Background
Methods
Patient data
Toxicity outcomes
Registration process
Obtaining dose-volume histograms
Response modelling
Results
Toxicity type | Distribution-adding | Parameter-adding | ||
---|---|---|---|---|
Odds ratioa
| VX
b
| DX%
c
| DX%
c
| |
Rectal bleeding | 01–05 Gy 48–80 Gy | 48–80 Gy | 01–25 % 68–78 % | 01–25 % 62–78 % |
Stool frequency | 49–55 Gy | 49–57 Gy | 07–18 % | 02–24 % 58–73 % |
Diarrhoea | 51 Gy | 50–59 Gy | 08–13 % | None |
Completeness of evacuation | None | None | None | None |
Anorectal pain | 44–48 Gy | 45–48 Gy | None | None |
Urgency/tenesmus | 25–26 Gy 40–63 Gy | 25–27 Gy 43–64 Gy | 05–38 % 56–74 % | None |
Proctitis | None | None | None | 59–70 % |
Toxicity type | Findings for α/β = 5.4 Gy compared to α/β = 3 Gya
|
---|---|
Rectal bleeding | Similar trends |
Stool frequency | Similar trends |
Diarrhoea | Odds ratios not significant for α/β = 5.4 Gy |
Completeness of evacuation | No significance for α/β = 3 Gy or α/β = 5.4 Gy |
Anorectal pain | Similar trends |
Urgency/tenesmus | Similar trends |
Proctitis | Similar trends |
Discussion
It is important to explore dose-toxicity modelling in a variety of registration contexts
Studies had identified important dose-volume metrics for a variety of prostate radiotherapy techniques
Toxicity | Dose-volume consideration | Reference | RT technique |
---|---|---|---|
Rectal toxicity | Constrain the V30-70 Gy
| HDR, EBRT | |
Constrain the V40 Gy and V65-80 Gy
| [37] | EBRT | |
Constrain the V100%
| [38] | HDR | |
Limit the D1cc-10cc
| [34] | HDR | |
D5%-90% were not significant | [34] | HDR | |
Rectal bleeding |
Limit the high/near maximum doses
|
Current study
|
EBRT+HDR
|
Limit doses > 48 Gy
|
Current study
|
EBRT+HDR
| |
Some association with low doses (0–5 Gy) |
Current study
|
EBRT+HDR
| |
Constrain the V40-80 Gy
| EBRT | ||
Limit the D2cc and near maximum doses | EBRT+HDR, LDR, EBRT+LDR | ||
Near maximum doses were not significant | [3] | EBRT+HDR | |
Limit doses > 30 Gy | EBRT | ||
Constrain the V30%, V50%, V80% and V90%
| [44] | EBRT | |
Constrain the V10%, V30% and V50%
| [45] | EBRT+HDR | |
Stool frequency |
Limit the mid-high dose range (49–57 Gy) |
Current study
|
EBRT+HDR
|
Limit the low-mid dose range (4–38 Gy) | [30] | EBRT | |
Constrain the V50-60 Gy
| [26] | EBRT | |
Constrain the V40 Gy
| [32] | EBRT | |
Diarrhoea |
Some association with mid-high doses (50–59 Gy) |
Current study
|
EBRT+HDR
|
Limit the low-mid doses (22–32 Gy) | [30] | EBRT | |
Completeness of evacuation |
No dose range is significant
|
Current study
|
EBRT+HDR
|
Limit the low-mid doses (12–36 Gy) | [30] | EBRT | |
Anorectal pain |
Some association with mid-dose range (45–48 Gy) |
Current study
|
EBRT+HDR
|
Urgency/tenesmus |
Limit the mid-high doses (43–64 Gy) |
Current study
|
EBRT+HDR
|
Some association with low doses (25–27 Gy) |
Current study
|
EBRT+HDR
| |
Constrain the V40-60 Gy
| [26] | EBRT | |
Constrain the V25-75 Gy
| [37] | EBRT | |
Limit the low-mid doses (5–38 Gy) | [30] | EBRT | |
Proctitis |
No dose range is significant
|
Current study
|
EBRT+HDR
|
Constrain the V40-70 Gy
| [26] | EBRT |
The findings indicate a serial response for rectal bleeding
The mid-dose region is important for bleeding/non-bleeding toxicities
Toxicity is also influenced by low doses and the lower end of the mid-dose range
Software developments to improve contour consistency and registration accuracy for the prostate/rectum interface would be of great benefit
Inter-fraction motion should be considered
Avenues and recommendations for further analysis
-
Given this is the first study to apply deformable registration prior to correlating combined EBRT/HDR dose with toxicity, it is important that the model and findings be validated in other contexts with standardised contouring, implanting and planning guidelines for EBRT and HDR.
-
Image guided radiotherapy or further imaging could improve the reliability of accumulated dose-histogram metrics [13].
-
Customised registration algorithms for accurately handling the catheters within the HDR prostate or data for treatments which use plastic HDR catheters are encouraged as prostate and urethra doses are key clinical concerns in the RADAR trial [27].
-
It would also be useful to determine whether other aspects of the total registered dose distribution add predictive capability to dose-toxicity modelling e.g. including dose-shape toxicity modelling [60].