A Randomised Phase III Trial of Highly Conformal Hypofractionated Image Guided ("Stereotactic") Radiotherapy (HypoRT) Versus Conventionally Fractionated Radiotherapy (ConRT) for Inoperable Early Stage I Non-small Cell Lung Cancer (CHISEL)
This is a multicentre randomised phase III trial comparing hypo-fractionated
("stereotactic') radiotherapy with conventional radiotherapy with or without chemotherapy in
patients with inoperable stage 1 peripherally located non-small cell lung cancer.
The accepted standard of care for stage 1 non-small cell lung cancer (NSCLC), that is, T1 or
T2 tumors that have not metastasised to the regional lymph nodes, is surgical resection.
However, many patients with lung cancer have significant cardiovascular and respiratory co
morbidities which render them unfit for an operation. For these patients, the standard of
care is radiotherapy - conventional fractionation (ConRT) which is administered as 20-30
fractions over a period of four to six weeks. This reduces the likelihood of long term
damage to incidentally irradiated normal tissues compared with non-fractionated treatment.
Local failure for this method, varies considerably between reports ranging from 6-70% with a
median value of 40% using a current best practice for inoperable NSCLC dose of about 60 Gy.
Concomitant chemotherapy in addition to CF improves local progression free survival by 16%
at two years compared with radiotherapy alone.
Highly conformal hypo-fractionated image guided radiotherapy is an emerging technically
complex method for precision irradiation of stage 1 NSCLC using doses with a higher
biological effect than can be achieved with standard treatment techniques. Although rates of
local control using hypo-fractionation appear greater, there are risks with serious late
toxicity. However, there is recent evidence that 54-57Gy delivered in 3 fractions can be
delivered safely with no excessive toxicity, provided the tumour has a peripheral location,
the chest wall is not included in the high dose volume and the treatment plan is highly
conformal. Although hypo-fractionation under the above conditions appears to be tolerable,
and is associated with high levels of local control, the results of a small number of phase
II trials cannot be regarded as sufficient evidence to recommend it as the standard of care
for inoperable stage I NSCLC.
This randomised phase III trial tests whether highly conformal hypo-fractionated image
guided radiotherapy for peripherally located inoperable T1 and T2a NSCLC using a dose of 54
Gy in three fractions results in superior control of disease at the primary site compared
with standard care consisting of conventionally fractionated radiotherapy with or without
Treatment summary: Investigational arm - radical radiotherapy to a total dose of 54 Gy in 3
fractions of 18 Gy each, delivered weekly on days 0, 7 and 14 with a maximum deviation of
+/- 2 days from the specified time allowed. Conventional arm - radical radiotherapy to a
total dose of 60-66 Gy in 30-33 daily 2 Gy fractions over 6 weeks, with or without
chemotherapy consisting of weekly carboplatin at an AUC of 2 and paclitaxel 45 mg/m2.
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Time to Local Failure
Completion of the two year follow up period for all patients.
David Ball, MB BS, MD, FRANZCR
Peter MacCallum Cancer Centre, Australia
Australia: Department of Health and Ageing Therapeutic Goods Administration