Emad Youssef

Long-term outcome of combined modality therapy in retroperitoneal and deep-trunk soft-tissue sarcoma: analysis of prognostic factors

PURPOSEnTo evaluate the long-term outcome of surgery and postoperative radiotherapy (RT) in retroperitoneal and deep-trunk soft-tissue sarcoma, and to identify the prognostic factors for local control, disease-free survival, and overall survival.nnnMETHODS AND MATERIALSnBetween January 1980 and December 1998, 60 patients with nonmetastatic retroperitoneal and deep-trunk soft-tissue sarcoma were treated at Wayne State University using combined surgery and RT. The location was retroperitoneal in 38 patients (63%) and deep trunk in 22 (27%). Forty-six patients (76%) were treated for primary disease and 14 (24%) for recurrent disease. The resection margins were negative in 24 patients (40%), close in 3 (5%), and positive in 33 (55%; 18 microscopic and 15 macroscopic). The median tumor size was 8.6 cm (range 2-55). External beam RT (EBRT; median dose 5220 cGy) was given to 44 patients (73%) and combined EBRT (median dose 4200 cGy) and brachytherapy (median dose 1600 cGy) to 16 patients (27%). Univariate and multivariate Cox regression analyses were conducted to identify the possible associations between patient age, race, gender, tumor site, histologic features, grade, size, stage, surgical margin, RT dose, modality (EBRT vs. EBRT plus brachytherapy), and presentation (primary vs. recurrent) and disease control.nnnRESULTSnThe actuarial 5- and 10-year disease-free survival rate was 53% and 44%, respectively. Disease-free survival was significantly associated with female gender on univariate analysis (67% for female patients and 37% for male patients at 5 years, p = 0.05). On multivariate analysis, both gender and surgical margin had borderline significance (p = 0.06). The actuarial local control rate was 71% and 54% at 5 and 10 years, respectively. The median time to local relapse was 10.2 months, with 75% of all failures occurring within 29 months. The surgical margin status was significantly associated with local control (78% for patients with negative or close margins vs. 52% for patients with positive margins at 5 years, p = 0.04). Gender was borderline significant (85% for female patients vs. 54% for male patients at 5 years, p = 0.06). On multivariate analysis, only surgical margin status remained significant (p = 0.032). The distant metastasis-free survival rate at 5 and 10 years was 58% and 54%, respectively. The median time to distant metastases was 15.6 months. The lungs were the most common site of metastases. The only significant factor associated with distant metastasis-free survival was local control (73% for patients with locally controlled tumors vs. 19% for patients with local recurrence at 5 years, p = 0.0013). The actuarial 5- and 10-year overall survival rate was 56% and 47%, respectively. Gender (74% for female patients vs. 37% for male patients at 5 years), surgical margin status (66% for patients with negative or close margins vs. 48% for patients with positive margins at 5 years), and local control (64% for patients with locally controlled tumors vs. 21% for patients with uncontrolled primary tumors at 5 years) were significant predictors on both univariate and multivariate analyses (p <0.05).nnnCONCLUSIONnThe results of this study demonstrate the paramount importance of local control and complete surgical resection in the management of soft-tissue sarcoma of the retroperitoneum and deep trunk.

Dosimetric improvements following 3D planning of tangential breast irradiation.

Abstract Purpose: To evaluate the dosimetric difference between a simple radiation therapy plan utilizing a single contour and a more complex three-dimensional (3D) plan utilizing multiple contours, lung inhomogeneity correction, and dose-based compensators. Methods and Materials: This is a study of the radiation therapy (RT) plans of 85 patients with early breast cancer. All patients were considered for breast-conserving management and treated by conventional tangential fields technique. Two plans were generated for each patient. The first RT plan was based on a single contour taken at the central axis and utilized two wedges. The second RT plan was generated by using the 3D planning system to design dose-based compensators after lung inhomogeneity correction had been made. The endpoints of the study were the comparison between the volumes receiving greater than 105% and greater than 110% of the reference dose, as well as the magnitude of the treated volume maximum dose. Dosimetric improvement was defined to be of significant value if the volume receiving > 105% of one plan was reduced by at least 50% with the absolute difference between the volumes being 5% or greater. The dosimetric improvements in 49 3D plans (58%) were considered of significant value. Patients field separation and breast size did not predict the magnitude of improvement in dosimetry. Conclusion: Dose-based compensator plans significantly reduced the volumes receiving > 105%, >110%, and volume maximum dose.

External beam radiotherapy for painful osseous metastases: pooled data dose response analysis

PURPOSEnAlthough the effectiveness of external beam irradiation in palliation of pain from osseous metastases is well established, the optimal fractionation schedule has not been determined. Clinical studies to date have failed to demonstrate an advantage for higher doses. To further address this issue, we conducted a pooled dose response analysis using data from published Phase III clinical trials.nnnMETHODS AND MATERIALSnComplete response (CR) was used as an endpoint because it was felt to be least susceptible to inconsistencies in assessment.The biological effective dose (BED) was calculated for each schedule using the linear-quadratic model and an alpha/beta of 10. Using SAS version 6.12, the data were fitted using a weighted linear regression, a logistic model, and the spline technique. Finally, BED was categorized, and odds ratios for each level were calculated.nnnRESULTSnCR was assessed early and late in 383 and 1,007 patients, respectively. Linear regression on the early-response data yielded a poor fit and a nonsignificant dose coefficient. With the late-response data, there was an excellent fit (R-square = 0.842) and a highly significant dose coefficient (p = 0.0002). Fitting early CR to a logistic model, we could not establish a significant dose response relationship. However, with the late-response data there was an excellent fit and the dose coefficient was significantly different from zero (0.017 +/- 0.00524; p = 0.0012). Application of the spline technique or removal of an outlier resulted in an improved fit (p = 0.048 and p = 0.0001, respectively). Using BED of < 14.4 Gy as a reference level, the odds ratios for late CR were 2.29-3.32 (BED of 19.5-51.4 Gy, respectively).nnnCONCLUSIONnOur results demonstrate a clear dose-response for pain relief. Further testing of high intensity regiments is warranted.

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

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

Dosimetric imrovements following 3-D planning of tangential breast irradiation

PURPOSEnTo evaluate the dosimetric difference between a simple radiation therapy plan utilizing a single contour and a more complex three-dimensional (3D) plan utilizing multiple contours, lung inhomogeneity correction, and dose-based compensators.nnnMETHODS AND MATERIALSnThis is a study of the radiation therapy (RT) plans of 85 patients with early breast cancer. All patients were considered for breast-conserving management and treated by conventional tangential fields technique. Two plans were generated for each patient. The first RT plan was based on a single contour taken at the central axis and utilized two wedges. The second RT plan was generated by using the 3D planning system to design dose-based compensators after lung inhomogeneity correction had been made. The endpoints of the study were the comparison between the volumes receiving greater than 105% and greater than 110% of the reference dose, as well as the magnitude of the treated volume maximum dose. Dosimetric improvement was defined to be of significant value if the volume receiving > 105% of one plan was reduced by at least 50% with the absolute difference between the volumes being 5% or greater. The dosimetric improvements in 49 3D plans (58%) were considered of significant value. Patients field separation and breast size did not predict the magnitude of improvement in dosimetry.nnnCONCLUSIONnDose-based compensator plans significantly reduced the volumes receiving > 105%, >110%, and volume maximum dose.