Faculty Bibliography

OBJECTIVE:To report the long-term tumor control and survival outcomes after conformal external-beam radiotherapy for patients with clinical stage T3 prostate cancer. METHODS:Between 1988 and 2000, 296 patients with clinical stage T3 prostate cancer were treated with three-dimensional conformal radiotherapy and intensity-modulated radiotherapy. Of these, 130 patients (44%) had stage T3a (extracapsular extension without seminal vesicle involvement [SVI]) and 166 patients (56%) had stage T3b disease (SVI). Prior to radiotherapy, 189 patients (43%) were treated with short-course androgen-deprivation therapy (ADT). The median follow-up time was 8 yr. RESULTS:The 5- and 10-yr prostate-specific antigen (PSA) relapse-free survival (PRFS) outcomes for stage T3a tumors were 69% and 44%, respectively. The corresponding PRFS outcomes for T3b tumors were 49% and 32% (p=0.005). Despite the presence of locally advanced disease, the 5- and 10-yr local progression-free survival (LPFS) outcomes for all patients were 87% and 83%. Among patients who received > or =8100 cGy and ADT, the 5- and 10-yr local control rates were 96% and 88%. The 5- and 10-yr distant metastases-free survival (DMFS) outcomes for stage T3a tumors were 85% and 73%. The corresponding DMFS outcomes for T3b tumors were 49% and 32% (p=0.005). Multivariate analysis demonstrated that ADT conferred a 7-fold risk reduction for local failure. Pretreatment PSA levels and the presence of SVI on clinical staging were important predictors of distant metastases. CONCLUSIONS:Conformal radiotherapy for T3 prostate cancer is associated with excellent tumor control and survival outcomes. These results are at least comparable to reported outcomes from surgical series for T3 disease and substantiate the role of radiotherapy as the standard management option for locally advanced stage prostate cancer.

We seek to identify dosimetric and anatomic indicators of late rectal toxicity in prostate cancer patients treated with intensity modulated radiation therapy (IMRT). Data from 49 patients sampled from 698 patients treated for clinically localized prostate cancer at the Memorial Sloan-Kettering Cancer Center with IMRT to a dose of 81 Gy were analyzed. The end point of the study was late Grade 2 or worse rectal toxicity within 30 months of treatment. Dosimetric analysis was performed on the rectum surface in three dimensions and on two-dimensional dose maps obtained by flattening the rectum surface using a conformal mapping procedure. Several parameters including the percentage and absolute surface area of the rectum irradiated, mean dose as a function of location on the rectum, planning target volume (PTV) size and rectum size were analyzed for correlation to toxicity. Significance was set at p < 0.05 for a two-sided t-test. Correlation between absolute areas irradiated and toxicity was observed on both the rectum surface and flattened rectum. Patients with toxicity also received a significantly higher mean dose to the superior 25% of the rectum surface and 15% of the flattened rectum. PTV volume, PTV height, rectum surface area and average cross-sectional area were significantly larger in patients with toxicity. The conformal mapping procedure has potential utility for evaluating dose to the rectum and risk of toxicity. Late rectal toxicity was related to the irradiation of the upper part of the rectum and also to the absolute area irradiated, PTV size, and rectum size on the planning computed tomography (CT) scan.

PURPOSE/OBJECTIVE:We report local control outcomes, as assessed by posttreatment biopsies in patients who underwent 3-dimensional conformal radiotherapy for clinically localized prostate cancer. In addition, we report the influence of local tumor control on long-term distant metastases and cause specific survival outcomes. MATERIALS AND METHODS/METHODS:Posttreatment prostate biopsies were performed in 339 patients who underwent 3-dimensional conformal radiotherapy for clinically localized prostate cancer. The histological outcome of prostate biopsy was classified as positive-prostatic adenocarcinoma without typical radiation induced changes or negative-no evidence of carcinoma or severe treatment effect. Median followup in this group of 339 patients was 10 years after the completion of treatment and 6.25 years after posttreatment biopsy. RESULTS:Overall biopsy outcomes in these patients were positive in 32%, severe treatment effect in 21% and negative in 47%. A higher radiation dose in the intermediate and high risk subgroups was associated with a lower incidence of positive biopsy. Of patients at intermediate risk who received a dose of 75.6 or greater 24% had a positive biopsy compared to 42% who received 70.2 Gy or less (p = 0.03). In the high risk group positive treatment biopsies were noted in 51% of patients who received 70.2 Gy or less, 33% of those who received 75.6 Gy and 15% of those who received 81 Gy or greater (70.2 or less vs 75.6 Gy p = 0.07 and 75.6 vs 81 Gy or greater p = 0.05). Short course neoadjuvant androgen deprivation therapy before 3-dimensional conformal radiotherapy had a significant impact on the posttreatment biopsy outcome. Of patients who did not receive androgen deprivation therapy 42% had a positive biopsy compared to 16% who received androgen deprivation therapy (p <0.0001). Patients with negative and severe treatment effect biopsies had similar 10-year prostate specific antigen relapse-free survival outcomes that were markedly different from outcomes in those with positive treatment biopsies. Multivariate analysis indicated that the strongest predictor of biochemical failure was posttreatment biopsy status (positive vs severe treatment effect or negative p <0.001), followed by pretreatment prostate specific antigen (p = 0.05) and clinical T stage (p = 0.09). Similarly multivariate analysis revealed that a positive posttreatment biopsy was one of the strongest predictors of distant metastasis and prostate cancer death in this cohort of patients. CONCLUSIONS:As assessed by posttreatment prostate biopsies, local control is improved with higher radiation doses. Long-term biochemical outcomes in patients with posttreatment biopsies demonstrating severe treatment effect changes were not different than those in patients with negative biopsies. We also noted that local tumor control was associated with a decrease in distant metastases and prostate cancer mortality, further highlighting the importance of achieving optimal tumor control in patients with clinically localized disease.

PURPOSE/OBJECTIVE:To report the incidence and predictors of treatment-related toxicity at 10 years after three-dimensional conformal radiotherapy (3D-CRT) and intensity-modulated radiotherapy (IMRT) for localized prostate cancer. METHODS AND MATERIALS/METHODS:Between 1988 and 2000, 1571 patients with stages T1-T3 prostate cancer were treated with 3D-CRT/IMRT with doses ranging from 66 to 81 Gy. The median follow-up was 10 years. Posttreatment toxicities were all graded according to the National Cancer Institute's Common Terminology Criteria for Adverse Events. RESULTS:The actuarial likelihood at 10 years for the development of Grade>or=2 GI toxicities was 9%. The use of IMRT significantly reduced the risk of gastrointestinal (GI) toxicities compared with patients treated with conventional 3D-CRT (13% to 5%; p<0.001). Among patients who experienced acute symptoms the 10-year incidence of late toxicity was 42%, compared with 9% for those who did not experience acute symptoms (p<0.0001). The 10-year incidence of late Grade>or=2 genitourinary (GU) toxicity was 15%. Patients treated with 81 Gy (IMRT) had a 20% incidence of GU symptoms at 10 years, compared with a 12% for patient treated to lower doses (p=0.01). Among patients who had developed acute symptoms during treatment, the incidence of late toxicity at 10 years was 35%, compared with 12% (p<0.001). The incidence of Grade 3 GI and GU toxicities was 1% and 3%, respectively. CONCLUSIONS:Serious late toxicity was unusual despite the delivery of high radiation dose levels in these patients. Higher doses were associated with increased GI and GU Grade 2 toxicities, but the risk of proctitis was significantly reduced with IMRT. Acute symptoms were a precursor of late toxicities in these patients.

PURPOSE/OBJECTIVE:Unknown primary head and neck cancers often require comprehensive mucosal and bilateral neck irradiation. With conventional techniques, significant toxicity can develop. Intensity-modulated radiotherapy (IMRT) has the potential to minimize the toxicity. METHODS AND MATERIALS/METHODS:Between 2000 and 2005, 21 patients underwent IMRT for unknown primary head and neck cancer at our center. Of the 21 patients, 5 received IMRT with definitive intent and 16 as postoperative therapy; 14 received concurrent chemotherapy and 7 IMRT alone. The target volumes included the bilateral neck and mucosal surface. The median dose was 66 Gy. Acute and chronic toxicities, esophageal strictures, and percutaneous endoscopic gastrostomy tube dependence were evaluated. Progression-free survival, regional progression-free survival, distant metastasis-free survival, and overall survival were estimated with Kaplan-Meier curves. RESULTS:With a median follow-up of 24 months, the 2-year regional progression-free survival, distant metastasis-free survival, and overall survival rate was 90%, 90%, and 85%, respectively. Acute grade 1 and 2 xerostomia was seen in 57% and 43% of patients, respectively. Salivary function improved with time. Percutaneous endoscopic gastrostomy tube placement was required in 72% with combined modality treatment and 43% with IMRT alone. Only 1 patient required percutaneous endoscopic gastrostomy support at the last follow-up visit. Two patients treated with combined modality and one treated with IMRT alone developed esophageal strictures, but all had improvement or resolution with dilation. CONCLUSION/CONCLUSIONS:The preliminary analysis of IMRT for unknown primary head and neck cancer has shown acceptable toxicity and encouraging efficacy. The analysis of the dosimetric variables showed excellent tumor coverage and acceptable doses to critical normal structures. Esophageal strictures developed but were effectively treated with dilation. Techniques to limit the esophageal dose could help further minimize this complication.

Since its introduction into clinical use in the mid-1990s, intensity-modulated radiation therapy (IMRT) has emerged as the most effective and widely used form of external-beam radiotherapy for localized prostate cancer. Multiple studies have confirmed the importance of delivering sufficiently high doses to the prostate to achieve cure. The dosimetric superiority of IMRT over conventional techniques to produce conformal dose distributions that allow for organ sparing has been shown. A growing number of reports have confirmed that IMRT is the safest way to deliver high doses of external-beam irradiation to the prostate and the regional lymph nodes. Advances in imaging and onboard verification systems continue to advance the capabilities of IMRT and have potential implications with regards to further dose escalation and hypofractionated regimens. The clinical data in support of IMRT and the associated technical aspects of IMRT treatment planning and implementation are highlighted in this review.