Steven J. Buskirk

RADIOTHERAPY FOR ISOLATED SERUM PROSTATE SPECIFIC ANTIGEN ELEVATION AFTER PROSTATECTOMY FOR PROSTATE CANCER

PURPOSE Elevated serum prostate specific antigen (PSA) may be the initial and only indication of disease recurrence after prostatectomy for prostate cancer. External beam radiotherapy may be given in this setting in an attempt to eradicate the disease but therapeutic outcomes after this approach require further description. We describe the intermediate term outcome in a large group of patients treated with radiotherapy and identify pre-therapy factors associated with disease outcome. MATERIALS AND METHODS We retrospectively studied a cohort of 166 consecutive patients treated with radiotherapy between July 1987 and May 1996. The Kaplan-Meier method was used to describe patient outcome for the overall study group, and statistical associations of pre-therapy variables with outcome were sought to identify predictive factors. RESULTS At a median followup of 52 months 46% (95% confidence interval 38 to 55) of patients were expected to be free of biochemical relapse 5 years after radiotherapy. Multivariate analysis identified pathological classification (seminal vesicle invasion), tumor grade and preradiotherapy serum PSA as independent factors associated with biochemical relapse. Although in 1 of 6 patients a chronic complication was attributed to radiotherapy, it was often mild and self-limited in nature. CONCLUSIONS In our current series approximately half of the patients treated with radiotherapy for an isolated elevation of serum PSA after prostatectomy were free of biochemical relapse at 5 years of followup. Radiotherapy may be given in this setting with modest long-term morbidity.

INITIAL EXPERIENCE WITH ULTRASOUND LOCALIZATION FOR POSITIONING PROSTATE CANCER PATIENTS FOR EXTERNAL BEAM RADIOTHERAPY

PURPOSE Transabdominal ultrasound localization of the prostate gland and its immediate surrounding anatomy has been used to guide the positioning of patients for the treatment of prostate cancer. This process was evaluated in terms of (1) the reproducibility of the ultrasound measurement; (2) a comparison of patient position between ultrasound localization and skin marks determined from a CT treatment planning scan; (3) the predictive indicators of patient anatomy not well suited for ultrasound localization; (4) the measurement of prostate organ displacement resulting from ultrasound probe pressure; and (5) quality assurance measures. METHODS AND MATERIALS The reproducibility of the ultrasound positioning process was evaluated for same-day repeat positioning by the same ultrasound operator (22 patients) and for measurements made by 2 different operators (38 patients). Differences between conventional patient positioning (CT localization with skin markings) and ultrasound-based positioning were determined for 38 patients. The pelvic anatomy was evaluated for 34 patients with pretreatment CT scans to identify predictors of poor ultrasound image quality. The displacement of the prostate resulting from pressure of the ultrasound probe was measured for 16 patients with duplicate CT scans with and without a simulated probe. Finally, daily, monthly, and semiannual quality assurance tests were evaluated. RESULTS Self-verification tests of ultrasound positioning indicated a shift of <3 mm in approximately 95% of cases. Interoperator tests indicated shifts of <3 mm in approximately 80-90% of cases. The mean difference in patient positioning between conventional and ultrasound localization for lateral shifts was 0.3 mm (SD 2.5): vertical, 1.3 mm (SD 4.7 mm) and longitudinal, 1.0 mm (SD 5.1). However, on a single day, the differences were >10 mm in 1.5% of lateral shifts, 7% of longitudinal shifts, and 7% of vertical shifts. The depth to the isocenter, thickness of tissue overlying the bladder, and position of the prostate relative to the pubic symphysis, but not the bladder volume, were significant predictive indicators of poor ultrasound imaging. The pressure of the ultrasound probe displaced the prostate in 7 of the 16 patients by an average distance of 3.1 mm; 9 patients (56%) showed no displacement. Finally, the quality assurance tests detected ultrasound equipment defects. CONCLUSION The ultrasound positioning system is reproducible and may indicate the need for significant positioning moves. Factors that predict poor image quality are the depth to the isocenter, thickness of tissue overlying the bladder, and position of the prostate relative to the pubic symphysis. The prostate gland may be displaced a small amount by the pressure of the ultrasound probe. A quality assurance program is necessary to detect ultrasound equipment defects that could result in patient alignment errors.

The use of radiotherapy for patients with isolated elevation of serum prostate specific antigen following radical prostatectomy

PURPOSE An analysis was performed to assess the outcome of patients who received radiotherapy for isolated elevation of serum prostate specific antigen (PSA) levels following radical retropubic prostatectomy. MATERIALS AND METHODS Forty-six patients were initially treated for localized prostate cancer with radical retropubic prostatectomy following negative pelvic lymphadenectomy. These patients had detectable serum PSA 6 or more months postoperatively. No patient had other clinical evidence of recurrent disease as determined by history, physical examination, bone scan, computerized tomography of the abdomen and pelvis, chest radiographs, complete blood cell counts and serum chemistry profiles. The patients received prostate bed irradiation using 10 MV. x-rays and a 4-field approach. Doses ranged from 60.0 to 67.0 Gy. in 1.8 to 2.0 Gy. fractions. Freedom from failure after radiotherapy was defined as maintaining a PSA of 0.3 ng./ml. or less without hormonal intervention. RESULTS In 27 of the 46 patients (59%) PSA had decreased to 0.3 ng./ml. or less at last measurement without hormonal intervention. The freedom from failure rate was 50% at 3 and 5 years. More favorable responses to salvage radiotherapy occurred in patients with low grade tumors and serum PSA 1.1 ng./ml. or less at initiation of radiotherapy. Patients, receiving radiation doses of 64 Gy. or more had more favorable response rates than those receiving lesser doses. CONCLUSIONS Isolated elevations of serum PSA following prostatectomy reflect residual disease. Radiotherapy administered to the prostate bed effectively decreased serum PSA in approximately half of the cases. This effect appears to be accomplished by eradicating tumor cells in the prostate bed.

Impact of Organizational Leadership on Physician Burnout and Satisfaction

OBJECTIVE To evaluate the impact of organizational leadership on the professional satisfaction and burnout of individual physicians working for a large health care organization. PARTICIPANTS AND METHODS We surveyed physicians and scientists working for a large health care organization in October 2013. Validated tools were used to assess burnout. Physicians also rated the leadership qualities of their immediate supervisor in 12 specific dimensions on a 5-point Likert scale. All supervisors were themselves physicians/scientists. A composite leadership score was calculated by summing scores for the 12 individual items (range, 12-60; higher scores indicate more effective leadership). RESULTS Of the 3896 physicians surveyed, 2813 (72.2%) responded. Supervisor scores in each of the 12 leadership dimensions and composite leadership score strongly correlated with the burnout and satisfaction scores of individual physicians (all P<.001). On multivariate analysis adjusting for age, sex, duration of employment at Mayo Clinic, and specialty, each 1-point increase in composite leadership score was associated with a 3.3% decrease in the likelihood of burnout (P<.001) and a 9.0% increase in the likelihood of satisfaction (P<.001) of the physicians supervised. The mean composite leadership rating of each division/department chair (n=128) also correlated with the prevalence of burnout (correlation=-0.330; r(2)=0.11; P<.001) and satisfaction (correlation=0.684; r(2)=0.47; P<.001) at the division/department level. CONCLUSION The leadership qualities of physician supervisors appear to impact the well-being and satisfaction of individual physicians working in health care organizations. These findings have important implications for the selection and training of physician leaders and provide new insights into organizational factors that affect physician well-being.

SALVAGE RADIOTHERAPY FOR RISING PROSTATE-SPECIFIC ANTIGEN LEVELS AFTER RADICAL PROSTATECTOMY FOR PROSTATE CANCER: DOSE-RESPONSE ANALYSIS

PURPOSE To investigate the association between external beam radiotherapy (EBRT) dose and biochemical failure (BcF) of prostate cancer in patients who received salvage prostate bed EBRT for a rising prostate-specific antigen (PSA) level after radical prostatectomy. METHODS AND MATERIALS We evaluated patients with a rising PSA level after prostatectomy who received salvage EBRT between July 1987 and October 2007. Patients receiving pre-EBRT androgen suppression were excluded. Cox proportional hazards models were used to investigate the association between EBRT dose and BcF. Dose was considered as a numeric variable and as a categoric variable (low, <64.8 Gy; moderate, 64.8-66.6 Gy; high, >66.6 Gy). RESULTS A total of 364 men met study selection criteria and were followed up for a median of 6.0 years (range, 0.1-19.3 years). Median pre-EBRT PSA level was 0.6 ng/mL. The estimated cumulative rate of BcF at 5 years after EBRT was 50% overall and 57%, 46%, and 39% for the low-, moderate-, and high-dose groups, respectively. In multivariable analysis adjusting for potentially confounding variables, there was evidence of a linear trend between dose and BcF, with risk of BcF decreasing as dose increased (relative risk [RR], 0.77 [5.0-Gy increase]; p = 0.05). Compared with the low-dose group, there was evidence of a decreased risk of BcF for the high-dose group (RR, 0.60; p = 0.04), but no difference for the moderate-dose group (RR, 0.85; p = 0.41). CONCLUSIONS Our results suggest a dose response for salvage EBRT. Doses higher than 66.6 Gy result in decreased risk of BcF.

Analysis of failure following curative irradiation of gallbladder and extrahepatic bile duct carcinoma

Twenty patients with carcinoma of the gallbladder (GB-4 patients) or extrahepatic bile ducts (EHBD-16 patients) received radiation therapy with curative intent between January, 1980 and December, 1982. All 20 received 4500-5000 rad in 180-200 rad fractions to the tumor and regional lymph nodes. A 1000 to 1500 rad external beam boost was delivered in 180-200 rad fractions in 10 patients who received external beam alone or concomitant 5-Fluorouracil (5-FU). Three of the four GB and 5 of the 16 EHBD patients received a transcatheter boost with 192-Iridium (192Ir) to a dose of 2000-2500 rad calculated at a 0.5-0.1 cm radius. An additional 2 patients with EHBD lesions received an intraoperative electron (IORT) boost of 1500-2000 rad in one fraction calculated to the 90% isodose. Survival and patterns of failure were analyzed by site and treatment method. All four patients with GB carcinoma are dead of disease at 5 1/2, 6, 9 and 10 months from the date of diagnosis respectively. Three of the four developed diffuse peritoneal carcinomatosis. Five of the 16 patients with EHBD carcinoma are alive with a median follow-up of 18 months (range 6-23 months). Four of the 5 patients received a transcatheter 192Ir or IORT boost and all are without evidence of disease. Four of 9 patients who had a subtotal resection with transection of tumor, dilatation of the bile ducts with probes or curettement of the bile ducts developed either diffuse peritoneal carcinomatosis (3 patients) or a recurrence in the surgical scar (2 patients). Local failure was documented in 3 of the nine patients treated with external beam alone +/- 5-FU, and has been documented in one of the seven patients who received an IORT or transcatheter 192Ir boost. Further experience is necessary to determine whether this aggressive treatment will result in long-term disease-free survival in these patients.

Radiotherapy for large symptomatic hemangiomas

Between 1974 and 1988, 13 patients presented with large (3 to greater than 20 cm) symptomatic unresectable or partially resected hemangiomas. Tumor sites were extremities (five cases), vertebral bodies (three cases), face (two cases), pituitary fossa (one case), pelvic bones (one case), and bladder (one case). Symptoms included severe pain in eight patients, inability to use an extremity in five, vision problems in three, weakness in two, and hematuria with decreased urinary stream in one. Many patients had more than one symptom. Two of the cases were associated with life-threatening consumptive coagulopathies (Kasabach-Merritt syndrome). Therapy was delivered with both orthovoltage and megavoltage photons. Doses ranged from 6.25 to 40.0 Gy in 1.6- to 2.5-Gy fractions. Follow-up ranged from 2 to 15 years (median, 13 years). Tumor shrinkage was noted in 9 (82%) of the 11 cases in which tumor size data were collected before and after therapy. Complete response of tumor mass occurred in 4 (36%) of 11, partial response occurred in 5 (45%), and no response occurred in 2 (18%). No tumor grew after radiotherapy. Some relief in symptoms occurred in all 13 patients; 10 (77%) had complete resolution of symptoms. In both patients with life-threatening cytopenias, hematologic values returned to normal after treatment. Because the majority of the patients responded to all dose levels administered, no firm dose-response relationship was evident. However, objective (measurable) complete responses occurred in two (50%) of the four patients receiving doses of 30 Gy or greater compared with only two (29%) of the seven patients who received lesser doses. No long-term morbidity occurred. Radiotherapy of large unresectable and partially resected hemangiomas yields long-term relief of symptoms and tumor shrinkage in the majority of patients treated.

Analysis of failure after curative irradiation of extrahepatic bile duct carcinoma

Thirty-four patients with subtotally resected or unresectable carcinoma of the extrahepatic bile ducts received radiation therapy; a minimum of 45 Gy (external beam) to the tumor and regional lymph nodes ± 5-fluorouracil (5-FU). Seventeen patients received an external beam boost of 5 to 15 Gy to the tumor, and a specialized boost was used in the remaining 17 patients (iridium-192 transcatheter seeds in 10 and intraoperative radiation therapy [IORTJ with electrons in seven). The median time to death in all 34 patients was 12 months (range, 4 to 98 months). The only patients who survived longer than 18 months were those either with gross total or subtotal resection before external irradiation (2 of 6) or who received specialized boosts (192Ir, 3 of 10; IORT, 3 of 7). Local failure was documented in 9 of 17 patients who received external beam irradiation alone ± 5-FU, 3 of 10 patients who received an 192Ir boost, and 2 of 6 patients who received an IORT boost with curative intent.

Patterns of failure in primary testicular non-Hodgkin's lymphoma.

Patterns of failure were analyzed in 30 patients with testicular non-Hodgkins lymphoma: 16 had stage IE disease, ten had stage IIE, and four had stage IV. After orchiectomy, two of the 16 patients with stage IE disease received no additional therapy, one received multiagent chemotherapy, and 13 received pelvic and para-aortic radiation. Twelve patients with stage IE disease had progression, and the median time to progression was 12 months. Of the 14 patients with extratesticular involvement (stage IIE or IV), one (stage IV) received no treatment after orchiectomy, three (stage IIE) received para-aortic and pelvic radiation, and ten (seven stage IIE and three stage IV) received multiagent chemotherapy with or without radiation. Eight of the patients with stage IIE or IV disease had progression, and the median time to progression was 11 months. Widespread extranodal progression was observed in 17 of the 20 patients who had progression. The tendency of testicular lymphoma for early systemic progression suggests a need for multiagent chemotherapy in initial management.

Improved Metastasis-Free and Survival Outcomes With Early Salvage Radiotherapy in Men With Detectable Prostate-Specific Antigen After Prostatectomy for Prostate Cancer

Purpose To describe outcomes of salvage radiotherapy (SRT) for men with detectable prostate-specific antigen (PSA) after radical prostatectomy for prostate cancer and identify associations with outcomes. Patients and Methods A total of 1,106 patients received SRT between January 1987 and July 2013, with median follow-up 8.9 years. Outcomes were estimated using Kaplan-Meier for overall survival (OS) and cumulative incidence for biochemical recurrence (BcR), distant metastases (DM), and cause-specific mortality (CSM). Variable associations with outcomes used Cox or Fine-Gray methods, as appropriate. Multiple variable analyses used backward selection with P < .05 for retention. Results In multiple variable analyses, pathologic tumor stage, Gleason score, and pre-SRT PSA were associated with BcR, DM, CSM, and OS; androgen suppression and SRT doses > 68 Gy were associated with BcR; and age was associated with OS. Each pre-SRT PSA doubling increased significantly the relative risk of BcR (hazard ratio [HR], 1.30; P < .001), DM (HR, 1.32; P < .001), CSM (HR, 1.40; P < .001), and all-cause mortality (HR, 1.12; P = .02). Using a pre-SRT PSA cutoff ≤ 0.5 versus > 0.5 ng/mL, 5-year and 10-year cumulative incidences for BcR were 42% versus 56% and 60% versus 68% ( P < .001), DM 7% versus 14% and 13% versus 25% ( P < .001), CSM 1% versus 4% and 6% versus 13% ( P < .001), and OS of 94% versus 92% and 83% versus 73% ( P > .05). Conclusion SRT outcomes are in part affected by factors associated with prostatectomy findings but may be positively affected by using SRT at lower PSA levels, including reductions in BcR, DM, CSM, and all-cause mortality. These findings argue against prolonged monitoring of detectable postprostatectomy PSA levels that delay initiation of SRT.