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Eric M Horwitz

Publications and source records attributed to Eric M Horwitz.

At least 37 records · Page 2Linked to original sources
PubMed2005

Role of prostate dose escalation in patients with greater than 15% risk of pelvic lymph node involvement.

PURPOSE: To determine whether the radiation dose is a determinant of clinical outcome in patients with a lymph node risk of >15% treated using whole pelvic (WP), partial pelvic (PP), or prostate only (PO) fields. METHODS AND MATERIALS: A total of 420 patients with prostate cancer treated with three-dimensional conformal radiotherapy with or without short-term androgen deprivation (STAD) between June 1989 and July 2000 were included in this study. Patients had an initial pretreatment prostate-specific antigen level of <100 ng/mL and a lymph node index of > or =15% or T2c tumors with a Gleason score of 6-10. No patient had radiologic evidence of lymph node involvement. Of the 460 patients, 48 were treated with PO, 74 with PP, and 298 with WP fields. The median prostate dose was 74 Gy for PO, 82 Gy for PP, and 76 Gy for WP. The median radiation dose to the pelvis was 46 Gy for both PP and WP. Of the 460 patients, 72 underwent STAD for a median of 3 months (range, 3-6 months). Cox regression multivariate analysis was used to identify independent predictors of freedom from biochemical failure (FFBF) defined according to the American Society for Therapeutic Radiology Oncology consensus guidelines. Univariate comparisons were done using the Kaplan-Meier method and the log-rank test. RESULTS: At a median follow-up of 43 months, 121 patients had treatment failure: 22, 7, and 92 in the PO, PP, and WP arms, respectively. Independent predictors of FFBF in multivariate analysis included radiation dose, T stage, Gleason score, and initial prostate-specific antigen level. The 5-year FFBF rate by dose group was 48% for <73 Gy, 64% for 73-76.9 Gy, and 74% for > or =77 Gy (p = 0.002). The use of STAD and radiation field size were not significantly associated with FFBF. CONCLUSION: The radiation dose was the most significant determinant of FFBF in patients with a lymph node risk >15% in the patient population studied. These data suggest that the primary tumor takes precedence over lymph node coverage or the use of STAD. Doses >70 Gy are of paramount importance in such intermediate- and high-risk patients.

Aged↗
PubMed2005

Toxicity and outcome analysis of patients with recurrent head and neck cancer treated with hyperfractionated split-course reirradiation and concurrent cisplatin and paclitaxel chemotherapy from two prospective phase I and II studies.

BACKGROUND: Patients with local recurrences or new head and neck primary tumors in previously irradiated tissues have few options for salvage treatment. One option for select patients is to undergo reirradiation with concurrent chemotherapy. The purpose of this study is to report the initial clinical results of the Fox Chase phase I and II prospective reirradiation and chemotherapy studies. METHODS: Between July 1996 and January 2002, 38 patients with locally recurrent unresectable squamous cell carcinoma of the head and neck were treated with concurrent chemotherapy and reirradiation on two prospective trials. All patients had received prior radiation therapy to the head and neck region (median dose, 64.2 Gy). Patients received cisplatin and paclitaxel along with hyperfractionated external beam radiation therapy to the site of recurrence. RESULTS: The median follow-up was 10 months. The median survival was 12.4 months, with actuarial rates of overall survival of 50% and 35% at 1 and 2 years, respectively. During follow-up, 63% of patients experienced local progression of disease, all in the irradiated field. Actuarial progression-free survival at 1 year was 33%, with a median time to progression of 7.3 months. Acute grade 3 to 4 toxicity included neutropenia, nausea, emesis, and mucositis. CONCLUSIONS: Hyperfractionated split-course reirradiation and concurrent cisplatin and paclitaxel chemotherapy demonstrates durable locoregional control in select patients, although late toxicity may occasionally be significant. Only sites of disease recurrence need to be covered in the reirradiation fields.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2005

Definitions of biochemical failure that best predict clinical failure in patients with prostate cancer treated with external beam radiation alone: a multi-institutional pooled analysis.

PURPOSE: Pooled data on 4,839 patients with T1-2 prostate cancer treated with external beam radiation therapy (RT) alone at 9 institutions have previously provided long-term biochemical failure (BF) and clinical outcomes using the American Society for Therapeutic Radiology and Oncology (ASTRO) definition. In this report we determined the sensitivity and specificity of several BF definitions using distant failure (DF) alone or clinical failure (CF), defined as local failure (LF) and/or DF. MATERIALS AND METHODS: The pooled cohort was treated between 1986 and 1995 with external beam RT (60 Gy or greater) without pre-RT androgen suppression or planned post-RT adjuvant androgen suppression. Median followup was 6.3 years. The sensitivity and specificity of 102 definitions of BF relative to DF and LF were assessed. RESULTS: The BF definitions with higher sensitivity and specificity than the ASTRO definition for DF only and CF are reported. The sensitivity and specificity of the ASTRO definition to predict DF alone was 55% and 68%, respectively. Three definitions had higher sensitivity and specificity, namely prostate specific antigen (PSA) greater than current nadir (lowest PSA prior to current measurement) plus 3 ng/ml (sensitivity 76% and specificity 72%), dated at the call (failure date as the date when the criterion was met), PSA greater than absolute nadir plus 2 ng/ml (sensitivity 72% and specificity 70%), dated at the call, or 2 consecutive increases of at least 0.5 ng/ml, back dated (sensitivity 69% and specificity 73%). The sensitivity and specificity of the ASTRO definition to predict CF was 60% and 72%, respectively. Three definitions had higher sensitivity and specificity, namely PSA greater than current nadir plus 3 ng/ml (sensitivity 66% and specificity 77%), dated at the call, PSA greater than absolute nadir plus 2 ng/ml (sensitivity 64% and specificity 74%), dated at the call, or 2 consecutive increases of at least 0.5 ng/ml, back dated (sensitivity 67% and specificity 78%). CONCLUSIONS: Using what is to our knowledge the largest data set of patients with prostate cancer treated with RT alone we correlated multiple definitions of BF with the strict clinical end points of DF alone and CF (DF or local failure). Defining BF as PSA greater than absolute nadir plus 2 ng/ml, dated at the call, PSA greater than current nadir plus 3 ng/ml, dated at the call, or 2 consecutive increases of at least 0.5 ng/ml, back dated, had higher sensitivity and specificity for DF alone or CF compared with the ASTRO definition. This information should contribute to the discussion regarding suggested modifications to the ASTRO definition of biochemical failure.

Adult↗
PubMed2004

The radiation doses to erectile tissues defined with magnetic resonance imaging after intensity-modulated radiation therapy or iodine-125 brachytherapy.

PURPOSE: To report penile bulb (PB) and corporal bodies (CB) doses during intensity-modulated radiation therapy (IMRT) and permanent (125)I prostate implant alone (BT) for favorable, early stage, clinically localized prostate cancer using computed tomography (CT) and magnetic resonance imaging (MRI) to provide a basis for comparison as the initial report of a comprehensive project to develop erectile tissues sparing techniques. METHODS AND MATERIAL: Prostate, PB and CB volumes were defined by a fused CT/MRI simulation study performed before treatment in 29 IMRT patients and verification study performed 30 days postimplant in 15 BT patients. The median prescribed prostate dose for the IMRT and BT groups was 74 Gy and 145 Gy, respectively. Dose volume histograms (DVHs) were generated to determine the dose characteristics for the PB, CB, and prostate for each patient. D(90), V(100), and V(50) were used, where D(i) was defined as the dose that covers i% of the prostate volume and V(i) is the fractional volume of the prostate that receives i% of the prescribed dose. The Wilcoxon rank sum test was used to evaluate significance between the groups. RESULTS: The median PB D(90), V(100), and V(50) values were 17.5 Gy, 0%, and 31.9% for the IMRT group; and 52.5 Gy, 21.5%, and 89.7% for the BT group. The median CB D(90), V(100), and V(50) values were 7.3 Gy, 0%, and 0.9% for the IMRT group; and 26.9 Gy, 2.4%, and 20.1% for the BT group. The differences between the IMRT vs. BT V(100) values, but not V(50), were statistically significant for the PB (p = 0.001) and CB (p = 0.001). CONCLUSIONS: Radiation dose to the PB and CB is low with IMRT or BT. Magnetic resonance imaging is superior to CT for the imaging of erectile tissues. Intensity-modulated radiation therapy may offer further reductions in the doses received by the PB and CB; however, at what cost to prostate coverage and normal tissue sparing will be the subject of a follow-up study.

Aged↗
PubMed2004

A comparison of the single and double factor high-risk models for risk assignment of prostate cancer treated with 3D conformal radiotherapy.

PURPOSE: Two models for stratification of prostate cancer aggressiveness predominate for the purposes of daily treatment decision making. This study investigates the relationships between these two clinically popular models. METHODS: Both risk stratification models use the same definition for low risk: Gleason score (GS) 10-20 ng/mL, without the presence of any high-risk feature; high risk (HR) was defined as the presence of GS 8-10, iPSA >20, or palpation stage T3. For the double factor high risk (DF) model, IR and HR were defined as one and more than one of the following: GS >or=7, iPSA >10, or stage T3. Between April 1989 and October 2001, 1,597 patients were treated definitively with 3D conformal radiation therapy (3D-CRT) alone for prostate cancer at our institution. The main clinical endpoint was freedom from biochemical failure (FFBF). RESULTS: The 5-year actuarial FFBF rate for the low-risk group was 83%. The SF model resulted in FFBF rates of 76% and 47% for IR and HR patients respectively. The DF model resulted in FFBF rates of 70% and 52% for IR and HR patients, respectively. The FFBF rate for patients defined as IR and HR by both models was 76% and 40%, respectively. Those classified as IR by the DF model and then further subdivided into IR and HR by the SF model had a 76% and 52% 5-year FFBF rate (p = 0.0004). Those classified as HR by the DF model and then further subdivided into IR and HR by the SF model had a 71% and 40% 5-year FFBF (p = 0.0014). CONCLUSIONS: The SF model created prognostic groups with a greater internal consistency than the DF model. The SF was also better at identifying patients with high-risk prostate cancer who may benefit from a more aggressive approach.

Aged↗
PubMed2004

Intensity-modulated radiotherapy with MRI simulation to reduce doses received by erectile tissue during prostate cancer treatment.

PURPOSE: The radiation doses received by erectile tissue may contribute to erectile dysfunction after treatment of prostate cancer. This is the first description of the ability to limit the dose received by the penile bulb (PB) and corporal bodies (CB) using intensity-modulated radiotherapy (IMRT). METHODS AND MATERIALS: Twenty-three patients with palpation Stage T1c-T2bN0M0 prostate cancer received IMRT alone. The dose prescribed to the planning target volume was 74-78 Gy. All patients underwent CT and MRI simulation to define the target and normal structures. Three plans with identical beam arrangements and energy were generated for each patient, with varying dose constraints for the PB and CB: no dose constraint, intermediate-dose constraint (20 Gy and 15 Gy, respectively) and low-dose constraint (15 Gy and 7 Gy, respectively). All plans were normalized, such that 95% of the planning target volume received at least 100% of the prescribed dose. For each plan, the ability to meet prostate dose homogeneity criteria (PHC; prostate maximal dose </=120% prescribed dose) and rectal tolerance dose-volume histogram criteria (RTC; </=35% and </=17% of rectal volume received 40 Gy and 65 Gy, respectively) was determined. The D(90), V(50), and V(75) were determined for both PB and the CB, where D(i) was the dose received by i% of the target volume and V(i) was the target volume receiving i% of the prescribed dose. RESULTS: The median PB D(90), V(50), and V(75) for the plans with no dose, intermediate-dose, and low-dose constraints was 20.8 Gy, 33.8%, and 9.9%; 8.0 Gy, 1.7%, and 0%; and 7.1 Gy, 0.1%, and 0%, respectively. The median CB D(90), V(50), and V(75) for plans with no dose, intermediate-dose, and low-dose constraints was 10.2 Gy, 3.8%, and 0%; 6.0 Gy, 0%, and 0%; and 4.9 Gy, 0%, and 0%, respectively. Overall differences in the D(90), V(50), and V(75) among the groups were significant for both the PB and the CB (p <0.0001). All plans with no dose constraint met the PHC and RTC. Twenty plans with an intermediate-dose constraint met the PHC and 21 met the RTC. Eighteen plans with a low-dose constraint met the PHC and 19 met the RTC. No statistically significant difference was found in the number of beam segments for the three groups (median of 51, 55, and 53; p = 0.8). CONCLUSION: In the vast majority of cases, it is possible to limit the dose to erectile tissue with IMRT, usually by >/=50% without significantly compromising the PHC, RTC, or treatment duration. A Phase III randomized trial has been designed to test the clinical significance of the erectile tissue-sparing technique described here.

Aged↗
PubMed2004

The relationship of increasing radiotherapy dose to reduced distant metastases and mortality in men with prostate cancer.

BACKGROUND: The association of increasing radiotherapy (RT) dose with reduced biochemical failure (BF) is accepted widely. However, there is little direct evidence that dose escalation has an impact on distant metastasis (DM) or overall mortality (OM). These associations were examined in the current study. METHODS: The outcome of 835 patients who were treated at the Fox Chase Cancer Center (Philadelphia, PA) between 1989 and 1997 using 3-dimensional, conformal RT alone (median dose, 74 Gray [Gy]) was analyzed. Stepwise multivariate Cox proportional hazards regression analyses (MVAs) were performed with RT dose included as a covariate along with log-transformed initial pretreatment PSA level, Gleason score, palpation T status, age, and year of treatment (YOT), where indicated. To minimize the effect of YOT, an analysis was performed on a subgroup of 363 patients who were treated prior to 1994. RESULTS: With a median follow-up of 64 months, there were 220 PSA failures, 44 distant metastases, and 162 deaths. In MVA, RT dose (as a continuous variable) was a significant predictor for BF, DM, and OM. When YOT was included as a covariate, it was related strongly to all endpoints, and the correlations of RT dose with DM and OM were lost. When the effect of YOT was minimized by limiting the MVA to patients who were treated prior to 1994, RT dose again emerged as a significant predictor of DM. CONCLUSIONS: Escalation of RT dose reduced the rates of BF, DM, and OM significantly in patients with prostate cancer. The inclusion of YOT had a pronounced effect on these correlations that may confound interpretation.

Adenocarcinoma↗
PubMed2004

Short-term androgen deprivation and PSA doubling time: their association and relationship to disease progression after radiation therapy for prostate cancer.

PURPOSE: The goal of this study was to investigate the relationship between PSA doubling time (PSADT) and initial management of prostate cancer with short-term androgen deprivation (STAD) and the impact of these factors on disease progression after radiation therapy. METHODS AND MATERIALS: Between May 1989 and October 1998, 284 patients treated with 3D-CRT experienced biochemical failure (BF) as defined under the ASTRO consensus statement. All patients had sufficient follow-up data for PSADT calculations. Linear regression was used to assess predictors of PSADT among STAD, time to biochemical failure (TTBF), Gleason Score, tumor stage, dose, posttreatment PSA nadir, pretreatment PSA, and age. A composite covariate was created from the various combinations of factors found to be predictive of PSADT. The composite covariate was then included, along with PSADT and the factors previously mentioned, in proportional hazards modeling of freedom from distant metastasis (FDM), cause-specific survival (CSS), and overall survival (OS). RESULTS: Fifty-four (19%) patients developed distant metastasis, 20 (7%) died of prostate cancer, and 53 (19%) died of any cause. The median PSADT was 12 months. Predictors of a longer PSADT were TTBF >12 months, Gleason Score 2-6, and STAD. An ordinal composite covariate was created with eight levels on the basis of the magnitude of observed mean PSADT within the eight possible combinations of the three dichotomized predictors. The most significant predictor of higher FDM rates in Cox modeling was the composite covariate, followed by longer PSADT, STAD, lower PSA nadir, higher RT dose, and Gleason Score 2-6. Predictors of higher CSS rates were lower nadir, longer PSADT, T1/T2ab tumors, the composite covariate, and STAD. The most significant predictor of a higher OS rate was STAD, followed by longer PSADT, younger age at diagnosis, the composite covariate, lower nadir, and T1/T2ab tumors. CONCLUSIONS: Longer TTBF, Gleason Score 2-6 tumors, and STAD were predictive of longer PSADT. Even after adjusting for these factors in the capacity of their predictive properties for PSADT, STAD and observed PSADT continued to be significant independent predictors of FDM, CSS, and OS. STAD appears to have a pronounced impact on disease progression, probably the result partly of the prolongation of PSADT.

Aged↗
PubMed2004

Prostate cancer radiotherapy dose response: an update of the fox chase experience.

PURPOSE: The effectiveness of increasing radiotherapy dose for men with prostate cancer was evaluated with reference to prognostic groups as defined by pretreatment serum prostate specific antigen (PSA), Gleason score, T stage and perineural invasion. MATERIALS AND METHODS: There were 839 men treated between April 1989 and December 1997 with conformal radiotherapy alone. Cox multivariate analysis was used to establish important predictors of biochemical failure (BF) separately for patients with an initial pretreatment PSA (iPSA) of less than 10, 10 to 19.9, or 20 or greater ng/ml. Radiotherapy (RT) dose was evaluated as a continuous and categorical (dose groups of less than 72, 72 to 75.9 and 76 Gy or greater) variable. RESULTS: At a median 63-month followup multivariate analysis demonstrated that iPSA and radiotherapy (RP) dose were the most significant predictors of BF, followed by Gleason score and T stage. Perineural invasion was not an independent correlate of outcome. RT dose was significant in all iPSA groups (less than 10, 10 to 19.9 and 20 or greater ng/ml). Gleason score was significant when iPSA was less than 10 ng/ml. T stage was significant when iPSA was 20 ng/ml or greater and it was borderline when iPSA was 10 to 19.9 ng/ml (p = 0.08). Prognostic subgroups were derived from these results and tested for an effect of RT dose on univariate analysis. Radiation dose was not a correlate of BF in the most favorable (PSA less than 10 ng/ml and Gleason score 2 to 6) and the most unfavorable (PSA 20 ng/ml or greater and stage T3-T4) prognostic groups but it was otherwise an influential determinant of outcome. CONCLUSIONS: RT dose escalation to 76 Gy or greater improved patient outcome for all prognostic groups except those at the favorable and unfavorable extremes.

Adult↗
PubMed2004

Matched-cohort analysis of patients with prostate cancer followed with observation or treated with three-dimensional conformal radiation therapy.

OBJECTIVES: To compare the outcome of similar patients with prostate cancer treated by either observation or three-dimensional conformal radiation therapy (3-DCRT). PATIENTS AND METHODS: The study included 69 patients with nonmetastatic prostate cancer who were observed only; the indications included indolent disease, significant medical comorbidities and refusal of treatment. Of these, 62 patients had palpable T1-T2a and seven T2b-T3a disease, a median Gleason score of 6 and a median initial prostate-specific antigen (PSA) level of 5.3 ng/mL. A matched-cohort analysis of 69 patients, based on palpation T category, Gleason score and initial PSA, was used to compare the outcome between the observation and 3-DCRT groups. The median radiation dose for latter was 72 Gy. RESULTS: The median follow-up for the observed patients was 49 months. The 5- and 8-year actuarial rates of freedom from distant metastases were 100% and 93%, respectively, and the actuarial overall survival rates 94% and 73%, respectively. Seven observed patients had local disease progression on physical examination. Four patients who initially were observed received radiation therapy later for a rising PSA and/or local disease progression. For the 69 matched 3-DCRT patients, the overall 5-year rate for no biochemically evident disease was 74%. The respective 5- and 8-year actuarial rates of freedom from distant metastases were 95% and 95%, and actuarial overall survival rates 95% and 75%. There were no significant differences in distant metastasis and overall survival rates between the groups, and no deaths from prostate cancer in either group. CONCLUSIONS: Observation is a reasonable alternative to treatment in selected patients. During the 5-year follow-up the progression rates were relatively low, and there was no difference in distant metastasis or overall survival between the groups. As the follow-up was short a longer follow-up is needed to determine whether the outcome of those patients who chose observation will remain comparable to that in those undergoing immediate 3-DCRT.

Adenocarcinoma↗
PubMed2003

Comparison of alternative biochemical failure definitions based on clinical outcome in 4839 prostate cancer patients treated by external beam radiotherapy between 1986 and 1995.

PURPOSE: To assess the merit of the American Society for Therapeutic Radiology and Oncology (ASTRO) definition of biochemical failure after external beam radiotherapy for prostate cancer by testing alternative prostate-specific antigen (PSA) failure definitions against the "gold standard" of clinical failure and to study the effect of backdating the time of failure. METHODS AND MATERIALS: Nine participating institutions agreed to submit follow-up results for all patients with clinically localized prostatic cancer (Stage T1b, T1c, T2, N0M0) treated between 1986 and 1995 by external beam radiotherapy only, to doses of >or=60 Gy, with no androgen deprivation before treatment. A total of 4839 men met the study criteria, with a median follow-up time of 6.3 years. The prediction of clinical failure by 102 definitions of biochemical failure was assessed using various quantitative measures. RESULTS: Four definitions were superior as measured by the sensitivity, specificity, positive and negative predictive values, and hazard of clinical failure after biochemical failure: two rises of at least 0.5 ng/mL backdated, PSA level at or greater than the absolute nadir plus 2 ng/mL at the call date, and PSA level at or greater than the current nadir plus 2 or 3 ng/mL at the call date. The absolute nadir was the lowest measured PSA level during all of follow-up, and the current nadir was the lowest PSA measured previous to a particular PSA measurement during follow-up. With the possible exception of patients in the low-risk group, the likelihood of ultimate clinical failure decreased as the time of biochemical failure increased. Failure definitions based on PSA levels >0.2 or 0.5 ng/mL were inferior to other definitions. Backdating the failure time introduced bias into the estimate of freedom from biochemical failure, which was increasingly overestimated at shorter median follow-up times. This bias can be circumvented either by using a failure definition based on the call date or by backdating the censoring times of patients with one or two rises who could potentially have failure at a future (unobserved) time. A short follow-up time as such does not result in bias unless the failures are backdated; in the absence of backdating, it is the precision of failure-free survival that is increasingly compromised as the follow-up time is reduced. CONCLUSION: The ASTRO failure definition ended the confusion resulting from different failure definitions that had been in use, and it did so accurately enough that it is probably not necessary to recalculate previously published results. Nevertheless, for the current pooled analysis of outcome in 4839 men with a 6.3-year median follow-up, other definitions of biochemical failure were superior as assessed by various quantitative measures of concordance of biochemical and ultimate clinical failure. An additional disadvantage of the ASTRO definition is the bias introduced by backdating failures, as well as the necessarily retrospective nature of its application. Some "current" definitions, but not those based on the PSA level rising above a fixed threshold, have significantly higher sensitivity and specificity, do not lead to biased estimations of biochemical disease-free survival, and are directly applicable during patient counseling. These are all issues that would play a role in replacing the ASTRO consensus definition.

Adenocarcinoma↗
PubMed2003

Long-term multi-institutional analysis of stage T1-T2 prostate cancer treated with radiotherapy in the PSA era.

PURPOSE: To report the long-term outcome for patients with Stage T1-T2 adenocarcinoma of the prostate definitively irradiated in the prostate-specific antigen (PSA) era. METHODS AND MATERIALS: Nine institutions combined data on 4839 patients with Stage T1b, T1c, and T2 adenocarcinoma of the prostate who had a pretreatment PSA level and had received >or=60 Gy as definitive external beam radiotherapy. No patient had hormonal therapy before treatment failure. The median follow-up was 6.3 years. The end point for outcome analysis was PSA disease-free survival at 5 and 8 years after therapy using the American Society for Therapeutic Radiology and Oncology (ASTRO) failure definition. RESULTS: The PSA disease-free survival rate for the entire group of patients was 59% at 5 years and 53% at 8 years after treatment. For patients who had received >or=70 Gy, these percentages were 61% and 55%. Of the 4839 patients, 1582 had failure by the PSA criteria, 416 had local failure, and 329 had distant failure. The greatest risk of failure was at 1.5-3.5 years after treatment. The failure rate was 3.5-4.5% annually after 5 years, except in patients with Gleason score 8-10 tumors for whom it was 6%. In multivariate analysis for biochemical failure, pretreatment PSA, Gleason score, radiation dose, tumor stage, and treatment year were all significant prognostic factors. The length of follow-up and the effect of backdating as required by the ASTRO failure definition also significantly affected the outcome results. Dose effects were most significant in the intermediate-risk group and to a lesser degree in the high-risk group. No dose effect was seen at 70 or 72 Gy in the low-risk group. CONCLUSION: As follow-up lengthens and outcome data accumulate in the PSA era, we continue to evaluate the efficacy and durability of radiotherapy as definitive therapy for early-stage prostate cancer. Similar studies with higher doses and more contemporary techniques will be necessary to explore more fully the potential of this therapeutic modality.

Adenocarcinoma↗
PubMed2003

Phase III trial of long-term adjuvant androgen deprivation after neoadjuvant hormonal cytoreduction and radiotherapy in locally advanced carcinoma of the prostate: the Radiation Therapy Oncology Group Protocol 92-02.

PURPOSE: Radiation Therapy Oncology Group (RTOG) Protocol 92-02 was a randomized trial testing long-term (LT) adjuvant androgen deprivation (AD) after initial AD with external-beam radiotherapy (RT) in patients with locally advanced prostate cancer (PC; T2c-4) and with prostate-specific antigen level less than 150 ng/mL. PATIENTS AND METHODS: Patients received a total of 4 months of goserelin and flutamide, 2 months before and 2 months during RT. A radiation dose of 65 to 70 Gy was given to the prostate and a dose of 44 to 50 Gy to the pelvic lymph nodes. Patients were randomly assigned to receive no additional therapy (short-term [ST]AD-RT) or 24 months of goserelin (LTAD-RT); 1,554 patients were entered onto the study. RESULTS: The LTAD-RT arm showed significant improvement in all efficacy end points except overall survival (OS; 80.0% v 78.5% at 5 years, P =.73), compared with the STAD-RT arm. In a subset of patients not part of the original study design, with tumors assigned Gleason scores of 8 to 10 by the contributing institutions, the LTAD-RT arm had significantly better OS (81.0% v 70.7%, P =.044). There was a small but significant increase in the frequency of late radiation grades 3, 4, and 5 gastrointestinal toxicity ascribed to the LTAD-RT arm (2.6% v 1.2% at 5 years, P =.037), the cause of which is not clear. CONCLUSION: The RTOG 92-02 trial supports the addition of LT adjuvant AD to STAD with RT for T2c-4 PC. In the exploratory subset analysis of patients with Gleason scores 8 to 10, LT adjuvant AD resulted in a survival advantage.

Adenocarcinoma↗
PubMed2003

Incorporating clinical measurements of hypoxia into tumor local control modeling of prostate cancer: implications for the alpha/beta ratio.

BACKGROUND AND PURPOSE: The recently obtained low value of approximately 1.5 for the alpha/beta of prostate cancer has led us to reexamine the optimal prostate tumor biology parameters, while taking into account everything known about the radiation response of prostate clonogens for use in a predictive dose-response model. METHODS AND MATERIALS: Averages of the literature values of the alpha- and beta-inactivation coefficients for human prostate cancer cell lines were calculated. A robust tumor local control probability (TLCP) model was used that required average alpha and beta, as well as sigma(alpha), for the interpatient variation in single-hit killing (alpha). Median PO(2) values <or=1 mm Hg in the prostates of Fox Chase Cancer Center brachytherapy patients had been found in 21% of 115 cases. The oxygen enhancement ratios of 1.75 and 3.25 for alpha- and beta-inactivation, respectively, measured for tumor cells in vitro, were incorporated into the TLCP model, together with a clonogen density of approximately 10(5) cells/cm(3). Severe hypoxia and radioresistance were estimated for a proportion of tumors that was increased with PSA level. RESULTS: For asynchronous human prostate cell lines irradiated in air, alpha(mean) was 0.26 +/- 0.07 (standard error) Gy(-1), sigma(alpha) = 0.06 Gy(-1), and beta(mean) was 0.0312 Gy(-2) +/- 0.0064 (standard error) Gy(-2). The TLCP data indicated that most tumors that contained aerobic cells would be cured, whereas most tumors that contained hypoxic cells would not be cured by total doses of 76 to 80 Gy. Clinical response data from the literature for external beam dose escalation, stratified by PSA value, and for low-dose-rate brachytherapy, were well predicted by the model, where the alpha/beta ratio was 8.5 and 15.5 for well-oxygenated and hypoxic clonogens, respectively. CONCLUSIONS: Neither alpha/beta ratio nor clonogen number need be extremely low to explain the response of prostate cancer to brachytherapy and external beam therapy, contradicting other recent analyses. It is strongly suggested that severe hypoxia in the prostates of certain patients limits the overall cancer cure rate by conventional radiation therapy.

Brachytherapy↗