Biomedical subjects

J D Forman

Publications and source records attributed to J D Forman.

At least 37 records · Page 2Linked to original sources

PubMed1999

The cost-effectiveness of mixed beam neutron-photon radiation therapy in the treatment of adenocarcinoma of the prostate.

The results of clinical trials in the treatment of adenocarcinoma of the prostate using, mixed beam neutron/photon therapy, neutrons alone and photon therapy in combination with hormone treatment are compared. These trials indicate that neutron therapy is superior to photon/hormone therapy in achieving local control. The costs of delivering these two different therapies in a large US academic radiation oncology center at Wayne State University (WSU) are compared. The cost of a full course of mixed beam therapy is $20,142 compared to $18,871 for the photon/hormone treatment. Although the WSU neutron facility is a state-of-the-art installation, it is also a prototype device; it is estimated that a modern neutron facility based on this design would operate more cost effectively reducing the cost of a course of mixed beam therapy to $18,532.

Adenocarcinoma↗

PubMed1999

Urinary diversion-related outcome in patients with pelvic recurrence after radical cystectomy for bladder cancer.

OBJECTIVES: To evaluate the impact of urinary diversion on disease status, complications, and subsequent treatment in patients with pelvic tumor recurrence after radical cystectomy for bladder cancer. METHODS: A retrospective review of 201 consecutive cases of radical cystectomy for bladder cancer, performed at our institution between March 1991 and March 1996, identified 33 patients (16.4%) with disease recurrence in the pelvis with or without systemic metastasis. Urinary diversion in patients with tumor recurrence was an ileal conduit, continent cutaneous diversion, or orthotopic neobladder in 19, 3, and 11 patients, respectively. The mean follow-up for all patients undergoing cystectomy was 25.9 months (range 8 to 75). The mean time to diagnosis of local disease recurrence after cystectomy was 13.9 months (range 5 to 50). RESULTS: In 21 (63.6%) of 33 patients, pelvic recurrence and systemic metastasis were present simultaneously. Disease recurrence was associated with poor outcome: only 8 patients (24.2%) were alive and disease free, 7 of whom had isolated local recurrence without evidence of systemic metastasis. There was no difference in overall survival or type of therapy delivered once disease recurrence was diagnosed between patients with an orthotopic neobladder and those with a cutaneous (continent or incontinent) urinary diversion. The only diversion-related complication resulting from pelvic recurrence was 1 case of tumor invasion into an orthotopic neobladder, requiring conversion to an ileal conduit. CONCLUSIONS: The type of urinary diversion did not impact a patient's risk of complications, the ability to receive salvage treatment, or overall survival once pelvic recurrence was diagnosed. Patients at high risk of pelvic recurrence should not be excluded from receiving an orthotopic urinary diversion.

Adult↗

PubMed1999

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.

Actuarial Analysis↗

PubMed1999

Radiation therapy for a rising PSA level after radical prostatectomy.

With the advent of routine prostate-specific antigen (PSA) testing in asymptomatic young men, the number of patients undergoing radical prostatectomy is increasing. Effective therapy for the 30% to 40% of men who recur following radical prostatectomy is essential. Salvage radiation therapy for a rising serum PSA level is an effective therapy for controlling local recurrence. The impact of salvage radiotherapy on disease-free survival is promising, but the guidelines of therapy are not well established. The best candidates for salvage radiotherapy are those with a serum PSA level < 2 ng/mL with no palpable recurrence and complete urinary continence.

Humans↗

PubMed1998

Predicting the outcome of radiotherapy for prostate carcinoma: a model-building strategy.

BACKGROUND: Clinical research of prostate carcinoma could be enhanced by models that allow early and reliable prediction of outcome. In this study, the authors describe a model-building strategy and compare different models. METHODS: The sample population was comprised of 158 patients treated definitively with radiotherapy. Univariate and multivariate logistic regression analyses were conducted to identify prognostic factors and select the best predictive model. Variables included age, race, method of diagnosis (needle biopsy vs. transurethral resection of the prostate), stage, grade, pretreatment prostate specific antigen (PSA), in-treatment PSA (PSA(tx)), posttreatment PSA (PSA(post)), and nadir PSA. The following indices were used to compare discriminatory power: log-likelihood function, Akaike information criterion, the generalized coefficient of determination, and the area under the receiver operating characteristic curve. RESULTS: At last follow-up, 49 patients (31%) had recurrence of carcinoma. By univariate analysis, the failure rate was significantly higher in patients with advanced stage, higher grade, higher pretherapy PSA, and nadir PSA > 1 ng/mL (P < 0.0001). Pretherapy PSA was associated significantly with stage, age, and nadir PSA (P = 0.001, P = 0.001, and P = 0.001, respectively). All PSA measurements were significantly interrelated. Nadir PSA was the most predictive variable. Significant gains (P = 0.01) in predictive power were derived from inclusion of PSA(tx), but not PSA (post). Age, race, stage, grade, and method of diagnosis contributed predictive power in addition to that derived from PSA levels (P = 0.01, log-likelihood test). The authors' model of choice predicts outcome with an overall correctness, sensitivity, specificity, and false-negative rate of 81.8%, 87.2%, 79.6%, and 12.8%, respectively. CONCLUSIONS: Applying the strategy described, a model was selected that allowed accurate prediction of failure shortly after the completion of therapy.

Aged↗

PubMed1998

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.

Disease-Free Survival↗

PubMed1998

Therapeutic radiation in patients with a rising post-prostatectomy PSA level.

The optimal management of patients with an elevated post-prostatectomy prostate-specific antigen (PSA) level remains to be determined. In the pre-PSA era, many patients received immediate adjuvant radiation therapy on the basis of adverse pathologic features following prostatectomy. However, since the advent of postoperative PSA monitoring, the PSA level has become the most specific measure for determining the presence of residual disease. An elevated postoperative PSA in correlation with other factors, such as pathologic stage and imaging studies, can be a specific marker of local recurrence in most patients. Through careful case selection, treatment design, and dose delivery, up to 80% of patients can achieve a complete response (PSA < 0.1 ng/mL) following postoperative therapeutic irradiation for an elevated PSA. This treatment can be delivered with minimal toxicity to the rectum and minimal risk of increasing incontinence. Pending the results of randomized trials, an appropriate therapeutic option for high-risk patients following prostatectomy would be to wait for an elevated PSA and then proceed with a course of potentially curative radiotherapy.

Disease-Free Survival↗

PubMed1998

The influence of race on the efficacy of curative radiation therapy for carcinoma of the prostate.

The purpose of this study was to examine the effect of race on the outcome of patients treated curatively with external beam irradiation for carcinoma of the prostate. The study was performed between January 1980 and December 1993 of 1,529 men with prostate cancer. Similar percentages of Caucasian men (CM) and African-American men (AAM) had localized disease (stages T1 and T2) and advanced stage disease (stage T3). There was no difference in crude survival by race (P = .13). At 5 years, crude survival by race was 75% for CM and 73% for AAM. At 10 years, the crude survivals, were 50% and 40%, respectively. Disease-specific survival rates were equivalent for AAM and CM (P = .66). The 5-year disease-specific survival was 83% for CM and 85% for AAM. At 10 years, the disease-specific survival was 65% for CM and 69% for AAM. There was no difference in disease-specific survival by race when stage-for-stage comparisons were made. Among those patients referred for curative radiation therapy, AAM and CM had a similar age, stage, and grade distribution. This study demonstrated that there was no difference in disease-specific survival between CM and AAM treated curatively with radiation for prostate cancer.

Adult↗

PubMed1997

Enhancement of prostate tumor volume definition with intravesical contrast: a three-dimensional dosimetric evaluation.

PURPOSE: To assess the impact of intravesical contrast during computed tomography (CT) simulation on prostate tumor volume definition and dose distribution. METHODS AND MATERIALS: Sixteen patients with localized adenocarcinoma of the prostate underwent CT-based virtual simulation in preparation for definitive radiotherapy. Patients were immobilized with a foam cradle and an initial CT was performed after oral but without intravesical contrast (noncontrast scan). A second scan was performed following administration of intravesical contrast (contrast scan). Beam apertures were designed on the noncontrast scans and digitized into the contrast scan file. Beam apertures were also designed on the contrast scans. Isodose plans were generated for several beam apertures and arrangements. RESULTS: There was enhanced visualization of the prostate at the cephalad portion of the field for 15 of the 16 cases. The mean differences between the noncontrast and contrast volumes was significant (p = 0.0001). The mean percent underdosage to the prostate ranged from 3.9% to 18.6%, depending upon the target volume and beam arrangement. CONCLUSION: This study demonstrates the necessity of using intravesical contrast for defining the location of the prostate during CT simulation. The underestimation of the extent of the prostate when omitting intravesical contrast leads to significant underdosage. The value of intravesical contrast is most evident when small (prostate only) conformal fields are used.

Adenocarcinoma↗

PubMed1997

p53 status and prognosis of locally advanced prostatic adenocarcinoma: a study based on RTOG 8610.

BACKGROUND: The p53 tumor suppressor gene (also known as TP53) is one of the most frequently mutated genes in human cancer. Several studies have shown that p53 mutations are infrequent in prostate cancer and are associated with advanced disease. PURPOSE: We assessed the prognostic value of identifying abnormal p53 protein expression in the tumors of patients with locally advanced prostate cancer who were treated with either external-beam radiation therapy alone or total androgen blockade before and during the radiation therapy. METHODS: The study population consisted of a subset of patients entered in Radiation Therapy Oncology Group protocol 8610 ("a phase III trial of Zoladex and flutamide used as cytoreductive agents in locally advanced carcinoma of the prostate treated with definitive radiotherapy"). Immunohistochemical detection of abnormal p53 protein in pretreatment specimens (i.e., needle biopsies or transurethral resections) was achieved by use of the monoclonal anti-p53 antibody DO7; specimens in which 20% or more of the tumor cell nuclei showed positive immunoreactivity were considered to have abnormal p53 protein expression. Associations between p53 protein expression status and the time to local progression, the incidence of distant metastases, progression-free survival, and overall survival were evaluated in univariate (logrank test) and multivariate (Cox proportional hazards model) analyses. Reported P values are two-sided. RESULTS: One hundred twenty-nine (27%) of the 471 patients entered in the trial had sufficient tumor material for analysis. Abnormal p53 protein expression was detected in the tumors of 23 (18%) of these 129 patients. Statistically significant associations were found between the presence of abnormal p53 protein expression and increased incidence of distant metastases (P = .04), decreased progression-free survival (P = .03), and decreased overall survival (P = .02); no association was found between abnormal p53 protein expression and the time to local progression (P = .58). These results were independent of the Gleason score and clinical stage. A significant treatment interaction was detected with respect to the development of distant metastases: Among patients receiving both radiation therapy and hormone therapy, those with tumors exhibiting abnormal p53 protein expression experienced a reduced time to the development of distant metastases (P = .001); for patients treated with radiation therapy alone, the time to distant metastases was unrelated to p53 protein expression status (P = .91). CONCLUSIONS: Determination of p53 protein expression status yield significant, independent prognostic information concerning the development of distant metastases, progression-free survival, and overall survival for patients with locally advanced prostate cancer who are treated primarily with radiation therapy. IMPLICATIONS: The interaction of radiation therapy plus hormone therapy and abnormal p53 protein expression may provide a clinical link to experimental evidence that radiation therapy and/or hormone therapy act, at least in part, by the induction of apoptosis (a cell death program) and suggests that this mechanism may be blocked in patients whose tumors have p53 mutations.

Adenocarcinoma↗

PubMed1997

Musculoskeletal complications of neutron therapy for prostate cancer.

The purpose of this study was to investigate the cause of hip complaints following conformal neutron therapy delivered by opposed lateral and oblique anterior ports to treat prostate cancer. Twenty-seven patients with hip complaints following neutron or mixed neutron and photon therapy for prostate cancer had 34 magnetic resonance imaging (MRI) studies 3-39 (mean 15.3) months following treatment; for comparison, 13 similarly treated patients without hip complaints were imaged 1-32 (mean 13.8) months post-treatment; 25/40 imaged patients received concurrent nonsteroidal hormone therapy. Coronal and axial images of the hips/pelvis were obtained utilizing T1 weighted spin echo and fat suppressed inversion recovery (STIR) sequences. Signal amplitude (SA) of involved muscles was measured on the STIR images and normalized to that of the psoas outside the treatment field. Hip complaints ranged from mild soreness or motion limitation to severe pain and limitation of ambulation; presence and severity of symptoms (sx) were significantly related to neutron dose (P = 0.020 and 0.0001) but not to hormone therapy (each P > 0.17). Normalized SA of the obturator muscles differed significantly with neutron dose (P = 0.013), the presence, and the severity, of sx (P = 0.0002 and 0.0007); estimated extent of abnormal muscle also differed significantly with neutron dose (P = 0.039), presence, and severity, of sx (P = 0.00004 and 0.0007); [hormone treatment had a profound effect on SA (P = 0.0001) and extent (P = 0.005) which was independent of sx (P = 0.10 and 0.14, respectively) and neutron dose (P = 0.33 and 0.32, respectively)]. Subcutaneous changes localized lateral to the greater trochanter were seen in all, and edema of the subjacent gluteus muscles in many, symptomatic hips; only 4/13 asymptomatic hips showed subcutaneous changes, 6 had mild gluteus edema. Avascular necrosis of the femoral head was seen in 5 symptomatic hips, with marked acetabular necrosis in 3 of these; small joint effusions were seen in 8 symptomatic hips; asymptomatic hips had no significant bone or joint abnormalities. Neutron therapy for prostate cancer designed to spare the rectum results in significant dose-dependent, musculoskeletal complications which are well demonstrated by MRI. SA abnormalities of irradiated muscle correlate significantly with neutron dose and both presence and severity of hip sx. Protocol modifications have been implemented to reduce these complications. MRI provides an objective means to assess both complications and the success of new protocols in ameliorating them. Concurrent hormone therapy has a profound effect on muscle changes on MRI which is independent of neutron dose and sx.

Adipose Tissue↗

PubMed1997

Patient self-assessment of complications and quality of life after conformal neutron and photon irradiation for localized prostate cancer.

Although neutron irradiation for prostate cancer has been associated with significant morbidity, pilot data in patients with early stage disease suggested that conformal neutron and photon irradiation was well tolerated without severe complications. A self-assessment questionnaire was mailed to the first 83 patients treated with conformal neutron and photon irradiation to objectively evaluate the impact on quality of life of this regimen. In total, 75 patients (90%) returned the completed questionnaire. These patients had received either 9 neutron Gy (N Gy) plus 38 photon Gy (50 patients) or 10 N Gy plus 38 photon Gy (33 patients) for stage T1/T2 N0 M0 prostate cancer (Gleason score < or = 7). The irradiated volume included the prostate and seminal vesicles with a 1.5 cm margin. Neutrons were delivered as a boost to the prostate only with a non-axial four field beam arrangement. Approximately 50% of the dose to the prostate was from neutron irradiation. Follow-up ranged from 6 to 25 months (median 13 months). The questionnaire used was a validated quality of life instrument used previously in patients treated with surgery or radiation. Prior to irradiation, 29% of patients reported urinary symptoms and 11% had prostate surgery (TURP). At follow-up, 23% reported persistent urinary symptoms. Of these, 21% dripped a few drops of urine, 3% used pads but none leaked > 1 tablespoon/day. One patient underwent surgery to dilate a urethral stricture. Although 55% of patients had gastrointestinal symptoms during radiation therapy, only 26% had persistent symptoms at the time of questioning. These included minor rectal bleeding in 20% and significant hematochezia in 3%. Of the 85% of patients able to obtain full or partial erections prior to irradiation, 87% maintained their potency. Fifteen percent sought treatment for impotence. Overall, at last follow-up, 84% felt little or no physical discomfort, 91% were very satisfied with their treatment, and 97% would choose radiation therapy again. This patient self-assessment questionnaire confirmed that this regimen of conformal neutron and photon irradiation resulted in levels of chronic toxicity acceptable to the patient.

Abdominal Pain↗

PubMed1997

Outcome analysis of penile implant surgery after external beam radiation for prostate cancer.

PURPOSE: We evaluated the success and possible complication rates of penile implant surgery in patients who underwent external beam radiation therapy for prostate cancer. MATERIALS AND METHODS: We reviewed the charts of 43 patients who underwent penile implant surgery after radiation therapy for prostate cancer. The type, dose and volume of radiation were assessed. The types of surgical approach and prosthesis as well as complications were recorded. A total of 34 patients was alive and traceable, and 9 were untraceable (7 dead and 2 missing). The 34 traceable patients were interviewed personally or by telephone to evaluate the function of and satisfaction with the penile implant. Followup of the 9 untraceable patients was assessed through a chart review. RESULTS: A total of 35 patients (81%) received definitive radiation therapy to the prostate and seminal vesicles, and 8 (19%) underwent radical retropubic prostatectomy followed by radiation therapy to the prostatic bed. Mean age at implant surgery was 67 years (range 36 to 83). In the 43 men 46 procedures were done and mean followup was 40 months. None of the patients in this series had infection or erosion. Of the men 24 (71%) use the prosthesis at least once weekly or more for sexual intercourse, 6 (17%) use it twice monthly, 4 (12%) are not sexually active despite a functioning implant, 2 are not sexually active because of a lack of sexual partners, and 2 are not satisfied with the implant and would not recommend this device. Discomfort from the penile implant was reported by 2 patients, although they currently use the implant for intercourse at least twice weekly. CONCLUSIONS: Penile prosthesis surgery can be safely and effectively performed after radiation therapy with minimal intraoperative and postoperative complications, and an excellent patient satisfaction rate.

Adult↗

PubMed1997

Differences in dosimetry and toxicity between definitive and postprostatectomy radiation therapy.

PURPOSE: To compare the volumes of normal tissue irradiation and toxicity in patients treated with definitive radiation therapy or postprostatectomy radiation therapy. MATERIALS AND METHODS: Results were analyzed prospectively in 49 patients who underwent definitive or postprostatectomy radiation therapy after three-dimensional conformal treatment planning. Dose-volume histograms and the effective area irradiated were analyzed. Patient charts were reviewed and scored for acute and chronic toxicity. The mean bladder volume was 200 mL in the definitive group and 226 mL in the postprostatectomy group. The mean rectal volume was 87 mL in the definitive group and 81 mL in the postprostatectomy group. RESULTS: The dose to 25% of the rectal volume was 91% and 86% in the definitive and postprostatectomy groups, respectively. The dose to 25% of the bladder volume was 89% in the definitive group and 82% in the postprostatectomy group. The incidence of acute and chronic gastrointestinal and chronic genitourinary toxicity was similar in both groups, but acute genitourinary toxicity in the postprostatectomy group was significantly lower (P = .026). The volume of normal tissue irradiated was similar in both groups. Also, similar doses were delivered to the normal tissue. CONCLUSION: Differences in acute genitourinary toxicity are most likely secondary to radiation-induced prostatitis. Postprostatectomy radiation therapy is safe and is not associated with increased toxicity.

Acute Disease↗

PubMed1997

Therapeutic irradiation for patients with an elevated post-prostatectomy prostate specific antigen level.

PURPOSE: This study was initiated to determine the efficacy of post-prostatectomy therapeutic radiation for patients with elevated prostate specific antigen (PSA). MATERIALS AND METHODS: A total of 47 patients received 66 Gy. therapeutic irradiation to the prostate bed for a PSA level greater than 0 ng./ml. postoperatively. Univariate and multivariate survival analyses were performed to identify prognostic variables. RESULTS: At a median followup of 36 months (range 18 to 48) 83 and 33% of the patients with PSA 2 ng./ml. or less and 2 ng./ml. or greater, respectively, had no evidence of disease (p = 0.001). Pathological stage and a complete biochemical response (PSA less than 0.05 ng./ml.) were also significant prognostic variables. CONCLUSIONS: Therapeutic irradiation for patients with elevated PSA postoperatively is highly effective. At a median followup of 36 months 64% of the patients remain disease-free.

Actuarial Analysis↗

PubMed1997

The experience with neutron irradiation in locally advanced adenocarcinoma of the prostate.

Patients with locally advanced adenocarcinoma of the prostate, defined as those with extraprostatic disease, a Gleason score of 7 or higher, or a PSA of 15 ng/mL or higher, have a significantly worse prognosis with standard external beam radiotherapy. Post-treatment PSA and biopsy data confirm that most patients have residual local disease as a component of failure in most cases. Two randomized trials of neutron irradiation mixed with photon irradiation and neutron irradiation alone compared with standard photon irradiation to a dose of 70 cGy have both confirmed an improvement in the disease-free survival of patients treated with neutron irradiation. The high complication rate in the second study and the limited number of neutron facilities led to a dramatic decline in the utilization of neutrons in prostate cancer. However, at Wayne State University, using a super conducting cyclotron, a number of clinical studies have been performed to demonstrate the safety and efficacy of neutron irradiation. Chronic complication rates have been low. Biochemical freedom from relapse rates have been excellent. For patients with a pretreatment PSA <10 ng/mL, 10 to 20 ng/mL or >20 ng/mL, 92%, 85%, and 38% of patients have no evidence of disease at 4 years. Thus, neutron irradiation has been proven to be a safe method of dose intensification that can lead to a significant improvement in the overall outcome of patients with nonmetastatic adenocarcinomas of the prostate.

Adenocarcinoma↗

PubMed1996

Results of a phase II trial of external beam radiation with etanidazole (SR 2508) for the treatment of locally advanced prostate cancer (RTOG Protocol 90-20).

PURPOSE: RTOG Protocol 90-20 was designed to evaluate the effect of the hypoxic cell sensitizer Etanidazole (SR-2508) on locally advanced adenocarcinoma of the prostate treated with concurrent external beam irradiation. METHODS AND MATERIALS: Patients with biopsy-proven adenocarcinoma of the prostate with locally advanced T2b, T3, and T4 tumors were eligible for this study. No patients with disease beyond the pelvis were eligible. Serum prostate specific antigen (PSA) was mandatory. All patients received definitive external beam irradiation using standard four-field whole pelvis treatment to 45-50 Gy, followed by a cone down with a minimum total dose to the prostate of 66 Gy at 1.8-2.0 Gy/fraction over 6.5-7.5 weeks. Etanidazole was delivered 1.8 g/m2 given 3 times a week to a total of 34.2 g/m2 or 19 doses. RESULTS: Thirty-nine patients were entered onto the study. Three patients refused treatment; therefore, 36 patients were eligible for further evaluation. Median follow-up was 36.9 months from treatment end. All patients had elevated initial PSA levels, and 18 patients had PSAs of > 20 ng/ml. Tumor classification was T2, 12 patients (33.3%); T3, 22 patients (61.1%); and T4, 2 patients (5.6%). Complete clinical response, defined as PSA < 4 ng/ml and complete clinical disappearance, was attained in 17.9% of (5/28 pts) with information at 90 days and 56% of patients by 12 months following treatment. Relapse-free survival was 13% at 3 years with PSA < 4 ng/ml. There were no Grade 4 or 5 toxicities, either acute (during treatment) or in follow-up. CONCLUSIONS: Results of this trial regarding PSA response and clinical disappearance of disease are similar to historical controls and do not warrant further investigation of etanidazole as was done in this trial. Drug toxicity that, in the past, has been unacceptably high with other hypoxic cell sensitizers does not appear to be a significant problem with this drug.

Adenocarcinoma↗

PubMed1996

Potency following conformal neutron/photon irradiation for localized prostate cancer.

PURPOSE: To assess the effect of conformal neutron/photon irradiation with or without neoadjuvant hormonal therapy on posttreatment potency. MATERIALS AND METHODS: Seventy-six patients with localized adenocarcinoma of the prostate, State T1 or T2 N0 M0, Gleason score < or = 7, were enrolled on a prospective Phase II study. Each patient received 9-10 Neutron + 38 Photon Gy. Twenty-eight patients received neoadjuvant hormonal therapy in conjunction with radiation therapy. Potency was assessed prior to starting treatment and was assessed at each subsequent follow-up visit. RESULTS: Fifty-two of patients (70%) were potent at the start of therapy. Thirty-eight of 52 (73%) had functional erections and 14 of 52 (27%) had erections termed nonfunctional, which were of insufficient strength for intercourse. After treatment, 35 of 52 (67%) retained potency. Twenty-nine of 38 (76%) with functional erections pretreatment maintained this ability. Only 6 of 14 patients (43%) with nonfunctional erection pretreatment maintained their level of potency. Neoadjuvant hormonal therapy did not impact on the ability to maintain erections. Sixty-five percent of those patients receiving hormones retained erectile function, while 69% of those who did not receive hormones maintained erectile function. Age was not a significant factor in posttreatment potency, although a trend towards potency in younger patients was observed. (p = 0.74). CONCLUSION: The majority (67%) of patients maintained their level of erectile function following conformal sequential neutron photon irradiation. This is comparable to that achieved with photon irradiation alone. No significant change in potency was seen with neoadjuvant hormonal therapy or with increasing patient age.

Adenocarcinoma↗