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M J Zelefsky

Publications and source records attributed to M J Zelefsky.

At least 19 recordsLinked to original sources
PubMed2003

Intraoperative dynamic dosimetry for prostate implants.

This paper describes analytic tools in support of a paradigm shift in brachytherapy treatment planning for prostate cancer--a shift from standard pre-planning to intraoperative planning using dosimetric feedback based on the actual deposited seed positions within the prostate. The method proposed is guided by several desiderata: (a) bringing both planning and evaluation in the operating room (i.e. make post-implant evaluation superfluous) therefore making rectifications--if necessary--still achievable; (b) making planning and implant evaluation consistent by using the same imaging system (ultrasound); and (c) using only equipment commonly found in a hospital operating room. The intraoperative dosimetric evaluation is based on the fusion between ultrasound images and 3D seed coordinates reconstructed from fluoroscopic projections. Automatic seed detection and registration of the fluoroscopic and ultrasound information, two of the three key ingredients needed for the intraoperative dynamic dosimetry optimization (IDDO), are explained in detail. The third one, the reconstruction of 3D coordinates from projections, was reported in a previous article. The algorithms were validated using a custom-designed phantom with non-radioactive (dummy) seeds. Also, fluoroscopic images were taken at the conclusion of an actual permanent prostate implant and compared with data on the same patient obtained from radiographic-based post-implant evaluation. To offset the effect of organ motion the comparison was performed in terms of the proximity function of the two seed distributions. The agreement between the intra- and post-operative seed distributions was excellent.

Algorithms↗
PubMed2001

Intraoperative planning and evaluation of permanent prostate brachytherapy: report of the American Brachytherapy Society.

PURPOSE: The preplanned technique used for permanent prostate brachytherapy has limitations that may be overcome by intraoperative planning. The goal of the American Brachytherapy Society (ABS) project was to assess the current intraoperative planning process and explore the potential for improvement in intraoperative treatment planning (ITP). METHODS AND MATERIALS: Members of the ABS with expertise in ITP performed a literature review, reviewed their clinical experience with ITP, and explored the potential for improving the technique. RESULTS: The ABS proposes the following terminology in regard to prostate planning process: *Preplanning--Creation of a plan a few days or weeks before the implant procedure. *Intraoperative planning--Treatment planning in the operating room (OR): the patient and transrectal ultrasound probe are not moved between the volume study and the seed insertion procedure. * Intraoperative preplanning--Creation of a plan in the OR just before the implant procedure, with immediate execution of the plan. *Interactive planning--Stepwise refinement of the treatment plan using computerized dose calculations derived from image-based needle position feedback. *Dynamic dose calculation--Constant updating of dose distribution calculations using continuous deposited seed position feedback. Both intraoperative preplanning and interactive planning are currently feasible and commercially available and may help to overcome many of the limitations of the preplanning technique. Dosimetric feedback based on imaged needle positions can be used to modify the ITP. However, the dynamic changes in prostate size and shape and in seed position that occur during the implant are not yet quantifiable with current technology, and ITP does not obviate the need for postimplant dosimetric analysis. The major current limitation of ITP is the inability to localize the seeds in relation to the prostate. Dynamic dose calculation can become a reality once these issues are solved. Future advances can be expected in methods of enhancing seed identification, in imaging techniques, and in the development of better source delivery systems. Additionally, ITP should be correlated with outcome studies, using dosimetric, toxicity, and efficacy endpoints. CONCLUSION: ITP addresses many of the limitations of current permanent prostate brachytherapy and has some advantages over the preplanned technique. Further technologic advancement will be needed to achieve dynamic real-time calculation of dose distribution from implanted sources, with constant updating to allow modification of subsequent seed placement and consistent, ideal dose distribution within the target volume.

Brachytherapy↗
PubMed2001

Fitting tumor control probability models to biopsy outcome after three-dimensional conformal radiation therapy of prostate cancer: pitfalls in deducing radiobiologic parameters for tumors from clinical data.

PURPOSE: The goal of tumor control probability (TCP) models is to predict local control for inhomogeneous dose distributions. All existing fits of TCP models to clinical data have utilized summaries of dose distributions (e.g., prescription dose). Ideally, model fits should be based on dose distributions in the tumor, but usually only dose-volume histograms (DVH) of the planning target volume (PTV) are available. We fit TCP models to biopsy outcome after three-dimensional conformal radiation therapy of prostate cancer using either a dose distribution summary or the full DVH in the PTV. We discuss differences in the radiobiologic parameters and dose-response curves and demonstrate pitfalls in interpreting the results. METHODS AND MATERIAL: Two mechanistic TCP models were fit with a maximum likelihood technique to biopsy outcome from 103 prostate patients treated at Memorial Sloan-Kettering Cancer Center. Fits were performed separately for different patient subgroups defined by tumor-related prognostic factors. Fits were based both on full DVHs, denoted TCP(DVH(calc)), and, alternatively, assuming a homogeneous PTV dose given by the mean dose (Dmean) of each DVH, denoted TCP(Dmean(calc)). Dose distributions for these patients were very homogeneous with any cold spots located on the periphery of the PTV. These cold spots were uncorrelated with biopsy outcome, likely because the low-dose regions may not contain tumor cells. Therefore, fits of TCP models that are potentially sensitive to cold spots (e.g., TCP(DVH(calc))) likely give biologic parameters that diminish this sensitivity. In light of this, we examined differences in fitted clonogenic cell number, N(C), or density, rho(C), surviving fraction after 2 Gy, SF(2), or radiosensitivity, alpha, and their standard deviations in the population, sigma(SF(2)) and sigma(alpha), resulting from fits based on TCP(DVH(calc)) and TCP(Dmean(calc)). Dose-response curves for homogeneous irradiation (characterized by TCD(50), the dose for a TCP of 50%) and differences in TCP predictions calculated from the DVH using alternatively derived parameters were evaluated. RESULTS: Fits of TCP(Dmean(calc)) are better (i.e., have larger likelihood) than fits of TCP(DVH(calc)). For TCP(Dmean(calc)) fits, matching values of SF(2) and sigma(SF(2)) (or alpha and sigma(alpha)) exist for all N(C) (rho(C)) above a threshold that give fits of equal quality, with no maximum in likelihood. In contrast, TCP(DVH(calc)) fits have maximum likelihood for high SF(2) (low alpha) values that minimize effects of cold spots. Consequently, small N(C) (rho(C)) values are obtained to match the observed control rate. For example, for patients in low-, intermediate-, and high-risk groups, optimum values of SF(2) and N(C) are 0.771 and 3.3 x 10(3), 0.736 and 2.2 x 10(4), and 0.776 and 1.0 x 10(4), respectively. The TCD(50) of dose-response curves for intermediate-risk patients is 2.6 Gy lower using TCP(DVH(calc)) parameters (TCD(50) = 67.8 Gy) than for TCP(Dmean(calc)) parameters (TCD(50) = 70.4 Gy). TCP predictions calculated from the DVH using risk group-dependent TCP(Dmean(calc)) parameters are up to 53% lower than corresponding calculations with TCP(DVH(calc)) parameters. CONCLUSION: For our data, TCP parameters derived from DVHs likely do not reflect true radiobiologic parameters in the tumor, but are a consequence of the reduced importance of low-dose regions at the periphery of the PTV. Deriving radiobiologic parameters from TCP(Dmean(calc)) fits is not possible unless one parameter is already known. TCP predictions using TCP(DVH(calc)) and TCP(Dmean(calc)) parameters may differ substantially, requiring consistency in the derivation and application of model parameters. The proper derivation of radiobiologic parameters from clinical data requires both substantial dose inhomogeneities and understanding of how these coincide with tumor location.

Adenocarcinoma↗
PubMed2001

Failure of a 3D conformal boost to improve radiotherapy for nasopharyngeal carcinoma.

PURPOSE: To determine whether the use of 3-dimensional (3D) boost for patients with nasopharynx cancer improves local control and reduces the risk of long-term complications. METHODS AND MATERIALS: From 1988 to 1998, 68 patients with nasopharynx cancer received conventional external beam therapy followed by a 3D boost. Disease characteristics of treated patients were as follows: WHO I histology 7%, WHO II 62%, WHO III 31%, clinical AJCC stage T1--2 45%, T3--4 55%, N0--1 63%, N2--3 37%, M0 100%. The median radiation dose was 70 Gy (68--75.6 Gy). Thirty-five patients (52%) received cisplatin-based chemotherapy. The median follow-up of surviving patients was 42 months (12--118 months). RESULTS: Five-year actuarial local control was 77%, regional control was 97%, progression-free survival was 56%, and overall survival was 58%. Stage was the only identifiable prognostic factor: 5-year progression-free survival was 65% for Stages I--III vs. 40% for Stage IV (p = 0.01). The incidence of Grade 3-4 complications was 25% and included hearing loss, trismus, dysphagia, chronic sinusitis, and cranial neuropathy. These results are comparable to outcomes reported with conventional radiation techniques for similarly staged patients. CONCLUSION: The lack of a major benefit with the 3D boost may be related to the fact that CT planning was only used for a fraction of the total dose. We are now using intensity modulated radiation therapy to deliver the entire course of radiation. Intensity modulated radiation therapy achieves better conformal distributions than conventional 3D planning, allowing dose escalation and increased normal tissue sparing.

Adolescent↗
PubMed2001

Treatment planning and delivery of intensity-modulated radiation therapy for primary nasopharynx cancer.

PURPOSE: To implement intensity-modulated radiation therapy (IMRT) for primary nasopharynx cancer and to compare this technique with conventional treatment methods. METHODS AND MATERIALS: Between May 1998 and June 2000, 23 patients with primary nasopharynx cancer were treated with IMRT delivered with dynamic multileaf collimation. Treatments were designed using an inverse planning algorithm, which accepts dose and dose-volume constraints for targets and normal structures. The IMRT plan was compared with a traditional plan consisting of phased lateral fields and a three-dimensional (3D) plan consisting of a combination of lateral fields and a 3D conformal plan. RESULTS: Mean planning target volume (PTV) dose increased from 67.9 Gy with the traditional plan, to 74.6 Gy and 77.3 Gy with the 3D and IMRT plans, respectively. PTV coverage improved in the parapharyngeal region, the skull base, and the medial aspects of the nodal volumes using IMRT and doses to all normal structures decreased compared to the other treatment approaches. Average maximum cord dose decreased from 49 Gy with the traditional plan, to 44 Gy with the 3D plan and 34.5 Gy with IMRT. With the IMRT plan, the volume of mandible and temporal lobes receiving more than 60 Gy decreased by 10-15% compared to the traditional and 3D plans. The mean parotid gland dose decreased with IMRT, although it was not low enough to preserve salivary function. CONCLUSION: Lower normal tissue doses and improved target coverage, primarily in the retropharynx, skull base, and nodal regions, were achieved using IMRT. IMRT could potentially improve locoregional control and toxicity at current dose levels or facilitate dose escalation to further enhance locoregional control.

Algorithms↗
PubMed2001

Late rectal bleeding after conformal radiotherapy of prostate cancer. II. Volume effects and dose-volume histograms.

PURPOSE AND OBJECTIVE: Late rectal bleeding is a potentially dose limiting complication of three-dimensional conformal radiotherapy (3D-CRT) for prostate cancer. The frequency of late rectal bleeding has been shown to increase as the prescription dose rises above 70 Gy. The purpose of this study is to identify features of the cumulative dose-volume histogram (DVH) for the rectal wall that correlate with late rectal bleeding after 3D-CRT for prostate cancer. METHODS AND MATERIALS: Follow-up information on rectal bleeding is available for 261 and 315 patients treated using 3D-CRT at Memorial Sloan-Kettering Cancer Center for Stage T1c-T3 prostate cancer with minimum target doses of 70.2 and 75.6 Gy, respectively. All patients in this study were treated with a coplanar 6-field technique (2 lateral and 4 oblique fields). Patients were classified as having rectal bleeding if they bled (> or = Grade 2) before 30 months, and nonbleeding (< or = Grade 1) if they were without bleeding at 30 months, using the RTOG morbidity scale. Rectal bleeding was observed in 13 and 38 of the patients treated at 70.2 and 75.6 Gy, respectively. Treatment plans were analyzed for 39 nonbleeding and 13 bleeding patients receiving 70.2 Gy, and 83 nonbleeding and 36 bleeding patients receiving 75.6 Gy. Dose-volume histograms (DVHs) for the anatomic rectal wall were calculated. Average DVHs of the bleeding and nonbleeding patients were generated, and a permutation test was used to assess the significance of differences between them, for each dose group. The confounding effect of total rectal wall volume (V(RW)) was removed by calculating the average differences in DVHs between all combinations of bleeding and nonbleeding patients with similar V(RW)s. Finally, multivariate analysis using logistic regression was performed to test the significance of the DVH variables in the presence of anatomic, geometric, and medical variables previously found to correlate with rectal bleeding in a companion analysis of the same patients. RESULTS: The area under the average percent volume DVH for the rectal wall of patients with bleeding was significantly higher than those of patients without bleeding in both dose groups (p = 0.02, 70.2 Gy; p < 0.0001, 75.6 Gy). However, small V(RW)s were associated with rectal bleeding (p = 0.06, 70.2 Gy; p < 0.01, 75.6 Gy), resulting in an increase in average percent volumes exposed to all doses for patients with rectal bleeding. For patients with similar V(RW)s, rectal bleeding was significantly correlated with the volumes exposed to 46 Gy in both dose groups (p = 0.02, 70.2 Gy; p = 0.005, 75.6 Gy, tolerance in V(RW): 5 ccs). For the 75.6 Gy dose group, the percent volume receiving 77 Gy was significantly correlated with rectal bleeding (p < 0.005). Bivariate analysis using logistic regression, including V(RW) together with a single DVH variable, showed good agreement with the above analysis. Multivariate analysis revealed a borderline significant correlation of the percent volume receiving 71 Gy in the 70.2 Gy dose group. It also showed that the DVH variables were highly correlated with geometric and dosimetric variables previously found to correlate with rectal bleeding in multivariate analysis. CONCLUSION: Significant volume effects were found in the probability of late rectal bleeding for patients undergoing 3D-CRT for prostate cancer with prescription doses of 70.2 and 75.6 Gy. The percent volumes exposed to 71 and 77 Gy in the 70.2 and 75.6 Gy dose groups respectively were significantly correlated with rectal bleeding. The independent correlation of small V(RW) with rectal bleeding may indicate the existence of a functional reserve for the rectum. The independent association with larger percent volumes exposed to intermediate doses ( approximately 46 Gy) seen in both dose groups may indicate that a large surrounding region of intermediate dose may interfere with the ability to repair the effects of a central high dose region.

Algorithms↗
PubMed2001

Accelerated concomitant boost radiotherapy and chemotherapy for advanced nasopharyngeal carcinoma.

PURPOSE: To evaluate the feasibility and efficacy of concomitant boost radiotherapy (RT) plus cisplatin-based chemotherapy compared with standard fractionation RT for patients with advanced nasopharyngeal cancer. PATIENTS AND METHODS: From 1988 through 1999, 50 patients with American Joint Committee on Cancer stage II-IVb nasopharyngeal carcinoma were treated with 70-Gy concomitant boost RT (1.8 Gy/d, weeks 1 through 6; 1.6 Gy second daily fraction, weeks 5 through 6) and two cycles of concurrent cisplatin 100 mg/m(2) days 1 and 22. Thirty-seven patients also received three cycles of cisplatin-based adjuvant chemotherapy. These 50 patients were compared with a nonrandomized cohort of 51 patients with nasopharyngeal cancer treated with 70-Gy standard fractionation RT (1.8 Gy/d) without chemotherapy from 1988 through 1995. The groups were well matched for prognostic factors except stage, for which the concomitant boost RT/chemotherapy group was more advanced (54%, T3-4; 54%, N2-3; 44%, stage IV) compared with the standard RT group (31%, T3-4, P =.03; 22%, N2-3, P <.001; 20%, stage IV, P <.01). RESULTS: With a median follow-up of 42 months (range, 12 to 129 months), the 3-year actuarial local control, progression-free survival, and survival rates were 89% v 74% (P <.01), 66% v 54% (P =.01), and 84% v 71% (P =.04) for the concomitant boost RT/chemotherapy group and the standard RT patients, respectively. Acute grade 3 mucositis was more prevalent with combined therapy, 84% v 43% (P <.001), resulting in a higher rate of temporary gastrostomy tube placement, 46% v 20% (P <.01). CONCLUSION: Concomitant boost RT with cisplatin-based chemotherapy is feasible and improves local-regional control as well as survival for patients with advanced nasopharyngeal cancer compared with standard RT alone.

Adolescent↗
PubMed2001

A survival model for fractionated radiotherapy with an application to prostate cancer.

This paper explores the applicability of a mechanistic survival model, based on the distribution of clonogens surviving a course of fractionated radiation therapy, to clinical data on patients with prostate cancer. The study was carried out using data on 1,100 patients with clinically localized prostate cancer who were treated with three-dimensional conformal radiation therapy. The patients were stratified by radiation dose (group 1: <67.5 Gy; group 2: 67.5-72.5 Gy; group 3: 72.5-77.5 Gy; group 4: 77.5-87.5 Gy) and prognosis category (favourable, intermediate and unfavourable as defined by pre-treatment PSA and Gleason score). A relapse was recorded when tumour recurrence was diagnosed or when three successive prostate specific antigen (PSA) elevations were observed from a post-treatment nadir PSA level. PSA relapse-free survival was used as the primary end point. The model, which is based on an iterated Yule process, is specified in terms of three parameters: the mean number of tumour clonogens that survive the treatment, the mean of the progression time of post-treatment tumour development and its standard deviation. The model parameters were estimated by the maximum likelihood method. The fact that the proposed model provides an excellent description both of the survivor function and of the hazard rate is prima facie evidence of the validity of the model because closeness of the two survivor functions (empirical and model-based) does not generally imply closeness of the corresponding hazard rates. The estimated cure probabilities for the favourable group are 0.80, 0.74 and 0.87 (for dose groups 1-3, respectively); for the intermediate group: 0.25, 0.51, 0.58 and 0.78 (for dose groups 1-4, respectively) and for the unfavourable group: 0.0, 0.27, 0.33 and 0.64 (for dose groups 1-4, respectively). The distribution of progression time to tumour relapse was found to be independent of prognosis group but dependent on dose. As the dose increases the mean progression time decreases (41, 28.5, 26.2 and 14.7 months for dose groups 1-4, respectively). This analysis confirms that, in terms of cure rate, dose escalation has a significant positive effect only in the intermediate and unfavourable groups. It was found that progression time is inversely proportional to dose, which means that patients recurring in higher dose groups have shorter recurrence times, yet these groups have better survival, particularly long-term. The explanation for this seemingly illogical observation lies in the fact that less aggressive tumours, potentially recurring after a long period of time, are cured by higher doses and do not contribute to the recurrence pattern. As a result, patients in higher dose groups are less likely to recur; however, if they do, they tend to recur earlier. The estimated hazard rates for prostate cancer pass through a clear-cut maximum, thus revealing a time period with especially high values of instantaneous cancer-specific risk; the estimates appear to be nonproportional across dose strata.

Disease-Free Survival↗
PubMed2001

High dose radiation delivered by intensity modulated conformal radiotherapy improves the outcome of localized prostate cancer.

PURPOSE: We present the long-term outcome and tolerance of 3-dimensional (D) conformal and intensity modulated radiation therapy for localized prostate cancer. MATERIALS AND METHODS: Between October 1988 and December 1998, 1,100 patients with clinical stages T1c-T3 prostate cancer were treated with 3-D conformal or intensity modulated radiation therapy. Patients were categorized into prognostic risk groups based on pretreatment prostate specific antigen (PSA), Gleason score and clinical stage. Sextant biopsies were performed 2.5 years or greater after treatment to assess local control. PSA relapse was defined according to the consensus guidelines of the American Society for Therapeutic Radiation Oncology. Late toxicity was classified according to the Radiation Therapy Oncology Group morbidity grading scale. Median followup was 60 months. RESULTS: At 5 years the PSA relapse-free survival rate in patients at favorable, intermediate and unfavorable risk was 85% (95% confidence interval [CI] +/- 4), 58% (95% CI +/- 6) and 38% (95% CI +/- 6), respectively (p <0.001). Radiation dose was the most powerful variable impacting PSA relapse-free survival in each prognostic risk group. The 5-year actuarial PSA relapse-free survival rate for patients at favorable risk who received 64.8 to 70.2 Gy. was 77% (95% CI +/- 8) compared to 90% (95% CI +/- 8) for those treated with 75.6 to 86.4 Gy. (p = 0.04) [corrected]. The corresponding rates were 50% (95% CI +/- 8) versus 70% (95% CI +/- 6) in intermediate risk cases (p = 0.001), and 21% (95% CI +/- 8) versus 47% (95% CI +/- 6) in unfavorable risk cases (p = 0.008) [corrected]. Only 4 of 41 patients (10%) who received 81 Gy. had a positive biopsy 2.5 years or greater after treatment compared with 27 of 119 (23%) after 75.6, 23 of 68 (34%) after 70.2 and 13 of 24 (54%) after 64.8 Gy. The incidence of toxicity after 3-D conformal radiation therapy was dose dependent. The 5-year actuarial rate of grade 2 rectal toxicity in patients who received 75.6 Gy. or greater was 14% (95% CI +/- 2) compared with 5% (95% CI +/- 2) in those treated at lower dose levels (p <0.001). Treatment with intensity modulated radiation therapy significantly decreased the incidence of late grade 2 rectal toxicity since the 3-year actuarial incidence in 189 cases managed by 81 Gy. was 2% (95% CI +/- 2) compared with 14% (95% CI +/- 2) in 61 managed by the same dose of 3-D conformal radiation therapy (p = 0.005). The 5-year actuarial rate of grade 2 urinary toxicity in patients who received 75.6 Gy. or greater 3-D conformal radiation therapy was 13% compared with 4% in those treated up to lower doses (p <0.001). Intensity modulated radiation therapy did not affect the incidence of urinary toxicity. CONCLUSIONS: Sophisticated conformal radiotherapy techniques with high dose 3-D conformal and intensity modulated radiation therapy improve the biochemical outcome in patients with favorable, intermediate and unfavorable risk prostate cancer. Intensity modulated radiation therapy is associated with minimal rectal and bladder toxicity, and, hence, represents the treatment delivery approach with the most favorable risk-to-benefit ratio.

Adenocarcinoma↗
PubMed2001

Results of high dose rate brachytherapy, anterior pelvic exenteration and external beam radiotherapy for carcinoma of the female urethra.

PURPOSE: We evaluated a multimodality approach to locally advanced urethral carcinoma in women. MATERIALS AND METHODS: Between August 1996 and July 1999, 6 women were treated for locally advanced carcinoma of the urethra with anterior pelvic exenteration followed by high dose 192iridium intraoperative radiation therapy. Four of the 6 patients were also treated with neoadjuvant or concomitant platinum based chemotherapy. RESULTS: Two patients had no evidence of disease, 3 had distant metastasis and 2 had local recurrence at a mean followup of 21 months (range 12 to 47). Radiation was relatively well tolerated with no major adverse events. CONCLUSIONS: High dose intraoperative brachytherapy followed by external beam radiation is relatively well tolerated. Local control seems to have improved. We must evaluate a larger cohort of patients to determine this impact of the combined modality on local control and patient survival.

Adult↗
PubMed2000

Adjuvant radiotherapy for margin-positive high-grade soft tissue sarcoma of the extremity.

PURPOSE: Adjuvant radiotherapy (RT) has been shown to improve local control in patients with soft tissue sarcoma of the extremities (STS). The specific impact of adjuvant radiation on patients with positive margins, however, has not been clearly defined. The purpose of this study was to determine if adjuvant RT improves local control in patients with high-grade STS who had positive margins of resection. METHODS AND MATERIALS: Between 8/82 and 2/97, 110 adult patients with primary high-grade STS of an extremity underwent limb sparing surgery and were found to have a histologically positive microscopic surgical margin. Ninety-one (83%) received RT and 19 (17%) had no RT. The two groups were balanced with regard to size, site, location, and tumor depth. Adjuvant RT was delivered with brachytherapy (BRT) alone in 34 patients, external beam radiotherapy (EBRT) alone in 33 patients, or BRT+EBRT in 24 patients. The BRT dose was 45 Gy when used alone and 15-20 Gy when used as a boost. The EBRT dose was 60-70 Gy when used alone and 45-50 Gy when given with BRT. The median follow-up time was 41 months (range, 3-186 months). RESULTS: The overall 5 year local control rate was 71%. This rate was significantly higher in the RT group compared to the no RT group (74% vs. 56%, respectively) (p = 0.01). On univariate analysis, lower extremity site and proximal location were also found to be predictors of improved local control (p = 0.03 and 0.03, respectively). However, only proximal location and the use of RT retained their significance as predictors of improved local control on multivariate analysis (p = 0.003 and 0.01, respectively). The overall 5-year distant relapse-free survival, disease-free survival, and overall survival rates were 54%, 44%, and 53%, respectively. No statistical differences were found in these survival rates between RT and no RT groups. CONCLUSION: Based on this study, adjuvant radiotherapy seems to improve local control in patients with high-grade STS of the extremity with positive margins. However, local recurrence still occurs in a substantial proportion of patients, mandating further need for improvement.

Adolescent↗
PubMed2000

Combined 3-dimensional conformal radiotherapy and transperineal Pd-103 permanent implantation for patients with intermediate and unfavorable risk prostate cancer.

PURPOSE: To evaluate the efficacy and morbidity of combined 3-dimensional conformal radiation therapy (3D-CRT) and brachytherapy for intermediate/unfavorable risk prostate cancer. MATERIALS AND METHODS: Between May 1996 and November 1997, 65 patients with intermediate/unfavorable risk prostate cancer were treated with 3D-CRT (50.4 Gy) followed by a transperineal permanent Pd-103 implant. Patients with one or two adverse prognostic features (PSA > 10 and Gleason > or = 7) were classified as intermediate risk and unfavorable risk, respectively. Forty-seven patients (71%) had intermediate risk and 18 (29%) had unfavorable disease risk. The median age of this group was 65 years (range, 42-76 years), and the median pretreatment PSA level was 8.0 ng/ml (range, 1.7-42.0 ng/ml). The clinical stage of these patients was as follows: Tlc, 36 (55%); T2a, 27 (42%); T2b/T3, 2 (3%). Fifteen patients (23%) had a Gleason < or = 6, 41 patients (63%) were classified as Gleason 7, and 9 (14%) as Gleason > or = 8. Fifty-two (80%) received neoadjuvant androgen deprivation (NAAD) for cytoreduction. The median follow-up was 36 months (range, 24-42 months). RESULTS: The PSA relapse-free survival rate at 3 years was 87%, with a median PSA value at last follow-up of 0.25 ng/ml. The relapse-free survival was 90% for those who had an initial PSA < or = 10 ng/ml and 80% for patients who had an initial PSA > 10 ng/ml (p = 0.5). No difference in outcome was observed between patients with intermediate and unfavorable risk disease. Eight patients (13%) developed late Grade 2 rectal bleeding. Twenty-three patients (42%) required medication for urinary symptoms during the first 6 months after therapy. Three patients (5 %) noted rare stress incontinence at last follow-up. Of the 44 patients who were potent prior to therapy, 17 (26%) developed erectile dysfunction (ED). CONCLUSION: Although the follow-up is short, the early biochemical outcome of combined 3D-CRT and brachytherapy for intermediate/unfavorable risk prostate cancer is promising. While rectal toxicity is minimal, urinary side effects are more common. Further follow-up is necessary to fully evaluate the efficacy of this combined therapeutic approach.

Adult↗
PubMed2000

Long-term urinary toxicity after 3-dimensional conformal radiotherapy for prostate cancer in patients with prior history of transurethral resection.

PURPOSE: To report on the long-term urinary morbidity among prostate cancer patients with a prior history of a transurethral resection of the prostate (TURP) treated with high-dose 3-dimensional conformal radiotherapy (3D-CRT). METHODS AND MATERIALS: Between 1988 and 1997, 1100 patients with clinically localized prostate cancer were treated with 3D-CRT. Of these, 120 patients (8%) were identified as having had a prior TURP and are the subjects of this analysis. The median age was 71 years (range: 49-83 years). The clinical stages of the patients were T1c: 33 (28%); T2a: 38 (32%); T2b: 15 (13%); and T3: 34 (27%). Neoadjuvant androgen ablation therapy was given to 39 (33%). The median radiation dose prescribed to the planning target volume was 75.6 Gy (range: 64.8-81 Gy). The median elapsed time from TURP to initiation of 3D-CRT was 69 months (range: 4-360 months). The median follow-up time was 51 months (range: 18-109 months). RESULTS: Five patients of the 120 with a prior history of TURP (4%) developed a urethral stricture after 3D-CRT which was corrected with dilatation. The 5-year actuarial likelihood of >/= Grade 2 late urinary toxicities was 9%. No Grade 4 urinary toxicities were observed in this group of patients. Among 110 patients who were completely continent of urine prior to 3D-CRT, 10 (9%) developed stress incontinence requiring 1 pad daily for protection or experienced occasional leakage (not requiring pad protection). The 5-year incidence of >/= Grade 1 stress incontinence was 18% in patients who developed acute >/= Grade 2 GU symptoms during the course of 3D-CRT compared to 7% for patients who experienced Grade 1 or no acute urinary symptoms (p = 0.05). The radiation dose (>/=75.6 Gy vs. <75.6 Gy), the number of prior TURP procedures, or the volume of resected tissue at the time of TURP had no significant impact on the long-term urinary morbidity outcome. A multivariate analysis demonstrated that the presence of Grade 2 acute urinary symptoms was the only predictor of >/= Grade 1 stress incontinence after 3D-CRT in this group of patients. CONCLUSIONS: Despite prior TURP, the incidence of >/= Grade 3 urinary toxicities is low. Nevertheless, especially among patients with a prior history of TURP who experience Grade 2 acute urinary symptoms during radiation treatment, a higher risk of stress incontinence is observed.

Aged↗
PubMed2000

Pretreatment nomogram for predicting the outcome of three-dimensional conformal radiotherapy in prostate cancer.

PURPOSE: Several studies have defined risk groups for predicting the outcome after external-beam radiotherapy of localized prostate cancer. However, most models formed patient risk groups, and none of these models considers radiation dose as a predictor variable. The purpose of this study was to develop a nomogram to improve the accuracy of predicting outcome after three-dimensional conformal radiotherapy. MATERIALS AND METHODS: This study was a retrospective, nonrandomized analysis of patients treated at the Memorial Sloan-Kettering Cancer Center between 1988 and 1998. Clinical parameters of the 1,042 patients included stage, biopsy Gleason score, pretreatment serum prostate-specific antigen (PSA) level, whether neoadjuvant androgen deprivation therapy was administered, and the radiation dose delivered. Biochemical (PSA) treatment failure was scored when three consecutive rises of serum PSA occurred. A nomogram, which predicts the probability of remaining free from biochemical recurrence for 5 years, was validated internally on this data set using a bootstrapping method and externally using a cohort of patients treated at the Cleveland Clinic, Cleveland, OH. RESULTS: When predicting outcomes for patients in the validation data set from the Cleveland Clinic, the nomogram had a Somers' D rank correlation between predicted and observed failure times of 0.52. Predictions from this nomogram were more accurate (P<.0001) than the best of seven published risk stratification systems, which achieved a Somers' D coefficient of 0.47. CONCLUSION: The development process illustrated here produced a nomogram that seems to predict more accurately than other available systems and may be useful for treatment selection by both physicians and patients.

Aged↗
PubMed2000

Postimplantation dosimetric analysis of permanent transperineal prostate implantation: improved dose distributions with an intraoperative computer-optimized conformal planning technique.

PURPOSE: To compare the target coverage and dose to normal tissues after I-125 transperineal permanent implantation (TPI) of the prostate in 90 patients treated with one of three different transperineal techniques. METHODS AND MATERIALS: Detailed postimplant dosimetric evaluations of permanent I-125 implantation procedures were performed on 30 consecutive patients treated between 1995-1996 who underwent TPI using a preplanning CT-based technique, on 30 consecutive patients treated in 1997-1998 who underwent an ultrasound-guided approach with intraoperative determination of seed distribution based on an I-125 nomogram, and on 30 consecutive patients in 1998-1999 who underwent TPI with intraoperative computer-based 3-dimensional conformal optimization. For all three techniques, postimplant CT scans were obtained 4-6 hours after TPI. Dosimetric parameters included V(100), V(90), V(150), D(100), D(90), D(80), as well as maximal and average doses to the urethra and rectal wall. These parameter outcomes are reported as a percentage of the prescription dose. RESULTS: The intraoperative 3D-optimized technique (I-3D) provided superior target coverage with the prescription dose for all dosimetric variables evaluated compared to the other treatment techniques. The median V(100), V(90), and D(90) values for the I-3D technique were 96%, 98%, and 116%, respectively. In contrast, the V(100), V(90), and D(90) values for the CT preplan and ultrasound manual optimization approaches were 86%, 89%, and 88%, respectively and 88%, 92%, and 94%, respectively (I-3D versus other techniques: p < 0.001). The superior target coverage with the I-3D technique was also associated with a higher cumulative implant activity required by the optimization program. A multivariate analysis determined that the treatment technique (I-3D versus other approaches) was an independent predictor of improved target coverage for each parameter analyzed (p < 0.001). In addition, higher cumulative implant activities and smaller prostate target volumes were independent predictors of improved target coverage. The maximum and average urethral doses were significantly lower with the I-3D technique compared to the other techniques; a modest increase in the average rectal dose was also observed with this approach. CONCLUSION: Three-dimensional intraoperative computer optimized TPI consistently provided superior target coverage with the prescription dose and significantly lower urethral doses compared to two other techniques used. These data provide proof-of-principle that improved therapeutic ratios can be achieved with the integration of more sophisticated intraoperative planning for TPI and may potentially have a profound impact on the outcome of patients treated with this modality.

Algorithms↗
PubMed2000

High-dose-rate intraoperative brachytherapy for recurrent colorectal cancer.

PURPOSE: Management of locally recurrent colorectal adenocarcinoma represents a significant challenge. Many of these tumors adhere to or invade into vital pelvic structures rendering surgery or external beam radiotherapy (EBRT) as palliative treatment. Therefore, a treatment approach was developed to evaluate the role of high-dose-rate intraoperative brachytherapy (HDR-IORT) and surgery as a component of therapy in the management of locally recurrent colorectal cancer. This is an update of our preliminary report with longer follow-up and larger patient numbers. METHODS AND MATERIALS: Between January 1992 and September 1998, 74 patients with locally recurrent rectal cancer were treated with surgery and HDR-IORT. Additional EBRT was given to 29 patients, and 33 patients received 5-fluorouracil based chemotherapy. All patients underwent complete gross resection, and 21 of 74 had positive microscopic margin. The dose of HDR-IORT ranged from 10 to 18 Gy. RESULTS: With a median follow-up of 22 months, the 5-year local control, distant metastasis disease-free, disease-free, and overall survival rates were 39%, 39%, 23%, and 23%, respectively. The only predictor of improved local control was a negative margin of resection with a 5-year local control rate of 43%, compared to 26% in those with positive margin (p = 0.02). For overall survival, a negative microscopic margin (p = 0.04) and the use of IORT + EBRT (p = 0.04) were significant predictors of improved survival. The incidence of peripheral neuropathy was 16%. CONCLUSION: The results with HDR-IORT in this group of patients are encouraging. Further improvements in local and distant control are still needed.

Adenocarcinoma↗