Racial Analysis of Clinical and Biochemical Outcomes in Patients With Prostate Cancer Treated With Low-Dose-Rate Brachytherapy.

PURPOSE: Black men in the United States experience significantly higher incidence of and mortality from prostate cancer (PCa) than non-Black men. The cause of this disparity is multifactorial, though inequitable access to curative radiation modalities, including low-dose-rate (LDR) brachytherapy, may contribute. Despite this, there are few analyses evaluating the potential of different radiation therapies to mitigate outcome disparities. Therefore, we examined the clinical outcomes of Black and non-Black patients treated with definitive LDR brachytherapy for PCa. METHODS: Data were collected for all patients treated with definitive LDR brachytherapy between 2005 and 2018 on a retrospective institutional review board approved protocol. Pearson χ2 analysis was used to assess demographic and cancer differences between Black and non-Black cohorts. Freedom from biochemical failure (FFBF) was calculated using Kaplan-Meier analysis. Univariate and multivariate analyses were used to identify factors predictive of biochemical failure. RESULTS: One hundred and sixty-seven patients were included in the analysis (Black: n = 81; 48.5%) with a median follow-up of 88.4 months. Black patients were from lower income communities (P < .01), had greater social vulnerability (P < .01), and had a longer interval between diagnosis and treatment (P = .011). Overall cumulative FFBF was 92.3% (95% confidence interval [CI], 87.8%-96.8%) at 5 years and 87.7% (95% CI, 82.0%-93.4%) at 7 years. There was no significant difference in FFBF in Black and non-Black patients (P = .114) and Black race was not independently predictive of failure (hazard ratio, 1.51; 95% CI, 0.56-4.01; P = .42). Overall survival was comparable between racial groups (P = .972). Only nadir prostate-specific antigen was significantly associated with biochemical failure on multivariate (hazard ratio, 3.57; 95% CI, 02.44-5.22; P < .001). CONCLUSIONS: Black men treated with LDR brachytherapy achieved similar FFBF to their non-Black counterparts despite poorer socioeconomic status. This suggests that PCa treatment with brachytherapy may eliminate some disparities in clinical outcomes.

Adding Short-Term Androgen Deprivation Therapy to Radiation Therapy in Men With Localized Prostate Cancer: Long-Term Update of the NRG/RTOG 9408 Randomized Clinical Trial.

PURPOSE: For men with localized prostate cancer, NRG Oncology/Radiation Therapy Oncology Group (RTOG) 9408 demonstrated that adding short-term androgen deprivation therapy (ADT) to radiation therapy (RT) improved the primary endpoint of overall survival (OS) and improved disease-specific mortality (DSM), biochemical failure (BF), local progression, and freedom from distant metastases (DM). This study was performed to determine whether the short-term ADT continued to improve OS, DSM, BF, and freedom from DM with longer follow-up. METHODS AND MATERIALS: From 1994 to 2001, NRG/RTOG 9408 randomized 2028 men from 212 North American institutions with T1b-T2b, N0 prostate adenocarcinoma and prostate-specific antigen (PSA) ≤20ng/mL to RT alone or RT plus short-term ADT. Patients were stratified by PSA, tumor grade, and surgical versus clinical nodal staging. ADT was flutamide with either goserelin or leuprolide for 4 months. Prostate RT (66.6 Gy) was started after 2 months. OS was calculated at the date of death from any cause or at last follow-up. Secondary endpoints were DSM, BF, local progression, and DM. Acute and late toxic effects were assessed using RTOG toxicity scales. RESULTS: Median follow-up in surviving patients was 14.8 years (range, 0.16-21.98). The 10-year and 18-year OS was 56% and 23%, respectively, with RT alone versus 63% and 23% with combined therapy (HR 0.94; 95% confidence interval [CI], 0.85-1.05; P = .94). The hazards were not proportional (P = .003). Estimated restricted mean survival time at 18 years was 11.8 years (95% CI, 11.4-12.1) with combined therapy versus 11.3 years with RT alone (95% CI, 10.9-11.6; P = .05). The 10-year and 18-year DSM was 7% and 14%, respectively, with RT alone versus 3% and 8% with combined therapy (HR 0.56; 95% CI, 0.41-0.75; P < .01). DM and BF favored combined therapy at 18 years. Rates of late grade ≥3 hepatic, gastrointestinal, and genitourinary toxicity were ≤1%, 3%, and 8%, respectively, with combined therapy versus ≤1%, 2%, and 5% with RT alone. CONCLUSIONS: Further follow-up demonstrates that OS converges at approximately 15 years, by which point the administration of 4 months of ADT had conferred an estimated additional 6 months of life.

Radiation and Hyperthermia Combination Therapy for Recalcitrant Verruca Vulgaris.

A 47-year-old white woman presented to our clinic complaining of recalcitrant warts on her trunk and extremities. She had an extensive past medical history including immunodeficiency of unknown origin, pulmonary hypertension, rheumatoid arthritis, and systemic lupus erythematosus, for which she was being treated with chronic immunosuppressive therapy with methylprednisolone and belimumab. The patient had previously failed treatments at an outside facility with liquid nitrogen, trichloroacetic acid, topical cidofovir, imiquimod, topical 5-fluorouracil, intralesional candida antigen, pulsed-dye laser (Vbeam Perfecta), surgical excision, and photodynamic therapy. (SKINmed. 2019;17:68-71).

A Phase II Study Evaluating Bone Marrow-Sparing, Image-guided Pelvic Intensity-Modulated Radiotherapy (IMRT) With Cesium-131 Brachytherapy Boost, Adjuvant Chemotherapy, and Long-Term Hormonal Ablation in Patients With High Risk, Nonmetastatic Prostate Cancer.

PURPOSE/OBJECTIVE(S): Management of localized high-risk prostate cancer remains challenging. At our institution we performed a prospective phase II study of 2 years of androgen deprivation therapy (ADT), pelvic radiation, Cesium (Cs)-131 brachytherapy boost, and adjuvant docetaxel in high risk, localized prostate cancer with a primary endpoint of 3-year disease-free survival. MATERIALS/METHODS: Acute/chronic hematologic, gastrointestinal (GI) and genitourinary (GU) toxicities were scored based on the CTCAE v3.0/RTOG-EORTC criteria, respectively. Actuarial biochemical recurrence free survival (bRFS), bRFSdisease free survival (DFS) and overall survival (OS) were calculated. Patients had a median age of 62 years (range, 45 to 82), median Gleason score 8 (74% Gleason 8-10), median PSA of 11.2 (range, 2.8 to 96), and 47% cT2-T3a stage disease. Androgen deprivation was given for 2 years, 45 Gy whole-pelvis IMRT was followed by an 85 Gy Cs-131 boost to the prostate gland, and adjuvant docetaxel was given for 4 cycles. RESULTS: In total 38 patients enrolled from 2006 to 2014, with 82% completing protocol specified treatment, and 84.2% completing 4 cycles of docetaxel. Median follow-up for the entire and alive cohorts were 44 months and 58 months (range, 3.4 to 118), respectively. Acute grade ≥2 GI and GU toxicity rates were 18.4% and 23.7%, respectively. Chronic grade ≥2 GI and GU toxicity rates were 2.6% and 2.6%, respectively. Twelve patients (31.6%) developed grade 4 hematologic toxicity, with no grade 5 toxicity. The 5-year DFS, bRFS and OS rates were 74.1%, 86.0%, and 80.3%, respectively. CONCLUSIONS: This aggressive pilot multimodal approach appears to be safe and well-tolerated, providing disease control in a significant proportion of patients with particularly high-risk prostate cancer.

Dosimetric effects of the prone and supine positions on image guided localized prostate cancer radiotherapy.

PURPOSE: To compare target coverage and doses to rectum and bladder in IMRT of localized prostate cancer in the supine versus prone position, with the inclusion of image guidance. MATERIALS AND METHODS: Twenty patients with early stage localized prostate carcinoma who received external beam radiotherapy in the supine and prone positions underwent approximately 10 serial CT examinations in their respective treatment position in non-consecutive days, except for one patient who was treated prone but serially imaged supine. The prostate, bladder and rectum were contoured on all CT scans. A PTV was generated on the first scan of each patient's CT series by expanding the prostate with a 5mm margin and an IMRT plan was created. The resultant IMRT plan was then applied to that patient's remaining serial CT scans by aligning the initial CT image set with the subsequent serial CT image sets using (1) skin marks, (2) bony anatomy and (3) center of mass of the prostate. The dosimetric results from these three alignments were compared between the supine and prone groups. To account for the uncertainties associated with prostate delineation and intra-fractional geometric changes, a fictional "daily PTV" was generated by expanding the prostate with a 3mm margin on each serial CT scan. Thus, a more realistic target coverage index, V95, was quantified as the fraction of the daily PTV receiving at least 95% of the prescription dose. Dose-volume measures of the organs at risk were also compared. The fraction of the daily PTV contained by the initial PTV after each alignment method was quantified on each patient's serial CT scan, and is defined as PTV overlap index. RESULTS: As expected, alignment based on skin marks yielded unacceptable dose coverage for both groups of patients. Under bony alignment, the target coverage index, V95, was 97.3% and 93.6% for prone and supine patients (p<0.0001), respectively. The mean PTV overlap indices were 90.7% and 84.7% for prone and supine patients (p<0.0002), respectively. In the supine position 36% of cases showed a V95<95% after bony alignment, while only 12.5% of prone patients with V95<95% following bony alignment. Under soft-tissue alignment matching the center of mass of the prostate, the mean V95 was 99.3% and 98.6% (p<0.03) and the PTV overlap index was 97.7% and 94.8% (p<0.0002) for prone and supine groups, respectively. CONCLUSIONS: Soft-tissue alignment combined with 5mm planning margins is appropriate in minimizing treatment planning and delivery uncertainties in both the supine and prone positions. Alignment based on bony structures showed improved results over the use of skin marks for both supine and prone setups. Under bony alignment, the dose coverage and PTV overlap index for prone setup were statistically better than for supine setup, illustrating a more consistent geometric relationship between the prostate and the pelvic bony structures when patients were treated in the prone position.

Efficacy and quality of life outcomes in patients with atypical trigeminal neuralgia treated with gamma-knife radiosurgery.

PURPOSE: To assess efficacy and quality of life (QOL) outcomes associated with gamma-knife radiosurgery (GK-RS) in treating atypical trigeminal neuralgia (ATN) compared with classic trigeminal neuralgia (CTN). METHODS AND MATERIALS: Between September 1996 and September 2004, 35 cases of ATN were treated with GK-RS. Patients were categorized into two groups: Group I comprised patients presenting with ATN (57%); Group II consisted of patients presenting with CTN then progressing to ATN (43%). Median prescription dose 75 Gy (range, 70-80 Gy) was delivered to trigeminal nerve root entry zone. Treatment efficacy and QOL improvements were assessed with a standardized questionnaire. RESULTS: With median follow-up of 29 months (range, 3-74 months), 72% reported excellent/good outcomes, with mean time to relief of 5.8 weeks (range, 0-24 weeks) and mean duration of relief of 62 weeks (range, 1-163 weeks). This rate of pain relief is similar to rate achieved in our previously reported experience treating CTN with GK-RS (p = 0.36). There was a trend toward longer time to relief (p = 0.059), and shorter duration of relief (p = 0.067) in patients with ATN. There was no difference in rate of, time to, or duration of pain relief between Groups I and II. Of the patients with ATN, 88% discontinued or decreased the use of pain medications. Among the patients with sustained pain relief, QOL improved an average of 85%. CONCLUSION: This is the largest reported GK-RS experience for the treatment of ATN. Patients with ATN can achieve rates of pain relief similar to those in patients with CTN. Further follow-up is necessary to assess adequately the durability of response.

Docetaxel followed by hormone therapy in men experiencing increasing prostate-specific antigen after primary local treatments for prostate cancer.

PURPOSE: Prostatectomy or radiation for localized prostate cancer (PC) can fail in up to 15% to 30% of patients. The purpose of this study was to determine feasibility, tolerability, and outcome of docetaxel followed by hormone therapy in men experiencing an increasing prostate-specific antigen (PSA) after their primary local treatments for PC. PATIENTS AND METHODS: Men with increasing serum PSA after prostatectomy or/and radiation were eligible. Serum PSA had to be > or = 4 ng/mL and serum testosterone had to be in the noncastrate range. Treatment included docetaxel 70 mg/m2 every 3 weeks for up to six cycles, followed by total androgen suppression (luteinizing hormone-releasing hormone agonist plus bicalutamide) and peripheral androgen blockade (finasteride plus bicalutamide) for 12 to 20 months. RESULTS: Thirty-nine men were enrolled; 32 had PSA-only failure, seven also had clinical metastasis. Baseline median PSA was 13.7 ng/mL. Serum PSA decreased > or = 50% in 17 of 35 patients (48.5%) and > or = 75% in seven of 35 patients (20%) with docetaxel. The PSA decreased to a median of 0.1 ng/mL with subsequent hormone therapy. In 28 of 33 patients the PSA increased (median, 0.41 ng/mL) at a median follow-up of 2.3 months after treatment. In contrast, in five of 33 men the PSA remains at 0.1 ng/mL at a median of 18.9 months after therapy; three of these five men had soft tissue metastasis at entry but remain in complete remission. The most common grade 3 to 4 toxicity was neutropenia (61.5%). CONCLUSION: Docetaxel followed by hormone therapy of limited duration may provide disease control in subgroups of men experiencing failure after local treatments for PC.

Salvage external beam radiotherapy for locally recurrent prostate cancer after definitive brachytherapy.

PURPOSE: Patients with locally recurrent prostate cancer after definitive prostate brachytherapy have few evidence-based salvage options. We evaluate the efficacy and treatment-related side-effects of salvage external-beam radiotherapy (EBRT) after definitive prostate brachytherapy (PBT). METHODS AND MATERIALS: Eleven patients previously treated with definitive PBT and with biopsy-proven local-only recurrence received salvage reirradiation with EBRT. Genitourinary (GU) function was assessed with International Prostate Symptom Scores. Treatment-related toxicities were graded using CTCAE v 4.03. RESULTS: Median follow-up was 26.5 months (range, 1-53.6 months); median age at EBRT salvage was 67 years (range, 61-81 years). Salvage EBRT included the whole pelvis in 8 patients. Two patients were treated with 3D-CRT; 9 underwent IMRT. Five patients (45%) received androgen deprivation therapy concurrent with salvage EBRT as part of long- or short-course hormone therapy. The median prostate dose was 70.2 Gy (range, 64.8-75.6 Gy). Actuarial 3-year overall and biochemical failure-free survival were 77% and 69%, respectively. Five patients (45%) had worsening GU symptoms, and 9 (82%) experienced a decline in erectile function. One patient experienced acute grade 2 GU toxicity. Four patients (36%) experienced late grade ≥2 GI/GU toxicities, including 2 who experienced grade 3 toxicities (rectourethral fistula/incontinence, bladder outlet obstruction). No grade 4/5 toxicities were noted. CONCLUSIONS: Our data suggest that salvage EBRT can provide similar disease control and treatment-related toxicity to more established salvage therapies. This approach warrants further investigation on a larger scale.

Pretreatment tumor volume as a prognostic factor in metastatic colorectal cancer treated with selective internal radiation to the liver using yttrium-90 resin microspheres.

BACKGROUND: Yttrium-90 (90Y)-resin microspheres can prolong intrahepatic disease control and improve overall survival (OS) in patients with metastatic colorectal cancer (CRC). Prognostic factors for improved outcomes in patients undergoing selective internal radiation therapy (SIRT) have been studied, but the relationship between pre-SIRT liver tumor volume and outcomes has not well described. METHODS: We retrospectively reviewed the records of patients with metastatic CRC who were treated at our institution with 90Y-resin microspheres. Each patient underwent either MR or CT imaging of the liver with intravenous (IV) contrast before and within ~2-3 months after SIRT. Imaging data were transferred into our treatment planning system. Each metastatic liver lesion was contoured, and the volume of each lesion was summed to determine the total liver tumor volume at a given time point. We evaluated whether pretreatment liver tumor volume was related to OS. We also evaluated the relationship between pre-SIRT tumor volume and radiographic treatment response by either unidimensional Response Evaluation Criteria in Solid Tumors (RECIST) or three-dimensional volumetric criteria. RESULTS: We included 60 patients with a median age of 59 years (range, 38-97 years); 60% of patients received sequential lobar treatment. The median number of chemotherapy cycles received prior to SIRT was 2. Median follow-up from first SIRT was 8.9 months. Pre- and post-SIRT tumor volumes were primarily calculated on CT (87%). The median pre-SIRT tumor volume was 77 cc (range, 4.5-2,170.4 cc). The median intervals between the first SIRT and the first, second, and third follow-up scans were 2.2, 4.4, and 7.7 months, respectively. No patient experienced a radiographic complete response. Pretreatment volume was a significant predictor for estimating the odds of a patient having stable disease or partial response using volumetric response criteria at first (P=0.016), second (P=0.023), and third (P=0.015) follow-ups. For each unit increase in log volume, a patient's odds of having a stable or partial response were 0.57, 0.63, and 0.61 times as likely at first, second, and third follow-up, respectively. OS was not significantly associated with pretreatment tumor volume. CONCLUSIONS: Patients with metastatic CRC with larger overall pretreatment liver tumor volumes, regardless of number of individual liver lesions, are less likely to have radiographic evidence of stable disease or partial response following SIRT using volumetric response criteria. However, pretreatment volume was not significantly associated with OS, and thus SIRT should be considered for patients with larger pretreatment volumetric tumor burden.

Repeat gamma knife radiosurgery for refractory or recurrent trigeminal neuralgia: treatment outcomes and quality-of-life assessment.

PURPOSE: Stereotactic radiosurgery (SRS) has become a minimally invasive treatment modality for patients with refractory trigeminal neuralgia. It is unclear, however, how best to treat patients with pain that is refractory or recurrent after initial SRS. We report on treatment outcomes and quality of life for patients treated with repeated SRS for refractory or recurrent trigeminal neuralgia. METHODS AND MATERIALS: Between June 1996 and June 2001, 112 patients with trigeminal neuralgia were treated with SRS at the University of Maryland Medical Center. Eighteen patients underwent repeat SRS 3-42 months (median, 8 months) after initial radiosurgery because of unsatisfactory or unsustained pain relief. Patients received a median prescription dose of 75 and 70 Gy, respectively, for the first and second treatments. Self-reports of pain control were assessed with a standard questionnaire containing the complete Barrow Neurologic Institute Pain Scale. RESULTS: The median follow-up was 37.5 months (range, 12-68 months) after initial SRS and 24.5 months (range, 6-65 months) after repeat SRS. For the 18 patients in this series, the percentage of patients reporting excellent, good, fair, and poor responses after the initial and repeat SRS was 50%, 28%, 6%, and 16% and 45%, 33%, 0%, and 22%, respectively. None of the 3 patients with pain refractory to initial SRS responded to repeat SRS. Among those with recurrent pain after initial SRS, 14 patients (93%) achieved excellent or good pain outcomes after repeat SRS. The actuarial analysis revealed a 1-year recurrence rate of 22%, with no patients reporting recurrent pain after 9 months of follow-up. Two patients (11%) reported new or increased facial numbness after retreatment, which was described as bothersome by one. Repeat SRS resulted in a median 60% improvement in quality of life, and 56% of patients believed that the procedure was successful. CONCLUSION: Despite a modest dose reduction, repeat SRS provided similar rates of complete pain control as the initial procedure, but was not effective for patients with no response to initial treatment. Repeat SRS was more efficacious for those patients who experienced longer periods of pain relief after the initial SRS. The incidence of complications was not significantly different from that observed for initial SRS. In this series, most patients had significant improvements in quality of life.

Risk group stratification in patients undergoing permanent (125)I prostate brachytherapy as monotherapy.

PURPOSE: Patients undergoing prostate brachytherapy (PB) as monotherapy are often selected on the basis of favorable pretreatment factors. However, intermediate and high-risk prostate cancer patients are commonly offered PB as monotherapy without the addition of external beam radiotherapy (EBRT) or hormonal therapy. This series reports the outcome of patients undergoing PB as monotherapy who were stratified into low, intermediate, and high-risk groups with extended follow-up. METHODS AND MATERIALS: A total of 102 patients with clinically localized prostate cancer underwent PB alone as monotherapy. EBRT or hormonal therapy was not part of their initial treatment. Prostate-specific antigen (PSA) relapse-free survival (PRFS) was determined in accordance with the American Society for Therapeutic Radiology and Oncology consensus statement. Patients were stratified as at favorable risk (Stage T1-2a, pretreatment PSA < or =10.0 ng/mL, and Gleason score < or =6), intermediate risk (one prognostic indicator with a higher value), or unfavorable risk (> or =2 indicators with higher values). The median follow-up period for patients in this series was 7 years (range 2.1-9.7). The median age at treatment was 71 years (range 54-80), and the median prescribed dose of (125)I was 145 Gy. RESULTS: Forty patients experienced a biochemical relapse at a median of 1.9 years (range 0.4-4.2). The 5-year actuarial PRFS rate for patients with favorable, intermediate, and unfavorable risk was 85%, 63%, and 24%, respectively (p <0.0001). All but 1 patient had the relapse within the first 5 years of treatment. When stratifying patients on the basis of their pretreatment PSA level, the 5-year PRFS rate for men with a PSA < or =10 ng/mL vs. >10 ng/mL was 78% vs. 35%, respectively (p = 0.0005). Furthermore, the 5-year PRFS rate for men with a Gleason score of < or =6 vs. > or =7 was 74% vs. 33%, respectively (p = 0.0001). No difference was found between Stage T1-T2a and Stage T2b or higher (64% vs. 54%, respectively; p = 0.353). CONCLUSION: On the basis of risk stratification, PB as monotherapy produces comparable PRFS to EBRT and surgery at 7 years of follow-up. PB as monotherapy is particularly ineffective in patients with unfavorable risk factors, and additional therapy is warranted.

Factors predicting local tumor control after gamma knife stereotactic radiosurgery for benign intracranial meningiomas.

PURPOSE: To determine the long-term outcomes and prognostic factors in benign intracranial meningiomas treated with gamma knife stereotactic radiosurgery (GK-SRS). METHODS AND MATERIALS: Between 1992 and 2000, 162 patients with benign meningiomas were treated with GK-SRS at the University of Maryland Medical Center. Complete follow-up was available in 137 patients. All patients underwent magnetic resonance imaging (MRI)-based treatment planning. Serial MRIs and clinical exams were performed to assess tumor response. GK-SRS was the primary treatment in 85 patients (62%), whereas 52 patients (48%) had prior surgical resections. The median prescribed dose was 14 Gy (range, 4-25 Gy) to the 50% isodose line. The median tumor volume, treatment volume, and conformity index were 4.5 cc (range, 0.32-80.0 cc), 6.3 cc (range, 1.0-75.2 cc), and 1.34 (range, 0.65-3.16), respectively. The median follow-up for the entire cohort was 4.5 years (range, 0.33-10.5 years). The following factors were included in the statistical analysis for disease-free survival (DFS) and overall survival (OS): sex, age, dose, gross tumor volume (GTV), conformity index (CI), and dural tail coverage. RESULTS: Serial MRI analysis was available in 121 patients (88.3%). Decrease in tumor size was observed in 34 patients (28.1%), whereas there was no change in 77 patients (63.6%), for a crude radiographic control rate of 91.7%. Increase in tumor size was seen in 10 patients (8.3%). New neurologic deficits attributed to the treatment developed in 10 patients (8.3%). The mean DFS and OS for the entire cohort are 4.6 years and 5.0 years, respectively. The 5-year actuarial DFS and OS were 86.2% and 91.0%, respectively. Univariate analysis revealed GTV, sex, CI, and dural tail treatment to be significant prognostic factors. Patients with GTV < or =10 cc also had longer survivals, with the 5-years DFS and OS of 91.9% vs. 68.0% (p = 0.038) and 100% vs. 59.7% (p = 0.0001), respectively. The 5-years actuarial DFS and OS for females vs. males were 90.2% vs. 74.2% (p = 0.0094) and 91.6% vs. 89.1% (p = 0.016), respectively. Patients with CI > or =1.4 achieved a longer DFS, with a 5-year DFS of 95.2% vs. 77.3% (p = 0.01). Patients who had the dural tail treated also had higher 5-year DFS (96.0% vs. 77.9%, p = 0.038). Patients with lower conformity (i.e., CI > or =1.4) tended to have the dural tail covered in the prescription isodose line (p = 0.04). The only factor significant in the multivariate analysis was for patients with GTV >10 cc, who had a worse DFS (hazard ratio 4.58, p = 0.05). CONCLUSIONS: This report adds to the literature that supports the efficacy and safety of GK-SRS in the management of patients with benign intracranial meningiomas. Our report identified male patients, patients with a CI <1.4, and tumor size greater than 10 cc to have a worse prognosis. Patients who were treated with less conformal plans to cover the dural tail had better outcomes. Our data clearly demonstrate the need to adequately cover the dural tail in patients treated with GK-SRS for benign intracranial meningiomas.

Gamma knife stereotactic radiosurgery for synchronous versus metachronous solitary brain metastases from non-small cell lung cancer.

A retrospective study was conducted analyzing the clinical outcome and various prognostic factors in patients treated with gamma knife stereotactic radiosurgery (GK-SRS) for solitary brain metastasis from non-small cell lung carcinoma (NSCLC). A total of 72 patients from June of 1992 to January of 1999 were treated. All patients received GK-SRS to a median dose of 18Gy, with 45 patients receiving additional whole-brain radiation therapy. No one had evidence of extra-cranial metastasis at the time of diagnosis of brain metastases. The median follow-up was 15.7 months for the entire population and 99.5 months for those who were alive at the last follow-up. Univariate and multivariate analyses were used to test the impact of various prognostic factors on survival. The median and 5-year actuarial survivals for the entire cohort were 15.7 months and 10.4%, respectively. The presence of a metachronous versus a synchronous brain metastasis was the only factor significant in the univariate (P=0.045) and multivariate (P=0.002) analyses. Patients with metachronous solitary brain metastases had a significant median survival advantage compared to those with synchronous metastases (33.3 months versus 8.6 months, P=0.001). However, there was no statistically significant difference in median survival from the time of metastasis when treated with GK-SRS in these groups (12.5 months versus 8.4 months, P=0.50). The addition of WBRT did not improve overall survival (12.0 months versus 7.7 months, P=0.73). The 5-year actuarial survival for the metachronous and synchronous groups were 13.2 and 8.1%, respectively. In conclusion, patients presenting with a solitary metachronous brain metastasis from NSCLC achieved longer survivals than those with a synchronous metastasis. The tail in the survival curves demonstrates that a prolonged survival may be attained in patients with solitary metastases from NSCLC. This study adds to the growing body of literature that supports the use of SRS in the management of this patient population.

Gamma knife stereotactic radiosurgery for patients with glioblastoma multiforme.

OBJECTIVE: Stereotactic radiosurgery (SRS) has become an effective therapeutic modality for the treatment of patients with glioblastoma multiforme (GBM). This retrospective review evaluates the impact of SRS delivered on a gamma knife (GK) unit as an adjuvant therapy in the management of patients with GBM. METHODS: Between August 1993 and December 1998, 82 patients with pathologically confirmed GBM received external beam radiotherapy (EBRT) at the University of Maryland Medical Center. Of these 82 patients, 64 with a minimum follow-up duration of at least 1 month are the focus of this analysis. Of the 64 assessable patients, 33 patients were treated with EBRT alone (Group 1), and 31 patients received both EBRT plus a GK-SRS boost (Group 2). GK-SRS was administered to most patients within 6 weeks of the completion of EBRT. The median EBRT dose was 59.7 Gy (range, 28-070.2 Gy), and the median GK-SRS dose to the prescription volume was 17.1 Gy (range, 10-28 Gy). The median age of the study population was 50.4 years, and the median pretreatment Karnofsky performance status was 80. Patient-, tumor-, and treatment-related variables were analyzed by Cox regression analysis, and survival curves were generated by the Kaplan-Meier product limit. RESULTS: Median overall survival for the entire cohort was 16 months, and the actuarial survival rate at 1, 2, and 3 years were 67, 40, and 26%, respectively. When comparing age, Karnofsky performance status, extent of resection, and tumor volume, no statistical differences where discovered between Group 1 versus Group 2. When comparing the overall survival of Group 1 versus Group 2, the median survival was 13 months versus 25 months, respectively (P = 0.034). Age, Karnofsky performance status, and the addition of GK-SRS were all found to be significant predictors of overall survival via Cox regression analysis. No acute Grade 3 or Grade 4 toxicity was encountered. CONCLUSION: The addition of a GK-SRS boost in conjunction with surgery and EBRT significantly improved the overall survival time in this retrospective series of patients with GBM. A prospective, randomized validation of the benefit of SRS awaits the results of the recently completed Radiation Therapy Oncology Group's trial RTOG 93-05.

Long-term follow-up of a prospective trial of trimodality therapy of weekly paclitaxel, radiation, and androgen deprivation in high-risk prostate cancer with or without prior prostatectomy.

PURPOSE: Weekly paclitaxel, concurrent radiation, and androgen deprivation (ADT) were evaluated in patients with high-risk prostate cancer (PC) with or without prior prostatectomy (RP). METHODS AND MATERIALS: Eligible post-RP patients included: pathological T3 disease, or rising prostate-specific antigen (PSA) ≥ 0.5 ng/mL post-RP. Eligible locally advanced PC (LAPC) patients included: 1) cT2b-4N0N+, M0; 2) Gleason score (GS) 8-10; 3) GS 7 + PSA 10-20 ng/mL; or 4) PSA 20-150 ng/mL. Treatment included ADT (4 or 24 months), weekly paclitaxel (40, 50, or 60 mg/m(2)/wk), and pelvic radiation therapy (total dose: RP = 64.8 Gy; LAPC = 70.2 Gy). RESULTS: Fifty-nine patients were enrolled (LAPC, n = 29; RP, n = 30; ADT 4 months, n = 29; 24 months, n = 30; whites n = 29, African Americans [AA], n = 28). Baseline characteristics (median [range]) were: age 67 (45-86 years), PSA 5.9 (0.1-92.1 ng/mL), GS 8 (6-9). At escalating doses of paclitaxel, 99%, 98%, and 95% of doses were given with radiation and ADT, respectively, with dose modifications required primarily in RP patients. No acute Grade 4 toxicities occurred. Grade 3 toxicities were diarrhea 15%, urinary urgency/incontinence 10%, tenesmus 5%, and leukopenia 3%. Median follow-up was 75.3 months (95% CI: 66.8-82.3). Biochemical progression occurred in 24 (41%) patients and clinical progression in 11 (19%) patients. The 5- and 7-year OS rates were 83% and 67%. There were no differences in OS between RP and LAPC, 4- and 24-month ADT, white and AA patient categories. CONCLUSIONS: In addition to LAPC, to our knowledge, this is the first study to evaluate concurrent chemoradiation with ADT in high-risk RP patients. With a median follow-up of 75.3 months, this trial also represents the longest follow-up of patients treated with taxane-based chemotherapy with EBRT in high-risk prostate cancer. Concurrent ADT, radiation, and weekly paclitaxel at 40 mg/m(2)/week in RP patients and 60 mg/m(2)/week in LAPC patients is feasible and well-tolerated.

Phase I clinical trial assessing temozolomide and tamoxifen with concomitant radiotherapy for treatment of high-grade glioma.

PURPOSE: The new standard treatment of glioblastoma multiforme is concurrent radiotherapy (RT) and temozolomide. The proliferation of high-grade gliomas might be partly dependent on protein kinase C-mediated pathways. Tamoxifen has been shown in vitro to inhibit protein kinase C through estrogen receptor-independent antineoplastic effects. This Phase I trial was designed to determine the maximal tolerated dose (MTD) of tamoxifen when given with temozolomide and concurrent RT to patients with high-grade gliomas. METHODS AND MATERIALS: A total of 17 consecutive patients in four cohorts with World Health Organization Grade 3 (n = 2) and 4 (n = 15) gliomas were given tamoxifen twice daily during 6 weeks of concurrent RT and temozolomide. Eligibility included histologic diagnosis, age >18 years old, Karnofsky performance status ≥ 60, and no previous brain RT or chemotherapy. The starting dose was 50 mg/m(2) divided twice daily. If no dose-limiting toxicities (DLTs) occurred in 3 patients, the dose was escalated in 25-mg/m(2) increments until the MTD was reached. When ≥ 2 patients within a cohort experienced a DLT, the MTD had been exceeded. Temozolomide was given with RT at 75 mg/m(2). A dose of 60 Gy in 2 Gy/d fractions to a partial brain field was delivered. RESULTS: A total of 6 patients in Cohort 4 had received tamoxifen at 125 mg/m(2). One patient was excluded, and the fourth patient developed Grade 4 thrombocytopenia (DLT). Thus, 3 more patients needed to be enrolled. A deep venous thrombosis (DLT) occurred in the sixth patient. Thus, the MTD was 100 mg/m(2). CONCLUSIONS: The MTD of tamoxifen was 100 mg/m(2) when given concurrently with temozolomide 75 mg/m(2) and RT. Tamoxifen might have a role in the initial treatment of high-grade gliomas and should be studied in future Phase II trials building on the newly established platform of concurrent chemoradiotherapy.

Long-term results of a prospective, Phase II study of long-term androgen ablation, pelvic radiotherapy, brachytherapy boost, and adjuvant docetaxel in patients with high-risk prostate cancer.

PURPOSE: We report the long-term results of a prospective, Phase II study of long-term androgen deprivation (AD), pelvic radiotherapy (EBRT), permanent transperineal prostate brachytherapy boost (PB), and adjuvant docetaxel in patients with high-risk prostate cancer. METHODS AND MATERIALS: Eligibility included biopsy-proven prostate adenocarcinoma with the following: prostate-specific antigen (PSA) > 20 ng/ml; or Gleason score of 7 and a PSA >10 ng/ml; or any Gleason score of 8 to 10; or stage T2b to T3 irrespective of Gleason score or PSA. Treatment consisted of 45 Gy of pelvic EBRT, followed 1 month later by PB with either iodine-125 or Pd-103. One month after PB, patients received three cycles of docetaxel chemotherapy (35 mg/m(2) per week, Days 1, 8, and 15 every 28 days). All patients received 2 years of AD. Biochemical failure was defined as per the Phoenix definition (PSA nadir + 2). RESULTS: From August 2000 to March 2004, 42 patients were enrolled. The median overall and active follow-ups were 5.6 years (range, 0.9-7.8 years) and 6.3 years (range, 4-7.8 years), respectively. Grade 2 and 3 acute genitourinary (GU) and gastrointestinal (GI) toxicities were 50.0% and 14.2%, respectively, with no Grade 4 toxicities noted. Grade 3 and 4 acute hematologic toxicities were 19% and 2.4%, respectively. Of the patients, 85.7% were able to complete the planned multimodality treatment. The 5- and 7-year actuarial freedom from biochemical failures rates were 89.6% and 86.5%, and corresponding rates for disease-free survival were 76.2% and 70.4%, respectively. The 5- and 7-year actuarial overall survival rates were 83.3% and 80.1%, respectively. The 5- and 7-year actuarial rates of late Grade 2 GI/GU toxicity (no Grade 3-5) was 7.7%. CONCLUSIONS: The trimodality approach of using 2 years of AD, external radiation, brachytherapy, and upfront docetaxel in high-risk prostate cancer is well tolerated, produces encouraging long-term results, and should be validated in a multi-institutional setting.

Role of image-guided patient repositioning and online planning in localized prostate cancer IMRT.

PURPOSE: To determine the expected benefit of image-guided online replanning over image-guided repositioning of localized prostate cancer intensity-modulated radiotherapy (IMRT). MATERIALS AND METHODS: On 10 to 11 CT scans of each of 10 early-stage prostate cancer patients, the prostate, bladder and rectum are manually segmented. Using a 3-mm PTV margin expansion from the CTV, an IMRT plan is made on the first CT scan of each patient. Online repositioning is simulated by recalculating the IMRT plan from the initial CT scan on the subsequent CT scans of each patient. For online replanning, IMRT is replanned twice on all CT scans, using 0-mm and 3-mm margins. The doses from subsequent CT images of each patient are then deformed to the initial CT anatomy using a mesh-based thin-plate B-spline deformation method and are accumulated for DVH and isodose review. RESULTS: Paired t-tests show that online replanning with 3-mm margins significantly increases the prostate volume receiving the prescribed dose over replanning with 0-mm margins (p-value 0.004); gives marginally better target coverage than repositioning with 3-mm margins(p-value 0.06-0.343), and reduces variations in target coverage over repositioning. Fractional volumes of rectum and bladder receiving 75%, 80%, 85%, 90%, and 95% (V75, V80, V85, V90, and V95) of the prescription dose are evaluated. V90 and V95 values for the rectum are 1.6% and 0.7 % for 3-mm margin replanning and 1% and 0.4 % for 0-mm margin replanning, with p-values of 0.010-0.011. No significant differences between repositioning and replanning with 3-mm margins are found for both the rectum and the bladder. CONCLUSIONS: Image-guided replanning using 3-mm margins reduces target coverage variations, and maintains comparable rectum and bladder sparing to patient repositioning in localized prostate cancer IMRT. Marginal reductions in doses to rectum and bladder are possible when planning margins are eliminated in the online replanning scenario. However, further reduction in treatment planning margins is not recommended.