Time, dose, fractionation Flashcards
Which of the following total doses, given as daily 1.5 Gy fractions, is approximately equivalent to a conventional schedule of 30 fractions of 2 Gy for late normal tissue reactions? Assume the a/B ratio is equal to 3 Gy.
A. 53 Gy
B. 60 Gy
C. 67 Gy
D. 75 Gy
E. 81 Gy
C
This can be calculated using the linear-quadratic formula that allows comparison of two different fractionation schedules and the resulting relative biological effective dose (BED).
π΅πΈπ· = nd [1 + (d/(a/B))]
n β number of fractions
d β dose per fraction
a and B β tissue specific dose response curve parameters
If the two schedules are isoeffective, BED1 = BED2, which reduces to n1d1/n2d2 = (a/B+d2)/(a/B+d1).
Assuming no difference in overall treatment time, which of the following statements is CORRECT concerning isoeffect curves?
A. Tissues with a greater repair capacity have steeper isoeffect curves.
B. Increased proliferation of the critical cell population during the course of radiotherapy will decrease the slope of the isoeffect curve.
C. Tissues with steep isoeffect curves have high a/B ratios.
D. Isoeffect curves for tumor control will be steeper if significant reoxygenation occurs between dose fractions.
A
An isoeffect curve describes the relationship between total dose for a given level of tissue effect and the different fractionation parameters (overall time, dose per fraction, number of fractions, etc). Isoeffect curves are often plotted with the log of the total dose on the y-axis and the log of the fraction size (from high to low) on the x-axis. Tissues with a greater repair capacity will show greater sparing with increasing fractionation (smaller fraction sizes) and therefore will have steeper isoeffect curves.
Increased proliferation will cause an increase in the slope of an isoeffect curve because it would take a higher total dose to kill the larger number of cells produced during the course of treatment (Answer Choice B).
Tissues with steep isoeffect curves have low, not high, a/B ratios (Answer Choice C).
Reoxygenation decreases the slope of the isoeffect curve because it decreases the number of radioresistant hypoxic cells and hence reduces the total dose required to control the tumor, everything else being equal (Answer Choice D).
A total dose of 70 Gy delivered in 2 Gy fractions is used to treat a particular tumor. Assume that the tumor is characterized by an a/B ratio of 2 Gy and a Tpot of 30 days. For the dose-limiting normal tissue, the a/B ratio is 4 Gy. Which one of the following treatment schedules would most likely yield the highest therapeutic ratio?
A. Standard fractionation
B. Accelerated treatment
C. Split-course treatment
D. Hyperfractionation
E. Hypofractionation
E
In principle, a hypofractionated protocol would yield the highest therapeutic ratio because if treating with either standard or small fraction sizes (i.e., hyperfractionation) there would be greater sparing of this tumor (a/B ratio = 2 Gy) than for the critical dose-limiting normal tissue (a/B ratio = 4 Gy). There would not be much point to using accelerated treatment since this is a relatively slow-growing tumor (Tpot = 30 days), nor would split course treatment be indicated since, again, the a/B ratio suggests greater recovery in the tumor versus the normal tissue.
Which of the following fractionation schedules would likely produce the highest incidence of late normal tissue toxicity? (Assume a/B = 2 Gy for the critical normal tissue injury)
A. 20 Gy in 4 fractions over 1 week
B. 24 Gy in 6 fractions over 2 weeks
C. 45 Gy in 15 fractions over 3 weeks
D. 50 Gy in 25 fractions over 5 weeks
E. 60 Gy in 60 fractions over 6 weeks
C
Since the focus of this question concerns late effects, the overall treatment time (a maximum of 6 weeks) should not be an important determinant of outcome. The BEDs calculated for each of the different fractionation schedules are 70, 72, 113, 100 and 90 Gy2, respectively. The protocol of
45 Gy delivered in 15 fractions results in the greatest value for BED and, therefore, should be the most likely to produce late normal tissue complications. This illustrates the point that both fraction size and total dose play important roles in determining the probability of late effects.
A standard treatment protocol for a particular type of cancer is 60 Gy delivered in once-daily 2 Gy fractions. If the fraction size is decreased to 1.3 Gy in an attempt to reduce the incidence of late effects, approximately what total dose should be delivered to maintain the same level of tumor control? (Assume an equal effect per fraction, no repopulation, and an a/B ratio for the tumor of 10 Gy.)
A. 64 Gy
B. 68 Gy
C. 72 Gy
D. 76 Gy
E. 80 Gy
A
Since there is the assumption of an equal effect per fraction and no repopulation, the basic BED equation can be used:
π΅πΈπ· = nd [1 + (d/(a/B))]
Thus, the standard treatment results in a BED of:
π΅πΈπ· = 30 * 2 [1 + (2/10)] = 72 Gy(10)
Therefore, in order to determine the number of fractions to be used if the
fraction size is reduced to 1.3 Gy:
72 Gy(10) = nd [1 + (1.3/10)] nd = 64 Gy
Thus, 49 fractions of 1.3 Gy should be used, to a total dose of 64 Gy.
Which of the following statements is correct? One goal of hyperfractionation is to:
A. Decrease toxicity to early-responding tissues
B. Deliver the total radiation dose in a shorter overall time
C. Reduce the number of fractions used
D. Prevent tumor cell repopulation
E. Decrease the incidence of late effects while maintaining or improving tumor control
E
One goal of hyperfractionation is to improve the therapeutic ratio by decreasing the incidence of late reactions, while maintaining or improving tumor control. Therapeutic gain can be achieved only if the late-responding normal tissue has a lower a/B ratio than that of the tumor.
Hyperfractionation would be likely to have no effect on early-responding tissues or may slightly increase toxicity; it would not decrease these toxicities (Answer Choice A).
For hyperfractionation, the larger number of smaller-sized dose fractions is typically delivered over about the same overall treatment time as conventional therapy, meaning that there would be no change in the potential of surviving tumor clonogens to repopulate (Answer Choices B, C, and D).
Which of the following statements is TRUE concerning experimental support for the hypothesis that late-responding tissues have lower a/B ratios than early-responding tissues?
A. High LET radiations exhibit RBEs that are greater for early effects than for late effects
B. The use of hyperfractionation results in an increased severity of late effects if the dose is titrated to produce equal early effects
C. Isoeffect curves are steeper for late effects than for early effects
D. When a treatment plan is changed from many small doses to a few large fractions and the total dose is titrated to produce equal early effects, late effects tend to be less severe
E. The isoeffect curve for skin acute effects is steep, indicating a high sensitivity to fractionation
C
Isoeffect curves are steeper for late effects than for early effects, meaning that late-responding tissues are more sensitive to changes in dose per fraction than early-responding tissues (and tumors).
RBEs for high LET forms of radiation are greater for late effects compared to early effects when hyperfractionation is used (Answer Choice A).
Hyperfractionation would reduce the severity of late effects if the total dose was titrated to maintain the same level of early effects m(Answer Choice B).
When a treatment plan is changed from many small doses to a few large fractions and the total dose is titrated to produce equal early effects, late effects would be more severe (Answer Choice D).
The isoeffect curve for skin acute effects is shallow, indicating a lower sensitivity to fractionation; in other words, fractionation does not greatly alter the severity of acute dermatitis (Answer Choice E).
A clinician changes from the usual fractionation schedule of 1.8 Gy given once per day to an accelerated treatment using 1.6 Gy fractions delivered twice per day. In order to avoid the possibility of reduced normal tissue tolerance due to incomplete repair, what should be the minimum inter-fraction interval for the accelerated schedule?
A. 0.5-1 hour
B. 1-2 hours
C. 2-3 hours
D. 3-6 hours
E. 6-8 hours
E
Results from clinical trials of hyperfractionation and accelerated fractionation employing more than one fraction per day have shown worse late complications when the time between fractions was less than 6 hours. This finding has been attributed to incomplete repair, because sublethal damage recovery is generally slower in late-responding tissues. It has since been suggested that even an inter-fraction interval of 6 hours may not be sufficient for those normal tissues with the slowest repair rates and that a longer time between fractions may be necessary to avoid a reduction in tolerance dose.
A conventional treatment for a particular type of tumor is 25 fractions of 2 Gy delivered once per day. A hyperfractionated regimen is proposed that would consist of 1.2 Gy fractions delivered twice per day. What would be the approximate therapeutic gain in changing from the standard to hyperfractionated schedule if both were designed to produce the same probability of late complications? (Assume that there is no tumor cell repopulation during treatment, full repair of sublethal damage occurs, the tumor has an a/B ratio of 10 Gy and the normal tissue has an a/B ratio of 2 Gy.)
A. 0.8
B. 1.0
C. 1.2
D. 1.4
E. 1.6
C
The BEDs for the standard protocol are 60 Gy10 and 100 Gy2, respectively, for the tumor and late-responding normal tissue, as determined from the equation:
π΅πΈπ· = nd [1 + (d/(a/B))]
Assuming the BED of 100 Gy2 for the normal tissue is maintained for the hyperfractionated protocol, this would correspond to a total dose of 1.2 Gy per fraction multiplied by 52 fractions, or 62.4 Gy. Putting these values into the BED equation for the tumor, the BED would increase from 60 Gy10 for the standard treatment, to 70 Gy10 for the hyperfractionated treatment.
The therapeutic index (TI), BED(tumor)-hyperfractionated/BED(tumor)-standard divided by BED(normal)-hyperfractionated /BED(normal)-standard, equals 70 Gy(10) / 60 Gy(10) / 100 Gy(2) / 100 Gy(2) = 1.2.
All of the following processes could be involved in the increased efficacy and safety of conventionally fractionated radiation in the clinic compared to single or hypofractionated treatment, EXCEPT:
A. Sublethal damage repair in normal tissues between fractions
B. Reoxygenation in tumors
C. Redistribution/reassortment of cells in tumors
D. Repopulation of critical cell populations in normal tissues
E. Potentially lethal damage repair in tumors
E
Sublethal damage repair (SLDR) and repopulation in normal tissues treated with fractionated radiation therapy may contribute to reduced toxicity associated with treatment. Reoxygenation in tumors and possible redistribution of proliferating tumor cells into more sensitive phases of the cell cycle may contribute to increased efficacy of dose fractionation, at least in theory. Potentially lethal damage repair in tumors would not contribute to the efficacy of dose fractionation as this would enhance the survival of tumor cells.
Data suggests that treatment breaks are detrimental to tumor control in head and neck cancer. The radiobiological basis of this phenomenon is:
A. Redistribution
B. Reoxygenation
C. Repair
D. Repopulation
E. Radiosensitization
D
Accelerated repopulation is triggered several weeks after the initiation of a course of radiation therapy. A dose increase of approximately 0.6 Gy per day is needed to compensate for this repopulation. Hence, any interruptions in treatment, once it has begun, can compromise tumor control due to accelerated repopulation.
Continuous hyperfractionated accelerated radiation therapy (CHART) involved all of these EXCEPT:
A. Short overall treatment time of 12 consecutive days
B. Three fractions of radiation per day
C. Total dose of 50 β 54 Gy
D. Low dose per fraction (1.4 β 1.5 Gy)
E. Concurrent chemotherapy
E
The CHART protocol was performed in the 1990s in the UK for the treatment of head and neck squamous cancers and non-small cell lung cancer. It involved 36 fractions over 12 consecutive days with three fractions delivered daily. Each fraction was between 1.4 β 1.5 Gy with a total dose of 50 β 54 Gy. The strategy was based on the thought that low dose/fraction would minimize late effects and a short treatment time would maximize tumor control. There was no concurrent chemotherapy given.
Long-term results showed no differences in disease outcomes for head and neck cancer patients, but there was an improvement in late morbidity with CHART compared to conventional fractionation. For NSCLC, there was an improvement in local progression and overall survival. Despite these promising results, CHART has had limited adoption due to the resource intensive nature of the treatment as well as the more widespread use of concurrent chemotherapy.
Data has suggested that overall treatment time is crucial for which of the following tumors:
A. Head and neck cancer
B. Endometrial cancer
C. Melanoma
D. Breast cancer
E. Basal cell carcinoma
A
Data has shown that local tumor control is decreased by about 1.4% for each day that treatment is prolonged for head and neck cancer and 0.5% for uterine cervix cancer. There is no data suggesting a similar effect in melanoma, breast, or basal cell cancer.
Considering our current knowledge of typical alpha/beta values and basic radiobiological concepts, which of the following organ sites would be most likely to gain therapeutic benefit with hypofractionation?
A. Prostate
B. Head and Neck
C. Breast
D. Bladder
E. Brain
A
Because of the low a/B ratio of prostate cancer cells, a hypofractionated protocol would not result in greater normal tissue damage than tumor kill. In the case of other tumors, the higher a/B ratio of the tumor than that of critical dose-limiting normal tissue would result in hypofractionation causing greater recovery in the tumor versus the normal tissue.
