Exploiting biological and physical determinants of radiotherapy toxicity to individualize treatment.
AffiliationUniversity of Cambridge Department of Oncology, Cambridge Biomedical Campus, Addenbrooke's Hospital, Cambridge, UK
MetadataShow full item record
AbstractThe recent advances in radiation delivery can improve tumour control probability (TCP) and reduce treatment-related toxicity. The use of intensity-modulated radiotherapy (IMRT) in particular can reduce normal tissue toxicity, an objective in its own right, and can allow safe dose escalation in selected cases. Ideally, IMRT should be combined with image guidance to verify the position of the target, since patients, target and organs at risk can move day to day. Daily image guidance scans can be used to identify the position of normal tissue structures and potentially to compute the daily delivered dose. Fundamentally, it is still the tolerance of the normal tissues that limits radiotherapy (RT) dose and therefore tumour control. However, the dose-response relationships for both tumour and normal tissues are relatively steep, meaning that small dose differences can translate into clinically relevant improvements. Differences exist between individuals in the severity of toxicity experienced for a given dose of RT. Some of this difference may be the result of differences between the planned dose and the accumulated dose (DA). However, some may be owing to intrinsic differences in radiosensitivity of the normal tissues between individuals. This field has been developing rapidly, with the demonstration of definite associations between genetic polymorphisms and variation in toxicity recently described. It might be possible to identify more resistant patients who would be suitable for dose escalation, as well as more sensitive patients for whom toxicity could be reduced or avoided. Daily differences in delivered dose have been investigated within the VoxTox research programme, using the rectum as an example organ at risk. In patients with prostate cancer receiving curative RT, considerable daily variation in rectal position and dose can be demonstrated, although the median position matches the planning scan well. Overall, in 10 patients, the mean difference between planned and accumulated rectal equivalent uniform doses was -2.7 Gy (5%), and a dose reduction was seen in 7 of the 10 cases. If dose escalation was performed to take rectal dose back to the planned level, this should increase the mean TCP (as biochemical progression-free survival) by 5%. Combining radiogenomics with individual estimates of DA might identify almost half of patients undergoing radical RT who might benefit from either dose escalation, suggesting improved tumour cure or reduced toxicity or both.
CitationExploiting biological and physical determinants of radiotherapy toxicity to individualize treatment. 2015, 88 (1051):20150172 Br J Radiol
JournalThe British Journal of Radiology
- Rectal wall sparing by dosimetric effect of rectal balloon used during intensity-modulated radiation therapy (IMRT) for prostate cancer.
- Authors: Teh BS, Dong L, McGary JE, Mai WY, Grant W 3rd, Butler EB
- Issue date: 2005 Spring
- Preliminary toxicity analysis of 3-dimensional conformal radiation therapy versus intensity modulated radiation therapy on the high-dose arm of the Radiation Therapy Oncology Group 0126 prostate cancer trial.
- Authors: Michalski JM, Yan Y, Watkins-Bruner D, Bosch WR, Winter K, Galvin JM, Bahary JP, Morton GC, Parliament MB, Sandler HM
- Issue date: 2013 Dec 1
- Nomogram to predict rectal toxicity following prostate cancer radiotherapy.
- Authors: Delobel JB, Gnep K, Ospina JD, Beckendorf V, Chira C, Zhu J, Bossi A, Messai T, Acosta O, Castelli J, de Crevoisier R
- Issue date: 2017
- Improvement in toxicity in high risk prostate cancer patients treated with image-guided intensity-modulated radiotherapy compared to 3D conformal radiotherapy without daily image guidance.
- Authors: Sveistrup J, af Rosenschöld PM, Deasy JO, Oh JH, Pommer T, Petersen PM, Engelholm SA
- Issue date: 2014 Feb 4
- The normal tissue sparing obtained with simultaneous treatment of pelvic lymph nodes and bladder using intensity-modulated radiotherapy.
- Authors: Søndergaard J, Høyer M, Petersen JB, Wright P, Grau C, Muren LP
- Issue date: 2009