1. Treatment With Continuous, Hyperfractionated, Accelerated Radiotherapy (CHART) For Non-Small Cell Lung Cancer (NSCLC): The Weston Park Hospital Experience
Lester JE, Das T, Din OS and Hatton MQ
Weston Park Hospital, Sheffield, UK
Introduction
Multivariate Analysis
Multivariate analysis comparing Age (</>65yrs), Performance status, Stage, Tumour type, Prior Chemo and Prior PET CT are shown in figures 2a-f.
Increasing age was not associated with worse survival and outcomes of patients with performance status 0,1 or 2 were similar but the 2 patients treated with performance status 3 did badly. As expected patients with stage 1 disease (median survival 22.5 months) survived longer than stage 2 (14.3 months) and stage 3 (16.1 months) patients.
Prior Chemotherapy was not associated with a worse outcome despite the greater proportion of chemotherapy patients with stage 3 disease (38/46) than those not treated with chemotherapy (59/108). This is in contrast to Din et al. where chemotherapy patients did worse. In this analysis PET scanning was associated with a survival benefit (15.1 vs months) with a trend towards significance (p=0.057).
CHART is now an established treatment for NSCLC and is currently offered at a number of centres across the UK. CHART involves 54Gy in 36 fractions over 12 consecutive days treating 3 times a day with each fraction at least 6 hours apart. In comparison to conventional radiotherapy (60Gy in 30 Fractions over 6 weeks) 2 year survival improved from 21% to 29% with CHART (Saunders et al. 1999). In a more recent analysis of CHART outcomes 583 patients treated with CHART in 5 UK centres from 1998 to 2003 reported 2 and 3 year survival figures of 33.6 and 20.1% respectively (Din et al. 2008). In the multivariate analysis tumour subtype did not effect survival but patients treated with chemotherapy prior to CHART did worse (2yr OS 18% vs. 38%, p<0.001)
In this review of patients treated in Sheffield we present treatment toxicity and outcomes from 2005 to 2010.
Methods
Figure 2a. Age
Figure 2b. Performance status
PS 0
N=35
Median survival 25.2 months
PS 1
N=92
Median survival 16.6 months
PS 2
N=24
Median survival 21.5 months
PS 3
N=2
Median survival 2.2 months
<65 years
N=64
Med survival months
>65 years
N=90
Med survival months
We carried out a retrospective analysis of data from patients treated in Sheffield to assess patient demographics, tumour characteristics, treatment details, toxicity and outcome in patients who underwent CHART between November 2004 and December A standard database was used to collect data from all patients. Follow-up was for a minimum of 15 months from the date of starting radiotherapy. Statistical analysis was performed using SPSS version 16.0.
p=0.827
p=0.192
Results
Figure 2c. Stage
Table 1. Patient Demographics
Figure 2d. Tumour type
154 patients with a median age of 69 years (range 43-87) underwent CHART between November 2004 and December Patient demographics are shown in Table 1. Stage III cancers were the most commonly treated with 97 (63%) patients. Early stage cancers were less common with 36 (23%) stage I and 20 (13%) stage II.
Prior chemotherapy was offered to 46 (30%) patients all with stage III cancer. Most patients had a performance status of 0 or 1 (127, 83%) prior to treatment but 26 (17%) were performance status 2 or more.
Squamous cancers (72, 46.7%) were the most commonly treated followed by NSCLC unspecified (54, 35.1%), Adenocarcinomas (20, 13.0%) and Large cell cancers (8, 5.2%).
Most patients had a PET scan prior to commencing CHART (126, 82%).
Stage I
N=36
Med survival 22.5 months
Stage II
N=20
Med survival 14.3 months
Stage III
N=97
Med survival 16.1 months
Squamous
N=72
Median survival 16.1 months
Adenocarcinoma
N=20
Median survival 22.5 months
Large cell
N=8
Median survival NA
Unspecified/Unknown
N=54
Median survival 25.8 months
p=0.168
P=0.145
Figure 2e. Prior Chemotherapy
Figure 2f. Prior PET scan
No Chemo
N=108
Med survival 19.5 months
Chemo
N=46
Med survival 15.1 months
PET
N=126
Med survival 15.1 months
No PET
N=28
Med survival 21.5 months
p=0.057
p=0.359
Treatment Outcomes
The median survival was 19.5 months with a 2 and 3 year overall survival of 45.0 and 29.2% respectively (see figure 1).
6 week post treatment CT responses were as follows: complete response 18 (12%), partial response 83 (54%) patients, stable disease 36 (23%) and progressive disease 14 (9%) patients. 92 (48%) of the patients had recurrent disease and 93 (60%) had died at the time the data was analysed (March 2011)(See table 2).
Treatment toxicity and tolerability
126 (79%) patients experienced a radiotherapy related toxicity of which 97% were recorded as grade 1 or 2. Only 4 (3%) patients experienced a grade 3 or higher toxicity.
153/154 (99%) patients received the prescribed dose
Table 3. Toxicity from CHART
Figure 1. Overall survival
Conclusions
Median survival 19.5 months
6 month survival 86.9%
12 month survival 65.0%
24 month survival 44.4%
36 month survival 32.1%
CHART was well tolerated and initial responses to treatment are comparable with previously published series.
Similar outcomes were also observed to those estimated from concurrent chemoradiotherapy for stage III NSCLC (median survival months)(O’Rourke et al. 2010).
CHART is well tolerated with very few patients not completing therapy
Age >65yrs and performance status of 2 were not predictors of poor prognosis
Squamous cancers in this analysis did not confer a better outcome from CHART than other tumour types
PET scanning in this analysis was associated with an improvement of median survival of 6.4 months
Table 2. Treatment responses and recurrences
References
• Din O, et al. Routeine use of continuous, hyperfractionated, accelerated radiotherapy for non-small call lung cancer: A five centre experience. Int J Radiation Oncology Biol Phys :
• O’Rourke et al. Is Concurrent chemoradiation the standard of care for locally advanced non-small cell lung cancer? A review of guidelines and evidence. Clinical Oncology :
• Saunders M et al. Continuous, hyperfractionted, accelerated radiotherapy (CHART) versus conventional radiotherapy in non-small cell lung cancer:mature data from the randomised multicentre trial. Radiother Oncol :