Relationships between rectal and perirectal doses and rectal bleeding or tenesmus in pooled voxel-based analysis of 3 randomised phase III trials.

BACKGROUND AND PURPOSE: This study aimed to identify anatomically-localised regions where planned radiotherapy dose is associated with gastrointestinal toxicities in healthy tissues throughout the pelvic anatomy. MATERIALS AND METHODS: Planned dose distributions for up to 657 patients of the Trans Tasman Radiation Oncology Group 03.04 RADAR trial were deformably registered onto a single exemplar computed tomography dataset. Voxel-based multiple comparison permutation dose difference testing, Cox regression modelling and LASSO feature selection were used to identify regions where dose-increase was associated with grade ≥2 rectal bleeding (RB) or tenesmus, according to the LENT/SOMA scale. This was externally validated by registering dose distributions from the RT01 (n = 388) and CHHiP (n = 241) trials onto the same exemplar and repeating the tests on each of these data sets, and on all three datasets combined. RESULTS: Voxel-based Cox regression and permutation dose difference testing revealed regions where increased dose was correlated with gastrointestinal toxicity. Grade ≥2 RB was associated with posteriorly extended lateral beams that manifested high doses (>55 Gy) in a small rectal volume adjacent to the clinical target volume. A correlation was found between grade ≥2 tenesmus and increased low-intermediate dose (∼25 Gy) at the posterior beam region, including the posterior rectum and perirectal fat space (PRFS). CONCLUSIONS: The serial response of the rectum with respect to RB has been demonstrated in patients with posteriorly extended lateral beams. Similarly, the parallel response of the PRFS with respect to tenesmus has been demonstrated in patients treated with the posterior beam.

Socio-economic inequalities in testicular cancer survival within two clinical studies.

BACKGROUND: Testicular cancer is the most common cancer in men under 35 years of age, and has the highest survival for adult male malignancies. Despite the fact that survival is very high, there is evidence that survival differs between socio-economic groups. METHODS: We analysed survival patterns for 1606 testicular cancer patients diagnosed during 1984-2001 and recruited to one of two clinical studies. The first was a surveillance study to determine relapse-free survival after orchidectomy in 865 patients with stage I nonseminomatous germ-cell testicular cancer diagnosed during 1984-1991 (TE04). The second study was a trial in which 1174 men with stage I seminomatous germ-cell tumours were randomised to receive radiotherapy or one injection of carboplatin between 1996 and 2001 (TE19). The number of men available for analysis from these two studies was 578 and 1028, respectively. We followed these patients up for their vital status, and assigned them an ecological measure of deprivation. Crude and relative survival were estimated at 5 and 10 years by socio-economic deprivation. RESULTS: No significant socio-economic gradient was seen: 1.3% (95% CI -0.3% to 3.1%) at 5 years and 2.1% (95% CI -0.5% to 4.7%) at 10 years. CONCLUSION: We conclude that, given equal treatment at a given stage of disease, survival from testicular cancer does not depend on socio-economic status. This suggests that the socio-economic gradient in testicular cancer survival in the general population is more likely to be attributable to health care system factors than to personal or socio-economic factors in the men themselves.