Samuel Tekyi-Mensah

Impact of postprostatectomy prostate-specific antigen nadir on outcomes following salvage radiotherapy

OBJECTIVES To evaluate the relationship between the postprostatectomy prostate-specific antigen (PSA) nadir and the outcome of patients treated with salvage radiotherapy. METHODS Seventy-eight patients received definitive external beam radiation for recurrence following radical prostatectomy (RP). The PSA nadir was undetectable in 41 patients (less than 0.05 ng/mL). All patients received salvage radiotherapy (median dose 66 Gy) for a median of 19 months (range 2 to 149) following prostatectomy. The median follow-up time was 25 months (range 1 to 59) from the date of completion of radiation. RESULTS Among patients having an undetectable or detectable postoperative PSA, 78% and 68% were free of disease, respectively, at the last follow-up. At 3 years, the disease-free survival rates were 65% and 60%, respectively (P = 0.6). Overall, the disease-free survival rate at 3 years was 78% in patients with a PSA level 2 ng/mL or less at the time of radiotherapy compared to 31% with a PSA greater than 2 ng/mL (P < 0.0001). CONCLUSIONS Many patients who never achieve an undetectable postprostatectomy PSA level may still be salvaged with therapeutic radiotherapy. The best predictor of a favorable outcome is a low (2 ng/mL or less) PSA level at the time of radiation.

Intermittent androgen deprivation for patients with recurrent/metastatic prostate cancer.

This study was designed to assess the duration of response to intermittent androgen deprivation therapy (IAD) in patients with recurrent and/or metastatic prostate cancer. Between January 1993 and March 2000, 74 patients with recurrent and/or metastatic prostate cancer had IAD with either luteinizing hormone-releasing hormone agonist (LHRH) or an LHRH with an oral antiandrogen. Forty-one patients were treated for an increasing prostate-specific antigen (PSA) level after primary local treatment. Of the remaining 33 patients, 17 patients were treated for metastases (9 for bone metastases, 8 for lymph nodes metastases, and 16 for local recurrence). Patients who had undergone IAD completed between 1 and 6 cycles. A cycle was defined as the period during which the patient was actively taking the hormone medication. Seventy-four patients completed the first cycle, 49 completed the second cycle, and 23 completed the third cycle. The pattern of PSA changes with each cycle, the length of each cycle, and the time interval between successive cycles were studied. The time to progression (defined as an increasing PSA level on two consecutive measurements or radiologic evidence of progression of disease while the patient was on androgen deprivation) was also studied. The median PSA before the IAD was 11.4 ng/mL (range 0.12–378). The median PSA nadir at the end of each cycle increased progressively (0.1 ng/mL after the first cycle to 3.3 ng/mL after the fifth cycle). The time interval between the cycles progressively decreased from 9.5 months between the first and second cycles to 6 months between the third and fourth cycles. The 4-year actuarial androgen-independent free survival was 71%. For the subgroups of patients treated for biochemical failure, locoregional recurrence, and bone metastases, the 4-year actuarial progression-free survival rates were 80%, 67%, and 45% respectively (P = 0.018). The median time of 18 months to progression in patients with bone metastases is similar to that reported with continuous hormonal therapy. In patients with biochemical failure, the median time to progression (more than 5 years) suggests that the IAD approach may be a viable option for this group of patients.

The impact of race on biochemical disease-free survival in early stage prostate cancer patients treated with surgery or radiation therapy

PURPOSE To assess the impact of race on biochemical freedom from recurrence in patients with early-stage prostate cancer treated either by radical prostatectomy or radiation therapy. METHODS Between July 1989 and December 1994, 693 patients with early-stage prostate cancer were treated with radiation (302 patients) or by radical prostatectomy (391 patients) at Barbara Ann Karmanos Cancer Institute/Wayne State University. Stage, Gleason score, race, pretreatment PSA, and follow-up PSA values were abstracted. There were 387 Caucasian males (CM) and 306 African-American males (AAM). None of the patients received hormone therapy. Radiation therapy was delivered using photon irradiation (249 patients, median dose 69 Gy) or mixed neutron/photon irradiation (53 patients, median dose 10 NGy + 38 PGy). Median follow-up was 36 months (range 2-70) for CM and 35 months (range 1-70) for AAM. RESULTS Thirty-seven percent of patients treated surgically were AAM, compared to 53% in the radiation group (p = 0001). AAM had a higher median prostate-specific antigen (PSA) than CM (9.78 ng/ml vs. 8.0 ng/ml, p = 0.01). Thirty-three percent of AAM had a pretreatment PSA greater than 15 ng/ml compared to 20% of CM (p = 0.00001). Disease-free survival (DFS) by race was equivalent at 36 months, 81% for CM and 77% for AAM (p = NS). For patients with PSA < or =15, DFS rates were 87% and 85% for CM and AAM, respectively. DFS rates for patients with PSA >15 were 61% for CM and 64% for AAM (p = NS). Significant prognostic factors on multivariate analysis included pretreatment PSA (p = 0.0001) and Gleason score (p = 0.0001). CONCLUSION Race does not appear to adversely affect biochemical disease-free survival in males treated for early-stage prostate cancer. African-American males with early-stage prostate cancer should expect similar biochemical disease-free survival rates to those seen in Caucasian males.

Value of radiation therapy in the management of chemoresistant intermediate grade non-Hodgkin's lymphoma

The purpose of this study was to evaluate the probability and extent of response to radiation therapy in patients with chemotherapy-resistant intermediate grade non-Hodgkins lymphoma. Thirty-five patients with chemotherapy-resistant non-Hodgkins lymphoma received local radiation therapy after initial treatment with at least six cycles of systemic chemotherapy. There were 17 men and 18 women in our study. Ages ranged from 15 to 68 years, median age was 42 years. Chemotherapy resistance was defined as relapse after initial chemotherapy (11 patients) or failure to achieve complete remission (partial response in 18 patients, stable disease in 1 patient, and disease progression in 5 patients). Radiation doses were between 1,980-5,040 cGy (median dose of 3,200 cGy). Treatment outcome was evaluated with respect to any subsequent relapse either within or outside the irradiated region. The 2-year actuarial survival was 65%. The cumulative incidence of isolated local failure and any local failure at 2 years were 33% and 54%, respectively. Tumors that responded to initial chemotherapy had a better local control probability than tumors that did not respond. The 2-year actuarial local failure rates for these two groups were 51% and 83%, respectively (P = 0.01). There was a trend for improved local control with radiation doses > or = 3,960 cGy, suggesting the presence of a dose-control relationship. The rate of disease progression within an irradiated region in patients with intermediate grade non-Hodgkins lymphoma that relapsed after or failed to respond completely to full course chemotherapy was substantially higher than the historical in-field failure rates when radiation therapy was used as the sole modality of treatment. Prior response to initial chemotherapy was a predicting factor for local control following radiation therapy.

Radiation Improves Intratumoral Gene Therapy for Induction of Cancer Vaccine in Murine Prostate Carcinoma

Our goal was to convert murine RM-9 prostate carcinoma cells in vivo into antigen-presenting cells capable of presenting endogenous tumor antigens and triggering a potent T-helper cell-mediated immune response essential for the generation of a specific antitumor response. We showed that generating the major histocompatibility complex (MHC) class I+/class II+/Ii- phenotype, within an established subcutaneous RM-9 tumor nodule, led to an effective immune response limiting tumor growth. This phenotype was created by intratumoral injection of plasmid cDNAs coding for interferon gamma, MHC class II transactivator, and an antisense reverse gene construct (RGC) for a segment of the gene for Ii protein (-92,97). While this protocol led to significant suppression of tumor growth, there were no disease-free survivors. Nevertheless, irradiation of the tumor nodule on the day preceding initiation of gene therapy yielded 7 of 16 mice that were disease-free in a long-term follow up of 57 days compared to 1 of 7 mice receiving radiotherapy alone. Mice receiving radiotherapy and gene therapy rejected challenge with parental RM-9 cells and demonstrated specific cytotoxic T-cell activity in their splenocytes but not the mouse cured by radiation alone. These data were reproduced in additional experiments and confirmed that tumor irradiation prior to gene therapy resulted in complete tumor regression and specific tumor immunity in more than 50% of the mice. Increasing the number of plasmid injections after tumor irradiation induced tumor regression in 70% of the mice. Administering radiation before this novel gene therapy approach, that creates an in situ tumor vaccine, holds promise for the treatment of human prostate carcinoma.

Permanent Iodine-125 Interstitial Radiation Therapy in the Treatment of Non-Glioblastoma multiforme High-Grade Gliomas

Background: This study evaluates prognostic factors influencing survival outcomes for 60 patients with permanent iodine-125 implants in the primary treatment of non-glioblastoma multiforme (GBM) high-grade gliomas. Methods: Stereotactic treatment planning aimed to encompass the contrast-enhancing rim of the tumor visualized by CT, with an initial dose rate of 0.05 Gy/h with 125I, delivering 100 Gy at 1 year and 103.68 Gy at infinity. Survival was evaluated using the Kaplan-Meier method for univariate analysis and the Cox regressional method for multivariate analysis. In addition to the implant, 34 patients received external radiation therapy (5,000–6,000 cGy) before the implant; 13 patients were implanted without additional external beam radiation, and 13 patients underwent external radiation therapy before implant placement. Results: With a mean follow-up of 77.6 months (range 3.5–164 months), 1-, 3-, 5- and 10-year survival were 86.7% (±0.05%), 60% (±0.07%), 50% (±0.07%) and 45.7% (±0.7%), respectively. The median survival time was 57 months. Second surgery was performed following the implant in 19 patients. Findings were tumor recurrence in 11 patients (22.5%), radiation necrosis in 7 patients (14.3%) and brain abscess in 1 patient (2%). Age, sex, tumor location, side of brain, tumor volume, Karnofsky score and neurological status were correlated with survival outcome. Favorable prognostic factors were age younger than 45 years, superficial tumor location and preoperative Karnofsky score greater than 70. RPA classification was used to define this group of patients. In RPA classes I and II (n = 43), 1-year survival was 93%, while 3-, 5- and 10-year survival was 67.4, 60.5 and 55.5%, respectively, and median survival time was 91 months. In RPA class III (n = 7), 1-year survival was 71.4%, while 3- and 5-year survival was 42.9 and 28.6%, respectively, and median survival time was 47 months. In RPA class IV (n = 10), 1-year survival was 60%, while 3-, 5- and 10-year survival was 50, 22.2 and 11.1%, respectively, and median survival time was 37 months. Conclusion: Brachytherapy with permanent implant of 125I appears promising in the treatment of primary non-GBM malignant gliomas. It improved survival time and reduced the incidence of complications and provided good quality of life. In order to further confirm these results, multicenter randomized prospective studies are needed. RPA analysis is a valid tool to define prognostically distinct survival groups. In this study, 2-year survival and median survival time were improved in all prognostic classes. This would suggest that selection bias alone does not account for the survival benefit seen with 125I implants. Further randomized studies with effective stratification are needed.

Postneoadjuvant hormone PSA levels and prognosis in locally advanced prostate cancer

OBJECTIVES To determine whether the response to hormonal therapy before radiation predicts the rate of biochemical relapse in patients with locally advanced prostate cancer. METHODS Between October 1991 and December 1997, 105 patients with locally advanced adenocarcinoma of the prostate received radiotherapy in two dose-escalation studies. Sixty-seven patients received neoadjuvant hormonal therapy. The mean and median duration of hormonal therapy before radiotherapy was 4 months each. All treatments were designed using three-dimensional conformal therapy. The total dose to the gross tumor volume ranged from 73 to 87 Gy in 2 Gy per fraction photon equivalent dose. The median follow-up time was 30 months (range 1 to 66). RESULTS The median prostate-specific antigen (PSA) nadir after neoadjuvant hormonal therapy but before radiotherapy was 1.7 ng/mL (range less than 0.05 to 71.2). The median nadir after radiation for patients who did and did not receive neoadjuvant androgen deprivation was 0.25 ng/mL (range less than 0.05 to 6.2) and 1.35 ng/mL (range 0.08 to 10), respectively. Median time to achieve nadir was 6 months (range 1 to 42) with and 12 months (range 1 to 48) without hormonal therapy. There was no significant difference in the rate of biochemical failure for patients with a posthormone (before irradiation) PSA nadir less than 1 ng/mL versus 1 ng/mL or greater (overall P = 0.9). However, there was a significant difference in biochemical no evidence of disease rates between those with a PSA nadir less than 1 ng/mL and those with a PSA nadir of 1 ng/mL or greater after radiation (63% versus 22% at 3 years, overall P <0.001). CONCLUSIONS Our data showed that the initial response to hormonal therapy before radiation, as indicated by the PSA level, did not impact on the rate of recurrence. However, the time to reach nadir and the absolute nadir level achieved were lower in patients who did receive hormonal therapy.

γ-Knife Radiosurgery for Brainstem Lesions: The Wayne State University Experience

Stereotactic radiosurgery (SRS) is increasingly being used for tumors of the brainstem because it suits the anatomical constraints of this area. We now report on the 2-year experience at Wayne State University using γ-knife SRS for such lesions, with an emphasis on toxicity and morbidity. From January 1996 to January 1998, sixteen patients (6 males and 10 females) with lesions in the area of the brainstem were treated with SRS. Average age was 53 years (range 19–80). Nine lesions were malignant; 7 were benign. Median Karnofsky performance status (KPS) prior to SRS was 80 (range 50–100). Median follow-up period from initial diagnosis to analysis, and from the date of SRS to analysis, was 24 months (range 11–73) and 15 months (range 4–29), respectively. Results were analyzed for the whole population treated and then stratified by diagnosis: benign versus malignant. At analysis, 10 (62.6%) patients were alive and 6 (37.5%) were dead. No deaths followed SRS. Values for KPS prior to SRS were compared to 3 months post-SRS. No significant change in KPS scores could be observed for those with benign lesions, but 67% of patients with malignant tumors showed a KPS drop ≥30 points. There was no correlation between the treated volume and survival. At the time of review, no patients had developed new neurological symptoms after SRS. Results for benign lesions indicate that SRS is well tolerated, provides good local control, and does not cause unusual rates of morbidity or mortality. Results for malignant lesions demonstrate that pretreatment performance status influences the post-SRS values. The post-SRS Median Survival (MS) of 10 months for the Malignant Lesions (M) is impressive, in light of the drop of KPS observed; the outcome for such patients is likely determined by the activity of the primary disease process. Our results suggest that SRS in the brainstem is safe, feasible, and merits further study.