Jacques Laverdière

Beneficial effect of combination hormonal therapy administered prior and following external beam radiation therapy in localized prostate cancer

PURPOSE The aim of the present study is to investigate whether combined androgen blockade associated with radiation therapy for localized prostate cancer decreases at 12 and 24 months the rate of positive follow-up biopsies and serum PSA compared to radiation therapy alone. This is the report of an interim analysis. METHODS AND MATERIALS One hundred and twenty patients with clinical Stage B1-T2a, B2-T2b/T2c, and C-T3/T4, adenocarcinoma of the prostate were entered in a prospective randomized study. After written informed consent, the subjects were randomly allocated between external beam radiation therapy (EBRT) alone (group 1), 3 months of neoadjuvant combination therapy (LHRH-agonist + Flutamide) prior to EBRT (group 2), and a third group receiving combination therapy 3 months before, during, and 6 months after EBRT. There is no significant difference between the three groups concerning age, stage of disease, grade of tumor, and pretreatment PSA levels. Control transrectal ultrasound (TRUS)-guided needle biopsies (one core was taken from the initial cancer site regardless of the presence or absence of TRUS abnormalities) were done 12 and 24 months after the end of EBRT. Serum PSA measurements were done on schedule visits. RESULTS Ninety-two and 68 patients underwent biopsies at 12 and 24 months, respectively, after the end of radiation therapy. While 62% of control patients at 12 months in Group 1 disclosed residual neoplasm, only 30% and 4% showed residual disease in groups 2 and 3, respectively (p = 0.00005). When looking at 24 months, 65, 28, and 5% showed residual cancer for groups 1, 2, and 3, respectively (p = 0.00001). The PSA measurements indicate also at 12 months a difference between the three groups (p < 0.0001), except at 24 months, the difference between the group 2 and 3 is no longer significant. CONCLUSION The preliminary analysis of this clinical trial indicates that patients treated with radiation therapy alone show a significantly higher rate of positive biopsies at 12 and 24 months after the end of radiation therapy as compared with those treated with total antiandrogen blockade (TAB) and radiation therapy. When analyzing the median PSA serum levels, we found the same advantage at 12 months, but, at the time of the analysis at 24 months, the PSA levels are not different between groups 2 and 3.

Electronic portal imaging device detection of radioopaque markers for the evaluation of prostate position during megavoltage irradiation: A clinical study

PURPOSE This study was designed to assess daily prostatic apex motion relative to pelvic bone structures during megavoltage irradiation. METHODS AND MATERIALS Radioopaque markers were implanted under ultrasound guidance near the prostatic apex of 11 patients with localized prostatic carcinoma. Patients were subsequently treated with a four field-box technique at a beam energy of 23 MV. During treatment, on-line images were obtained with an electronic portal imaging device (EPID). The marker was easily identified, even on unprocessed images, and the distance between the marker and a bony landmark was measured. Timelapse movies were also reviewed. After the completion of treatment, a transrectal ultrasound examination was performed in 8 of 11 patients, to verify the position of the marker. RESULTS We acquired over 900 digital portal images and analyzed posterioanterior and right lateral views. The quality of portal images obtained with megavoltage irradiation was good. It was possible to evaluate pelvic bone structures even without image histogram equalization. Moreover, the radioopaque marker was easily visible on every online portal image. The review of timelapse movies showed important interfraction motion of the marker while bone structures remained stable. We measured the position of the marker for each fraction. Marker displacements up to 1.6 cm were measured between 2 consecutive days of treatment. Important marker motions were predominantly in the posteroanterior and cephalocaudal directions. In eight patients, we verified the position of the marker relative to the prostatic apex with ultrasound at the end of the treatments. The marker remained in the trapezoid zone. Intratreatment images reviewed in two cases showed no-change in marker position. Our results, obtained during the treatment courses, indicate similar or larger prostate motions than previously observed in studies that used intertreatment x-ray films and CT images. Marker implantation under transrectal ultrasound was well tolerated. CONCLUSIONS Radioopaque marker and the use of electronic portal imaging give a direct evaluation of prostatic motion during radiation treatment. As suggested in previous studies the motions observed are predominantly in the posteroanterior and cephalocaudal directions. Therefore, prostate motion during treatment is important and must be considered especially when using conformal therapy.

Local Failure Is Responsible for the Decrease in Survival for Patients With Breast Cancer Treated With Conservative Surgery and Postoperative Radiotherapy

PURPOSE The aim of the present study was to evaluate the role of local failure (LF) in the survival of patients treated with lumpectomy and postoperative radiotherapy and to investigate whether LF is not only a marker for distant metastasis (DM) but also a cause. METHODS Charts of patients treated with breast conservative surgery between 1969 and 1991 were reviewed retrospectively. There were 2,030 patients available for analysis. The median duration of follow-up was 6 years. A Cox regression multivariate analysis was performed using LF as a time-dependent covariate. RESULTS Local control (LC) was 87% at 10 years. Local failure led to poorer survival at 10 years than local control (55% v 75%, P < .00). In a Cox model, local failure was a powerful predictor of mortality. The relative risk associated with LF was 3.6 for mortality and 5.1 for DM (P < .00). In patients with LF, the rate of DM peaked at 5 to 6 years, whereas it peaked at 2 years for patients with LC. The mean time between surgery and DM was 1,050 days for patients without LF and 1,650 days for patients with LF (P < .00). CONCLUSION Our results show that local failure is associated with an increase in mortality. The difference in the time distribution of distant metastasis for LF and LC could imply distinct mechanisms of dissemination. Local failure should be considered not only as a marker of occult circulating distant metastases but also as a source for new distant metastases and subsequent mortality.