Radiobiological aspects of continuous low dose-rate irradiation and fractionated high dose-rate irradiation

The biological effects of continuous low dose-rate irradiation and fractionated high dose-rate irradiation in interstitial and intracavitary radiotherapy and total body irradiation are discussed in terms of dose-rate fractionation sensitivity for various tissues. A scaling between dose rate and fraction size was established for acute and late normal-tissue effects which can serve as a guideline for local treatment in the range of dose rates between 0.02 and 0.005 Gy/min and fraction sizes between 8.5 and 2.5 Gy. This is valid provided cell-cycle progression and proliferation can be ignored. Assuming that the acute and late tissue responses are characterised by alpha/beta values of about 10 and 3 Gy and a mono-exponential repair half-time of about 3 h, the same total doses given with either of the two methods are approximately equivalent. The equivalence for acute and late non-hemopoietic normal tissue damage is 0.02 Gy/min and 8.5 Gy per fraction; 0.01 Gy/min and 5.5 Gy per fraction; and 0.005 Gy/min and 2.5 Gy per fraction. A very low dose rate, below 0.005 Gy/min, is thus necessary to simulate high dose-rate radiotherapy with fraction sizes of about 2 Gy. The scaling factor is, however, dependent on the repair half-time of the tissue. A review of published data on dose-rate effects for normal-tissue response showed a significantly stronger dose-rate dependence for late than for acute effects below 0.02 Gy/min. There was no significant difference in dose-rate dependence between various acute non-hemopoietic effects or between various late effects. The consistent dose-rate dependence, which justifies the use of a general scaling factor between fraction size and dose rate, contrasts with the wide range of values for repair half-time calculated for various normal-tissue effects. This indicates that the model currently used for repair kinetics is not satisfactory. There are also few experimental data in the clinical dose-rate range, below 0.02 Gy/min. It is therefore necessary to verify further the presented scaling between fraction size and dose rate.     

The radiobiology of prostate cancer including new aspects of fractionated radiotherapy

Total radiation dose is not a reliable measure of biological effect when dose-per-fraction or dose-rate is changed. Large differences in biological effectiveness (per gray) are seen between the 2 Gy doses of external beam radiotherapy and the large boost doses given at high dose-rate from afterloading sources. The effects are profoundly different in rapidly or slowly proliferating tissues, that is for most tumors versus late complications. These differences work the opposite way round for prostate tumors versus late complications compared with most other types of tumor. Using the Linear-Quadratic formula it is aimed to explain these differences, especially for treatments of prostate cancer. The unusually slow growth rate of prostate cancers is associated with their high sensitivity to increased fraction size, so a large number of small fractions, such as 35 or 40 "daily" doses of 2 Gy, is not an optimum treatment. Theoretical modeling shows a stronger enhancement of tumor effect than of late complications for larger (and fewer) fractions, in prostate tumors uniquely. Biologically Effective Doses and Normalized Total Doses (in 2 Gy fraction equivalents) are given for prostate tumor, late rectal reactions, and--a new development--acute rectal mucosa. Tables showing the change of fraction-size sensitivity (the alpha/beta ratio) with proliferation rates of tissues lead to the association of slow cell doubling times in prostate tumors with small alpha/beta ratios. Clinical evidence to confirm this biological expectation is reviewed. The alpha/beta ratios of prostate tumors appear to be as low as 1.5 Gy (95% confidence interval 1.3-1.8 Gy), in contrast with the value of about 10 Gy for most other types of tumor. The important point is that alpha/beta =1.5 Gy appears to be significantly less than the alpha/beta =3 Gy for late complications in rectal tissues. Such differences are also emerging from recent clinical results. From this important difference stems the superior schedules of, for example, 20 fractions of 3 Gy, or 10 fractions of 4.7 Gy, or 5 fractions of 7 Gy, which can all give tumor results equivalent to 80-90 Gy in 2 Gy fractions, while keeping late complications equivalent to only 72 Gy in 2 Gy fractions. Combination treatments of external beam (EBRT) and brachytherapy boost doses (25F x 2 Gy plus 2 x 10 Gy) can give higher biological tumor effects than any EBRT using daily 2 Gy doses, and with acceptable late complications. Monotherapy by brachytherapy for low-risk cancer prostate using two to four fractions in a few days can give even higher biological effects on the tumors.     

Pulsed reduced dose-rate radiotherapy: case report

The initial management of malignant gliomas is multimodality in nature, consisting of surgery, radiation therapy and chemotherapy. However, once progression has occurred, treatment options are limited both in terms of selection and efficacy. We report a case of a 37 year-old male diagnosed with a Grade II astrocytoma initially treated with surgery and external beam radiation therapy consisting of 54 Gy delivered in 1.8 Gy fractions that subsequently progressed to a Grade IV astrocytoma. This was managed with temozolomide chemotherapy until the patient exhibited further progression. Although the patient had received prior full dose radiotherapy, he was re-treated with external beam radiotherapy delivered at a substantially reduced dose-rate. This reduction in dose-rate is obtained by delivering treatment in a series of 0.2 Gy pulses separated by 3 min time intervals, creating an apparent dose rate of 0.0667 Gy/min. The region of recurrence was treated to a dose of 50 Gy delivered using 25 daily fractions of 2.0 Gy. The patient had both a radiographic response and clinical improvement following re-irradiation using pulsed reduced dose-rate radiotherapy with no apparent acute or late neurologic toxicities at a time when other treatment options were not available. Despite delivering 104 Gy to the tumor bed and the surrounding brain parenchyma, at no time was there radiographic evidence of radiation-induced normal tissue necrosis. The radiobiologic basis for the use of pulsed reduced dose-rate external beam radiotherapy in the management of recurrent glioma patients is discussed.     

Radiation oncology in a Canadian province: measures of workload and treatment complexity

Aims

A growing and aging population is associated with an increased incidence of cancer. Advances in radiotherapy technology have changed the way radiation is planned and delivered. This population-based study documented changes in workload and treatment complexity over a 10 year period in a Canadian province.

Materials and methods

We examined the population-based radiation records of a provincial Canadian cancer centre from 2000 (or from 2005 for some measures) to 2009 inclusive. We propose new measures of workload and treatment complexity currently used in our centre that can be easily adopted by other cancer centres.

Results

Workload measured by total new-to-doctor consultations increased 30% from 2000 to 2009 (3.3% annually, P = 0.0008). Total treatment commencements increased 35% over the same time (3.9% annually, P < 0.0001) but linear accelerator (linac) commencements increased at a slower rate of 2.0% annually (P = 0.0002). The rates of increase in consultations and total commencements were faster than the rates of increase in the total population, the population over age 50 years, or the incidence of cancer. Implementation of stereotactic radiosurgery and increased brachytherapy treatments explain much of the increased workload. Measures of treatment complexity including simulations per linac course and radiation computer plans per linac course increased at steady rates of 3.6% (P = 0.0019) and 3.2% (P = 0.0088) annually, respectively, but portals (fields) per linac treatment course increased exponentially after the implementation of intensity-modulated radiotherapy. The number of fractions per linac patient declined by 2.6% annually (P < 0.0001).

Conclusions

This population-based study showed that radiation oncology workload increased at faster rates than the population or incidence of cancer. Measures of treatment complexity indicate an increasing investment for each course of linac treatment, but also the adoption of hypofractionated regimens. These results indicate that radiotherapy manpower requirements cannot be based on population or cancer incidence alone if current technological trends continue.     

Hypofractionation in radiotherapy

Major changes in cancer radiotherapy have followed a greater understanding of the biological effects of radiation on tumours and normal tissues. Clinical radiotherapy is today a solid body of knowledge with well defined scientific foundations. Key concepts in current radiobiology include lethal and sublethal injuries, dose-effect coefficients, α/β ratios, acute and late response, biologically equivalent dose, fraction dose, irradiation time and tumour regeneration between others. Effects of irradiation time and dose per fraction on tumours versus normal tissues are of special importance. Dose per fraction must be considered for analysis of effects in normal late-responding tissues. In contrast, both dose per fraction and irradiation time influence the response to radiation of malignant tumours and acute-responding tissues. Finally, the ability to quantify relationships between radiation dose and biological effect has been of particular value in the development of radiotherapy. This is illustrated by the growing use of high doses per fraction for the treatment of some cancers. *Supported by an unrestricted educational grant from Roche Farma S.A.     

Efficacy and safety of intraoperative radiotherapy in breast cancer: a systematic review

The objective of this study is to assess the efficacy and safety of intraoperative radiotherapy (IORT) for early breast cancer through a systematic review. Fifteen studies met the inclusion criteria. Most studies assessed the combined treatment with IORT (10-24 Gy) and external beam radiotherapy (EBRT) (45-50 Gy) on early stage breast cancer (T_0-2). Local control was over 95% for 1 and 4 years of follow-up and the 5-year overall survival was 99%. The TARGIT-A study found a similar survival comparing IORT with standard treatment. The incidence of acute and chronic complications was scarce. IORT is well tolerated by patients and acute and late toxicities are low. There are no differences in survival for IORT treated patients versus standard treatment.     

Quantitative comparison of radiolabeled antibody therapy and external beam radiotherapy in the treatment of human glioma xenografts.

Using 90Yttrium radiolabeled antibodies, radioimmunotherapy was compared to fractionated external beam radiotherapy in the treatment of human glioma xenografts. Antibody treatments required administration of an approximately threefold greater total dose compared to external beam treatments to achieve the same tumor regrowth delay. Following multi-fraction external beam radiation treatments, tumor regrowth delay demonstrated a large fractionation effect (alpha/beta = 2.3 Gy, 95% confidence limits 0.4-4.2 Gy), suggesting that much of the ineffectiveness of the antibody treatments could be caused by a large dose-rate effect in this system. Despite the large fractionation effect, the regrowth delay was small for a large single-fraction external beam irradiation, possibly because of tumor hypoxia. When compared to external beam radiation, radiolabeled antibody treatments resulted in a comparatively diminished tumor bed effect, suggesting radioimmunotherapy spares normal tissue surrounding the tumor.     

Is single fraction 15 Gy the preferred high dose-rate brachytherapy boost dose for prostate cancer?

Background and purpose

High dose-rate (HDR) brachytherapy is most commonly administered as a boost in two or more fractions combined with external beam radiotherapy (EBRT). Our purpose is to compare outcomes with a single fraction HDR boost to that with a standard fractionated boost in intermediate risk prostate cancer.

Materials and methods

Results of two sequential phase II clinical trials are compared. The Single Fraction protocol consists of 15 Gy HDR in one fraction followed by 37.5 Gy EBRT in 15 fractions over 3 weeks; the Standard Fractionation protocol consisted of two HDR fractions each of 10 Gy, 1 week apart, followed by 45 Gy EBRT in 25 fractions. Patients had intermediate risk disease, and were well balanced for prognostic factors. Patients were followed prospectively for efficacy, toxicity and health-related quality of life (Expanded Prostate Index Composite). Efficacy was assessed biochemically using the Phoenix definition, and by biopsy at 2 years.

Results

The Single Fraction protocol accrued 123 patients and the Standard Fractionation protocol, 60. With a median follow-up of 45 and 72 months, respectively, the biochemical disease-free survival was 95.1% and 97.9% in the Single and Standard Fractionation trials (p = 0.3528). Two-year prostate biopsy was positive in only 4% and 8%, respectively. There was no difference in late urinary or rectal toxicity rates, or in health-related quality of life between the two protocols.

Conclusions

The Single Fraction HDR protocol results in high disease control rate and low toxicity similar to our previous protocol using two HDR insertions, with significant savings in resources. While mature results with longer follow-up are awaited, a single 15 Gy may be considered as a standard fractionation regimen in combination with EBRT for men with intermediate risk disease.     

Multiple-fraction-per-day external beam radiotherapy for adults with supratentorial malignant gliomas

The prognosis following therapy for adults with supratentorial malignant gliomas is poor. Standard therapy of 60 Gy of external beam radiotherapy with chemotherapy achieves a median survival time of 35 to 51 weeks following surgery. A variety of innovative therapies have been considered for therapy of malignant gliomas. Multiple-fraction-per-day (MFD) external beam radiotherapy has been evaluated by many investigators. The rationale for MFD teletherapy is based upon exploiting differences in the recovery capacity for radiation damage between slowly and rapidly proliferating tissues and/or shortening the overall treatment time. A large number of clinical trials have, for the most part, failed to show any survival benefit from MFD radiotherapy. These trials have utilized b.i.d. and t.i.d. radiotherapy with fraction sizes of 0.89 to 2 Gy to total doses of 30–81.6 Gy. The linear quadratic model of the radiation cell survival curve suggests that a biological effective tumoricidal dose 10% higher than standard daily radiotherapy, with approximately isoeffective normal tissue damage, could be achieved at 1.2 Gy b.i.d. to a total dose of approximately 72 Gy. Trials of low dose per fraction MFD radiotherapy, to total doses less than 72 Gy, would be predicted to be inadequate to the task.     

图像引导的放射治疗技术

胸腹部肿瘤因呼吸等生理运动处于不断运动的状态,影响成像、治疗计划和治疗过程的精确度。图像引导放疗(IGRT)技术有望解决运动肿瘤的精确治疗问题,它主要分为3个研究方向。其中,呼吸门控放疗开展较早,已经进入临床应用;集成放疗成像系统把定位和治疗设备合二为一,实现常规模拟定位、锥形束CT和实时成像等功能;射束同步放疗技术以四维CT成像技术为基础,控制动态多叶光栅使射束随着肿瘤的运动而不断运动,是最理想的放疗实现模式。     

The impact of gastrointestinal and genitourinary toxicity on health related quality of life among irradiated prostate cancer patients

Purpose

To determine the impact of late radiation-induced toxicity on health-related quality of life (HRQoL) among patients with prostate cancer.

Patients and methods

The study sample was composed of 227 patients, treated with external beam radiotherapy. Common Terminology Criteria for Adverse Events version 3.0 were used to grade late genitourinary and gastrointestinal toxicity. The European Organization for Research and Treatment of Cancer Quality of life Questionnaire C30 (EORTC QLQ-C30) was used to assess HRQoL at baseline, and 6, 12 and 24 months after completion of radiotherapy. Statistical analysis was performed using a multivariate analysis of variance (MANOVA).

Results

Urinary incontinence and rectal discomfort significantly affected HRQoL. The impact of urinary incontinence on HRQoL was most pronounced 6 months after radiotherapy and gradually decreased over time. The impact of rectal discomfort on HRQoL was predominant at 6 months after radiotherapy, decreased at 12 months and increased again 2 years after radiotherapy. No significant impact on HRQoL was observed for any of the other toxicity endpoints, or non-toxicity related factors such as hormonal therapy, radiotherapy technique or age.

Conclusion

Urinary incontinence and rectal discomfort have a significant impact on HRQoL. Prevention of these side effects may likely improve quality of life of prostate cancer patients after completion of treatment.     

A review of alpha/beta ratios for experimental tumors: implications for clinical studies of altered fractionation

Clinical interest in the use of more and smaller dose fractions in radical radiotherapy has been stimulated by recent reviews of experimental results with normal tissues. It has been found that if the dose per fraction is reduced (i.e., in hyperfractionation) there is sparing of late responding normal tissues relative to those which respond early. This phenomenon can be understood in terms of the shapes of the underlying dose effect relationships, which can be described using the linear quadratic equation. The ratio (alpha/beta) of the linear (alpha) and quadratic (beta) terms is a useful measure of the curviness of such dose effect curves. Low alpha/beta values (1.5 to 5 Gy) have been observed for late responding normal tissues and indicate that radiation damage should be greatly spared by the use of dose fractions smaller than the 2 Gy used in conventional radiotherapy. By contrast the high alpha/beta values (6-14 Gy) observed for acutely responding normal tissues indicate that the response is relatively linear over the dose range of clinical interest. Hence less extra sparing effect is to be expected if lower doses per fraction are administered. If tumors respond in the same way as acutely responding normal tissues then hyperfractionation might confer a therapeutic gain relative to late responding normal tissues. We have reviewed published results for experimental tumors irradiated in situ and either assayed in situ or after excision. The alpha/beta ratios were usually at least as high as those for acutely responding normal tissues, and 36/48 tumors gave values greater than 8 Gy. Low values of less than 5 Gy were obtained for only 4/48 tumors. There are considerable technical problems in interpreting these experiments, but the results do suggest that hyperfractionation might confer therapeutic gain relative to late responding normal tissues on the basis of differences in repair capability. In clinical practice more efficient reoxygenation, cell cycle redistribution and decreased overall treatment time might also confer therapeutic gain.     

Radiation induced renal damage in mice: Influence of fraction size

Two functional assays (urine output and isotope clearance) have been used to assess the response of mouse kidneys to localized irradiation. The influence of the size of each X ray dose has been investigated by using single doses and two to 16 equal fractions. The X ray dose in each treatment ranged from 16 Gy as a single dose to 3.5 Gy (×16 fractions). Three separate experiments were performed, one with and two without anesthetic for the irradiation. Sequential testing of the mice was used to determine the latent period before radiation damage became manifest. Latency was found to be dose dependent; functional defects appeared earlier after higher doses but there was a minimum period of 14–19 weeks before the onset of damage. The repair capacity of the kidney was assessed by comparing isoeffective doses from the dose-response curves. Within 24 hours a recovered dose of 5 Gy was obtained if 2 doses were used instead of one. The isoeffective dose increased with fractionation and a fraction number exponent of 0.42 was obtained. Analysis of the data using a linear quadratic model yielded a low $\text{α}\text{β}$ ratio of 0–3.5 Gy. This is similar to values obtained for other late responding normal tissues and implies that the use of small dose fractions will spare the kidney relative to tumors and acutely reacting normal tissues. In conventional radiotherapy more effective sparing of the kidney should be achieved by using thin shielding with each fraction than by completely shielding the kidney for the latter part of the treatment course.     

Estimation of repair parameters in mouse lip mucosa during continuous and fractionated low dose-rate irradiation

The present study investigated the effect of fractionated low dose-rate (FLDR) treatments in mouse lip mucosa, a typically early reacting tissue. The relation between dose-rate and fractionation effect has been assessed with various interfraction intervals and dose-rates. A fixed overall treatment time of 10 h has been used for the present continuous and fractionated irradiation experiments with corresponding dose-rates of 3.1-84 Gy/h. Sophisticated mathematical models are now available to estimate repair parameters from data derived with different fraction numbers, fraction sizes and dose-rates. These formulas, allowing the calculations of isoeffect relationships are based on the incomplete repair model and assume that repair can operationally be described by a monoexponential function. A further assumption of these models is that repair of sublethal damage follows the same kinetics during irradiation and between fractions. The present FLDR experiments with small interfraction spacing were performed to investigate the validity of these assumptions and consequently the applicability of the models. In addition, it has been assessed whether the experimental approach of investigating repair kinetics as such [high dose-rate (HDR) split-course vs. continuous low dose-rate (CLDR) or FLDR] influences the estimation of these parameters, as has been suggested from the analysis of in vitro studies. Using the mucosal desquamation endpoint, virtually identical repair parameters have however been estimated with different approaches (alpha/beta = 14.1-18.2 Gy, T1/2 = 28-37 min). The available isoeffect models seem to be applicable to the present experimental data and might after further experimental tests also involving late reacting tissues, be a useful tool for clinical isoeffect calculations.     

Justification for inter-fraction correction of catheter movement in fractionated high dose-rate brachytherapy treatment of prostate cancer

Background and purpose

Fractionated high dose-rate (HDR) brachytherapy in the treatment of prostate cancer relies on reproducible catheter positions for each fraction to ensure adequate tumour coverage while minimising dose to normal tissues. Peri-prostatic oedema may cause caudal displacement of the catheters relative to the prostate gland between fractions. This can be corrected for by changing source dwell positions or by physical re-advancement of catheters before treatment.

Materials and methods

Data for 20 consecutive monotherapy patients receiving three HDR fractions of 10.5 Gy per fraction over 2 days were analysed retrospectively. Pre-treatment CT scans were used to assess the effect of catheter movement between fractions on implant quality, with and without movement correction. Implant quality was evaluated using dosimetric parameters.

Results

Compared to the first fraction (f1) the mean inter-fraction caudal movement relative to the prostate base was 7.9 mm (f2) (range 0-21 mm) and 3.9 mm (f3) (range 0-25.5 mm). PTV D90% was reduced without movement correction by a mean of 27.8% (f2) and 32.3% (f3), compared with 5.3% and 5.1%, respectively, with catheter movement correction. Dose to 2 cc of the rectum increased by a mean of 0.69 (f2) and 0.76 Gy (f3) compared with an increase of 0.03 and 0.04 Gy, respectively, with correction. The urethra V12 also increased by a mean of 0.36 (f2) and 0.39 Gy (f3) compared with 0.06 and 0.16 Gy, respectively, with correction.

Conclusions

Inter-fraction correction for catheter movement using pre-treatment imaging is critical to maintain the quality of an implant. Without movement correction there is significant risk of tumour under-dosage and normal tissue over-dosage. The findings of this study justify additional imaging between fractions in order to carry out correction.     

Stereotactic radiosurgery and fractionated stereotactic radiotherapy for the treatment of acoustic schwannomas: comparative observations of 125 patients treated at one institution

Stereotactic radiosurgery (SRS) and, more recently, fractionated stereotactic radiotherapy (SRT) have been recognized as noninvasive alternatives to surgery for the treatment of acoustic schwannomas. We review our experience of acoustic tumor treatments at one institution using a gamma knife for SRS and the first commercial world installation of a dedicated linac for SRT.

Patients were treated with SRS on the gamma knife or SRT on the linac from October 1994 through August 2000. Gamma knife technique involved a fixed-frame multiple shot/high conformality single treatment, whereas linac technique involved daily conventional fraction treatments involving a relocatable frame, fewer isocenters, and high conformality established by noncoplanar arc beam shaping and differential beam weighting.

Sixty-nine patients were treated on the gamma knife, and 56 patients were treated on the linac, with 1 NF-2 patient common to both units. Three patients were lost to follow-up, and in the remaining 122 patients, mean follow-up was 119 ± 67 weeks for SRS patients and 115 ± 96 weeks for SRT patients. Tumor control rates were high (≥97%) for sporadic tumors in both groups but lower for NF-2 tumors in the SRT group. Cranial nerve morbidities were comparably low in both groups, with the exception of functional hearing preservation, which was 2.5-fold higher in patients who received conventional fraction SRT.

SRS and SRT represent comparable noninvasive treatments for acoustic schwannomas in both sporadic and NF-2 patient groups. At 1-year follow-up, a significantly higher rate of serviceable hearing preservation was achieved in SRT sporadic tumor patients and may therefore be preferable to alternatives including surgery, SRS, or possibly observation in patients with serviceable hearing.     

Early fractionation methods and the origins of the NSD concept

The concept of the time factor in radiotherapy originated in the controversy surrounding single-dose and fractionated treatments during the first 20 years of this century. The success of Coutard's fractionated treatments of larynx tumors was an important factor in the abandonment of single-dose treatments. There was considerable research afterwards into the influence of dose rate and overall time of treatment on the responses of normal tissues. Recovery was modeled in terms of the Schwarzschild law of photochemistry, as exemplified by the analysis of Strandqvist in log dose-log time coordinates. Different conventions were followed in defining the time for a single-dose treatment. Subsequently the concept arose that the slopes of isoeffect lines relating dose and treatment time for normal tissues and tumors were different and moreover that the effects of fraction number and overall time could be separated; these developments constituted the foundation of the Ellis NSD model. It had an important influence on clinical practice and was reasonably successful in predicting isoeffective regimens for acute effects. It failed to predict severe late effects after large dose fractions. The dissociation between acute and late effects with altered fractionation led to recognition of the importance of the ratio alpha/beta in characterizing the fractionation sensitivity of tissues.     

Isodose-based methodology for minimizing the morbidity and mortality of thoracic hypofractionated radiotherapy

Background and purpose

Help identify and define potential normal tissue dose constraints to minimize the mortality and morbidity of hypofractionated lung radiotherapy.

Materials and methods

A method to generate isodose-based constraints and visually evaluate treatment plans, based on the published peer reviewed literature and the linear quadratic model, is presented. The radiobiological analysis assumes that the linear quadratic model is valid up to 28 Gy per fraction, the α/β ratio is 2 for the spinal cord and brachial plexus, 4 for pneumonitis, 4 or 10 for acute skin reactions depending on treatment length, and 3 for late complications in other normal tissues. A review of the literature was necessary to identify possible endpoints and normal tissue constraints for thoracic hypofractionated lung radiotherapy.

Results

Preliminary normal tissue constraints to reduce mortality and morbidity were defined for organs at risk based upon hypofractionated lung radiotherapy publications. A modified dose nomenclature was introduced to facilitate the comparison of hypofractionated doses. Potential side effects from hypofractionated lung radiotherapy such as aortic dissection, neuropathy, and fatal organ perforation rarely seen in conventional treatments were identified. The isodose-based method for treatment plan analysis and normal tissue dose constraint simplification was illustrated.

Conclusions

The radiobiological analysis based on the LQ method, biologically equivalent dose nomenclature, and isodose-based method proposed in this study simplifies normal tissue dose constraints and treatment plan evaluation. This may also be applied to extrathoracic hypofractionated radiotherapy. Prospective validation of these preliminary thoracic normal tissue dose constraints for hypofractionated lung radiotherapy is necessary.     

Tumor perfusion increases during hypofractionated short-course radiotherapy in rectal cancer: Sequential perfusion-CT findings

Purpose

The purpose of this study was to investigate perfusion of rectal tumors and to determine early responses to short-course hypofractionated radiotherapy (RT).

Material and methods

Twenty-three rectal cancer patients were included, which underwent perfusion-CT imaging before (pre-scan) and after treatment (post-scan). Contrast-enhancement was measured in tumor and muscle tissues and in the external iliac artery. Perfusion was quantified with three pharmacokinetic parameters: K^trans, v_e and v_p. Perfusion differences between tumor and normal tissue and changes of the pharmacokinetic parameters between both scans were evaluated.

Results

The median tumors K^trans values increased significantly from the pre-scan (0.36 ± 0.11 (min⁻¹)) to the post-scan (0.44 ± 0.13 (min⁻¹)) (p < 0.001). Also, histogram analysis showed a shift of tumor voxels from lower K^trans values towards higher K^trans values. Furthermore, the median K^trans values were significantly higher for tumor than for muscle tissue on both the pre-scan (0.10 ± 0.05 (min⁻¹), p < 0.001) and the post-scan (0.10 ± 0.04 (min⁻¹), p < 0.001). In contrast, no differences between tumor and muscle tissues were found for v_e and v_p. Also, no significant differences were observed for v_e and v_p between the two pCT-imaging time-points.

Conclusions

Hypofractionated radiotherapy of rectal cancer leads to an increased tumor perfusion as reflected by an elevated K^trans, possibly improving the bioavailability of cytotoxic agents in rectal tumors, often administered early after radiotherapy treatment.