Factors Associated With Cardiac Radiation Dose Reduction After Hypofractionated Radiation Therapy for Localized, Left-Sided Breast Cancer in a Large Statewide Quality Consortium.

PURPOSE: Limiting cardiac radiation dose is important for minimizing long-term cardiac toxicity in patients with left-sided early-stage breast cancer. METHODS AND MATERIALS: Prospectively collected dosimetric data were analyzed for patients undergoing moderately hypofractionated radiation therapy to the left breast within the Michigan Radiation Oncology Quality Consortium from 2016 to 2022. The mean heart dose (MHD) goal was progressively tightened from ≤2 Gy in 2016 to MHD ≤ 1.2 Gy in 2018. In 2021, a planning target volume (PTV) coverage goal was added, and the goal MHD was reduced to ≤1 Gy. Multivariate logistic regression models were developed to assess for covariates associated with meeting the MHD goals in 2016 to 2020 and the combined MHD/PTV coverage goal in 2021 to 2022. RESULTS: In total, 4165 patients were analyzed with a median age of 64 years. Overall average cardiac metric compliance was 91.7%. Utilization of motion management increased from 41.8% in 2016 to 2020 to 46.5% in 2021 to 2022. Similarly, use of prone positioning increased from 12.2% to 22.2% in these periods. On multivariate analysis in the 2016 to 2020 cohort, treatment with motion management (odds ratio [OR], 5.20; 95% CI, 3.59-7.54; P < .0001) or prone positioning (OR, 3.21; 95% CI, 1.85-5.57; P < .0001) was associated with meeting the MHD goal, while receipt of boost (OR, 0.25; 95% CI, 0.17-0.39; P < .0001) and omission of hormone therapy (OR, 0.65; 95% CI, 0.49-0.88; P = .0047) were associated with not meeting the MHD goal. From 2021 to 2022, treatment with motion management (OR, 1.89; 95% CI, 1.12-3.21; P = .018) or prone positioning (OR, 3.71; 95% CI, 1.73-7.95; P = .0008) was associated with meeting the combined MHD/PTV goal, while larger breast volume (≥1440 cc; OR, 0.34; 95% CI, 0.13-0.91; P = .031) was associated with not meeting the combined goal. CONCLUSIONS: In our statewide consortium, high rates of compliance with aggressive targets for limiting cardiac dose were achievable without sacrificing target coverage.

Quality rectal hydrogel placement allows for gel-enabled dose-escalated EBRT (GEDE-EBRT) without rectal interference in prostate cancer.

Multiple trials have shown that dose-escalation of radiation for prostate cancer provides a biochemical progression-free survival benefit (bPFS); however, rectal constraints are often limiting. In this dosimetric study, we hypothesized that a well-placed rectal hydrogel (RH) would permit improved dose-escalation and target coverage. We selected patients with good-quality RH and created plans with and without RH, prescribing 70 Gy in 28 fractions to the prostate and proximal seminal vesicles (PSV), and a peripheral zone (PZ) boost to 84 Gy, 98 Gy, or 112 Gy. We then compared plans with and without RH, prescribing a 112 Gy boost to 1 to 2 cm simulated dominant intraprostatic lesions (DIL). In the 18 plans created with a PZ boost, the PTV_boost D95% was higher in RH plans compared to non-RH plans (median 98.5 Gy vs 75.53 Gy, p < 0.01). The PSV planning target volume (PTV_PSV) D95% was also marginally higher with RH (71.87 Gy vs 71.04 Gy, p < 0.01). All rectal metrics were improved with RH. For the 32 plans created for simulated DILs treated to 112 Gy, the PTV_boost coverage (median D95% 112.48 Gy vs 102.63 Gy, p < 0.01) and rectal metrics were improved with RH. Four non-RH plans with at least a 4 mm rectal-PTV_boost gap achieved D95% > 98% of the prescription dose for the PTV_boost. Our study showed that placement of a high-quality RH allowed for GEDE-EBRT up to 112 Gy in 28 fractions (EQD2 160 Gy with α/ß = 2.5). This concept should be tested prospectively, particularly to assess for increases in nonrectal toxicities.

Rectal sparing in prostate radiotherapy with combination-brachytherapy and hydrogel spacer.

BACKGROUND: Though some techniques that facilitate rectal sparing such as brachytherapy and intensity modulated radiotherapy (IMRT) have been examined in detail, technical aspects of hydrogel spacer (HS) have been studied less exhaustively. We examined HS quality metrics and approaches to placement for superior dosimetric outcomes. MATERIALS AND METHODS: A single site retrospective review of radiation plans was conducted for patients who received combination-brachytherapy (CBT) with 90 Gy low-dose-rate implant followed by external beam radiotherapy (45 Gy/25 fractions) with operating room (OR) placed HS (2017-2021). A randomly selected set of patients that received CBT without HS over the same time period was used for comparison. Dosimetric outcomes included D1cc and D5% rectum. Dose gradients were quantified. Student's t-test was used for statistical comparisons. RESULTS: Sixty patients (30 with and 30 without HS) who received CBT for prostate cancer were examined. Those with HS had lower mean D1cc [65.31 Gy (SD = 13.53)] and D5% [53.20 Gy (SD = 10.18)] compared to those treated without HS [91.67 Gy (SD = 8.31) and 75.00 Gy (SD = 8.45), respectively, p < 0.001]. Patients with superior HS (average thickness ≥1 cm; n = 12) had lower mean D1cc [58.49 Gy (SD = 13.25, p = 0.026)] and D5% [48.69 Gy (SD = 9.85, p = 0.049)] than those with thinner HS. When dose gradients were considered, HS spanning the interface between the prostate and perirectal tissues to a thickness ≥1 cm can reduce rectal maximum dose to 50-60 Gy. CONCLUSIONS: Through effective use of CBT and HS, extreme rectal dose restriction is possible. The goal for HS placement should be thickness ≥1 cm from base to apex.

Gender Differences in Work-Life Integration Among Medical Physicists.

PURPOSE: To generate an understanding of the primary concerns facing medical physicists regarding integration of a demanding technical career with their personal lives. METHODS AND MATERIALS: In 2019, we recruited 32 medical physics residents, faculty, and staff via emails to US medical physics residency program directors to participate in a 1-hour, semistructured interview that elicited their thoughts on several topics, including work-life integration. Standard techniques of qualitative thematic analysis were used to generate the research findings. RESULTS: Of the participants, 50% were women and 69% were non-Hispanic White individuals, with a mean (SD) age of 37.5 (7.4) years. They were evenly split between residents and faculty or staff. Participant responses centered around 5 primary themes: the gendered distribution of household responsibilities, the effect of career or work on home and family life, the effect of family on career or work, support and strategies for reconciling work-life conflicts, and the role of professional societies in addressing work-life integration. Participants expressed concern about the effect of heavy workloads on home life, with female respondents more likely to report carrying the majority of the household burden. CONCLUSIONS: Medical physicists experience challenges in managing work-life conflict amid a diverse array of personal and professional responsibilities. Further investigations are needed to quantitatively assess the division of work and household labor by gender in medical physics, particularly after the outbreak of the COVID-19 pandemic, but this study's qualitative findings suggest that the profession should consider ways to address root causes of work-life conflict to promote the future success and well-being of all medical physicists, and perhaps women in particular.

Prostate radiotherapy in the setting of bilateral hip prostheses: All commonly used photon-based radiation approaches are feasible.

The prevalence of hip prostheses is increasing. Prostate radiation delivery in the setting of hip prostheses is complicated by both imaging artifacts that interfere with volume delineation and dosimetric effects that must be addressed in the planning process. We hypothesized that with specialized planning, any photon-based definitive prostate radiotherapy approach may be utilized in patients with bilateral hip prostheses. Imaging data from sequential patients with prostate cancer and bilateral hip prostheses treated definitively with radiation were retrospectively reviewed. Bimodality imaging was used to define targets and organs at risk (OARs) along with specialized MRI sequences and/or orthopedic metal artifact reduction (OMAR) for MRI and CT artifact suppression, respectively. Multiple VMAT plans were generated for each set of patient images to include three fractionation schemes (conventional, hypofractionated, and SBRT), each with hip avoidance and with simulated normal hip. The ability to meet standard dose constraints was assessed for each plan type. Differences in target and OAR dosing between plans accounting for prosthetic hips via avoidance vs plans with simulated absence of prosthetic hip were also assessed. T-tests were used to compare dosimetric parameters. Ten patients with bilateral hip prostheses were identified, and 6 plans were created for each patient for a total of 60 radiation plans. Prosthetic hip avoidance did not result in failure to meet dose constraints for any patient. Hip avoidance resulted in minimal increases in high dose to the rectum and bladder (increases in mean V80%, V90%, and V95% ranged from 0.1% to 2.4%). Larger increases were seen at lower dose levels, with rectal V50% significantly increased in all three plan types with hip avoidance (conventional: 26.0% [standard deviation, SD 13.9] vs 16.9% [SD 10.2, p = 0.003]; hypofractionation: 26.4% [SD 13.3] vs 17.1% [SD 10.1, p = 0.002]; SBRT: 18.3% [SD 10.7] vs 10.5% [SD 6.9, p = 0.008]). Similarly, hip avoidance resulted in increases in bladder V50% to 31.7% (SD 16.8) vs 23.3% (SD 14.0, p = 0.001), 31.3% (SD 17.0) vs 23.3% (SD 13.8, p = 0.002), and 22.7% (SD 12.3) vs 16.5% (SD 12.6, p < 0.001) for conventional, hypofractionated, and SBRT plans, respectively. Hydrogel spacer resulted in reductions in rectal dose. For example, V70% for hip avoidance plans decreased with spacer presence to 8.3% (SD 6.7) vs 21.1% (SD 5.8, p = 0.021), 8.6% (SD 6.5) vs 21% (SD 5.7, p = 0.022), and 3.7% (SD 3.2) vs 15% (SD 8.2, p = 0.010) for conventional, hypofractionated, and SBRT plans, respectively. Any photon-based definitive prostate radiotherapy approach can be used with bimodality imaging for target and OAR definition and planning techniques to avoid dose attenuation effects of hip prostheses. Hydrogel spacer is a useful adjunct.

Risk of in-hospital death associated with Covid-19 lung consolidations on chest computed tomography - A novel translational approach using a radiation oncology contour software.

PURPOSE: To determine whether the percentage of lung involvement at the initial chest computed tomography (CT) is related to the subsequent risk of in-hospital death in patients with coronavirus disease-2019 (Covid-19). MATERIALS AND METHODS: Using a cohort of 154 laboratory-confirmed Covid-19 pneumonia cases that underwent chest CT between February and April 2020, we performed a volumetric analysis of the lung opacities. The impact of relative lung involvement on outcomes was evaluated using multivariate logistic regression. The primary endpoint was the in-hospital mortality rate. The secondary endpoint was major adverse hospitalization events (intensive care unit admission, use of mechanical ventilation, or death). RESULTS: The median age of the patients was 65 years: 50.6 % were male, and 36.4 % had a history of smoking. The median relative lung involvement was 28.8 % (interquartile range 9.5-50.3). The overall in-hospital mortality rate was 16.2 %. Thirty-six (26.3 %) patients were intubated. After adjusting for significant clinical factors, there was a 3.6 % increase in the chance of in-hospital mortality (OR 1.036; 95 % confidence interval, 1.010-1.063; P = 0.007) and a 2.5 % increase in major adverse hospital events (OR 1.025; 95 % confidence interval, 1.009-1.042; P = 0.002) per percentage unit of lung involvement. Advanced age (P = 0.013), DNR/DNI status at admission (P < 0.001) and smoking (P = 0.008) also increased in-hospital mortality. Older (P = 0.032) and male patients (P = 0.026) had an increased probability of major adverse hospitalization events. CONCLUSIONS: Among patients hospitalized with Covid-19, more lung consolidation on chest CT increases the risk of in-hospital death, independently of confounding clinical factors.

Progress in Low Dose Rate Brachytherapy for Prostate Cancer.

Low dose rate (LDR) brachytherapy has a proven critical role in achieving the modern standard of successful prostate cancer treatment, cure with quality of life (QoL) preservation. In the past decade, cure has been demonstrated in the most lethal form of prostate cancer treated with combined external beam and LDR brachytherapy. Additionally, QoL has moved from toxicity avoidance to preservation of function, with unprecedented sexual function preservation proven with intensive combination therapy. The technical advances that have made such outcomes possible have defined the full, dynamic complexity of the permanent prostate implant procedure, as well as effective solutions. Progress in LDR brachytherapy as it relates to prostate cancer biology, local control, toxicity reduction with function preservation, external beam integration, medical event prevention, patient selection, and comparative brachytherapy is reviewed. As in all brachytherapy procedures, the final clinical outcomes of cure, and QoL depend entirely on a foundation of verifiable technical excellence.

External beam radiation therapy with or without low-dose-rate brachytherapy: Analysis of favorable and unfavorable intermediate-risk prostate cancer patients.

PURPOSE: To compare the tumor control and toxicity in men with intermediate-risk prostate cancer treated with either external beam radiation therapy (EBRT) or EBRT plus low-dose-rate brachytherapy (combo-RT). METHODS AND MATERIALS: Between 1995 and 2012, 579 men with intermediate-risk prostate cancer were treated with either EBRT (n = 388) or combo-RT (n = 191). Outcomes assessed included biochemical recurrence-free survival (bRFS), distant metastasis-free survival (DMFS), and cumulative incidence of genitourinary (GU) and gastrointestinal toxicity. Favorable and unfavorable intermediate-risk subgroups were analyzed. RESULTS: Median followup was 7.5 years. Combo-RT group had improved 10-year bRFS compared with EBRT (91.7% vs. 75.4%, p = 0.014). On multivariable analysis, combo-RT (hazard ratio, 0.48; 95% confidence interval: 0.25, 0.92; p = 0.03) was associated with improved bRFS. Combo-RT had significantly improved bRFS compared with EBRT in the unfavorable subgroup (p = 0.02) but not in the favorable subgroup (p = 0.37). DMFS was similar within the entire cohort and by risk group. Combo-RT was associated with an increased rate in the 6-year cumulative incidence of Grade 3 GU toxicity (hazard ratio, 3.48; 95% confidence interval: 1.1, 11.1; p = 0.026); however, 57% of Grade 3 GU toxicity was resolved, 29% had partial improvement, and only 1 patient had persistent Grade 3 GU toxicity. CONCLUSIONS: In intermediate-risk prostate cancer, combo-RT improved bRFS but not DMFS and increased Grade 3 GU toxicity. The bRFS benefit was limited to unfavorable intermediate-risk patients.

Vessel-sparing Radiotherapy for Localized Prostate Cancer to Preserve Erectile Function: A Single-arm Phase 2 Trial.

BACKGROUND: Erectile dysfunction remains the most common side effect from radical treatment of localized prostate cancer. We hypothesized that the use of vessel-sparing radiotherapy, analogous to the functional anatomy approach of nerve-sparing radical prostatectomy (RP), would improve erectile function preservation while maintaining tumor control for men with localized prostate cancer. OBJECTIVE: To determine erectile function rates after vessel-sparing radiotherapy. DESIGN, SETTING, AND PARTICIPANTS: Men with localized prostate cancer were enrolled in a phase 2 single-arm trial (NCT02958787) at a single academic center. INTERVENTION: Patients received vessel-sparing radiotherapy utilizing a planning MRI and MRI-angiogram to delineate and avoid the erectile vasculature. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Both physician- and patient-reported inventories were used to capture erectile function at baseline and at 2 and 5 yr after treatment. Validated model-based comparisons were performed to compare vessel-sparing results to nerve-sparing RP and conventional radiotherapy. RESULTS AND LIMITATIONS: From 2001 to 2009, 135 men underwent vessel-sparing radiotherapy. After a planned interim analysis, the trial was stopped after meeting the primary endpoint. The median follow-up was 8.7 yr, with a ≥94% response rate to all inventories at each time point. At 5 yr, 88% of patients were sexually active with or without the use of sexual aids. The 2-yr erectile function rates were significantly improved with vessel-sparing radiotherapy (78%, 95% confidence interval [CI] 71-85%) compared to modeled rates for convention radiotherapy (42%, 95% CI 38-45%; p<0.001) or nerve-sparing prostatectomy (24%, 95% CI 22-27%; p<0.001). At 2 yr after treatment, 87% of baseline-potent men retained erections suitable for intercourse. The 5- and 10-yr rates of biochemical relapse-free survival were 99.3% and 89.9%, and at 5 yr the biochemical failures were limited to the National Comprehensive Cancer Network high-risk group. The single-arm design is a limitation. CONCLUSIONS: Vessel-sparing radiotherapy appears to more effectively preserve erectile function when compared to historical series and model-predicted outcomes following nerve-sparing RP or conventional radiotherapy, with maintenance of tumor control. This approach warrants independent validation. PATIENT SUMMARY: In this interim analysis we looked at using a novel approach to spare critical erectile structures to preserve erectile function after prostate cancer radiotherapy. We found that almost 90% of patients at 5 yr after treatment remained sexually active, significantly higher than previous studies with surgery or radiotherapy.

Combination therapy improves prostate cancer survival for patients with potentially lethal prostate cancer: The impact of Gleason pattern 5.

PURPOSE: To investigate the impact of Gleason pattern 5 (GP5) prostate cancer after either external beam radiotherapy (EBRT) or the combination of EBRT with low-dose rate brachytherapy boost (combo). METHODS AND MATERIALS: Between 1998 and 2008, 467 patients with National Comprehensive Cancer Network high-risk prostate cancer were treated with EBRT (n = 326) or combo (low-dose rate to 90-108 Gy using I-125 followed by EBRT) (n = 141). Freedom from biochemical failure, freedom from metastasis (FFM), cancer-specific survival (CSS), and overall survival were evaluated. RESULTS: Combo patients were younger (66 vs. 72 years, p < 0.001) and had fewer comorbidities (Charlson comorbidity index 3.7 vs. 4.4, p < 0.001). EBRT patients had higher tumor stages (T3-4: 30% vs. 21%, p = 0.03) and lower Gleason scores (8-10: 61% vs. 75%, p = 0.01). Androgen deprivation therapy use was similar between cohorts (85% vs. 87%, p = 0.5), but EBRT patients had longer androgen deprivation therapy use (median 14 vs. 12 months, p = 0.05). GP5 predicted worse FFM (p < 0.001, hazard ratio [HR] 3.3, 95% confidence interval [CI]1.8-6.2]) and CSS (p < 0.001, HR 5.9, 95% CI 2.7-12.9) for the EBRT group, but not for the combo group (p = 0.86, HR 0.48, 95% CI 0.1-2.4 for metastasis and p = 0.5, HR 1.6, 95% CI 0.33-8.0 for CSS). In those with GP5 (n = 143), combo was associated with improved outcomes in all endpoints. On univariate analysis, 5-year outcomes for combo vs. EBRT were as follows: freedom from biochemical failure 89% vs. 65%, FFM 89% vs. 67%, CSS 93% vs. 78%, and overall survival 88% vs. 67% (p < 0.05 for all). CONCLUSION: Combo was associated with improved outcomes for men with GP5 prostate cancer. This highlights the importance of local therapy, especially in patients with the highest pathologic grade disease.

Expansion/de-expansion tool to quantify the accuracy of prostate contours.

PURPOSE: Accurate delineation of the prostate gland on computed tomography (CT) remains a persistent challenge and continues to introduce geometric uncertainty into the planning and delivery of external beam radiotherapy. We, therefore, developed an expansion/de-expansion tool to quantify the contour errors and determine the location of the deviations. METHODS AND MATERIALS: A planning CT scan and magnetic resonance imaging scan were prospectively acquired for 10 patients with prostate cancer. The prostate glands were contoured by 3 independent observers using the CT data sets with instructions to contour the prostate without underestimation but to minimize overestimation. The standard prostate for each patient was defined using magnetic resonance imaging and CT on multiple planes. After registration of the CT and magnetic resonance imaging data sets, the CT-defined prostates were scored for accuracy. The contours were defined as ideal if they were within a 2.5-mm expansion of the standard without underestimation, acceptable if they were within a 5.0-mm expansion and a 2.5-mm de-expansion, and unacceptable if they extended >5.0 mm or underestimated the prostate by >2.5 mm. RESULTS: A total of 636 CT slices were individually analyzed, with the vast majority scored as ideal or acceptable. However, none of the 30 prostate contour sets had all the contours scored as ideal or acceptable. For all 3 observers, the unacceptable contours were more likely from underestimation than overestimation of the prostate. The errors were more common at the base and apex than the mid-gland. CONCLUSIONS: The expansion/de-expansion tool allows for directed feedback on the location of contour deviations, as well as the determination of over- or underestimation of the prostate. This metric might help improve the accuracy of prostate contours.

Greater postimplant swelling in small-volume prostate glands: implications for dosimetry, treatment planning, and operating room technique.

PURPOSE: Postimplant prostatic edema has been implicated in suboptimal permanent implants, and smaller prostates have been reported to have worse dosimetric coverage. In this study we compare the degree of postimplant edema between larger and smaller prostates and examine the effects of prostate size on the dose delivered to 90% of the prostate (D90). METHODS AND MATERIALS: From September 2003 to February 2006, 105 hormone-naive patients underwent permanent prostate brachytherapy with (125)I Rapid Strand (Oncura Inc., Arlington Heights, IL). All patients underwent pelvic magnetic resonance imaging (MRI) within 3 weeks before implant, transrectal ultrasound at the time of implant, and both computed tomography and MRI 2.5 to 3 weeks after implant. Prostates were divided into 5 subgroups based on preimplant MRI volumes: less than 25 mL, 25 to 35 mL, 35 to 45 mL, 45 to 55 mL, and greater than 55 mL. Prostate swelling was assessed by use of preimplant and postimplant MRI volumes. Postimplant dosimetry was determined by MRI and compared between the subgroups. RESULTS: All prostates showed postimplant swelling on MRI when compared with preimplant MRI, with a mean increase of 31% ± 31% (p < 0.0001). The greatest swelling was noted in small prostates (volume less than 25 mL), with a mean increase of 70% ± 36%. The degree of swelling in the group with a volume less than 25 mL was significantly larger than the degree of swelling in all other prostate subgroups (p < 0.003). Transrectal ultrasound significantly overestimates the prostate volume when compared with MRI by a mean of 15% ± 25% (p = 0.0006) and is more pronounced for smaller prostates. Although prostates with volumes less than 25 mL did not have significantly worse D90 compared with larger prostates, they had the largest percent of suboptimal implants by the standard ratio of D90 divided by the prescription dose. CONCLUSIONS: Although small prostates have the greatest postimplant edema, planning ultrasound at the time of implant overestimates the volumes of smaller prostates to a greater degree than larger prostates, which may minimize the effects of edema on postimplant dosimetry.

Radiographic and anatomic basis for prostate contouring errors and methods to improve prostate contouring accuracy.

PURPOSE: Use of highly conformal radiation for prostate cancer can lead to both overtreatment of surrounding normal tissues and undertreatment of the prostate itself. In this retrospective study we analyzed the radiographic and anatomic basis of common errors in computed tomography (CT) contouring and suggest methods to correct them. METHODS AND MATERIALS: Three hundred patients with prostate cancer underwent CT and magnetic resonance imaging (MRI). The prostate was delineated independently on the data sets. CT and MRI contours were compared by use of deformable registration. Errors in target delineation were analyzed and methods to avoid such errors detailed. RESULTS: Contouring errors were identified at the prostatic apex, mid gland, and base on CT. At the apex, the genitourinary diaphragm, rectum, and anterior fascia contribute to overestimation. At the mid prostate, the anterior and lateral fasciae contribute to overestimation. At the base, the bladder and anterior fascia contribute to anterior overestimation. Transition zone hypertrophy and bladder neck variability contribute to errors of overestimation and underestimation at the superior base, whereas variable prostate-to-seminal vesicle relationships with prostate hypertrophy contribute to contouring errors at the posterior base. CONCLUSIONS: Most CT contouring errors can be detected by (1) inspection of a lateral view of prostate contours to detect projection from the expected globular form and (2) recognition of anatomic structures (genitourinary diaphragm) on the CT scans that are clearly visible on MRI. This study shows that many CT prostate contouring errors can be improved without direct incorporation of MRI data.

AAPM recommendations on dose prescription and reporting methods for permanent interstitial brachytherapy for prostate cancer: report of Task Group 137.

During the past decade, permanent radioactive source implantation of the prostate has become the standard of care for selected prostate cancer patients, and the techniques for implantation have evolved in many different forms. Although most implants use 125I or 103Pd sources, clinical use of 131Cs sources has also recently been introduced. These sources produce different dose distributions and irradiate the tumors at different dose rates. Ultrasound was used originally to guide the planning and implantation of sources in the tumor. More recently, CT and/or MR are used routinely in many clinics for dose evaluation and planning. Several investigators reported that the tumor volumes and target volumes delineated from ultrasound, CT, and MR can vary substantially because of the inherent differences in these imaging modalities. It has also been reported that these volumes depend critically on the time of imaging after the implant. Many clinics, in particular those using intraoperative implantation, perform imaging only on the day of the implant. Because the effects of edema caused by surgical trauma can vary from one patient to another and resolve at different rates, the timing of imaging for dosimetry evaluation can have a profound effect on the dose reported (to have been delivered), i.e., for the same implant (same dose delivered), CT at different timing can yield different doses reported. Also, many different loading patterns and margins around the tumor volumes have been used, and these may lead to variations in the dose delivered. In this report, the current literature on these issues is reviewed, and the impact of these issues on the radiobiological response is estimated. The radiobiological models for the biological equivalent dose (BED) are reviewed. Starting with the BED model for acute single doses, the models for fractionated doses, continuous low-dose-rate irradiation, and both homogeneous and inhomogeneous dose distributions, as well as tumor cure probability models, are reviewed. Based on these developments in literature, the AAPM recommends guidelines for dose prescription from a physics perspective for routine patient treatment, clinical trials, and for treatment planning software developers. The authors continue to follow the current recommendations on using D90 and V100 as the primary quantitles, with more specific guidelines on the use of the imaging modalities and the timing of the imaging. The AAPM recommends that the postimplant evaluation should be performed at the optimum time for specific radionuclides. In addition, they encourage the use of a radiobiological model with a specific set of parameters to facilitate relative comparisons of treatment plans reported by different institutions using different loading patterns or radionuclides.

Comparison of day 0 and day 14 dosimetry for permanent prostate implants using stranded seeds.

PURPOSE: To determine, using MRI-based dosimetry (Day 0 and Day 14), whether clinically significant changes in the dose to the prostate and critical adjacent structures occur between Day 0 and 14, and to determine to what degree any changes in dosimetry are due to swelling or its resolution. METHODS AND MATERIALS: A total of 28 patients with a permanent prostate implant using 125I rapid strands were evaluated at Days 0 and 14 by CT/MRI fusion. The minimal dose received by 90% of the target volume (prostate D90), percentage of volume receiving 100% of prescribed minimal peripheral dose (prostate V100), external sphincter D90, and 4-cm3 rectal volume dose were calculated. An acceptable prostate D90 was defined as D90 >90% of prescription dose. Prostate volume changes were calculated and correlated with any dosimetry change. A paradoxic dosimetric result was defined as an improvement in D90, despite increased swelling; a decrease in D90, despite decreased swelling; or a large change in D90 (>30 Gy) in the absence of swelling. RESULTS: The D90 changed in 27 of 28 patients between Days 0 and 14. No relationship was found between a change in prostate volume and the change in D90 (R2 = 0.01). A paradoxic dosimetric result was noted in 11 of 28 patients. The rectal dose increased in 23 of 28 patients, with a >30-Gy change in 6. The external sphincter D90 increased in 19 of 28, with a >50-Gy increase in 6. CONCLUSION: The dose to the prostate changed between Days 0 and 14 in most patients, resulting in a change in clinical status (acceptable or unacceptable) in 12 of 28 patients. Profound increases in normal tissue doses may make dose and toxicity correlations using Day 0 dosimetry difficult. No relationship was found between the prostate volume change and D90 change, and, in 11 patients, a paradoxic dosimetric result was noted. A differential z-axis shift of stranded seeds vs. prostate had a greater impact on final dosimetry and dose to critical adjacent tissues than did prostate swelling. These findings challenge the model that swelling is the principal cause of dosimetric changes after implantation. Stranded seeds may have contributed to this outcome. On the basis of these findings, a change in technique to avoid placement of stranded seeds inferior to the prostate apex has been adopted. These results may not apply to implants using single seeds within the prostate.

Functional anatomy of the prostate: implications for treatment planning.

PURPOSE: To summarize the functional anatomy relevant to prostate cancer treatment planning. METHODS AND MATERIALS: Coronal, axial, and sagittal T2 magnetic resonance imaging (MRI) and MRI angiography were fused by mutual information and registered with computed tomography (CT) scan data sets to improve definition of zonal anatomy of the prostate and critical adjacent structures. RESULTS: The three major prostate zones (inner, outer, and anterior fibromuscular) are visible by T2 MRI imaging. The bladder, bladder neck, and internal (preprostatic) sphincter are a continuous muscular structure and clear definition of the preprostatic sphincter is difficult by MRI. Transition zone hypertrophy may efface the bladder neck and internal sphincter. The external "lower" sphincter is clearly visible by T2 MRI with wide variations in length. The critical erectile structures are the internal pudendal artery (defined by MRI angiogram or T2 MRI), corpus cavernosum, and neurovascular bundle. The neurovascular bundle is visible along the posterior lateral surface of the prostate on CT and MRI, but its terminal branches (cavernosal nerves) are not visible and must be defined by their relationship to the urethra within the genitourinary diaphragm. Visualization of the ejaculatory ducts within the prostate is possible on sagittal MRI. The anatomy of the prostate-rectum interface is clarified by MRI, as is the potentially important distinction of rectal muscle and rectal mucosa. CONCLUSION: Improved understanding of functional anatomy and imaging of the prostate and critical adjacent structures will improve prostate radiation therapy by improvement of dose and toxicity correlation, limitation of dose to critical structures, and potential improvement in post therapy quality of life.

Use and uncertainties of mutual information for computed tomography/ magnetic resonance (CT/MR) registration post permanent implant of the prostate.

Post-implant dosimetric analysis for permanent implant of the prostate benefits from the use of a computed tomography (CT) dataset for optimal identification of the radioactive source (seed) positions and a magnetic resonance (MR) dataset for optimal description of the target and normal tissue volumes. The CT/MR registration process should be fast and sufficiently accurate to yield a reliable dosimetric analysis. Since critical normal tissues typically reside in dose gradient regions, small shifts in the dose distribution could impact the prediction of complication or complication severity. Standard procedures include the use of the seed distribution as fiducial markers (seed match), a time consuming process that relies on the proper identification of signals due to the same seed on both datasets. Mutual information (MI) is more efficient because it uses image data requiring minimal preparation effort. A comparison of MI registration and seed-match registration was performed for twelve patients. MI was applied to a volume limited to the prostate and surrounding structures, excluding most of the pelvic bone structures (margins around the prostate gland were approximately 2 cm right-left, approximately 1 cm anterior-posterior, and approximately 2 cm superior-inferior). Seeds were identified on a 2 mm slice CT dataset using an automatic seed identification procedure on reconstructed three-dimensional data. Seed positions on the 3 mm slice thickness T2 MR data set were identified using a point-and-click method on each image. Seed images were identified on more than one MR slice, and the results used to determine average seed coordinates for MR images and matched seed pairs between CT and MR images. On average, 42% (19%-64%) of the seeds (19-54 seeds) were identified and matched to their CT counterparts. A least-squares method applied to the CT and MR seed coordinates was used to produce the optimum seed-match registration. MI registration and seed match registration angle differences averaged 0.5 degrees, which was not significantly different from zero. Translation differences averaged 0.6 (1.2 standard deviation) mm right-left, -0.5(1.5) mm posterior-anterior, and -1.2(2.0) mm inferior-superior. Registration error estimates were approximately 2 mm for both the MI and seed-match methods. The observed standard deviations in the offset values were consistent with propagation of error. Registration methods as applied here using mutual information and seed matching are consistent, except for a small systematic difference in the inferior-superior axis for a minority of cases (approximately 15%). Cases registered with mutual information and with bony anatomy misregistration of greater than approximately 5 mm should be evaluated for rescan or seed-match registration. The improvement in efficiency of use for the MI registration method is substantial, approximately 30 min compared to several hours using seed match registration.