Kent Wallner

Patterns of failure following treatment for glioblastoma multiforme and anaplastic astrocytoma

Recurrence patterns of glioblastoma multiforme (25) and anaplastic astrocytoma (9) were studied using CT scans of 34 patients who received all or a portion of their surgical treatment at Memorial Sloan-Kettering Cancer Center from January 1983 through February 1987. Thirty-two patients presented with unifocal tumors and two with multifocal tumors. All patients received radiation therapy following initial surgery. Eighteen patients who underwent re-operation following CT evidence of recurrence had histologic verification of recurrent tumor; sixteen patients had radiographic evidence of recurrence only. Seventy-eight percent (25/32) of unifocal tumors recurred within 2.0 cm of the pre-surgical, initial tumor margin, defined as the enhancing edge of the tumor on CT scan. Fifty-six percent (18/32) of tumors recurred within 1.0 cm of the initial tumor margin. Tumors for which a gross total resection was accomplished tended to recur closer to the initial tumor margin than did subtotally resected tumors (p greater than 0.1). Extensive pre-operative edema was associated with a decreased distance between initial and recurrent tumor margins. Large tumors were generally not more likely to recur further from the initial tumor margin than were smaller tumors. No unifocal tumor recurred as a multifocal tumor. Only one tumor (initially near the midline) recurred in the contralateral hemisphere. The findings support the use of partial brain irradiation for post-operative treatment of glioblastoma multiforme and anaplastic astrocytomas, and may help to determine the most appropriate treatment volume for interstitial irradiation.

The effect of local control on metastatic dissemination in carcinoma of the prostate: Long-term results in patients treated with 1251 implantation

The study evaluates the effect of the locally recurring tumor on the incidence of metastatic disease in early stage carcinoma of the prostate. The probability of distant metastases was studied in 679 patients with Stage B-C/N0 carcinoma of the prostate treated at MSKCC between 1970 and 1985 (median follow-up of 97 months). Patients were staged with pelvic lymph node dissection and treated with retropubic 125I implantation. The actuarial distant metastases free survival (DMFS) for patients at risk at 15 years after initial therapy was 37%. Cox proportional hazard regression analysis of covariates affecting the metastatic outcome showed that local failure, used in the model as a time dependent variable, was the most significant covariate, although stage, grade, and implant volume were also found to be independent variables. The relative risk of metastatic spread subsequent to local failure was 4-fold increased compared to the risk without evidence of local relapse. The 15-year actuarial DMFS in 351 patients with local control was 77% compared to 24% in 328 patients who developed local relapses (p less than 0.00001). The relation of distant spread to the local outcome was observed regardless of stage, grade, or implant dose. Even stage B1/N0-Grade I patient with local control showed a 15-year actuarial DMFS of 82%, compared to 22% in patients with local relapse; p less than 0.00001). The median local relapse-free survival (LRFS) in the 268 patients with local recurrences who did not receive hormonal therapy before distant metastases were detected was 51 months, compared to a median of 71 months for DMFS in the same patients (p less than 0.001), consistent with the possibility that distant dissemination may develop secondary to local failure. Furthermore, distant metastases in patients with local control, apparently already existing as micrometastases before treatment, were detected earlier (median DMFS of 37 months) than in patients with local relapse (median DMFS of 54 months; p = 0.009). These data suggest that the existence and re-growth of local residual disease in localized prostatic carcinoma promotes an enhanced spread of metastatic disease, and that early and complete eradication of the primary tumor is required if a long term cure is to be achieved, although the clinical expression of secondary metastases may not become apparent for 6.5 years or more in one-half of the patients.

Tumor control and morbidity following transperineal iodine 125 implantation for stage T1/T2 prostatic carcinoma.

PURPOSE To quantify disease progression and morbidity following computer tomography (CT)-based transperineal iodine 125 prostate implantation. METHODS Ninety-two patients with clinical stage T1 or T2, Gleason score 2 to 7/10, prostatic carcinoma had outpatient, CT-based transperineal 125I prostate implantation and were monitored for 1 to 7 years (median, 3). The prescribed minimum radiation dose was 140 to 160 Gy. Lymph node dissection and postimplantation prostatic biopsies were not routinely performed. RESULTS In 46% of patients, radiation-related urinary symptoms were substantial enough at 1 month following implantation to require medication. Radiation-related urinary symptoms gradually resolved. Two years after implantation, 14% of patients had persistent urinary symptoms of Radiation Therapy Oncology Group (RTOG) > or = grade 2. Eight percent of patients underwent a transurethral resection of the prostate (TURP) within 2 years of implantation. Five patients developed radiation-induced rectal ulcerations. Of 56 patients who were sexually potent preimplantation, 86% retained potency at 3 years. Twenty-five patients had biochemical disease progression. The overall actuarial freedom from biochemical failure rate at 4 years following implantation was 63%. In Cox proportional hazards multivariate analysis, the strongest predictor of failure was prostate-specific antigen (PSA) level less than or greater than 10 ng/mL (P = .005), followed by Gleason score (2 to 4 v 5 to 7, P = .08) and stage (T1 v T2, P = .09). CONCLUSION The 5-year biochemical freedom-from-progression rates following transperineal 125I implantation are comparable with those achieved with prostatectomy. The morbidity has decreased with increased physician experience.

Comparison of the 5-year outcome and morbidity of three-dimensional conformal radiotherapy versus transperineal permanent iodine-125 implantation for early-stage prostatic cancer.

PURPOSE: To compare the prostate-specific antigen (PSA) relapse-free survival outcome and incidence of late toxicity for patients with early-stage prostate cancer treated at a single institution with either three-dimensional conformal radiotherapy (3D-CRT) or transperineal permanent implantation (TPI) with iodine-125 seeds. MATERIALS AND METHODS: Patients with favorable-risk prostate cancer, defined as a pretreatment PSA of less than or equal to 10.0 ng/mL, Gleason score of 6 or lower, and stage less than or equal to T2b, were selected for this analysis. Between 1989 and 1996, 137 such patients were treated with 3D-CRT and 145 with TPI. The median ages of the 3D-CRT and TPI groups were 68 years and 64 years, respectively. The median dose of 3D-CRT was 70.2 Gy, and the median implant dose was 150 Gy. Prostate-specific antigen relapse was defined according to the American Society of Therapeutic Radiation Oncology Consensus Statement, and toxicity was graded according to the Radiation Therapy Oncology Group ...

Dosimetry guidelines to minimize urethral and rectal morbidity following transperineal I-125 prostate brachytherapy

PURPOSE To establish dosimetry guidelines to minimize urethral and rectal morbidity following permanent I-125 prostatic brachytherapy. METHODS AND MATERIALS Dosimetric parameters were correlated with long-term morbidity for 65 patients following transperineal I-125 implantation for Stage T1/T2 prostatic carcinoma. The prescribed minimum prostatic dose was 150 Gy. The median total activity used was 48 mCi (range: 32-77 mCi). Patients were followed for 1-5 years (median follow-up: 2 years). Postimplant computerized tomography (CT)-based dosimetry was performed for 45 patients. Morbidity was evaluated using a modification of the RTOG grading system, with a scale of grade 0-5. RESULTS The incidence of grades 2 and 3 urinary morbidity was associated with the maximum central urethral dose (p = 0.03), and with the length of urethra that received greater than 400 Gy (p = 0.07). Patients with larger prostates had more long-term urinary morbidity (p = 0.06). Rectal bleeding (RTOG grade 1) or ulceration (RTOG grade 2) was associated with irradiation of the rectal wall to doses in excess of 100 Gy (p = 0.02). There was no relationship between the matched peripheral dose (MPD), mCi/source or total mCi implanted and long-term morbidity. CONCLUSIONS Postimplant, CT-based dosimetry can predict which patients are at higher risk of radiation-related morbidity. More simplistic parameters including the MPD, total activity implanted, or mCi/source, had no relationship with morbidity. To decrease the risk of long-term morbidity, an effort should be made to keep the central urethral dose below 400 Gy, and the rectal surface dose below 100 Gy.

Prostate Specific Antigen Based Disease Control Following Ultrasound Guided sup 125 Iodine Implantation for Stage T1/T2 Prostatic Carcinoma

PURPOSE We report the prostate specific antigen (PSA) based recurrence-free survival rate after 125iodine (125I) implantation for early stage prostatic carcinoma. MATERIALS AND METHODS A total of 197 patients with clinical stage T1 and T2 prostatic carcinoma underwent outpatient 125I seed implantation. Followup was 1 to 7 years (median 3). Pretreatment serum PSA levels were elevated (greater than 4.0 ng./ml.) in 138 patients (70%). There were 105 well differentiated (Gleason score 2 to 4), 87 moderately differentiated (Gleason score 5 to 6) and 5 indeterminate tumors. The prescribed minimum prostatic dose was 160 Gy. The total dosage of 125I implanted ranged from 15 to 62 mCi. (median 37). Staging lymph node dissection and seminal vesicle biopsies were not routinely performed. RESULTS Among 138 patients with an elevated PSA level before implantation and no prior hormonal treatment, the PSA value returned to normal in 98% and decreased to less than 1.0 ng./ml. in 82% within 24 months of treatment. In 97% of those 138 patients the PSA level decreased to less than 1.0 ng./ml. at 48 months after implantation. Of 8 patients with an increasing PSA value 5 also had clinically evident failure. The actuarial rate of chemical (increasing PSA) or clinical failure at 5 years following implantation was 7%, with 15 patients still at risk at 5 years. There was a trend for higher failure rates among patients with higher pretreatment PSA levels (p = 0.57), Gleason scores 5 and 6 versus 2 to 4 (p = 0.51) or higher stage of disease (p = 0.17). CONCLUSIONS There is a high rate of clinical and chemical freedom from progression following 125I implantation for select patients with early stage prostatic carcinoma.

Five-year biochemical outcome and toxicity with transperineal CT-planned permanent I-125 prostate implantation for patients with localized prostate cancer

PURPOSE To report the 5-year prostate-specific antigen (PSA) relapse-free survival outcome and incidence of long-term morbidity for patients with localized prostate cancer treated with CT-planned permanent I-125 prostate implantation using a transperineal technique (TPI). METHODS AND MATERIALS Between 1989-1996, 248 patients with clinically localized prostate cancer were treated with TPI. The median age was 65 years (range: 45-80 years). The clinical stage was T1c in 143 patients (58%), Stage T2a in 102 (41%), and T2b in 3 (1%). Thirty patients (12%) had Gleason scores <6, 158 patients (64%) had Gleason scores of 6, and 60 (24%) had scores >or =7. The median pretreatment PSA was 7 ng/mL (range: 1-58 ng/mL). The median prescribed implant dose was 150 Gy. Patients were characterized as having favorable risk disease if their pretreatment PSA level was < or =10.0 ng/mL and Gleason score < or = 6; those with one and two adverse prognostic features (PSA > 10 ng/mL and Gleason score >6) were classified as having intermediate and unfavorable risk disease, respectively. PSA relapse was defined according to the American Society of Therapeutic Radiation Oncology Consensus Statement, and toxicity was scored according to the Radiation Therapy Oncology Group morbidity scoring scale. The median follow-up was 48 months (range: 12-126 months). RESULTS Thirty-eight patients (15%) developed a PSA relapse, and the overall 5-year PSA relapse-free survival (PRFS) rate was 71%. The 5-year PRFS rates for favorable-risk (n = 146), intermediate-risk (n = 85), and unfavorable-risk (n = 17) patients were 88%, 77%, and 38%, respectively (p < 0.0001). The 5-year PRFS rates among patients treated with a 2-month course of neoadjuvant androgen deprivation (NAAD) prior to TPI compared to patients treated with TPI only were 100% and 77%, respectively (p = 0.03). Multivariate analysis identified pretreatment PSA > 10 ng/mL and Gleason score >6 as independent predictors for biochemical relapse after TPI. The 5-year actuarial likelihood of late Grade 2 urinary toxicity was 41%. The 5-year likelihood of urethral stricture development was 10%, and the median time to stricture development was 18 months. One patient (0. 4%) in the early phase of this clinical experience developed a Grade 4 urethral complication. The actuarial incidence of late Grade 2 rectal bleeding was 9%. One patient (0.4%) developed a Grade 4 rectal complication. CONCLUSIONS Especially for favorable risk disease, the 5-year biochemical outcome with this approach was excellent and appears to be comparable to other therapeutic interventions. Grade 2 urinary symptoms were common in these patients but gradually resolved in most. Improved treatment planning approaches that further constrain the urethral dose without compromising the target volume dose will likely decrease the incidence of Grade 2 and 3 urinary symptoms after TPI.

Treatment-related symptoms during the first year following transperineal 125I prostate implantation

PURPOSE To summarize the urinary, rectal, and sexual symptoms occurring during the first 12 months following 125I prostatic implantation. METHODS AND MATERIALS Thirty-one patients with Stage T1 or T2 prostatic carcinoma were evaluated for morbidity following computed tomography-guided transperineal 125I implants from 1988 to 1991. The median total activity used was 47 mCi (range 35-73 mCi). Toxicity was evaluated using a modification of the Radiation Therapy Oncology Group grading system. RESULTS Nocturia was the most common treatment-related symptom, reported by 80% of patients within 2 months after implantation, and persisted at 12 months in 45% of the patients. Mild dysuria developed in 48% of patients within 2 months of implantation; two patients needed analgesics for their dysuria. Terazosin hydrochloride (2-10 mg qd) provided subjective improvement of urinary symptoms in seven of eight patients in whom it was tried. Rectal urgency, soft stools, and increased frequency of bowel movements was reported by 25% of the patients within 1-2 months after implantation. The incidence of asymptomatic rectal bleeding or ulceration occurring at any time after implantation was 47%, but resolved in all patients with expectant treatment. Self-limited ulceration of the rectal mucosal occurred in 16%, but only one patient developed a prostato-rectal fistula, managed with an ileal conduit. Five of the 18 potent patients experienced discomfort on erection or ejaculation, beginning within several weeks of their implant. The discomfort resolved within 6 months in three of the patients, but persisted for 18 and 24 months in the other two. CONCLUSION 125I implantation, as performed in this series, is generally associated with only mild-moderate genitourinary and rectal symptoms that may persist 6 months or more after implantation. Prostatic carcinoma, Brachytherapy, Morbidity.

A CT-based evaluation method for permanent implants: application to prostate

A computerized tomography-based 3-dimensional evaluation scheme, using semi-automatic seed localization from transverse computerized tomography-images, has been developed for permanent implants. The treatment isodose contour is generated at each scan plane and overlaid on the corresponding target contour for coverage visualization. Volume and surface dose histograms are generated for the target and neighboring normal structures. Dose inhomogeneity within the target is also estimated from the full-width at half maximum of the differential volume dose histogram. The matched peripheral dose is calculated from the ellipsoidal volume approximation for the target. The present evaluation method has been applied here to 10 actual permanent I-125 prostatic implantations. Coverages by 150 Gy and 100 Gy levels are found to range from 78-96% and 91-99% of the target volume, respectively. The average matched peripheral dose is found to be about two times the average peripheral dose (the dose encompassing 99% target) and about three times the average minimum peripheral dose (the dose encompassing 100% target). The dose inhomogeneities within the target volume, in these 10 cases, range from 220-420 Gy.

LOW RISK OF URINARY INCONTINENCE FOLLOWING PROSTATE BRACHYTHERAPY IN PATIENTS WITH A PRIOR TRANSURETHRAL PROSTATE RESECTION

PURPOSE To review post implant morbidity in patients with prior transurethral prostate resection (TURP). METHODS AND MATERIALS Nineteen patients with stage T1-T2 prostatic carcinoma and prior TURP were treated with I-125 or Pd-103 implantation from 1991 through 1994. Follow-up ranged from 1 to 6 years (median: 3 years). The time from TURP to implantation ranged from 2 months to 15 years (median: 3 years). RESULTS Only one patient developed mild urinary stress incontinence, 6 months following his I-125 implant. The actuarial freedom from permanent urinary incontinence at 3 years after implantation was 94%. No patient required urethral dilatation for urethral stricture. Eleven patients were sexually potent prior to implantation. At 3 years after treatment, all patients had maintained potency. CONCLUSION In our experience, there has been remarkably little adverse sequelae following I-125 or Pd-103 implantation in patients with a prior history of TURP.