Barby Pickett

Static field intensity modulation to treat a dominant intra-prostatic lesion to 90 Gy compared to seven field 3-dimensional radiotherapy

PURPOSE/OBJECTIVE Recent studies supported by histopathological correlation suggest that the combined use of endorectal magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) allows differentiation of normal and carcinomatous prostate. The goal of this study was to use static field intensity modulated three-dimensional conformal radiotherapy (SF-IMRT) to treat the entire prostate to a total dose of >70 Gy, while concurrently treating a dominant intraprostatic lesion (DIL) defined by MRI+MRS to 90 Gy while not exceeding normal tissue tolerances. MATERIALS AND METHODS For the example chosen, the DIL consisted of a large portion of the peripheral zone of the left lobe of the prostate. University of Michigan (UM-PLAN) three-dimensional treatment planning software was used to design a partially shielded 7 field conformal isodose plan that would treat the entire prostate to >70 Gy at 1.8 Gy per day (80% isodose line), while concurrently treating the DIL to 2.25 Gy per day for a total dose of 90 Gy. Dose volume histograms (DVH) were used to compare the rectal doses to rectum and other adjacent normal tissues using these two techniques. RESULTS SF-IMRT as described, allowed a total dose of 90 Gy to encompass the DIL, while the rectal dose was slightly lower than that using the standard 7 field technique to the prostate alone. For example, the dose to 30 cm3 of the rectum was 40 Gy using SF-IMRT and 48 Gy for the standard 7 field technique. Because of differences in the dose per fraction the biologic advantages of the SF-IMRT technique are likely to be even greater. CONCLUSIONS This study demonstrates the feasibility of using SF-IMRT to treat a DIL involving a single lobe of the prostate, as defined by MRI/MRS, to 90 Gy, while simultaneously treating the prostate to >70 Gy without increasing the dose to surrounding normal tissues. A similar approach could be used to treat multifocal disease. This method of treatment is an alternative to dynamic intensity modulation. It is less expensive, and can be adapted to any radiation therapy department without the use of an inverse treatment planning programs.

(NON)-MIGRATION OF RADIOPAQUE MARKERS USED FOR ON-LINE LOCALIZATION OF THE PROSTATE WITH AN ELECTRONIC PORTAL IMAGING DEVICE

PURPOSE Radiopaque gold markers can be implanted in the prostate to visualize its position on portal images during radiation therapy. This procedure assumes that the markers do not move within the prostate. In this work we test this assumptiom. METHODS AND MATERIALS Three markers were implanted transrectally in the prostate of patients undergoing external radiation therapy. An orthogonal pair of portal images was acquired periodically throughout the course of radiation therapy with an a-Si electronic portal imaging device (EPID). The marker coordinates were determined, and the distances between the implanted markers were recorded. The distance time trend is used to evaluate the magnitude of marker migration. RESULTS The average standard deviation (SD) of the distances between markers was 1.3 mm (range 0.44 to 3.04 mm). Three of the 11 patients show a SD larger than 2 mm. For these patients, all three distances show a simultaneous reduction with time, compatible with a shrinking of the prostate. All had been treated with neoadjuvant hormone therapy. For 1 of the 3 patients, this reduction in volume was confirmed with a repeat computed tomographic scan. CONCLUSION None of the 33 markers studied migrated significantly. The implantation of three radiopaque gold markers enables accurate and precise on-line verification of the prostate position during external beam radiation therapy. The use of three markers provides a tool to monitor prostate position and volume changes that can occur over time due to hormone or radiation therapy.

Forward or inversely planned segmental multileaf collimator imrt and sequential tomotherapy to treat multiple dominant intraprostatic lesions of prostate cancer to 90 Gy

PURPOSE To investigate the technical feasibility of using forward or inversely planned segmental multileaf collimator (SMLC) intensity-modulated radiotherapy and sequential tomotherapy (ST) to escalate to a dose of 90 Gy to multiple dominant intraprostatic lesions within the prostate gland while delivering a dose of 75.6 Gy to the remaining prostate. METHODS AND MATERIALS A selected case with one dominant intraprostatic lesion located at the left base and a second dominant intraprostatic lesion at the right apex of the prostate was planned using three different intensity modulation techniques. Two plans were generated with inverse treatment planning, using either SMLC or ST with a special multivane collimator. The third plan also employed SMLC but was generated using forward planning. All three plans were compared based on dose-volume histograms, isodose distributions, and doses to sensitive normal structures. RESULTS All three plans meet and exceed the desired dose constraints, limiting doses to the rectum and bladder to an estimated RTOG Grade 2 complication rate of <10%. The ST plan achieved the best dose conformality, whereas the inverse SMLC plan gave the lowest dose to the rectal wall, and the forward SMLC plan obtained the best dose homogeneity inside the targets. CONCLUSIONS Using any of the three intensity-modulated techniques, it is technically feasible to concurrently treat multiple selected high-risk regions within the prostate to 90 Gy and the remaining prostate to 75.6 Gy, while keeping the doses to the rectum and the bladder significantly lower than those associated with a Grade 2 complication rate of 10%.

Immobilization improves the reproducibility of patient positioning during six-field conformal radiation therapy for prostate carcinoma☆

PURPOSE To determine the magnitude of patient positioning errors associated with six field conformal therapy for carcinoma of the prostate, and to assess the impact of alpha-cradle immobilization on these errors. METHODS AND MATERIALS The records of 22 patients, treated at two of the treatment facilities within our department, using computed tomography-planned conformal six field therapy for carcinoma of the prostate, were reviewed. At one facility (UCD), patients were routinely treated with immobilization, while at the other (UCSF) no rigid immobilization was used. Portal films of patients treated at both facilities were subsequently reviewed, and the deviation of each portal from the simulation film was determined (simulation-to-treatment variability). In addition, for each patient, the average deviation of each portal film from the average portal film (treatment-to-treatment variability) was determined. RESULTS The mean and median simulation-to-treatment variability was 0.4 cm for those patients treated with immobilization, versus 0.6 cm for those treated without immobilization. The 90th percentile of simulation-to-treatment variability was 0.7 cm for those patients treated with immobilization, versus 1.1 cm for those not immobilized. There was a significant reduction in the number of portals observed with errors of > or = 0.50 cm (132/201 vs. 37/87, 66% vs. 43%; p < 0.001), 0.75 cm (184/201 vs. 59/87, 92% vs. 68%; p < 0.001), and 1.0 cm (196/201 vs. 74/87, 98% vs. 85%; p < 0.001) for patients treated with immobilization. There was also a significant reduction in the number of patients with treatment-to-treatment variability > or = 0.5 cm (1/10 vs. 8/12; p = 0.01) for patients treated with immobilization. CONCLUSION The use of immobilization devices significantly reduces errors in patient positioning, potentially permitting the use of smaller treatment volumes. Immobilization should be a component of conformal radiation therapy programs for prostate carcinoma.

Indications for and the significance of seminal vesicle irradiation during 3D conformal radiotherapy for localized prostate cancer

PURPOSE To evaluate the use of pretreatment prostate specific antigen, Gleason score, and clinical stage as predictors of the risk of seminal vesicle involvement in patients with clinically localized prostatic cancer, and to determine the impact of excluding the seminal vesicles on the dose received by surrounding normal tissues. METHODS AND MATERIALS An empirically derived equation combining the preoperative prostate specific antigen and Gleason score was applied to 188 patients treated with radical prostatectomy, for whom pathologic evaluation of the seminal vesicles was available. High and low risk groups for seminal vesicle involvement were defined using this equation. The observed risks of seminal vesicle involvement was compared to the predicted risk using the preoperative prostate specific antigen, Gleason score or clinical stage alone or using the empirical equation. Dose-volume histograms for five patients treated using six-field conformal radiotherapy were compared including and excluding the seminal vesicles. RESULTS Using the empirically derived equation, a low risk group of 109 patients was identified with a calculated risk of seminal vesicle involvement of < or = 13% and an observed incidence of 7.3%. Among the high risk group of 79 patients, which included all patients with a calculated risk > 13%, 37% had seminal vesicle involvement (p < 0.001 low vs. high risk). Twenty percent of the rectal volume received on average above 86% of the total dose for the five plans which included the seminal vesicles compared to 68% for the five plans excluding the seminal vesicles. The doses to 40% of the rectal volume were 64% and 37% if the seminal vesicles were included and excluded, respectively. The dose to the bladder and femoral heads was also decreased but to a lesser extent. CONCLUSION The empirical formula predicts risk of seminal vesicle involvement with a higher degree of significance for a larger number of patients than either Gleason score, clinical stage, or prostate specific antigen alone. Based on an analysis of our first 100 patients treated with definitive conformal therapy alone, approximately 47% of those patients could have been treated excluding the seminal vesicles. Excluding the seminal vesicles may allow us to go to a higher total dose with less rectal toxicity.

The role of the urethrogram during simulation for localized prostate cancer

Urethrograms on 89 consecutive patients with localized prostate cancer were evaluated retrospectively, and the inferior border of the treatment field based on this study was compared with the inferior border that would have been defined by using the lower border of the ischial tuberosities. An analysis of the relationship between the margin used and the dose at the inferior border of the prostate supported our policy of requiring a 2 cm margin for optimal coverage of the prostate. Inclusion of at least 1 cm of proximal penile urethra was essential to ensure this 2 cm margin. Based on this assumption, twenty-five percent of patients would have had an inadequate margin if the lower border of the ischial tuberosities had been used instead of the urethrogram to define the inferior border of the treatment field. Assuming that a margin of more than 3 cm inferiorly is excessive, 11% of patients would have had excessive urethral irradiation if the bottom of the ischial tuberosities had been used to define the inferior border. Combining these two extremes, more than one in three patients would have had an inappropriate inferior margin if the bottom of the ischial tuberosities had been used to define the inferior border of the treatment field. There was no apparent increase in morbidity as a result of the urethrograms or an increase in treatment related toxicity in association with using the treatment fields defined by urethrography. Computed tomography was complimentary in defining the apex of the prostate. These data support the routine use of the urethrograms during simulation for localized prostate cancer. The use of the lower border of the ischial tuberosities to define the inferior border of the treatment field is associated with an unacceptable risk of either underdosing the apical portion of the prostate or overdosing the urethra.

The value of nonuniform margins for six-field conformal irradiation of localized prostate cancer.

PURPOSE Evaluate the hypothesis that by combining nonuniform margins with a technique for limiting the possible extent of posterior motion of the prostate during the delivery of six-field conformal radiotherapy (SFCRT) of the prostate, it is possible to adequately treat the clinical target volume (CTV) and minimize dose to normal structures. METHODS AND MATERIALS Serial computed tomography (CT) scans of prostate patients were taken at 0.5 cm intervals for treatment planning purposes. The initial treatment planning scans were performed with the rectum empty and the bladder full. Subsequent scans were taken at the end of the first week of treatment with the bladder full, but with no attempt to empty the rectum, to mimic the typical treatment situation. The gross tumor volume (GTV), consisting of the prostate and seminal vesicles, as well as the CTV, were defined on the CT images with the aid of a urethrogram to define the inferior border (apex) of the prostate. Variable blocking margins were designed around the CTV using the University of Michigan three dimensional (3D) treatment planning system (UM-PLAN). Isodose distributions displayed on axial, sagittal, coronal, and oblique slices were used to evaluate the adequacy of the various margins applied. Nonuniform margins varying from 0.75 cm posteriorly to 2.0 cm anteriorly and inferiorly were compared to uniform margins of 1.0, 1.5, and 2.0 cm for each patient. Dose volume histograms (DVH) were used to compare doses to the GTV, CTV, rectum, and bladder. RESULTS In a series of 10 patients scanned with the above protocol, treatment plans with nonuniform margins were compared with uniform margins of 1.0, 1.5, and 2.0 cm. Dose-volume histograms showed that nonuniform and 1.0 cm uniform margins deliver the lowest doses to the rectum and bladder, but the use of 1.0 cm uniform margins resulted in inadequate coverage of the CTV in 40% of the cases. The 1.5 and 2.0 cm uniform margins adequately covered the CTV but resulted in significantly higher doses to the bladder and rectum. CONCLUSIONS The use of nonuniform margins, when combined with CT scans performed with the rectum empty and bladder full, can improve tumor control probability while minimizing the risk of morbidity to adjacent critical structures.

Feasibility of MR Imaging/MR Spectroscopy-Planned Focal Partial Salvage Permanent Prostate Implant (PPI) for Localized Recurrence After Initial PPI for Prostate Cancer

PURPOSE To assess the feasibility of magnetic resonance imaging (MRI)-planned partial salvage permanent prostate implant (psPPI) among patients with biopsy-proven local recurrence after initial PPI without evidence of distant disease. METHODS AND MATERIALS From 2003-2009, 15 patients underwent MRI/magnetic resonance spectroscopy (MRS) planning for salvage brachytherapy (psPPI, I-125 [n=14; 144 Gy]; Pd-103 [n=1; 125 Gy]) without hormone therapy. Full dose was prescribed to areas of recurrence and underdosage, without entire prostate implantation. Limiting urethral and rectal toxicity was prioritized. Follow-up was from salvage date to prostate-specific antigen (PSA) concentration failure (Phoenix criteria = nadir + 2.0; ASTRO = 3 consecutive rises), recurrence, distant metastases, or last follow-up PSA level. Progression-free survival (PFS) was defined as no PSA failure or biopsy-proven recurrence without all-cause mortality. Toxicity was scored using Common Terminology Criteria for Adverse Events version 4.0. RESULTS At salvage, median age was 68 years, and PSA concentration was 3.5 ng/mL (range, 0.9-5.6 ng/mL). Abnormal MRI/MRS findings were evident in 40% of patients. Biopsy-proven recurrences consisted of a single focus (80%) or 2 foci (20%). At recurrence, Gleason score was 6 (67%) or ≥7 (27%). Median interval between initial and salvage implantation was 69 months (range, 28-132 months). psPPI planning characteristics limited doses to the rectum (mean V100 = 0.5% [0.07 cc]) and urethra (V100 = 12% [0.3 cc]). At median follow-up (23.3 months; range, 8-88 months), treatment failure (n=2) resulted only in localized recurrence; both patients underwent second psPPI with follow-up PSA tests at 12 and 26 months, resulting in 0.6 and 0.7 ng/mL, respectively. American Society for Radiation Oncology PFS rates at 1, 2, and 3 years were 86.7%, 78.4%, and 62.7%, respectively, with 5 patients for whom treatment failed (n=3 with negative transrectal ultrasound-guided biopsy results). Phoenix PFS rates at 1, 2, and 3 years were 100%, 100%, and 71.4%. 73%, respectively; achieved PSA nadir of <0.5 ng/mL; and 47% of patients had a nadir of <0.1 ng/mL. Treatment-related toxicity was minimal, with no operative interventions, fistulas, or other grade ≥3 gastrointestinal (GI)/genitourinary (GU) toxicity. Thirteen percent had grade 1 GI and 33% had grade 2 GU toxicities. Postsalvage, 20% of patients had no erectile dysfunction, 67% of patients had medication-responsive erectile dysfunction, and 13% of patients had erectile dysfunction refractory to medication. CONCLUSIONS Focal psPPI with MR-planning in highly selected patients is feasible with short-term control comparable to conventional salvage, with less toxicity. Longer follow-up is needed to confirm its impact on quality of life and treatment.

Normal tissue dosimetric comparison between hdr prostate implant boost and conformal external beam radiotherapy boost: potential for dose escalation

PURPOSE To compare the dose and volume of bladder and rectum treated using high-dose-rate (HDR) prostate implant boost versus conformal external beam radiotherapy boost, and to use the dose-volume information to perform a critical volume tolerance (CVT) analysis and then estimate the potential for further dose escalation using HDR brachytherapy boost. METHODS AND MATERIALS Using CT scan data collected before and after patients underwent HDR prostate implant, a 7-field conformal prostate-only external beam treatment plan and HDR brachytherapy treatment plan were constructed for each patient. Doses to the normal structures were calculated. Dose-volume histograms (DVH) were plotted for comparison of the two techniques. Wilcoxon signed rank test was performed at four dose levels to compare the dose to normal structures between the two treatment techniques. The acute and late effects of HDR brachytherapy were calculated based on the linear-quadratic (LQ) model. CVT analyses were performed to calculate the potential dose gain (PDG) using HDR brachytherapy boost. RESULTS The volume of bladder and rectum receiving high dose was significantly less from implant boost. On the average, 0.19 cc of the bladder received 100% of the brachytherapy prescription dose, compared with 5.1 cc of the bladder receiving 100% of the prescription dose in the 7-field conformal external beam radiotherapy boost. Similarly, 0.25 cc of the rectum received 100% of the dose with the implant boost, as compared to 2.9 cc in the conformal external beam treatment. The implant also delivered higher doses inside the prostate volume. On average, 47% of the prostate received > or =150% of the prescription dose. The CVT analysis revealed a range of PDG using the HDR brachytherapy boost which depended on the following variables: critical volume (CV), critical volume tolerance dose (CVTD), number of HDR fractions (N), and the dose of external beam radiotherapy (XRT) delivered with brachytherapy boost. The PDG varied from -3.45% to 10.53% for tumor with an alpha-beta ratio of 10 and 7.14% to 64.6% for tumor with an alpha-beta ratio of 1.5 based on the parameters used for calculation in this study. CONCLUSIONS HDR brachytherapy can provide better sparing of rectum and bladder while delivering a higher dose to the prostate. Even with the increased late effects of high dose per fraction, there is still a potential for dose escalation beyond external radiotherapy limits using HDR brachytherapy.

Equivalent Biochemical Control and Improved Prostate-Specific Antigen Nadir After Permanent Prostate Seed Implant Brachytherapy Versus High-Dose Three-Dimensional Conformal Radiotherapy and High-Dose Conformal Proton Beam Radiotherapy Boost

PURPOSE Permanent prostate implant brachytherapy (PPI), three-dimensional conformal radiotherapy (3D-CRT), and conformal proton beam radiotherapy (CPBRT) are used in the treatment of localized prostate cancer, although no head-to-head trials have compared these modalities. We studied the biochemical control (biochemical no evidence of disease [bNED]) and prostate-specific antigen (PSA) nadir achieved with contemporary PPI, and evaluated it against 3D-CRT and CPBRT. PATIENTS AND METHODS A total of 249 patients were treated with PPI at the University of California, San Francisco, and the outcomes were compared with those from a 3D-CRT cohort and the published results of a high-dose CPBRT boost (CPBRTB) trial. For each comparison, subsets of the PPI cohort were selected with patient and disease criteria similar to those of the reference group. RESULTS With a median follow-up of 5.3 years, the bNED rate at 5 and 7 years achieved with PPI was 92% and 86%, respectively, using the American Society for Therapeutic Radiology and Oncology (ASTRO) definition, and 93% using the PSA nadir plus 2 ng/mL definition. Using the ASTRO definition, a 5-year bNED rate of 78% was achieved for the 3D-CRT patients compared with 94% for a comparable PPI subset and 93% vs. 92%, respectively, using the PSA nadir plus 2 ng/mL definition. The median PSA nadir for patients treated with PPI and 3D-CRT was 0.10 and 0.40 ng/mL, respectively (p < .0001). For the CPBRT comparison, the 5-year bNED rate after a CPBRTB was 91% using the ASTRO definition vs. 93% for a similar group of PPI patients. A greater proportion of PPI patients achieved a lower PSA nadir compared with those achieved in the CPBRTB trial (PSA nadir < or =0.5 ng/mL, 91% vs. 59%, respectively). CONCLUSION We have demonstrated excellent outcomes in low- to intermediate-risk patients treated with PPI, suggesting at least equivalent 5-year bNED rates and a greater proportion of men achieving lower PSA nadirs compared with 3D-CRT or CPBRTB.