Small cell lung cancerradiotherapy

Background

Patients with small cell lung cancer (SCLC) are usually treated by primary chemotherapy because of its chemo-responsiveness and frequent dissemination at time of diagnosis. SCLC is, however, also the most radio-responsive variety of bronchial carcinoma and radiotherapy has an important role in its management. In patients with a localized tumour, thoracic irradiation (TI) and prophylactic cranial irradiation (PCI) improve disease control at these sites and lead to prolongation of survival when compared to chemotherapy alone. In addition, radiotherapy is a useful palliative treatment for patients relapsing after, resistant to, or refusing chemotherapy.

Thoracic irradiation (TI)

♦ 60% of relapses after chemotherapy are in the thorax

♦ TI reduces risk by 50% and improves survival

♦ Survival improves from 9 to 14% at 3 years

♦ Schedule is uncertain

♦ Early and concurrent with chemotherapy—best results but more side-effects

Prophylactic cranial irradiation (PCI)

♦ SCLC has propensity for brain metastases

♦ 20% have brain involvement at diagnosis

♦ 80% have brain involvement at death

♦ Blood-brain barrier limits effectiveness of chemotherapy (sanctuary site)

♦ Median survival once CNS disease develops is 3 months; 50% only have reasonable palliation with chemotherapy or radiotherapy

♦ Low-dose PCI halves risk of brain metastases

♦ Low-dose PCI—small improvement in survival

♦ Dose and schedule of PCI is uncertain

♦ Not given concurrently with chemotherapy

Palliative radiotherapy

A short course of irradiation to either the primary tumour or the site of metastases can provide useful symptom control. The choice of dose and radiation schedule is similar to that used in NSCLC and should follow the basic principles of using the lowest effective dose with minimal additional toxicity. In most situations a single fraction or up to five fractions of treatment will suffice.

Radiotherapy administration

Decisions about use of combined modality treatment for individual patients are based on assessment of their prognostic factors. This approach brings increased risks of toxicity and overall demands on patients and should be reserved for those with a realistic prospect of long-term survival. Exact timing of administration, dose, and fractionation schedule of TI and PCI will be determined by individual protocols and may be subject of study in a randomized clinical trial. Hyperfractionated schedules and concurrent administration of chemotherapy and irradiation remain investigational. For routine use outside clinical trials, the following are commonly used:

TI—50 Gy in 2 Gy daily fractions or biological equivalent PCI—24 Gy in 8 fractions, 30 Gy in 10 fractions, or 36 Gy in 18 fractions

Treatment volume of TI will depend on time of administration and on local practice. It is common practice to irradiate the mediastinum even in the absence of lymphadenopathy because of frequency of occult nodal metastases.

Pre-chemotherapy CT and chest radiographs are important to ensure that pre-chemotherapy sites of disease are encompassed by radiotherapy fields. Mega-voltage irradiation is used and sophisticated approaches to field placement and dosimetry are necessary to ensure optimal trade-off between preserving spinal cord tolerance and minimizing radiation dose to the surrounding normal lung. This often means a 'shrinking field' or phased approach.

For PCI planning it is important to encompass all meningeal surfaces, particularly the cribriform plate and middle cranial fossa.

Follow-up

This is designed to detect recurrences and monitor side-effects of treatment. Treatment of recurrent disease is always palliative in intent. Late effects of TI on lung and PCI on cognitive function are important limitations and need to be formally assessed by the team responsible for administration of radiotherapy. Follow-up chest radiographs will show mediastinal fibrosis in all patients. Associated functional impact depends on volume, previous respiratory reserve, and patients' activity levels.

Mediastinal fibrosis makes interpretation of follow-up radiology difficult and may lead to concerns about recurrence that can only be resolved by sequential radiology. Thoracic CT gives better definition of cross-sectional anatomy, but still needs to demonstrate a change to reliably confirm recurrence.

Following PCI about 30% of patients will develop 'somnolence' as a classical, self-limiting effect, 2-3 months after treatment. With longer follow-up patients may complain of recent memory loss, but formal neuropsychometric evaluations have failed to demonstrate significant deterioration attributable to PCI.

Future research

The question of optimal scheduling of TI needs to be resolved. Current evidence suggests early introduction may be more effective than traditional consolidation therapy. This approach may not be suitable for patients with bulky mediastinal disease or with tumour involvement outwith a safe size of radiation field. Further research needs to address the use of hyperfractionated or accelerated radiation techniques and use with concurrent chemotherapy. Similar uncertainties exist for radiation timing, dose, and optimal schedules of PCI.

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