This section provides a glossary of dosimetric terms evolving in radiation oncology. Originally, normal organ tissue tolerance was developed empirically and patterns of practice dose limits were described. With the development of modern treatment planning techniques in the mid-1980s and IMRT techniques in the mid-1990s, we began to take a serious look at normal tissue complication rates and the doses related to complications. Radiobiologic data has been incorporated, with the division of organs into serial and parallel structural arrangements. QUANTEC has consolidated some of the data to make recommendations on normal tissue tolerance doses. More recently in the 2000 to 2010 decades, the RTOG and other study groups have been quantifying dosimetry. Unfortunately, this has led to terminology that is not appropriately descriptive, from a physics perspective, and probably does not adequately describe what really needs to be described. Terms like "low dose spillage" and "high dose spillage" merely describe dose inhomogeneity. It is unfortunate that these ambiguous and non-descriptive terms have been used to identify radiation dose distribution physics. It is clear when we administer radiation to tissue, it will follow a specific and clearly identifiable fluence pattern which is a function of many factors, including but not limited to beam energy, media boundaries, media electron density, and changes to that density in the particle transit pathways. Dose will be delivered somewhere, and where that dose is delivered is what we need to be cognizant. This is what modern dosimetry is all about.
Many of the dosimetric volume definitions are described by the ICRU (International Commission on Radiation Units and Measurements), which was established in 1925. There are a number of references to these units and definitions. If they are not described here, a good resource is the ICRU itself, or the may descriptions available.
The specific ICRU reports describing these parameters are ICRU-50 (1992) and a supplement, ICRU-62 (1999).
The ICRU states that if the entire GTV cannot be covered with the desired dose, the treatment should be considered "palliative."
GTV describes the visualizable and clinically quantifiable disease. This is an anatomical target volume.
CTV describes the microscopic or volume at risk which is either an expansion on the GTV, a function of the disease natural history and growth characteristics, or a sub-clinical at risk volume after the primary tumor has been treated. This is a target volume that incorporates any GTV, and extensions which carry a probability of disease significant for radiotherapy. Thus the CTV is a clinical and anatomic target volume. The CTV may include just GTV and any uncertainty in delineating the GTV based on the availble imaging techniques. Consideration of this uncertainty should be made in establishing the CTV margin. CTV=GTV (if any) + clinical margin.
ITV describes the internal target volume which incorporates corrections for anatomic variance such as respiratory or other organ motion or displacement.
PTV describes the overall treatment setup uncertainty and describes the aperture necessary to establish a radiation field needed to treat the disease and constrain the radiation field to minimize normal tissue complications. The planning target volume is the volume which accounts for all internal motion, setup uncertainty, and CTV coverage. The PTV is used to shape the beam portals and isodose volume distributions to insure that a clinically acceptable dose will cover the entire CTV at an acceptable probability.
PTV = CTV + Expansion margins
The PTV expansion margins should incorporate all systematic setup errors/uncertainty, internal target motion uncertainty, random errors, beam physics (penumbra), and all other factors which may affect the actual dose delivered to the clinical target volume.
Note that some RTOG studies are now describing a PTV-EVAL which is a second PTV not used to define beam apertures, but rather is a dosimetric volume which is restricted to the actual tissue/body of a patient. This volume is used to study the actual dose tissue receives when the targets include the body surface and there is flash beyond the body. This is, in my opinion, a poor choice for this since this term/definition has the potential to created confusion in standard dosimetry. A better term might be DTVI or dosimetry target volume of interest. I'm sure that we can come up with a beter description for it.
Treated Volume: This volume is the volume enclosed by an isodose volume. This volume is selected by the radiation oncologist to be appropriate to acheive the treatment goals: cure, local control, palliation.
Irradiated Volume: This volume receives significant radiation with respect to the tissue and tolerances.
Organs at risk (OAR): Organs at risk are those organs whose radiation sensitivity will influence beam placement, dose distribution and coverage and will significantly influence treatment planning.
Internal Margin (IM): That margin which accounts for movement and physiologic changes in shape, size and position of a given volume of interest.
A variety of descriptors have been used to describe target volumes. No radiation field or techniques or beam type can provide 100% homogeneity of dose within the desired treatment field and zero dose elsewhere. These compromises are being quantified in present studies and analyzed using dose-volume-histograms. Radiobiologically, the important parameters are: organ tissue organization, dose sensitivity, and volume sensitivty.
Much of radiation therapy treatment planning is related to dose at margins of desired treatment areas and homogeneity. Marginal dose consists of two components: dose to areas we desire to treat (guaranteed coverage of therapeutic dose), and dose to areas we must avoid (no fly zones). Dose homogeneity becomes more problematic with the move to IMRT, where by definition, intensity is modulated throughout the course of treatment to enable shaped isodose volumes.
— a measure of the minimum and maximum doses in the treated area. Generally a ± 7% heterogenity is acceptable. Some protocols are more or less strict. There may be smaller volumes which will be allowed to receive a lesser or greater dose. If so, these volumes are constrained to approximately pixel or point dose/volume variances, rather than large volumes. Other protocols describe a minimum 95% isodose volume coverage, to a maximum of 107% coverage range.
The ICRU Dose Point: The isocenter, if possible. This point should be a single point within a PTV, in an area of uniform dose without steep dose gradients or significant inhomogeneity. This point should be easily defined, clinically relevant, and in an area of uniform dose.
The three ICRU dose reporting parameters are: ICRU dose point, Dmin (the minimum dose in the volume of interest), and Dmax (the maximum dose in the volume of interest).
Accepted metrics for Dose Planning in the ICRU schema:
There are two types of organs at risk: Serial organs where disruption of any part of the chain of the organ will cause loss of function to the remainder (spinal cord), and parallel organs where disruption of any part will affect only that part which is irradiated (parotid).
The OAR can be expanded to form a PRV or planning risk volume with appropriate margins.The planning risk volume is designed to insure there is a reasonable probability that the organ at risk is spared adequately.
The PRV is a geometric concept which ensures a reasonable probability that the function of the organ will be preserved. The PRV is larger than the serial OAR volume to be certain no portion of the organ receives excess dose. For parallel organs, the PRV may be smaller than the OAR volume, if part of the organ can be safely sacrificed without excessive morbidity. Priority will be established to determine what dose is acceptible with what goals we are trying to accomplish and what morbidity we are willing to accept to achieve those goals.
For serial organs at risk, the dose near maximum point or to a specific volume parameter should be determined. There is a dose to a small volume which must not be exceeded to avoid placing the function of the organ at risk. Generally, this is described as dose to 0.05 cm3 or greater, depending on the organ.
The conformity index is the ratio of the irradiated volume at the specific isodose percent or dose to the planning target volume (PTV). CI = Treated Volume (TV)isodose value/PTV = TVisodose value/PTV
This data comes primarily from the RTOG protocols of more recent (ca. 2010 and beyond) vintage.
Example CI: Breast prescription to 95% IDV reference. The PTV_eval volume is 800 cm3, and the volume incorporated by the prescription isodose volume (the 95% IDV reference in this example) is 835 cm3. The CI= 835 cm3/800 cm3 = 1.040. At the lowest acceptalbe CI value, assuming the same breast volume, the CI = 0.95 dictates that ≥ 760 cm3 will be covered by the prescription isodose volume. At the maximum acceptable CI = 2.0, 1600 cm3 will be covered. Generally, CI=1.2 is a reasonable coverage goal, which will insure clinically acceptable doses to the entire target volume (=960 cm3).
For a hypothetical lumpectomy cavity size of 50 cm3 the treated volume at the 90% IDV (the usual for electron dose prescriptions will range from 47.5 to 125 cm3.
Maximum dose is limited to 3.1 Gy and no more than 5% can exceed 1.86 Gy
No more than 10% can exceed 5 Gy
This data comes primarily from the RTOG protocols of more recent (ca. 2010 and beyond) vintage.
Example CI: Breast prescription to 95% IDV reference. The PTV_eval volume is 800 cm3, and the volume incorporated by the prescription isodose volume (the 95% IDV reference in this example) is 835 cm3. The CI= 835 cm3/800 cm3 = 1.040. At the lowest acceptalbe CI value, assuming the same breast volume, the CI = 0.95 dictates that ≥ 760 cm3 will be covered by the prescription isodose volume. At the maximum acceptable CI = 2.0, 1600 cm3 will be covered. Generally, CI=1.2 is a reasonable coverage goal, which will insure clinically acceptable doses to the entire target volume (=960 cm3).
For a hypothetical lumpectomy cavity size of 50 cm3 the treated volume at the 90% IDV (the usual for electron dose prescriptions will range from 47.5 to 125 cm3.
Maximum dose is limited to 2.4 Gy and no more than 5% can exceed 1.86 Gy
No more than 10% can exceed 4 Gy (V4 ≤ 10%)
OAR for CNS is relatively straightforward for conventional fractionation.
| Structure | Constraint |
|---|---|
| Lens | 7 Gy |
| Retina | 50 Gy |
| Optic Nerves | 55 Gy |
| Optic Chiasm | 56 Gy |
| Brainstem | 55 Gy |
For non-brachytherapy cases of whole pelvic radiation, current protocols are recommending in the standard arms doses of 45 Gy to 50.4 Gy at 1.8 Gy/fraction. RTOG 1203 is a study of post-operative 3d-conformal radiation against IMRT radiation in the post-operative uterus or cervix. The dose constraints recommended here come primarily from that protocol and the Quantec limits. The 4 field 3D conformal treatment follows traditional whole pelvic radiation techniques with coverage from L4/L5 to the bottom of the obturators. The lateral fields are the provervial chimney fields with the posterior border at the posterior edge of the sacrum to insure coverage of the vestigates of the uteral-sacral ligaments and pre-sacral nodes. The fields cover 2 cm lateral to the true pelvis and distal to the vagina.
The target volumes include the vagina and para-vaginal tissues (CTVprim) and the nodal volumes that drain the site and adjacent soft tissues. Generally the nodal CTVn is the obturator and hypogastric nodes, (internal iliac). If there is cervical or lower uterine segment involvement, the external iliac and common iliac chains should be included. In this case, also include the pre-sacral nodes between S1-S3 with a 1-2 cm anterior margin around the deliniating vessels. Muscle, bone and bowel should be excluded from the CTV. The most anterio-lateral aspect of the external iliacs near the inguinal canal can be excluded, and the lowest most nodal CTVn can end at the top of the femoral heads.
Vaginal target volumes, especially with IMRT plans should take into account motion. Motion can cause displacement due to rectal filling and bladder filling. Standard whole pelvis fields have broad enough coverage to cover the entire range of vaginal motion in the post-hysterectomy vagina. This may not be true for IMRT. A reasonable approach to this problem is to simulate the patient with the bladder full and repeat the simulation with the bladder empty. Then fuse the images to construct a vaginal ITV expansion from these images. The vaginal PTV (PTVp), will consist of the ITV + 7 mm margin.
The dose constraints for PTVp and PTVn are:
Constraints for Organs at risk are not evaluated for non-IMRT plans. These constraints are supplied by either Quantec or RTOG 1203 constraints for post-hysterectomy radiation. IMRT organs at risk include the bowel, rectum and bladder. The RTOG protocol includes the bone marrow, but does not include femoral heads, which were commonly considered for protection in traditional fields based on boney anatomy.
Most of the thorax constraints are from the Quantec and Emami data. Until recently, the RTOG protocols did not include esophageal dose constraints. More recently, RTOG/NRG (LU001) studies have been recommending a mean esophageal dose limit of ≤ 34 Gy and V35 Gy < 50-55%, V70 Gy ≤ 24-25%
Lung Protocols have always included the spinal cord with a broad limit of 45 Gy. More recent trials have recommended a volume peak dose limit of D0.03 cm3 < 50 Gy. This should be regarded as a hard limit.
For hypofractionated radiation of the cord at 1.5 Gy BID (separated by 6 hours), Turrisi originally used 36 Gy as the upper limit. NCCN originally used 39 Gy and now uses 41 Gy in treating SCLC.
If there is re-irradiation, there appears to be a 25% dose recovery at 6 months post-irradiation.
The spinal cord dose limits at standard fractionation are < 50 Gy to a single voxel (0.03 cm3)
For hypofractionated 1.5 Gy BID, the present NCCN guideline recommend 41 Gy
For SRS, a single fraction should be limited to ≤ 10 Gy
The organs at risk in lung/thorax treatment include the uninvolved lung, spinal cord, heart, esophagus. Priority of organ protection is 1. Spinal Cord, 2.) Lung, 3.) Esophagus, 4.) Heart, 5.) Brachial Plexus.
Note: The NCCN 105% is a recommended limit, but if large portions of the esophagus are irradiated to high doses, the risk of injury is likely higher. The NRG protocol limits are more conservative. We also note that the NRG places the esophagus dose constraints in a higher rank than the heart.
The NRG protocol recommends not allowing the full circumference of the esophagus to exceed 60 Gy (ie within the ≥ 60 Gy IDV).
The brachial plexus dose should be kept below 66 Gy (NCCN) and preferably below 63 Gy (NRG).
There have been no clear cut limits beyond those mentioned above. For small cell lung cancer, the CALGB 30610 study calculates a BED dose for 1.5 Gy BID to 45 Gy as 52 Gy. Turrisi mandated 6 hour treatment separation for the BID scheme. If one assumes for the purposes of safety the maximum dose of 3 Gy/day to 45 Gy total in 15 days, the esophagus could potentially receive higher BED doses, as can the cord. The NCCN recommends reducing the dose somewhat, but the recommendations are vague. Indeed esophageal doses have not been addressed until recently, and even then in RTOG 0624 they are not considered mandatory. NCCN spinal cord doses for BID radiation started with 36 Gy (Turrisi original constraint), then moved to 39 Gy, and are now set at 41 Gy. As it appears that radiobiologic injury repair in the cord is much longer than 6 hours, these values are probably reasonable. For the purposes of this discussion, the CALGB trial is used as a reference point, as is suggested by the NCCN.
The GTV consists of all visualized disease on imaging. This is defined as all disease that is primary tumor and lymphatics > 1 cm in short axis. An ITV consists of all GTV motion observed on 4D CT planning. The tumor may not be contiguous.
The CALGB definition of CTV-1 is the GTV/ITV and the ipsilateral hilum, and any positive mediastinal nodes. The PTV should be 1 cm to account for setup uncertainties. If daily CBCT/imaging is available and used, the PTV may be reduced to between 5 mm and 7 mm.
Dose to the GTV should be constrained to a minimum PTV dose ≥ 95% of the total prescribed dose to the volume. The CALGB allows the following:
The CALGB defines the spinal cord and lungs as the dose limiting structure. Turissi goes on to state that the lungs are the true dose limiting structures, but we cannot ignore the cord, either. The CALGB recommends but does not limit the esophagus to < 34 Gy, but states, "This is not an absolute requirement, but strongly recommended unless other, more critical constraints force the situation." The CALGB is silent on what those other more critical constraints are, but one can presume they include dose to uninvolved lung, spinal cord, and tumor. Other studies have recommended avoiding, if possible, circumferential irradiation of the esophagus, if possible. Finally recommendations for heart dose limits are included.
The spinal cord constraints are given the highest priority by the CALGB. They recommend a separate off cord plan for the second dose of the day, rather than using a consistent plan in the morning and afternoon treatment.
The CALGB considers the lungs the second highest priority.
The only esophageal goal stated by the CALGB is to keep the mean dose < 34 Gy. Other study protocols have recommended, if possible, keeping the circumferential esophageal dose below 60 Gy. That is, insuring at least a portion of the entire circumference of the esophagus is kept below 60 Gy at all times.
CALGB uses the Emami data and recommends the following (translated to more modern nomenclature:
These are derived from RTOG studies and lectures given by Tony D'Amico. Presently, NCCN recommends doses of 75.6 to 79.2 Gy at 1.8 Gy/fraction in 44 to 42 fractions for low risk prostate cancer and a dose of up to 81 Gy in high risk prostate cancer. The EQD2 equivalent dose using α/β=1.1 is 74.09 for tumor and 76.03 for late effects. For high risk disease, this is an EQD2 = 77.57 for early and 77.76 for late effects.
The NCCN recommendations allow for mildy hypofractionated radiation based on data from the University of Wisconsin protocol which demonstrates reasonable hypofractionation is reasonable. Forman dose escalated radiation at an inital dose of 1.8 Gy/fraction to 45 Gy followed by a boost to the prostate alone at 2.5 Gy/fraction to 78.5 Gy, based on RBE equivalent of neutron therapy which was delivered at 1 NGy/fraction to 10 NGy. Using an RBE quality factor of 3, this is probably an equivalent dose of 2.5 Gy/fraction to 32.5 Gy. This is an EQD2 dose of 79.84 Gy, and a late effects dose of 78.95 Gy. Kupellian treated to 72 Gy at 2.5 Gy/fraction, which equates to EQD2 dose of 81.9 Gy for early and 77.0 Gy for late effects. D'Amico is convinced that this is an inferior protocol, and data from Thomas Jefferson does not support low α/β ratios for prostate cancer. Ritter, at the University of Wisconsin has a dose escalation study that showed with modest dose escalation, the treatment was safe and the NCCN guidelines (2015) allow for mild dose hypofractionation between 2.5 Gy and 4 Gy per fraction. A reasonable compromise until more data is available is to treat the prostate and seminal vesicles and pelvic lymphatics (provided bowel can be spared).
If mild hypofractionation is used, it is probably reasonable to treat the larger volume at 2 Gy/fraction and the boost volume at 2.5 Gy per fraction. Foreman's approach was close to this, and with good dosimetry and IGRT, with daily prostate imaging and gold seed fiducials, the toxicity is reasonably close to conventional fractionation. For the larger field, 1.8 Gy to 45 Gy followed by a boost to the prostate itself at 2.5 Gy/fraction to an additional dose of 32.5 Gy for a total dose of 78.5 Gy yields an EQD2 dose of 83.74 Gy and a late effects dose of 81.75 Gy.
For now, the standard, "correct" doses for prostate are: Low risk: prostate only 76-79.2 Gy, Intermediate and high risk, at least 79.2 Gy to 81.0 Gy, and for high risk prostate cancer, include the pelvic lymphatics and entire seminal vesicles to 45 Gy followed by a boost to the prostate and proximal seminal vesicles to 81 Gy, all at 1.8 Gy/fraction.
Comparing the BED1.1 Gy doses and the BED3 Gy doses we find:
| Dose | Dose/fraction | Total Fractions | EQD2 | BED1.1 | BED3 |
|---|---|---|---|---|---|
| 79.2 Gy | 1.8 Gy | 44 | 77.57 Gy | 208 Gy | 126 Gy |
| 81 Gy | 1.8 Gy | 45 | 75.77 | 213.5 | 129.6 |
| 70 Gy | 2.5 Gy | 30 | 81.25 | 229.0 | 128 |
| 77.5 Gy | 1.8/2.5 Gy boost | 38 | 79.8 | 224.9 | 131.5 |
For the initial treatment to the CTV_45Gy the dose is 1.8 Gy/fraction to 45 Gy. This should cover the prostate PTV and entire seminal vesicles. For high risk disease, this should also cover the pelvic lymphatics.
The PTV_45Gy expansion should be treated to 45 Gy to cover at least 98% of the PTV. A single voxel (0.03 cm3) minimum point dose may be as low as 95% or 42.75 Gy. The maximum point dose (0.03 cm3) is 107% or 48.15 Gy. There should be no greater than 10% dose inhomogeneity within the prostate.
For prostate boost, the same constraints apply. The boost dose to the prostate and proximal seminal vesicles is 34.2 Gy at 1.8 Gy/fraction. The Dose to the boost PTV should cover 98% of the volume to 100% of the dose. (CI=98%/100%=.98). The minimum dose should be not less than 32.5 Gy (or 93%) and the maximum dose should be not greater than 36.6 Gy ( or 107%). Summarizing: 79.2 Gy ± 7%.
The prostate volumes are generally defined as:
The femoral heads should be limited to 45 Gy.
The bladder should be limited to the following constraints:
The NCCN has updated the list of acceptable treatments to include hypofractionation where adequate inter-fraction imaging is available. These constraints are felt to be reasonable radiobiologic equivalents to this regimen.
The rectum is the true dose limiting constraint. While the RTOG protocols describe Volume%-Dose limits, it is clear anatomically that the bulk of the high dose to the rectum comes from the dose to the prostate/prostate bed itself. Some (D'Amico, Mallinckrodt) advocate limiting a specific volume not to exceed a dose, rather than a percent. This make sense, given the nature of the fact that the rectum is a long organ with variability in size and lengh of contouring. I think we will be moving more to constraining absolute dose to an absolute, rather than a relative volume in the future.
The penile bulb should be constrained to ≤ 52.5 Gy
The bowel dose should be kept under 45 Gy.