3.2 1

How Eﬀ ective Is Radiotherapy at Palliating Thoracic Symptoms Related to NSCLC?

Despite its widespread use, there have been no randomised controlled trials (RCTs) comparing palliative radiotherapy with supportive care alone in symptomatic patients. The best information we have is from RCTs comparing different radiotherapy treatment schedules, and from a few other published non- randomised series (Table 3.2.3.1).

Symptom palliation is a difﬁ cult end point to measure accurately, because by deﬁ nition, assessment of symptom severity is subjective; it will differ between individual patients as well as between clinicians. In addition, evidence suggests that doctors underesti-

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mate the severity of physical symptoms (Stephens 1997) compared to patients. Some symptoms, in particular hemoptysis, may be intermittent and self-lim- iting, making any response to treatment difﬁ cult to assess. Most NSCLC patients will be on medication such as analgesics and antitussives before starting radiotherapy. Altering a drug dose during treatment may give misleading results when evaluating effectiveness. An increase in morphine use, for example, may result in reduced pain, cough and dyspnea all of which may be attributed to radiotherapy unless any change in medication is recorded very carefully.

Consequently, there are no well validated universally accepted methods in use to measure symptomatic response to treatment, and the studies in Table 3.2.3.1 used a variety of techniques to do this. For this rea- son, attempting to combine the numerical data in Table 3.2.3.1 would be inappropriate.

It can be seen, however, that palliative radiotherapy results in symptom improvement in the majority of patients. Hemoptysis and chest pain are particularly well palliated and over half of all patients in each study had improvement in cough. The results for dyspnea are less good, probably reﬂ ecting the varied causes of this particular symptom in patients with NSCLC.

3.2.3.2.2

What Are the Most Eﬀ ective Dose Regimens?

Patients with incurable NSCLC have a poor prog- nosis, and the aim of any therapeutic intervention should be to improve disease-related symptoms and

maintain quality of life. To date there have been 14 randomised trials, ten published (Table 3.2.3.2) and four in abstract form (Table 3.2.3.3) comparing different palliative radiotherapy fractionation schedules in incurable NSCLC. Overall, it seems that short radiotherapy schedules of 1 or 2 fractions are as effective in palliating thoracic symptoms as more prolonged treatment schedules. Only three published trials to date have shown signiﬁ cantly improved survival with a more fractionated, higher dose regimen.

The ﬁ rst is the Medical Research Council Lung Cancer Working Party trial (MRC LCWP 1996) which randomised 235 patients to 36 or 39 Gy in 12 or 13 daily fractions (36 Gy/12 fractions or 39 Gy/

13 fractions) or 17 Gy in 2 fractions over 8 days to the primary site and mediastinal lymph nodes. All the patients in this trial were of good performance status (WHO 0-2), and had disease too advanced for radical radiotherapy, but no evidence of metastatic disease outside the locoregional volume. The median survival was signiﬁ cantly greater in the 13-fraction arm (9 months vs 7 months, p=0.003). The 2-fraction schedule did however result in more rapid palliation of symptoms, with signiﬁ cantly less acute esophagitis.

This difference in survival may be explained by the signifi cantly lower incidence of distant metastases in the higher dose arm (64% vs 77% at 12 months). It is reasonable to conclude that higher doses of palliative thoracic radiotherapy can delay the development of systemic metastases if disease is confi ned to the chest and can be encompassed within a single treatment fi eld. This translates into a small but signifi cant survival advantage to patients of good performance

Author No. of

patients

Symptom assessment

Cough Hemoptysis Chest pain

Dyspnea Anorexia

Simpson et al. (1985) 409 clinician 99/180(55) 71/75(95) 67/134(50) 63/171(37) NR Collins et al. (1988) 96 clinician 58/86(67) 42/48(87) 28/39(72) 45/85(53) 24/59(41) Teo et al. (1988) 255 clinician Overall symptom control 146/255(57)

MRCLCWP (1991) 369 clinician 206/341(60) 144/172(84) 162/208(78) 156/255(61) 141/213(66) MRCLCWP (1992) 235 clinician 114/220(52) 80/109(73) 90/137(66) 84/198(42) 77/148(52) Muers and Round

(1993)

289 clinician (72) (98) (82) (82) NR

MRCLCWP (1996) 509 patient 210/404(52) NR 188/289(65) 146/255(57) NR Rees et al. (1997) 216 patient 107/168(64) 78/81(95) 78/89(88) 78/128(72) NR Erridge and Murray

(2003)

149 clinician 64/118(54) 61/66(92) 35/53(66) 66/117(56) NR

Number of patients with palliation/number with symptoms (%); NR, not recorded.

Table 3.2.3.1. The effect of palliative radiotherapy

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status. This is supported by the randomised trial reported by Reinfuss et al. (1993), which showed a signiﬁ cant survival advantage when treating good performance status (PS) stage III patients with more a prolonged treatment schedule.

A National Cancer Institute of Canada (NCIC) trial (Bezjak et al. 2002) also showed a signiﬁ cant survival

difference for a higher dose regimen. A total of 230 patients were randomised to either 20 Gy/5 fractions over 5 days or 10 Gy/1 fraction. Both regimens were effective in palliating symptoms, and resulted in limited toxicity, but a signiﬁ cant survival advantage was reported in the higher dose arm (median survival 6 months vs 4.2 months, p=0.0305). Subsequent sub-

Table 3.2.3.2. Published randomised trials comparing different regimens of palliative radiotherapy Author Patient number

and PS

Regimens Palliation Survival Esophagitis

Teo et al.

(1988)

273, any PS 45 Gy/18 fx 31.2 Gy/4 fx/4 weeks

Better with 45 Gy No difference No difference

Simpson et al.

(1985)

316, KPS=>60 40 Gy/20 fx 30 Gy/10 fx 40 Gy/10 fx

No difference No difference No difference

Abratt et al.

(1995)

84, PS 0–2 35 Gy/10 fx 45 Gy/15 fx

No difference No difference Worse with 45 Gy

MRC (1991) 369, any PS 30 Gy/10 fx 17 Gy/2 fx

No difference No difference No difference

MRC (1992) 235, PS 2–4 17 Gy/2 fx 10 Gy/1 fx

MRC (1996) 509, PS 0–1 36–39 Gy/

12-13 fx 17 Gy/2 fx

No difference Better with 39 Gy 9% vs 12% at 2 years

Worse with 39 Gy

Rees et al.

(1997)

216, any PS 17 Gy/2 fx 22.5 Gy/5 fx

No difference No difference NR

Reinfuss et al.

(1999)

240, KPS=>50 50 Gy/25 fx 40 Gy/10 fx 20-25 Gy/5 fx

NR Better with 50 Gy 2-

year survival 18% vs 6% vs 0%

No difference

Nestle et al.

(2000)

152, KPS=>50 36 Gy/15 fx(b.i.d.) 60 Gy/30 fx 17 Gy/2 fx

Bezjak et al.

(2002)

230, PS 0–3 10 Gy/1 fx 20 Gy/5 fx

Better with 20 Gy Better with 20 Gy MS 4.2 vs 6 months

No difference

PS, performance status; KPS Karnofsky performance status; NR, not recorded; MS, median survival, fx, fraction(s).

Table 3.2.3.3. Randomised trials comparing different regimens of palliative radiotherapy – abstract only Author Patient number

and PS

Regimens Palliation Survival Esophagitis

Gaze et al.

(2001)

148, PS 0–3 30 Gy/10 fx 10 Gy/1 fx

Better with 30 Gy

No difference No difference

Sundstrom et al.

(2001)

407, any PS 17 Gy/2 fx 42 Gy/15 fx 50 Gy/25 fx

No difference No difference Worse with 17 Gy at 2 weeks

Senkus-Konefka et al. (2001)

100, any PS 16 Gy/2 fx 20 Gy/5 fx

No difference No difference Worse with 20 Gy Kramer et al.

(2003)

297, PS 2-4 16 Gy/2 fx 30 Gy/10 fx

NA Mean survival

better with 30 Gy 26 vs 35.4 weeks

NA

NA, not available; fx, fraction(s).

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group analysis showed this difference persisted in patients with good PS (WHO 0-1) and localised cancer stage, but was not seen in poor PS patients or those with metastatic disease.

The ﬁ rst MRC LCWP RCT (MRC LCWP 1991) randomised 369 patients to 17 Gy in 2 fractions over 8 days or 30 Gy in 10 fractions over 12 days (or 27 Gy in 6 fractions over 8 days). Patients with poor PS were included, and nearly one third had metastatic disease at the time of randomisation. The schedules were equivalent with respect to symptom palliation, survival and toxicity. In an attempt to simplify treatment even further for patients with poor PS (WHO 2-4), MRC LCWP (1992) randomised 235 patients to 17 Gy in 2 fractions over 8 days or 10 Gy in 1 fraction.

There were no signiﬁ cant differences in palliation or survival between the two arms, although there was a higher incidence of esophagitis with the 2-fraction schedule. The conclusion from the MRC LCWP (1991, 1992) trials was that patients with poor PS and/or more extensive disease can be effectively palliated with one or two treatments; longer and higher dose fractionation schedules are unnecessary and offer no survival advantage.

The Norwegian Lung Cancer Study Group (NLCSG) randomised 407 patients to one of three palliative regimens; 17 Gy in 2 fractions over 8 days, 42 Gy in 15 fractions over 3 weeks or 50 Gy in 25 fractions over 5 weeks (Sundstrom et al. 2002, abstract only). There were no signiﬁ cant differences in symptom palliation or survival between the three arms.

In contrast to the MRC LCWP (1996) trial, subgroup analysis did not show any survival advantage with the higher dose regimens when looking at stage IIIa disease alone. This may be explained by the distribution of performance status in the two trials. In the MRC 1996 trial, 76% of patients were WHO PS 0–1 compared to only 25% in the NLCSG trial. It is probable that poorer performance status patients do not live long enough to beneﬁ t from a higher dose of thoracic radiotherapy.

Gaze et al. (2001, abstract only) randomised 149 patients to 30 Gy in 10 fractions over 12 days or 10 Gy in 1 fraction. Both regimens were effective in palliating thoracic symptoms, and there was no sig- niﬁ cant difference in survival between the two arms.

The 10-fraction regimen resulted in a greater proportion of patients having improvement in dyspnea, and was associated with less anxiety. But the symptoms were scored by the doctors, raising the question of bias, and results therefore should be inter- preted with caution. The reduction in anxiety with the 10-fraction regimen may simply have been due

to more contact with hospital staff over the course of treatment.

In a Dutch RCT (Kramer et al. 2003, abstract only) 297 patients with stage III disease and poor PS, or stage IV disease, were randomised to 30 Gy in 10 fractions over 12 days or 16 Gy in 2 fractions over 8 days. Mean life expectancy was signiﬁ cantly greater in the higher dose arm (35.4 weeks vs 26 weeks, p<0.02). This is the only randomised study to date to claim a survival advantage with a higher dose regimen in patients of poor PS or metastatic disease, but the statistical methods used are open to question. Mean (or average) values are rarely used in the analysis of survival, as a small number of long term survivors can skew results. Median values (time at which 50% of patients are alive) are not affected in the same way, and are generally felt to give a more ac- curate estimate of survival. It is possible that a hand- ful of long term survivors in the 10-fraction arm resulted in the apparent difference seen. In addition, if the survival difference is a true one, what explains it?

Poor performance status patients would not live long enough to beneﬁ t from the higher dose, and it seems unlikely that increased local control with the higher dose would result in a survival advantage in patients with established metastatic disease.

Overall, the evidence suggests that two principles can be applied when treating symptomatic NSCLC patients with palliative thoracic radiotherapy:

– 1. Poor PS patients and those with metastatic disease are effectively palliated with 1 or 2 fractions of radiotherapy and do not beneﬁ t from more fractionated regimens.

– 2. Patients with relatively localised disease and good PS may derive a modest survival advantage with higher doses.

3.2.3.2.3

Treatment-Related Toxicity

It is well recognised that palliative thoracic radiotherapy can be associated with signiﬁ cant acute and long term toxicity. Transient anorexia and nausea are common, as is dysphagia secondary to radiation esophagitis. These symptoms were investigated in detail in the three MRC LCWP trials. All three used patient-held daily diary cards to record signiﬁ cant symptoms. Overall, the proportion of patients suffer- ing some degree of nausea or anorexia following radiotherapy was about 20% and 35%, respectively, and these symptoms were usually mild. The incidence, severity and duration of dysphagia depended on the ra-

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diotherapy regimen used. With 30 Gy in 10 fractions over 12 days and 17 Gy in 2 fractions over 8 days, dysphagia started on day 7, peaking around day 17 when about 40% of patients reported moderate to severe symptoms, and falling to pre-radiotherapy levels by day 28. The 10-Gy/1-fraction regimen resulted in virtually no additional cases of dysphagia above pre-radiotherapy levels. As expected, the higher dose 36- and 39-Gy regimens resulted in more frequent (70% of patients) and prolonged dysphagia.

It has only relatively recently been recognised that palliative thoracic radiotherapy can be associated with other acute symptoms. Stevens and Begbie (1995) noted that 5/38 patients treated with 17 Gy in 2 fractions over 8 days developed acute chest pain.

Devereux et al. (1997) asked 118 patients to com- plete a questionnaire within 24 h of having their ﬁ rst fraction of palliative radiotherapy to the chest. The majority of patients were treated with 8.5- or 10-Gy fractions Chest pain was reported by 54 (45.8%) of patients after their ﬁ rst fraction of radiotherapy. In over 75% of cases, this was within 12 h of the treatment, and on 23 occasions lasted less than 2 h. In addition, 43 (36.4%) of patients reported one or more systemic symptoms (rigors, sweating, fevers). In the majority of cases, systemic symptoms occurred within 12 h of treatment and lasted less than 2 h.

Only 49 (41.6%) reported no immediate side effects.

The timing of symptoms suggests radiotherapy is the most likely cause, but the mechanism is not clear. Of interest is that prophylactic steroids did not prevent chest pain in the Stevens and Begbie (1995) series.

Acute radiation pneumonitis consisting of cough, shortness of breath and patchy radiological changes is a well recognised side effect of thoracic radiation given at radical doses. Using palliative radiotherapy regimens, symptoms are uncommon, usually mild, and resolve completely without long term sequelae.

The most serious late toxicities from thoracic radiotherapy are pulmonary ﬁ brosis and myelopathy.

Pulmonary fi brosis occurs as a consequence of tissue injury repair within a radiation fi eld. It becomes clin- ically evident 9 to 12 months after radiotherapy, and may cause progressive shortness of breath. Pulmonary fi brosis seems to depend, amongst other factors, on the volume of lung irradiated above a threshold of 20–30 Gy in 2-Gy fractions. However, large fraction sizes cause disproportionately more late toxicity, and certainly both 10 Gy in 1 fraction and 17 Gy in 2 fractions over 8 days have the potential to cause signifi - cant fi brosis. It is not usually a problem in this con- text as fi eld sizes are generally not too large, and most

patients do not survive long enough to develop late complications from radiotherapy.

Radiation myelopathy (RM) is a rare but poten- tially disastrous late effect of thoracic radiotherapy.

Clinical experience has demonstrated that regimens such as 30 Gy in 10 fractions over 12 days and 20 Gy in 5 fractions over 5 days are within the tolerance of the spinal cord. Higher dose regimens, and those using large doses per fraction have been associated with an unacceptable risk of RM. Macbeth et al. (1996) reported on the cumulative experience from the three MRC LCWP trials, in which ﬁ ve cases of probable RM were identiﬁ ed from the 1048 patients randomised.

The time of onset ranged from 8 to 42 months from the start of treatment. Three occurred in the 524 patients treated with 17 Gy in 2 fractions over 8 days, and two in the 159 treated with 39 Gy in 13 fractions over 17 days. The estimated cumulative risks for RM at 2 years were 2.2% for the 17-Gy group, and 2.5% for the 39-Gy group.

3.2.3.3

The Asymptomatic Patient

The majority of patients with incurable NSCLC referred for palliative radiotherapy will have symptoms related to their tumour. A proportion of patients referred will, however, be asymptomatic, or the present- ing symptom will have resolved and will no longer be troubling them. Is immediate palliative radiotherapy beneﬁ cial in this group of patients, or should treatment be deferred until the onset of thoracic symptoms?

The MRC LCWP (2002) trial randomised 230 people with previously untreated, incurable NSCLC and minimal thoracic symptoms to immediate radiotherapy or radiotherapy deferred until symptoms developed. The schedules used were 17 Gy in 2 fractions over 8 days or 10 Gy in 1 fraction. In the immediate radiotherapy group, 90% of patients received treatment, compared to 42% in the deferred arm. There were no signiﬁ cant differences in survival or quality of life between the two arms. These ﬁ ndings seem to suggest that about half of patients with unresectable disease and minimal thoracic symptoms will never need palliative radiotherapy during the course of their illness. However, 68% of patients in this trial were PS 0–1, and only 12% had distant metastases.

This trial was begun before the results of the MRC LCWP (1996) trial were known. It is probable that a proportion of patients in this trial with good PS and

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no evidence of metastases would have been suitable for 39 Gy in 13 fractions over 17 days or 36 Gy in 12 fractions over 16 days which has been shown to improve survival in this group. An earlier study reported by Carroll et al. (1986) looked at 48 patients who were treated with thoracic radiotherapy only when symptoms developed. Of 48 patients, 22 (46%) died without needing treatment, supporting the ﬁ ndings of the MRC LCWP (2002) trial.

Reinfuss et al. (1993) randomised 240 patients of good PS with stage III, unresectable, asymptomatic NSCLC to one of three arms: 50 Gy in 25 fractions over 5 weeks, 40 Gy in 10 fractions over 2 weeks split course, or deferred radiotherapy. Median survival was signiﬁ cantly greater with the 5-week regimen compared to the other two arms (12 months, 9 months and 6 months, p<0.05). The results of this study do not support the use of deferred radiotherapy in asymptomatic patients of good PS with locally advanced disease. The survival advantage seen with the 50-Gy regimen supports the use of higher doses in this group of patients, as would be expected, given the results of the MRC LCWP (1996) trial.

The available evidence therefore indicates that a policy of deferred radiotherapy in relatively asymptomatic, poor performance status patients is reasonable. Patients of good performance status with relatively localised incurable disease should be considered for higher dose palliative thoracic radiotherapy even in the absence of symptoms, because survival may be improved.

3.2.3.4

Radiotherapy, Chemotherapy or Both?

In the last 10 years, the use of chemotherapy in advanced and metastatic NSCLC has increased signiﬁ - cantly. Despite its wide use, there is very little data about the effectiveness of chemotherapy in palliating lung cancer symptoms. A meta-analysis carried out by the Non-Small Cell Lung Cancer Collaborative Group (NSCLCCG) using data from 11 RCTs has shown a modest improvement in median survival with cisplatin-based palliative chemotherapy over supportive care alone of around 2 months (NSCLCCG 1995). To date, there are no randomised trials which have compared palliative radiotherapy with palliative chemotherapy. In addition, it is not known how best to combine these treatment modalities. For example, are the survival gains additive if good PS patients with no evidence of metastases are treated with both

chemotherapy and high dose palliative radiotherapy?

Which modality should be used ﬁ rst, or should they be used together? At present, there is no evidence supporting the use of one treatment modality over the other.

3.2.3.5

Appropriate Treatment Strategies

The decision on how best to treat a patient with palliative intent can be complex, because the potential ben- eﬁ ts of any intervention must be carefully weighed against the risks of toxicity. Any treatment plan must take into account the patient’s performance status, symptoms, stage of disease, and individual wishes. A critical step in this decision making process is the assessment of performance status. The ﬁ ve-point World Health Organisation PS scale is a simple measure of functional impairment, which has consistently been shown to be a major prognostic factor in NSCLC.

The evidence suggests symptomatic poor PS patients and/or those with metastatic disease are effectively palliated with 1 or 2 fractions of chest radiotherapy and do not beneﬁ t from more prolonged regimens. The MRC LCWP (1992) trial showed that the 10-Gy/1-fraction regimen is as effective, and associated with less oesophagitis than 17 Gy in 2 fractions over 8 days. Although nausea and, rarely, vom- iting can occur with 10 Gy in 1 fraction, it does not seem to be more frequent than with other regimens, and can be simply managed with antiemetics which can be given prophylactically if felt necessary. With the short fractionation regimens, there may be a greater risk of chest pain and systemic symptoms such as rigors occurring within 24 h of radiotherapy, but the prophylactic use of analgesics and antipyret- ics is usually sufﬁ cient to control these effects. In addition, the short fractionation regimens have the advantage of reducing travelling time for patients who are often very frail.

The MRC LCWP (1996) and NCIC (Bezjak et al.

2002) trials showed that patients with good PS may derive a modest survival advantage with a higher dose regimen given over a more prolonged period, although at the expense of greater toxicity and no better palliation. These issues should be discussed with the patient before deciding on a particular radiotherapy regimen.

The spinal cord damage reported by Macbeth et al.

(1996) with 17 Gy in 2 fractions over 8 days and 39 Gy in 13 fractions over 17 days means these regimens

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should be used with caution. A pragmatic approach would be to reduce the total dose given to a safer level based on previous experience, for example 16 Gy in 2 fractions over 8 days and 36 Gy in 12 fractions over 16 days. In some cases, it is also possible to shield the spinal cord towards the end of treatment, minimising the chance of RM. The use of 16 Gy in 2 fractions in a total of 126 patients has been reported (Lupattelli et al. 2000; Senkus-Konefka et al. 2001) and found not be associated with myelopathy.

In addition, patients should be assessed for chemotherapy. This decision should take into account PS, co-morbidity, bone marrow, kidney, liver and heart function along with the treating health professional’s subjective opinion as to whether the patient is likely to cope with chemotherapy. Patients should be coun- selled about the relative advantages and disadvan- tages of all treatment options for which they are po- tentially suitable, allowing an informed choice to be made that takes into account their personal wishes.

Table 3.2.3.4 broadly outlines a strategy for manag- ing patients with incurable NSCLC, using the available evidence as outlined above. Finally, large fraction chest radiotherapy should be used cautiously in patients with stridor and signiﬁ cant tracheal ob- struction. Hatton et al. (1997) have shown that palliative radiotherapy is associated with a measurable decrease in respiratory function. This may be made worse with large fractions, and so caution would suggest that more fractionated regimens (e.g. 20 Gy in 5 fractions or 30 Gy in 10 fractions) are preferable in this clinical situation

important not to forget that palliative thoracic radiotherapy remains an effective treatment in this setting.

Research carried out over the last 15 years has given us valuable information on the most appropriate radiotherapy treatment regimens to use, has high- lighted the risks of toxicity, and how best to minimise them. There has been a tendency for recent research to concentrate solely on the role of chemotherapy;

however there are still many important unanswered questions. It is not clear which modality may be most beneﬁ cial for a given situation, how best to select patients to ensure they gain the most beneﬁ t, and whether combining treatment options is useful.

Patients with this disease have a limited life expectancy, and often suffer from many disease-related symptoms. It is the desire of all health professionals to apply what is known to make the experience of terminal lung cancer as symptom-free as possible.

Appropriate, coordinated research will hopefully help us achieve this aim.

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Table 3.2.3.4. A treatment strategy for locally advanced and metastatic NSCLC

Poor PS Good PS

Locally advanced:

Chest symptoms 16 Gy/2 fx or 10 Gy/1 fx

Chemotherapy or 36 Gy/12 fx (? or both) No chest symptoms Delayed

16 Gy/2 fx or 10 Gy/1 fx

Chemotherapy or 36 Gy/12 fx (? or both)

Metastatic:

Chest symptoms 10 Gy/1 fx Chemotherapy or 10 Gy/1 fx No chest symptoms Delayed

10 Gy/1 fx

Chemotherapy or delayed 10 Gy/1 fx

3.2.3.6 Conclusion

With chemotherapy playing an increasing role in the management of advanced and metastatic NSCLC, it is

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