Hypofractionated Regimens Research Articles

Hypofractionated Conformal Radiotherapy for Good Prognosis Carcinoma of the Prostate: Seven Year Outcome Analysis

The optimal external beam radiotherapy dose and fractionation in the radical treatment of localised prostate cancer continues to be investigated. This includes not only dose escalation using conventional fractionation, but also the exploration of hypo-fractionated regimes for prostate cancer given its suggested low α/β ratio. We report the long term efficacy of radiotherapy using a hypo-fractionated 50 Gy in 16 fractions (3.13 Gy per fraction) in men with localised prostate cancer. A retrospective review of men with localised prostate cancer treated consecutively with conformal radiotherapy at a single institution between January 1995 and May 2001 was performed. Only patient's in the good prognostic group (PSA ≤10 ng/ml and Gleason score ≤6 and clinical stage T1/2) were included in the study. A conformal external beam radiotherapy dose of 50 Gy in 16 fractions over 22 days was delivered using a 4 field arrangement on a linear accelerator with energy ≥6 MV. The planning target volume (PTV) was defined as GTV (Prostate ± base of seminal vesicles) + 1 cm in all directions except posteriorly where 7 mm was used. Patients treated with neo-adjuvant, concurrent or adjuvant hormonal therapies were excluded. Biochemical failure was defined using both the American Society for Therapeutic Radiology and Oncology consensus definition and Phoenix definition. One hundred and ninety nine men were identified. 73 with clinical T1 and 126 with clinical T2 disease at presentation. The median age at presentation was 67.9 years (49.9–81.65 years) and median initial PSA was 5.9 ng/ml (0.1–10 ng/ml). Histological review demonstrated that 78, 49 and 72 patients had Gleason scores of ≤4, 5 and 6 respectively. At a median follow-up of 84 months (4.6–134.9 months), the 7 year actuarial overall survival was 83.2% and the biochemical failure free survival was 55% and 76.8% as defined by the ASTRO consensus and Phoenix definition respectively. This data demonstrates the efficacy of a hypo-fractionated regime for good prognosis patients. It provides similar levels of biochemical control when compared with other reported long term outcomes using conventionally fractionated radiotherapy (2 Gy per fraction).

MO‐D‐BRA‐02: Application of Hypofractionation in the Prostate

Prostate cancer exhibits slow growth with a potential doubling time ranging from weeks to months (median 42 days). From these data emerged a hypothesis that adenocarcinoma of the prostate may behave more like a late reacting tissue. Brenner and colleagues (1) used data from prostate low dose rate permanent seed implants and external beam radiotherapy series and derived an α/β of approximately 1.5. Many other groups have also calculated the α/β ratio to be in the < 3.0 range; yet, hyperfractionation does not seem to compromise outcome after radiotherapy (2). There are many potential pitfalls of these analyses and some investigators have concluded that the α/β for prostate cancer is closer to that for late effects of the surrounding normal tissues (>3).Understanding the α/β ratio for prostate cancer is key to designing clinical trials that maximize the efficacy of radiotherapy. If the α/β for prostate cancer is lower than the surrounding normal tissues, hypofractionation will afford an advantage in terms of greater sensitivity of prostate cancer to this strategy, as compared to the bladder and rectum. Brenner et al (3) have estimated the α/β for the rectum to be over 5.0. Recently, Fiorino and Valdagni (4) have argued that these estimates may be inaccurate because of variation in, and dependence of toxicity on, the proportion of rectum receiving higher radiation doses.Clinical results in the PSA/IMRT era using hypofractionation show that this strategy is well tolerated by the surrounding normal tissues, with outcomes consistent with a low α/β. Kupelian et al. (5) have treated a large series of men to 70 Gy at 2.5 Gy per fraction with excellent results. As an offshoot of this strategy, RTOG 04‐15 contrasts this hypofractionation regimen with 73.8 Gy in 1.8 Gy fractions.The Cleveland Clinic data also prompted us at Fox Chase Cancer Center to devise a randomized hypofractionation trial comparing 76 Gy at 2.0 Gy per fraction to 70.2 Gy at 2.7 Gy/Fx. The latter hypofractionation regimen is equivalent to 84.4 Gy at 2.0 Gy/Fx, assuming an α/β of 1.5. A total of 307 patients were entered from 2002 to 2006. The trial has completed accrual. Acute toxicity in the first 100 men entered shows minor differences between the two treatment groups (6). Analysis of late toxicity during the first year of follow‐up also is revealing little difference. The encouraging results thus far with hypofractionation suggest that more significant hypofractionation (e.g., stereotactic radiotherapy) might be cost‐effective and potentially advantageous.Objectives1. To understand the alpha/beta ratio for prostate cancer.2. To appreciate the efficacy of hypofractionation and resultant toxicity.

High Dose Rate Brachytherapy as a Boost for the Treatment of Localized Prostate Cancer

We report the outcome and toxicities of high dose rate brachytherapy as a boost for localized prostate cancer. Between 1996 and 2003, 309 patients with prostate carcinoma were treated with external beam radiation therapy and high dose rate brachytherapy. Furthermore, 36% of the patients received neoadjuvant/concurrent or adjuvant androgen deprivation therapy. Patients were stratified into 3 groups. Group 1 of 67 patients had Gleason score 6 or less, pretreatment prostate specific antigen 10 ng/ml or less and clinical stage T2a or less. Group 2 of 109 patients had Gleason score 7 or greater, pretreatment prostate specific antigen greater than 10 ng/ml and clinical stage T2b or greater. Group 3 of 133 patients had 2 or more of these higher risk factors. At a median followup of 59 months the 5-year biochemical control rate, as defined by the American Society for Therapeutic Radiation and Oncology, was 86%, cause specific survival was 98% and overall survival was 91%. Biochemical control in stratified groups 1 to 3 was 98%, 90% and 78%, respectively. On univariate analysis risk group, pretreatment prostate specific antigen and Gleason score were significant predictors of biochemical control. However, on multivariate analysis only risk group and pretreatment prostate specific antigen were significant. Using the Common Toxicity Criteria scale there were 2 cases of grade 3 acute urinary toxicity. Regarding late side effects 4% of patients had grade 3 genitourinary toxicity and 1 had a grade 4 rectal complication. External beam radiation therapy and high dose rate brachytherapy for prostate cancer resulted in excellent biochemical control, cause specific survival and overall survival with minimal severe acute or late complications.

TH‐E‐230A‐07: Estimate of Radiobiological Parameters From Clinical Data for Treatment Planning of Liver Irradiation

Purpose: Several different dose fractionation regimens are being developed in clinical trials for liver irradiation. For example, RTOG is initiating a new hypofractionation regimen (RTOG 0438) to treat liver cancer patients. To evaluate the radiobiological equivalence between different regimens, which is useful in the design of these trials, requires reliable radiobiological parameters. The purpose of this work is to estimate a plausible set of such parameters for liver tumor based on published clinical data. Method and Materials: A phenomenological expression inspired by the linear‐quadratic (LQ) formalism was developed to fit a series of clinical survival data for radiotherapy of hepatocellular carcinoma patients. The data are from different institutes using different fractionation (e.g., 1.5, 1.8 or 4.88 Gy). The phenomenological expression consists of 6 fitting parameters including radiosensitivity parameters α and α/β, potential doubling time Tb, and clonogenic cell number K. The expression considers the prescription dose, dose per fraction, overall treatment time and the elapsed time at which the survival data were collected. We have developed an algorithm to take into account the tumor cell repopulation during the elapsed time. Results: The newly developed phenomenological expression was found to fit well to the available clinical data. Based on the fitting, we have estimated a set of plausible radiobiological parameters for liver tumor: α/β = 12.8 ± 1.0 Gy, α 0.013 ± 0.002 Gy, the potential doubling time: 123 ± 9 days, and colonogenic cell number: 1302 ± 47. Using this set of parameters we have calculated a series of dose fractionation regimens that are biologically equivalent based on BED. Conclusion: A plausible set of radiobiological parameters have been obtained based on clinical data. These parameters may be used for radiation treatment planning of liver tumor, in particular, for the design of new treatment regimens aimed for dose escalation.

SU-FF-T-258: Hypofractionated Stereotactic Radiotherapy for Prostate Cancer Using the CyberKnife

Purpose: To describe the investigational design, treatment planning,treatment delivery, and initial clinical results of a study on hypofractionated image‐guided prostate cancertreatment using the CyberKnife. Design characteristics of the CyberKnife that enable real‐time, 6‐D fiducial tracking with sub‐millimetric accuracy will be discussed. Treatment planning techniques, technical aspects of treatment delivery, and clinical outcome data will be presented. Method and Materials: Greater than 50 prostate cancer patients have been accrued. Patients were treated in five fractions of 7Gy each, for a total of 35 Gy over 5 to 7 days. Four fiducials were implanted using a transperineal approach. Technical details of each treatment were recorded along with treatment planning quality indicators. Follow‐up clinical data were collected including PSA kinetics and rectal and urinary complications. Results: Data will be presented from MDACC Dosimetry Service that independently confirm the dosimetric accuracy and spatial precision of the CyberKnife system used in this study. Results will be presented summarizing the mean and range of technical and physical parameters used for this study: number of beams, number of nodes, number and size of collimators,treatment time, DVH indices, along with dose conformality and homogeneity indices. Typical intra‐fraction drifts in prostate position detected by the real‐time tracking system will be discussed. At the time of abstract submission, follow‐up time for some patients exceeds twelve months. PSA and short‐term morbidity data will be presented. Conclusion: This paper reports on the first clinical study of image‐guidedrobotic x‐ray therapy for the hypofractionated treatment of prostate cancer. The study has shown that accurate, spatially precise hypofractionated treatment can be delivered in a reasonable time using the CyberKnife. The study has shown that the short‐term morbidity associated with this hypofractionated treatment regimen is very low. However, conclusions regarding long‐term morbidity and biochemical disease‐free survival will require significantly longer follow‐up.

The ‘QUAD SHOT’—a phase II study of palliative radiotherapy for incurable head and neck cancer

Background and purpose The primary objective of this study was to estimate the rate of tumour response to a cyclical hypofractionated palliative radiotherapy regimen (QUAD SHOT) in previously untreated patients with incurable squamous cell carcinoma of the head and neck. Secondary objectives were to prospectively evaluate toxicity, quality of life (QoL) and survival in these patients. Patients and methods The QUAD SHOT consisted of 14 Gy in four fractions, given twice a day and at least 6 h apart, for 2 consecutive days. This regimen was repeated at 4 weekly intervals for a further two courses if there was no tumour progression. The QoL tool used was an abbreviation of the EORTC QLQ-C30. Results Thirty eligible patients (29 Stage IV, 20 performance status 2–3) had at least one treatment and 16 patients completed all three cycles. Sixteen patients (53%) had an objective response (2CR, 14PR) and a further seven had stable disease. Median overall survival was 5.7 months, median progression free survival was 3.1 months. The treatment was very well tolerated, with improved QoL in 11 of 25 evaluable patients (44%). Conclusion The QUAD SHOT regimen is an effective palliative treatment with minimal toxicity and a good response rate, which impacts positively on patients' QoL.

486 ORAL Phase II study of erlotinib single agent therapy in recurrent glioblastoma multiforme

Targeted focal therapy strategies for treating single-lobe prostate cancer are under investigation. In this planning study, we investigate the feasibility of treating a portion of the prostate to full-dose external beam radiation with reduced dose to the opposite lobe, compared with full-dose radiation delivered to the entire gland using hypofractionated radiation. For 10 consecutive patients with low- to intermediate-risk prostate cancer, 2 hypofractionated, single-arc volumetric-modulated arc therapy (VMAT) plans were designed. The first plan (standard hypofractionation regimen [STD]) included the entire prostate gland, treated to 70 Gy delivered in 28 fractions. The second dose painting plan (DP) encompassed the involved lobe treated to 70 Gy delivered in 28 fractions, whereas the opposing, uninvolved lobe received 50.4 Gy in 28 fractions. Mean dose to the opposing neurovascular bundle (NVB) was considerably lower for DP vs STD, with a mean dose of 53.9 vs 72.3 Gy (p < 0.001). Mean penile bulb dose was 18.6 Gy for DP vs 19.2 Gy for STD (p = 0.880). Mean rectal dose was 21.0 Gy for DP vs 22.8 Gy for STD (p = 0.356). Rectum V70 (the volume receiving ≥70 Gy) was 2.01% for DP vs 2.74% for STD (p = 0.328). Bladder V70 was 1.69% for DP vs 2.78% for STD (p = 0.232). Planning target volume (PTV) maximum dose points were 76.5 and 76.3 Gy for DP and STD, respectively (p = 0.760). This study demonstrates the feasibility of using VMAT for partial-lobe prostate radiation in patients with prostate cancer involving 1 lobe. Partial-lobe prostate plans appeared to spare adjacent critical structures including the opposite NVB.

Randomized Trial Comparing Two Fractionation Schedules for Patients With Localized Prostate Cancer

The optimal radiation dose fractionation schedule for localized prostate cancer is unclear. This study was designed to compare two dose fractionation schemes (a shorter 4-week radiation schedule v a longer 6.5-week schedule). Patients with early-stage (T1 or T2) prostate cancer were randomly assigned to 66 Gy in 33 fractions over 45 days (long arm) or 52.5 Gy in 20 fractions over 28 days (short arm). The study was designed as a noninferiority investigation with a predefined tolerance of -7.5%. The primary outcome was a composite of biochemical or clinical failure (BCF). Secondary outcomes included presence of tumor on prostate biopsy at 2 years, survival, and toxicity. From March 1995 to December 1998, 936 men were randomly assigned to treatment; 470 were assigned to the long arm, and 466 were assigned to the short arm. The median follow-up time was 5.7 years. At 5 years, the BCF probability was 52.95% in the long arm and 59.95% in the short arm (difference = -7.0%; 90% CI, -12.6% to -1.4%), favoring the long arm. No difference in 2-year postradiotherapy biopsy or in overall survival was detected between the arms. Acute toxicity was found to be slightly higher in the short arm (11.4%) compared with the long arm (7%; difference = -4.4%; 95% CI, -8.1% to -0.6%); however, late toxicity was similarly low in both arms (3.2%). Given the results, we cannot exclude the possibility that the chosen hypofractionated radiation regimen may be inferior to the standard regimen. Further evaluation involving higher dose hypofractionated radiation regimens in contemporary radiation settings is necessary.

A phase II trial using carbon ion radiotherapy (C-ion RT) for prostate cancer

4630 Background: Carbon ion therapy (C-ion RT) is a heavy charged particle radiotherapy characterized with well-localized dose distribution and relatively higher biological effects compared with X-ray. A phase II clinical trial of hypofractionated C-ion RT for prostate cancer was performed in order to clarify the efficacy and safety of recommended dose which was obtained by the results of the preceded phase I/II studies. Methods: Primary endpoint of this study is biochemical relapse free survival (bNED) and secondary ones are local control and normal tissue morbidities. Between April 2000 and November 2003, histologically confirmed 175 patients with previously untreated and localized T1b-T3b prostate cancer were enrolled in this study. All patients were treated with C-ion RT using the recommended dose of 66.0 GyE in 20 fractions. For 33 patients of a low risk group (Stage ≤ T2a and PSA < 20ng/ml and Gleason score ≤ 6), C-ion RT alone was performed and the remaining 142 patients of a high risk group received combination of C-ion RT and hormonal therapy. Results: Biochemical relapses were observed in 16 patients and 4-year biochemical relapse free survival rate was 87.7%. Local control was obtained in all but one patients. By the date of the analysis, 4 patients died of prostate cancer and 3 died of intercurrent diseases. The rates of overall survival and cause-specific survival at 4 years in a low risk group were 95.7% and 100%, respectively, whereas the corresponding rates in a high risk group were 89.2% and 91.9 %, respectively. Incidences of radiation morbidities in the rectum and the genitourinary system were quite low. There was no grade 3 or higher morbidities and grade 2 rectal and urinary morbidities developed in 3 (1.7 %) and 9 (5.1%) patients, respectively. Conclusions: Hypofractionated C-ion RT could achieve excellent outcomes for prostate cancer with a low incidence of normal tissue damages. Based on low α/β of prostate cancer, a further hypofractionated regimen (16 fractions) has been tested since last year. No significant financial relationships to disclose.

Stereotactic Body Radiation Therapy

Stereotatic body radiation therapy (SBRT) is a rapidly evolving cancer treatment method in which concepts and techniques previously developed for brain tumor radiosurgery are adapted to eradicate tumors elsewhere in the body. The spatial accuracy, conformality, and steep radiation dose gradients of radiosurgery, which have been critical to its success in the treatment of intracranial tumors, are applied in SBRT to treat a variety of extracranial tumors. Early results demonstrate excellent response rates and low toxicity with a variety of hypofractionated dose regimens and localization/immobilization techniques. This article provides an overview of the rationale and results of SBRT for specific indications, descriptions of some methods of treatment delivery, and discussion of potential areas of future investigation.

Radiation therapy for Bowen’s disease of the skin

To assess the clinical outcome in the radiation therapy (RT) of squamous carcinoma in situ of the skin (Bowen's disease). We focused on the local control rate and the toxicity according to the biologically effective dose (BED). A retrospective review was performed on 44 patients with Bowen's disease treated at Princess Margaret Hospital from April 1985 to November 2000. RT was the primary treatment for 32 patients, whereas 12 received RT for residual disease after local ablative therapy. Lesions were located as follows: scalp, 9 patients (20%); face, 12 (27%); trunk, 6 (14%), extremity, 12 (27%), perianal, 3 (7%), and penis, 2 (5%). Orthovoltage X-rays were used in the majority (39 of 44, 89%). There was no standard fractionation regimen: some physicians prescribed high doses, as for invasive skin cancer, whereas others prescribed lower doses because of the noninvasive nature of the disease, a sensitive anatomic location (e.g., extremity), or large treatment area. Because of the variations in fractionation regimens, BED was used as a common metric for biologic effect in the comparison of different regimens and analyzed for correlation with recurrence and toxicity. Local control was defined as the lack of persistent or recurrent disease at the treated site for the follow-up period. Grade 4 toxicity was defined as necrosis (cartilage/bone damage) and/or ulceration for a duration of >3 months. The mean patient age was 67.7 years, and the male/female ratio was 29:15. The median pretreatment lesion size was 2.65 cm(2) (range, 0.07-34.56 cm(2)). Complete remission was achieved in 42 patients, with follow-up unavailable for the remaining 2 patients. Subsequently, 3 patients experienced recurrences at 0.2, 1.1, and 1-1.5 years after complete remission. One recurrence was Bowen's disease (local); the others were squamous cell carcinoma (one local, one marginal). Four patients experienced a new squamous lesion at a distant cutaneous site. As of last follow-up, 32 patients (73%) were known to be alive. Median follow-up was 2.6 years (range, 0-11.8 years). All but 3 patients were disease-free at last follow-up, 1 of whom died with distant, but not local disease. The 5-year overall survival rate was 68%. Biologically effective dose was not associated with recurrence. The crude local control rate was 93%. There was a trend toward higher radiation doses for smaller pretreatment tumor and field sizes. The BED did not correlate with Grade 4 toxicity; however, the three cases of Grade 4 toxicity occurred in patients treated with hypofractionated regimens (dose per fraction >4 Gy) for extremity lesions. Radiation therapy is an effective treatment option for Bowen's disease of the skin. Local recurrences seem to be equally low in patients treated with high- and low-dose regimens. Avoiding hypofractionated regimens (dose per fraction >4 Gy) in extremity locations might reduce the risk of Grade 4 toxicity.

Lack of benefit from a short course of androgen deprivation for unfavorable prostate cancer patients treated with an accelerated hypofractionated regime

High-dose radiotherapy, delivered in an accelerated hypofractionated course, was utilized to treat prostate cancer. Therapy consisted of external beam radiotherapy (EBRT) and transrectal ultrasound (TRUS)-guided conformally modulated high-dose rate (HDR) brachytherapy. The purpose of this report is (1) to assess long-term comparative outcomes from three trials using similar accelerated hypofractionated regimes; and (2) to examine the long-term survival impact of a short course of < or =6 months adjuvant/concurrent androgen deprivation when a very high radiation dose was delivered. Between 1986 and 2000, 1,260 patients were treated at three institutions with pelvic EBRT (36-50 Gy) integrated with HDR prostate brachytherapy. The total dose including brachytherapy was given over 5 weeks. The biologic equivalent EBRT dose ranged between 90 and 123 Gy (median, 102 Gy) using an alpha /beta of 1.2. Patient eligibility criteria included a pretreatment prostate-specific antigen > or =10, Gleason score > or =7, or clinical stage > or =T2b. A total of 1,260 patients were treated, and 934 meet the criteria. Kiel University Hospital treated 198 patients; William Beaumont Hospital, 315; and California Endocurietherapy Cancer Center, 459 patients. Brachytherapy dose regimes were somewhat different between centers and the dose was escalated from 5.5 x 3 to 15 Gy x 2 Gy. Patients were divided for analysis between the 406 who received up to 6 months of androgen deprivation therapy and the 528 patients who did not. All patients had a minimum follow-up of 18 months (3 times the exposure to androgen deprivation therapy). The American Society for Therapeutic Radiology and Oncology biochemical failure definition was used. Mean age was 69 years. Median follow-up time was 4.4 years (range, 1.5-14.5); 4 years for androgen deprivation therapy patients and 4.9 for radiation alone. There was no difference at 5 and 8 years in overall survival, cause-specific survival, or biochemical control among the three institutions. The corresponding 8-year rates with and without androgen deprivation therapy were biochemical control 85% and 81%; overall survival 83% and 78%; cause-specific survival 89% and 94%; and metastatic rates of 16.6% and 7.3%. A multivariate analysis revealed androgen deprivation therapy did not predict for biochemical failure for either the entire group or the subset of 177 patients harboring all three poor prognostic factors. Moreover, adding androgen deprivation therapy strongly correlated with higher rates of both metastasis (p = 0.09; hazard ratio, 2.08) and cancer-related deaths (p = 0.02, hazard ratio 3.25). These negative results for the most unfavorable group led us to question if androgen deprivation therapy might have a deleterious impact through delay in delivery of the potentially curative radiation or whether there may be a biologic basis by fixing the cycling cells in G0. Accelerated hypofractionated pelvic EBRT integrated with TRUS-guided conformally modulated HDR administered to 1,260 patients in three institutions was an excellent method of delivering very high radiation dose to the prostate in 5 weeks. Similar high overall, cause-specific, and biochemical no evidence of disease survival rates achieved show that prostate HDR can be successfully delivered in academic and community settings. At 8 years, the addition of a course of < or =6 months of neoadjuvant/concurrent androgen deprivation therapy to a very high radiation dose did not confer a therapeutic advantage but added side effects and cost. Furthermore, for the most unfavorable group, there was a higher rate of distant metastasis and more prostate cancer-related deaths. We question the value of a short course of androgen deprivation therapy when used with high-dose radiation.

Dosimetric advantages of IMRT simultaneous integrated boost for high-risk prostate cancer

A sequential two-phase process, initial and boost irradiation, is the common practice for the radiotherapy management of high-risk prostate cancer. In this work, we explore the feasibility of using intensity modulated radiation therapy (IMRT) simultaneous integrated boost (SIB), a single-phase process, to simultaneously deliver high dose to the prostate and lower dose to the pelvic nodes. In addition, we introduce the concept of voxel-equivalent dose for the comparison of treatment plans. The SIB is designed to deliver the same dose (e.g., 45 Gy, 25 x 1.8 Gy) as the conventional method to the pelvic nodes and to deliver higher doses to prostate in the same 25 fractions (i.e., hypofractionation). The equivalent uniform dose (EUD) was used to determine suitable SIB fractionations that deliver the biologically equivalent doses to prostate. For tumor, the EUD was estimated based on the linear quadratic (LQ) model. The most recent LQ parameters derived from clinical data for prostate cancer were used. The sensitivity of LQ parameters was evaluated. The EUD for normal tissue was computed based on the widely used Lyman model. To be able to consider biologic effectiveness spatially (e.g., voxel by voxel), we propose a new concept, termed the voxel-equivalent dose (VED). The calculation of VED was similar to that for EUD, except that it was done within a voxel. To demonstrate dosimetric feasibility and advantages of the proposed IMRT SIB, we have performed a retrospective planning study on selected patient cases using commercial IMRT and three-dimensional (3D) planning systems. Four treatment scenarios were considered: (1) the conventional 3D plan for initial whole-pelvic irradiation and subsequent conventional 3D boost plan for prostate gland, (2) the conventional 3D plan for initial whole-pelvic irradiation and subsequent IMRT boost plan for prostate, (3) IMRT plan for initial whole-pelvic irradiation and subsequent IMRT boost plan for prostate, and (4) IMRT SIB. EUDs and VED-based dose-volume histograms for prostate, pelvic nodes, small bowel, rectum, bladder, and other tissue for all 4 scenarios were compared. A series of equivalent hypofractionation regimens suitable for the IMRT SIB were obtained for high-risk prostate cancer. For example, the conventional treatment regimen of 42 x 1.8 Gy (EUD = 75.4 Gy) would be equivalent to a SIB regimen of 25 x 2.54 Gy. From the comparison of 3D VED dose distributions and dose-volume histograms between the SIB and the conventional two-phase irradiation, we found that the SIB offers better or equivalent dose conformity to prostate and pelvic nodes and better sparing to the critical structures. For example, for the 4 treatment scenarios with a prostate EUD of 75.4 Gy, the corresponding rectal EUDs are 67.1 (3D + 3D), 65.6 Gy (3D + IMRT), 63.7 Gy (IMRT + IMRT), and 62.0 Gy (SIB). A new IMRT simultaneous integrated boost strategy that irradiates prostate via hypofractionation while irradiating pelvic nodes with the conventional fractionation is proposed for high-risk prostate cancer. Compared to the conventional two-phase treatment, the proposed SIB technique offers potential advantages, including better sparing of critical structures, more efficient delivery, shorter treatment duration, and better biologic effectiveness.

211 poster workshop Multi-institutional results of 1493 patients treated with an hypofractionated regime combining external beam irradiation and high dose rate brachytherapy for prostate cancer

211 poster workshop Multi-institutional results of 1493 patients treated with an hypofractionated regime combining external beam irradiation and high dose rate brachytherapy for prostate cancer

Comparison of rectal dose volume histograms for definitive prostate radiotherapy among stereotactic radiotherapy, IMRT, and 3D-CRT techniques

To compare rectal dose volume histograms (DVH) between stereotactic radiotherapy, intensity modulated radiation therapy (IMRT), and 3D-conformal radiotherapy (3D-CRT) for prostate cancer. Radiotherapy plans for 28 patients treated with stereotactic radiotherapy, IMRT, and 3-D CRT techniques were reviewed. There were 10 stereotactic plans, 9 IMRT plans, and 9 3D-CRT plans. The planning systems utilized were Northwest Medical Physics Equipment/pReference for the stereotactic plans and ADAC/Pinnacle for IMRT and 3D-CRT plans. Fused MRI and CT were used for target delineation with IMRT and stereotactic radiotherapy. CT alone was utilized for 3D-CRT. For patients treated with IMRT and stereotactic radiotherapy, fiducial markers were placed within the gland and utilized for daily target localization with electronic portal imaging. Patients treated with 3D-CRT were localized with skin marks. The CTV was expanded by 0.4 cm for stereotactic radiotherapy plans and 0.5 cm for IMRT plans based on accuracy of the localization technique and on previous data related to intrafraction stability. CTV expansion was 1–1.5 cm for the 3D-CRT plans. Stereotactic radiotherapy was delivered with 6 noncoplanar fields and custom stereotactic cones on the 2100CD or 2100EX Varian linac with patients lying in a flex-prone position. IMRT was delivered with 9 coplanar beams, and 3D-CRT with 6 coplanar beams. Treatment was delivered with either 0.5 cm or 1 cm MLC on a Varian 2100CD or 2100EX linear accelerator for IMRT and 3D-CRT in supine position without other immobilization. The dose to the prostate was 33.5 Gy /6 fractions for stereotactic radiotherapy plans, and 75–78 Gy/35–42 fractions for IMRT and 3D-CRT plans. The rectal volume was contoured as a solid organ from anal canal to the level of the sacro-iliac joint in all plans and reported in cubic centimeters. There were notable differences in the rectal DVH among the three treatment techniques (see table(table 1)). IMRT produced the most rectal sparing at the high dose levels but below the 80% level, stereotactic radiotherapy produced better sparing. 3D-CRT plans provided the least rectal sparing at all dose levels. In our experience, IMRT and stereotactic radiotherapy plans resulted in smaller rectal volumes exposed to high dose radiation compared to 3D-CRT plans. In addition, stereotactic radiotherapy resulted in significantly less rectal volume exposed to the lower radiation dose levels than IMRT or 3D-CRT plans. These differences may be advantageous for hypofractionated treatment regimens. This analysis helps substantiate the use of this unique stereotactic technique for our phase I/II clinical trial of hypofractionated radiation therapy for prostate cancer.

Detrimental outcome of short term hormonal treatment and high dose radiation therapy (EBRT plus HDR) when compared to EBRT plus HDR alone for high risk prostate patients

We reviewed the combined experience of an accelerated hypofractionated regime used at 3 different institutions treating intermediate and high risk prostate cancer. The treatment schedule was a combination of EBRT plus HDR brachytherapy with and without hormonal therapy (HT). Overall treatment time was 5 weeks.

Detrimental outcome of short term hormonal treatment and high dose radiation therapy (EBRT plus HDR) when compared to EBRT plus HDR alone for high risk prostate patients

We reviewed the combined experience of an accelerated hypofractionated regime used at 3 different institutions treating intermediate and high risk prostate cancer. The treatment schedule was a combination of EBRT plus HDR brachytherapy with and without hormonal therapy (HT). Overall treatment time was 5 weeks.

Adjuvant nodal radiotherapy for node positive head and neck melanoma: A single institution experience

7537 Background: Despite adequate surgical treatment, head and neck melanoma frequently recurs. It is generally thought of as a chemotherapy and radiotherapy resistant malignancy. The goal of this study is to see if adjuvant post-operative radiotherapy improves outcome for lymph node positive head and neck melanoma. Methods: A single institution retrospective review. Results: All cases (n=86) of lymph node positive head and neck melanoma at Mayo Clinic Rochester were reviewed from 1985–2000. Though formal statistical conclusions could not be drawn, the irradiated and observed groups appeared similar with regards to most baseline characteristics. However, the irradiated group had more limited surgeries, fewer nodes removed but more involved, and more extracapsular extension. Most irradiated patients received a twice-weekly hypo-fractionated regimen. Neck recurrence was 25.0% vs 42.9% favoring the irradiated group, despite higher risk of recurrence. Rates of distant metastases (69.2% vs 52.9%) and overall failure (84.6% vs 67.1%) were higher in the irradiated group, confirming their higher-risk disease. Conclusions: Post-operative radiation appears to reduce the risk of cervical lymph node recurrence in node positive head and neck melanoma. No trial to date has compared radiation to observation in a randomized, controlled fashion. Our group is planning a Phase III trial to address this question. No significant financial relationships to disclose.

Adjuvant nodal radiotherapy for node positive head and neck melanoma: A single institution experience

7537 Background: Despite adequate surgical treatment, head and neck melanoma frequently recurs. It is generally thought of as a chemotherapy and radiotherapy resistant malignancy. The goal of this study is to see if adjuvant post-operative radiotherapy improves outcome for lymph node positive head and neck melanoma. Methods: A single institution retrospective review. Results: All cases (n=86) of lymph node positive head and neck melanoma at Mayo Clinic Rochester were reviewed from 1985–2000. Though formal statistical conclusions could not be drawn, the irradiated and observed groups appeared similar with regards to most baseline characteristics. However, the irradiated group had more limited surgeries, fewer nodes removed but more involved, and more extracapsular extension. Most irradiated patients received a twice-weekly hypo-fractionated regimen. Neck recurrence was 25.0% vs 42.9% favoring the irradiated group, despite higher risk of recurrence. Rates of distant metastases (69.2% vs 52.9%) and overall failure (84.6% vs 67.1%) were higher in the irradiated group, confirming their higher-risk disease. Conclusions: Post-operative radiation appears to reduce the risk of cervical lymph node recurrence in node positive head and neck melanoma. No trial to date has compared radiation to observation in a randomized, controlled fashion. Our group is planning a Phase III trial to address this question. No significant financial relationships to disclose.

Predicting the effect of temporal variations in p o2 on tumor radiosensitivity

Purpose Tumor hypoxia is associated with less effective radiation-mediated cell killing, increased metastatic potential, and poorer prognosis. Transient variations in hypoxia, with characteristic periodicity on the order of 1 to 10 min, have been observed in animal models. This article explores the effect of these temporal variations in P o 2 on the oxygen enhancement ratio, effective radiation dose to the tumor, and tumor control probability. Methods and materials P o 2 over a 50–60 min period was determined at multiple sites in rat fibrosarcomas, 9L gliomas, and R3230Ac mammary adenocarcinomas. Using a correlation derived from the data of Elkind et al. (1965), P o 2 data are converted into oxygen enhancement ratios (OERs.) A tumor is assumed to consist of 10 3–10 4 independent oxygenation subvolumes, each with a randomly chosen starting point on the OER-time curve. The effect of temporal variations in OER is examined for three cases: conventionally fractionated external beam radiotherapy (EBRT), stereotactic radiosurgery (SRS) and intraoperative radiotherapy (IORT). The oxygen effective dose (OED) for a subvolume is calculated from the dose to that subvolume modified by the OER. In turn, the distribution of OED for a tumor is analyzed for each treatment case and representative tumor control probabilities (TCPs) calculated. Results Oxygen enhancement ratio varied from 1 to 3 over the range of P o 2 measured in this study. Mean OER ranged from 1.6 to 2.6, and the variation in OER vs. time was greater with decreasing P o 2. In EBRT, the standard deviation in OED was small, <2%. In contrast, the standard deviation in OED was much higher for both SRS and IORT, typically ranging from 3 to 6%, with the greatest variation at the lowest P o 2s. Compared with a tumor with equal mean OED and uniform P o 2, TCP was minimally poorer for either EBRT or well-oxygenated tumors. However, for both SRS and IORT, temporal variations in more hypoxic tumors can produce a significant decrease in TCP. Conclusion Temporal variations in tumor P o 2 can produce significant variations OER, particularly at low P o 2, resulting in decreased TCP for hypofractionated treatment regimens.