Andrew M. McDonald

Reduced Radiation Tolerance of Penile Structures Associated With Dose-escalated Hypofractionated Prostate Radiotherapy

OBJECTIVE To investigate the effect of hypofractionated external beam radiation therapy (RT) on sexual function in patients treated for localized prostate cancer, and also to determine the effect of radiation dose to the penile bulb or crura of the corpus cavernosum on sexual function outcome. MATERIALS AND METHODS Forty-one patients treated with hypofractionated RT without androgen deprivation were prescribed 67.6-70.2 Gy to the prostate, delivered in 26-28 fractions. The primary endpoint was erectile dysfunction (ED) category based on the Sexual Health Inventory for Men (SHIM) score closest to 2 years from RT. The penile bulb and crura were contoured and mean radiation dose calculated for each structure. RESULTS The mean pretreatment SHIM score was 19.8, and the mean posttreatment SHIM score was 15.1. The ED category was decreased by ≥ 2 in 50% of patients with a mean penile bulb of >20 Gy compared with that in 9% of patients with a mean penile bulb dose of ≤ 20 Gy (P = .003). Mean dose to the crura was highly correlated with mean dose to the penile bulb (Pearson correlation = 0.842; P <.001) but did not reach statistical significance as a predictor of ED after radiation. CONCLUSION Radiation dose to the penile bulb is predictive of posttreatment ED in patients treated with dose-escalated hypofractionated prostate RT. The cutpoint at which this effect was observed with this treatment is substantially lower than the previous reports.

Efficacy and toxicity of conventionally fractionated pelvic radiation with a hypofractionated simultaneous versus conventionally fractionated sequential boost for patients with high-risk prostate cancer.

Abstract Purpose. To determine if high-risk prostate cancer responds differently to hypofractionation. Material and methods. One hundred and fifty-seven men with NCCN high-risk (T3, PSA > 20, or Gleason ≥ 8) clinically localized prostate cancer treated between 1998 and 2010 met the inclusion criteria for the analysis. Eighty-two were treated with conventional WPRT with a conventionally fractionated sequential boost to the prostate (cRT), with the prostate receiving 75–77 Gy in 1.8–2.0 Gy fractions. Seventy-five were treated with pelvic IMRT with a hypofractionated simultaneous boost to the prostate (hRT), with the prostate receiving 70 Gy in 2.5 Gy fractions. The dose to the pelvic lymph nodes was 45 Gy in the cRT group and 50.4 Gy in the hRT group, both at 1.8 Gy per fraction. Ninety-two percent received neoadjuvant hormonal ablation therapy, typically beginning two months prior to the start of RT. Results. Median follow-up was 6.5 years for men receiving cRT and 3.7 years for those receiving hRT. The actuarial rate of biochemical control at four years was 88% for cRT and 94% for hRT (p = 0.82). The rates of early rectal and urinary grade ≥ 2 toxicities were 35% (29 of 82) and 49% (40 of 82) for the cRT group and 36% (27 of 75) and 44% (33 of 75) for the hRT group. The actuarial rate of late grade ≥ 2 rectal toxicity at four years was 25% for the cRT group and 13% for the hRT group (p = 0.037). The rate of late grade 3 rectal complications was 4% (3 of 82) for patients receiving cRT and 1% (1 of 75) for patients receiving hRT. Conclusion. Initial follow-up indicates equivalent biochemical control between regimens. Patients receiving hRT experienced fewer late rectal complications.

Hypofractionated Prostate Radiotherapy with or without Conventionally Fractionated Nodal Irradiation: Clinical Toxicity Observations and Retrospective Daily Dosimetry.

Purpose. To evaluate toxicity associated with the addition of elective nodal irradiation (ENI) to a hypofractionated regimen for the treatment of prostate cancer. Methods and Materials. Fifty-seven patients received pelvic image-guided IMRT to 50.4 Gy in 28 fractions with a hypofractionated simultaneous boost to the prostate to 70 Gy. Thirty-one patients received prostate-only treatment to 70 Gy in 28 fractions. Results. Median followup was 41.1 months. Early grade ≥2 urinary toxicity rates were 49% (28 of 57) for patients receiving ENI and 58% (18 of 31) for those not (P = 0.61). Early grade ≥2 rectal toxicity rates were 40% (23 of 57) and 23% (7 of 31), respectively (P = 0.09). The addition of ENI resulted in a 21% actuarial rate of late grade ≥2 rectal toxicity at 4 years, compared to 0% for patients treated to the prostate only (P = 0.02). Retrospective daily dosimetry of patients experiencing late rectal toxicity revealed an average increase of 2.67% of the rectal volume receiving 70 Gy compared to the original plan. Conclusions. The addition of ENI resulted in an increased risk of late rectal toxicity. Grade ≥2 late rectal toxicity was associated with worse daily rectal dosimetry compared to the treatment plan.

CT Measures of Bone Mineral Density and Muscle Mass Can Be Used to Predict Noncancer Death in Men with Prostate Cancer

Purpose To determine if computed tomographic (CT) metrics of bone mineral density and muscle mass can improve the prediction of noncancer death in men with localized prostate cancer. Materials and Methods Institutional review board approval was obtained, with waiver of informed consent. All patients who underwent radiation therapy for localized prostate cancer between 2001 and 2012 with height, weight, and past medical history documented and who underwent CT that included the L4-5 vertebral interspace were included. On a single axial CT section obtained at the mid-L5 level, the mean CT attenuation of the trabecular bone of the L5 vertebral body (L5HU) was measured. The height-normalized psoas cross-sectional area (PsoasL4-5) was measured on a single CT section obtained at the L4-5 vertebral interface. Multivariable Cox proportional hazards models were used to assess effects on noncancer death. By using parameter estimates from an adjusted model, a prognostic index for prediction of noncancer death was generated and compared with age-adjusted Charlson Comorbidity Index (CCI) by using the Harrell c statistic. Results Six hundred fifty-three men met the inclusion criteria. Prostate cancer risk grouping, androgen deprivation, race, age-adjusted CCI, L5HU, and PsoasL4-5 were included in a multivariable model. Age-adjusted CCI (hazard ratio [HR] = 1.36, P < .001), L5HU (HR = 2.88 for L5HU < 105 HU, HR = 1.42 for 105 HU ≤ L5HU ≤ 150 HU, P < .001), PsoasL4-5 (HR = 1.95 for PsoasL4-5 < 7.5 cm2/m2, P = .003), and race (HR = 1.68 for African American race, HR = 1.77 for other nonwhite race, P = .019) were independent predictors of noncancer death. The prognostic index yielded a c value of 0.747 for the prediction of noncancer death versus 0.718 for age-adjusted CCI alone. Conclusion L5HU and PsoasL4-5, which are surrogates for bone mineral density and muscle mass, respectively, were independent predictors of noncancer death. The prognostic index that incorporated these measures with the CCI was associated with improved accuracy for prediction of noncancer death.

Increased radiation dose heterogeneity within the prostate predisposes to urethral strictures in patients receiving moderately hypofractionated prostate radiation therapy.

PURPOSE The purpose of this study was to determine whether radiation dose inhomogeneity within the prostate predisposes to late urinary strictures after moderately hypofractionated definitive external beam radiation therapy for prostate cancer. METHODS AND MATERIALS One hundred seventy-three men with clinically localized prostate cancer met the inclusion criteria for this analysis. All patients received 70 Gy to the prostate delivered over 28 fractions, had at least 2 years of clinical follow-up, and had dose-volume histogram information available for review. The endpoint of this study was the development of a urethral stricture that required a procedural intervention such as urethral dilation or suprapubic catheterization. Dosimetric parameters were evaluated for effect on the rate of urethral stricture formation by univariate Cox proportional hazards modeling. RESULTS The median follow-up was 49.5 months (range, 24.6-108 months). At 5 years, the actuarial rate of intervention for urethral strictures across all patients was 4.9%. The maximum point dose within the prostate (P = .034, hazard ratio = 1.006) and the mean prostate dose (P = .039, hazard ratio = 1.004) were the only parameters predictive of urethral stricture formation. All patients who developed a urethral stricture were treated by a plan with a maximum prostate dose of >75 Gy (median, 77.67 Gy). CONCLUSIONS For patients receiving moderately hypofractionated prostate radiation therapy over 28 fractions, a maximum point dose of 75 Gy within the prostate was associated with an increased probability of developing a urethral stricture that required procedural intervention. The hypothesis that hypofractionation increases susceptibility to toxicity from heterogeneity within the prostate should be confirmed by analyzing data from randomized trials with a conventionally fractionated control arm for comparison.

Fractionated stereotactic radiation therapy for intact brain metastases

Purpose Limited data exist on fractionated stereotactic radiation therapy (FSRT) for brain metastases. We sought to evaluate the safety and efficacy of FSRT and further define its role in brain metastasis management. Methods and materials A total of 72 patients were treated with linear accelerator–based FSRT to 182 previously untreated, intact brain metastases. Targets received 25 or 30 Gy in 5 fractions. All targets within the same course received the same prescription regardless of size. Toxicity was recorded per Radiation Therapy Oncology Group central nervous system toxicity criteria. Results The median follow-up was 5 months (range, 1-71 months). The Kaplan-Meier estimate of 12-month local control was 86%. Tumors <3 cm in diameter demonstrated improved 12-month local control of 95% compared with 61% in tumors ≥3 cm (P < .001). The Kaplan-Meier estimate of 12-month local control was 91% in tumors treated with 30 Gy and only 75% in tumors treated with 25 Gy (P = .015). Tumor diameter ≥3 cm resulted in increased local failure, and a 30 Gy prescription resulted in decreased local failure on multivariate analysis (hazard ratio [HR], 8.11 [range, 2.09-31.50; P = .003] and HR, 0.26 [range, 0.07-0.93; P = .038]). Grade 4 central nervous system toxicity occurred in 4 patients (6%) requiring surgery, and no patient experienced irreversible grade 3 or 5 toxicity. Increasing tumor diameter was associated with increased toxicity risk (HR, 2.45 [range, 1.04-5.742; P = .04]). Conclusions FSRT for brain metastases appears to demonstrate a high rate of local control with minimal risk of severe toxicity. Local control appears to be associated with smaller tumor sizeand a higher prescription dose. FSRT is a viable option for those who are poor single-fraction candidates.

Spontaneous Spinal Epidural Abscess Presenting in a Previously Healthy Young Adult Man

We report a case of spontaneous spinal epidural abscess (SEA) with initial chief complaint of shoulder pain and no appreciable neurologic symptoms. Since outcomes of SEA appear to be related to the degree of neurologic deficit at the time of intervention, we explore opportunities for earlier diagnosis.

Mesorectal node metastasis from gynecological cancer in the era of 3D conformal pelvic radiation therapy and intensity modulated radiation therapy

Whole pelvic radiation therapy (WPRT) is an integral part of treatment for locally advanced cervical and vaginal cancer prior to brachytherapy. The most common beam arrangements for WPRT are opposed anteroposterior/ posteroanterior beams and the 4-field box. The lateral fields of the 4-field box spare small bowel and a portion of the rectum from radiation. Intensity modulated radiation therapy (IMRT) is increasingly used for gynecologic (GYN) cancers to improve dose conformity. Before the availability of computed tomography (CT), the portals used for WPRTwere determined solely based on bony anatomy. Because fluoroscopy-based planning risks geometric miss,1,2 CT-based planning is now considered standard. Conventional WPRT portals are designed to include the primary tumor, uterus, upper vagina, and regional lymphatics (common, external and internal iliac, and presacral lymph nodes). However, the mesorectum is not consistently contoured as a target volume. The advent of fluorine-18 fludeoxyglucose (FDG) positron emission tomography (PET)/CT scan has increased

Combining Computed Tomography-Based Bone Density Assessment with FRAX Screening in Men with Prostate Cancer

To investigate the addition of a computed tomography (CT)-based method of osteoporosis screening to FRAX without bone mineral density (BMD) fracture risk assessment in men undergoing radiotherapy for prostate cancer, we reviewed the records of all patients with localized prostate cancer treated with external beam radiotherapy at our institution between 2001 and 2012. The 10-yr probability of hip fracture was calculated using the FRAX algorithm without BMD. The CT attenuation of the L5 trabecular bone (L5CT) was assessed by contouring the trabecular bone on a single CT slice at the level of the midvertebral body and by averaging the Hounsfield units (HU) of all included voxels. L5CT values of 105 and 130 HU were used as screening thresholds. The clinical characteristics of additional patients identified by each L5CT screening threshold value were compared to patients whose estimated 10-yr risk of hip fracture was 3% or greater by FRAX without BMD. A total of 609 patients treated between 2001 and 2012 had CT scans available for review and complete clinical information allowing for FRAX without BMD risk calculation. Seventy-four (12.2%) patients had an estimated 10-yr risk of hip fracture of 3% or greater. An additional 22 (3.6%) and 71 (11.6%) patients were identified by CT screening when thresholds L5CT = 105 HU and L5CT = 130 HU were used, respectively. Compared to the group of patients identified by FRAX without BMD, the additional patients identified by CT screening at each L5CT threshold level tended to be younger and heavier, and were more likely to be African-American or treated without androgen deprivation therapy. These results suggest that the addition of CT-based screening to FRAX without BMD risk assessment identifies additional men with different underlying clinical characteristics who may be at risk for osteoporosis and may benefit from pharmacological therapy to increase BMD and reduce fracture risk.

Subcutaneous adipose tissue characteristics and the risk of biochemical recurrence in men with high-risk prostate cancer

PURPOSE/OBJECTIVE(S) To assess subcutaneous adipose tissue characteristics by computed tomography (CT) as potential imaging biomarkers predictive of biochemical recurrence in men with high-risk prostate cancer receiving radiotherapy (RT). MATERIALS AND METHODS This retrospective study included men with high-risk prostate cancer (PSA>20ng/ml, Gleason score ≥8, or clinical extraprostatic extension) treated between 2001 and 2012. All patients received definitive, dose-escalated external beam RT along with a course of neoadjuvant, concurrent, and adjuvant androgen deprivation therapy (ADT). Each patient also had a treatment planning CT that included the L4-L5 vertebral interface and prostate specific antigen (PSA) measurements for at least 2 years following RT. The subcutaneous adipose tissue was contoured on a single axial CT slice at the level of L4-L5. The average CT attenuation, in Hounsfield units (HU), of the structure was calculated and defined as SATHU. SATAREA was defined as the cross-sectional area of the structure (in cm2) that was then normalized by the square of patient height. Biochemical failure (BF) was defined as a PSA rise of 2ng/ml from the nadir. Freedom from BF (FFBF) was calculated from start time of ADT using the Kaplan-Meier method. Estimates of FFBF were stratified by SATHU and SATAREA quartiles. RESULTS A total of 171 men met the inclusion criteria with a median follow-up of 5.6 years. The mean SATHU (±standard deviation) was -99.2HU (±6.1HU), and the mean SATAREA was 93.2cm2/m2 (±39.4cm2/m2). The 5- and 8-year rates of FFBF across all patients were 81.5% and 73.5%, respectively. Patients in the lowest quartile of SATHU experienced significantly higher FFBF compared to the other quartiles (Q4 vs. Q1, P = 0.017; Q4 vs. Q2, P = 0.045; Q4 vs. Q3, P = 0.044). No other differences in FFBF were observed between quartiles of SATAREA or other quartiles of SATHU. CONCLUSION Lower subcutaneous adipose tissue density was associated with a lower rate of BF following RT with ADT for men with high-risk prostate cancer. Further research is needed to elucidate the biological underpinnings of this clinical finding and the role adipose tissue plays in modulating oncologic behavior and outcomes.