positron emission tomography) for staging has improved patient selection by identifying patients with distant metastases for whom ‘curative’ radiotherapy would be futile. During the past decade, intensity modulated radiation therapy (IMRT), stereotactic radiotherapy, proton radiotherapy and carbon ion radiotherapy have attracted a great deal of publicity and resources, but their evidence base remains weak at present. They have not been proven to prolong the survival of cancer patients over standard 3-D conformal techniques. Furthermore, implementing adequate quality assurance measures for these techniques has proven difficult not only in less developed countries, but even in some more developed countries such as the United States of America. This chapter describes selected radiation oncology studies that have had a significant impact in the routine treatment of common adult cancers with radiotherapy. The authors have selected studies which in their opinion have changed or have the potential to change the practice of radiation oncology and improve the outcomes for cancer patients, both for cure and for effective palliation. 30 2.2. BREAST CANCER The British Columbia randomized radiotherapy trial [2.1] was designed to determine the survival impact of locoregional radiotherapy in premenopausal patients with lymph node positive breast cancer treated by modified radical mastectomy and adjuvant chemotherapy. Three hundred and eighteen patients were assigned to receive no further therapy or radiotherapy (37.5 Gy in 16 fractions). At the 20 year follow-up (the median follow-up for live patients was 249 months), compared with chemotherapy alone, chemotherapy and radiotherapy were associated with a statistically significant improvement in all end points analysed, including survival free of isolated locoregional recurrences (74% versus 90%, respectively; relative risk (RR) = 0.36, 95% confidence interval (CI) = 0.18 to 0.71; p = 0.002), systemic relapse free survival (31% versus 48%; RR = 0.66, 95% CI = 0.49 to 0.88; p = 0.004), breast cancer free survival (48% versus 30%; RR = 0.63, 95% CI = 0.47 to 0.83; p = 0.001), event free survival (35% versus 25%; RR = 0.70, 95% CI = 0.54 to 0.92; p = 0.009), breast cancer specific survival (53% versus 38%; RR = 0.67, 95% CI = 0.49 to 0.90; p = 0.008) and overall survival (47% versus 37%; RR = 0.73, 95% CI = 0.55 to 0.98; p = 0.03). Long term toxicities, including cardiac deaths (1.8% versus 0.6%), were minimal for both arms. For patients with high risk breast cancer treated with modified radical mastectomy, treatment with radiotherapy (schedule of 16 fractions) and adjuvant chemotherapy led to better survival outcomes than chemotherapy alone, and it was well tolerated, with acceptable long term toxicity. 2.3. LUNG CANCER A randomized controlled trial in locally advanced non-small cell lung cancer (NSCLC) [2.2] compared CHART (continuous hyperfractionated accelerated radiotherapy), which employs 36 fractions of 1.5 Gy three times per day to give 54 Gy in 12 consecutive days, with conventional radiotherapy — 30 fractions of 2 Gy to give a total dose of 60 Gy in six weeks. A total of 563 patients were entered between April 1990 and April 1995. This report is based upon the data updated to 1 April 1998. Overall, there was a 22% reduction in the relative risk of death with CHART, which is equivalent to an absolute improvement in two year survival of 9% from 20 to 29% (p = 0.008) and a 21% reduction in the relative risk of local progression (p = 0.033). In the large subgroup of patients with squamous cell cancer, which accounted for 81% of the cases, there was a 30% reduction 31 in the relative risk of death, which is equivalent to an absolute improvement in two year survival of 13% from 20 to 33% (p = 0.000 7) and a 27% reduction in the relative risk of local progression (p = 0.012). Furthermore, in squamous carcinoma, there was a 25% reduction in the relative risk of local and/or distant progression (p = 0.025) and a 24% reduction in the relative risk of metastasis (p = 0.043). There was no evidence that CHART yielded more or less benefit in any other subgroup. This analysis of mature data confirms that CHART is superior to