About 75% of patients will receive RT at some point in their disease.
Radiotherapy alone
Stage I - IIA
RT has been used in stage I-IIA disease where surgery is not possible. Overall survival improves from 12 months (nil active) to 18 months (RT alone). RT has never been compapred to surgery. See CALGB 9761 - D'Cunha - RT does worse because some malignancies are upstaged on surgical resection. 5 year survival is 30-40%.
To improve outcomes:
- Dose escalation - initial studies showed dose response up to 60 Gy. Newer studies (MSKCC Sura S 2007 13:238) with doses of 80+ Gy in a selected patient group showed overall survival of 3.4 years. RTOG 93-11 was a phase I/II study that increased doses up to 90 Gy, but was associated with highly toxic side effects. 77 Gy was the maximum dose used. 74 Gy can be used; keep V20 below 35%. A follow up to RTOG 93-11, 01-17 examined doses of 74 Gy / 37#, with median survival of 26 months.
- Hypofractionation - To avoid accelerated repopulation and lengthy treatment times other trials have examined hypofractionation. CALGB 39904 has examined this. Median survival was 38 months.
- Stereotactic body RT is becoming increasingly popular, particularly in the United States. Phase II studies show median survival of 2.5-4 years. Phase III studies either compare SBRT vs Surgery (ROSEL study; RTOG 06-18 study; JCOG 040-03 study) or SBRT vs 3D-CRT (eg. TROG 09-02 'CHISEL' - 54 Gy/3#/3 weeks) or Scandinavian SPACE study - 45 Gy/3#/3 weeks). Treatment toxicities are high in centrally placed tumours (see Timmerman R (2006) in JCO;24:4833). No consensus on dose. QA, IGRT and immobilisation are all required before stereotactic body RT can be introduced - see Han K Rad Onc 2010;95:103.
Locally Advanced Disease
WIth RT alone, outcomes are very poor and 5 year survival is < 5%. Conventionally fractionated RT is not recommended for locally advanced disease. Accelerated hyperfractionation has been explored as a potential option. RTOG 83-11 demonstrated hyperfractionation of doses over 70 Gy gave improved outcomes. CHART has been used for NSCLC; it demonstrated a 9% improvement in overall survival (20-29%) but at the cost of increased acute toxicity; no differences were seen in late toxicity.
Only one study has examined accelerated hyperfractionation with chemoradiotherapy; outcomes were similar but chemoradiotherapy was slightly better (13.2 versus 12 months) - see Sause et al in Chest (2000);117:358.
Chemotherapy and Radiotherapy
Locally Advanced Disease
Addition of chemotherapy to radiotherapy for locally advanced lung cancer has been established in three meta-analyses (see Cochrane review). Sequencing of CT and RT has also been extensivey investigated; again, see the 2004 Cochrane review. In general:
- Survival with no treatment = 6 months
- Survival with RT alone = 9 months
- Survival with neo-adjuvant CT followed by RT = 13 months
- Concurrent chemoradiotherapy = 18 months
The negative aspect of concurrent CRT are myelosuppression, a 6-fold increase of grade 3 oesophagitis and 3% increase in the rate of death.
Adjuvant RT
Adjuvant RT is detrimental in stage I - II disease - see Burdett S and Stewart L in Lung Cancer 2005;47:81.
Adjuvant RT in stage III disease is still under investigation, with non-significant results in previous studies.
Adjuvant RT can be considered in Stage III disease in the setting of positive margins; there is minimal evidence.
Prophylactic Cranial Irradiation
The brain is not as frequently involved in NSCLC when compared to SCLC - only 10-20% of patients will develop relapse in the brain following radical therapy for localised disease. This significantly impacts the patient and can lead to reduced quality of life or death. Completed studies demonstrate halved rates of brain metastases but at the expense of memory loss at 1 year. PCI for NSCLC is not routine treatment.
Palliative RT
Chest RT
Timing of chest RT has been explored; there is no change in quality of life, symptoms or survival if RT is delayed until symptoms are present (Falk SJ BMJ 2002;325:1). Symptoms are improved and survival is greater with doses of 30 Gy in 10 Gy (Fairchild A 2008 JCO 26:4001)
Palliative Brachytherapy
Has been the subject of a Cochrane review (2008); EBRT alone is more effective than brachytherapy alone; no consensus of effectiveness of EBRT + Brachytherapy versus single modality. Brachytherapy can be used for endobronchial lesions and is particularly useful for patients who have received external beam RT previously. It can not be used if the bronchus is obstructed. Doses vary; commonly used doses include 17 Gy/2 # delivered to 1 cm. There is significant symptom relief. Side effects can include haemoptysis or fistula.
Treatment Planning
Image Acquisition
Use contrast enhanced CT images for voluming. Pulmonary windows are best for contouring of the primary; soft tissue windows help with nodal metastases. PET should be fused if possible.
For dose escalation consider using:
- 4-dimensional CT to reduce the ITV
- Respiratory gating to reduce the ITV
- IGRT with fiducial markers to aid in targeting of tumour
Volumes
CTV = GTV + 6 mm for SCC; CTV = GTV + 8 mm for adenocarcinoma (giraud et al IJROBP 2000;48:1015)
CTVn = GTVn + 8 mm (variable reports; see Yu J et al.
Clip CTV to avoid vessels, airway, bones, other tissue planes.
Elective nodal irradiation is controversial; recurrence rates are <8% (see Senan S in IJROBP 2002;54:999). Avoiding lymph nodes reduces volumes and aids in tolerance of treatment.
ITV = CTV + internal margin. For accurate determination of this 4D CT is the best tool but is not always available.
PTV = ITV + 0.5 cm
ITV
Defining the ITV is one of the most difficult aspects of lung cancer treatment. There are several methods:
- Estimating tumour motion on a simulator
- 4D CT at all phases of the breathing cycle, then combining the images at each phase of the repiratory cycle (Maximum Intensity Projection) to determine the ITV.
- Guessing based upon the location of the tumour
4D CT is mandantory for ITV calculation in stereotactic treatment due to the risk of toxicity.
Simulators are not present in many departments and 4D CT is not introduced in many others. This makes 'guessing' the most available option but also the most risky.
- Overestimating the ITV can lead to increased and unnecessary toxicity
- Underestimating the ITV leads to poor tumour control
For tumours in the upper lobes, movement is usually less than 1 cm in all dimensions (mostly superior-inferior).
