Faculty Bibliography

PURPOSE/OBJECTIVE:To report the dosimetric outcome of patients with clinically localized prostate cancer treated with I-125 permanent implantation using an intraoperative real-time conformal planning technique. METHODS AND MATERIALS/METHODS:Five hundred and sixty-two patients with prostate cancer were treated with I-125 permanent interstitial implantation using a transrectal ultrasound-guided approach. Real-time intraoperative treatment planning software that incorporates inverse planning optimization was used. Dose-volume constraints for this inverse-planning system included: prostate V100 >or=95%, maximal urethral dose <or=120%, and average rectal dose <80% of the prescription dose. Day zero computed tomography scans were acquired for post-implantation dosimetric evaluation. RESULTS:The median V100 and D90 to the prostate target were 96% and 166 Gy, respectively. In 91% of cases a D90 of >or=140 Gy was achieved. In these patients, the V100 and D90 values did not have a significant influence on PSA relapse-free survival outcomes. The median maximum rectal dose and urethral doses were 104 Gy (72% of the prescription dose) and 187 Gy (130% of the prescription dose). The average and maximum rectal doses exceeding 100% of the prescription dose were less than 1% and 10% of patients, respectively. Average and maximum urethral doses exceeding 150% of the prescription dose were noted in 3% and 24% of patients, respectively. Average and maximum urethral doses exceeded 120% of the prescription dose in 21% and 58% of patients, respectively. Among patients where >or=2.5 cm(3) of the rectum was exposed to the prescription dose, the incidence of late grade 2 toxicity rectal toxicity was 9% compared to 4% for smaller volumes of the rectum exposed to similar doses (p=0.003). No dosimetric parameter in these patients with tight dose confines for the urethra influenced acute or late urinary toxicity. CONCLUSION/CONCLUSIONS:Real-time intraoperative planning was associated with a 90% consistency of achieving the planned intraoperative dose constraints for target coverage and maintaining planned urethral and rectal constraints in a high percentage of implants. Rectal volumes of >or=2.5 cm(3) exposed to the prescription doses were associated with an increased incidence of grade 2 rectal bleeding. Further enhancements in imaging guidance for optimal seed deposition are needed to guarantee optimal dose distribution for all patients. Whether such improvements lead to further reduction in acute and late morbidities associated with therapy requires further study.

PURPOSE/OBJECTIVE:To identify factors significantly influencing accrual to clinical protocols by analyzing radiation Patterns of Care Study (PCS) surveys of 3,047 randomly selected radiotherapy (RT) patients. METHODS AND MATERIALS/METHODS:Patterns of Care Study surveys from disease sites studied for the periods 1992-1994 and 1996-1999 (breast cancer, n = 1,080; prostate cancer, n = 1,149; esophageal cancer, n = 818) were analyzed. The PCS is a National Cancer Institute-funded national survey of randomly selected RT institutions in the United States. Patients with nonmetastatic disease who received RT as definitive or adjuvant therapy were randomly selected from eligible patients at each institution. To determine national estimates, individual patient records were weighted by the relative contribution of each institution and patients within each institution. Data regarding participation in clinical trials were recorded. The factors age, gender, race, type of insurance, and practice type of treating institution (academic or not) were studied by univariate and multivariate analyses. RESULTS:Overall, only 2.7% of all patients were accrued to clinical protocols. Of these, 57% were enrolled on institutional review board-approved institutional trials, and 43% on National Cancer Institute collaborative group studies. On multivariate analysis, patients treated at academic facilities (p = 0.0001) and white patients (vs. African Americans, p = 0.0002) were significantly more likely to participate in clinical oncology trials. Age, gender, type of cancer, and type of insurance were not predictive. CONCLUSIONS:Practice type and race significantly influence enrollment onto clinical oncology trials. This suggests that increased communication and education regarding protocols, particularly focusing on physicians in nonacademic settings and minority patients, will be essential to enhance accrual.

PURPOSE: To present a retrospective review of treatment outcomes for recurrent head and neck (HN) cancer patients treated with re-irradiation (re-RT) at a single medical center. METHODS AND MATERIALS: From July 1996-September 2005, 105 patients with recurrent HN cancer underwent re-RT at our institution. Sites included were: the neck (n = 21), nasopharynx (n = 21), paranasal sinus (n = 18), oropharynx (n = 16), oral cavity (n = 9), larynx (n = 10), parotid (n = 6), and hypopharynx (n = 4). The median prior RT dose was 62 Gy. Seventy-five patients received chemotherapy with their re-RT (platinum-based in the majority of cases). The median re-RT dose was 59.4 Gy. In 74 (70%), re-RT utilized intensity-modulated radiation therapy (IMRT). RESULTS: With a median follow-up of 35 months, 18 patients were alive with no evidence of disease. The 2-year loco-regional progression-free survival (LRPFS) and overall survival rates were 42% and 37%, respectively. Patients who underwent IMRT, compared to those who did not, had a better 2-year LRPF (52% vs. 20%, p < 0.001). On multivariate analysis, non-nasopharynx and non-IMRT were associated with an increased risk of loco-regional (LR) failure. Patients with LR progression-free disease had better 2-year overall survival vs. those with LR failure (56% vs. 21%, p < 0.001). Acute and late Grade 3-4 toxicities were reported in 23% and 15% of patients. Severe Grade 3-4 late complications were observed in 12 patients, with a median time to development of 6 months after re-RT. CONCLUSIONS: Based on our data, achieving LR control is crucial for improved overall survival in this patient population. The use of IMRT predicted better LR tumor control. Future aggressive efforts in maximizing tumor control in the recurrent setting, including dose escalation with IMRT and improved chemotherapy, are warranted

PURPOSE/OBJECTIVE:An increasing serum prostate-specific antigen (PSA) level is the initial sign of recurrent prostate cancer among patients treated with radical prostatectomy. Salvage radiation therapy (SRT) may eradicate locally recurrent cancer, but studies to distinguish local from systemic recurrence lack adequate sensitivity and specificity. We developed a nomogram to predict the probability of cancer control at 6 years after SRT for PSA-defined recurrence. PATIENTS AND METHODS/METHODS:Using multivariable Cox regression analysis, we constructed a model to predict the probability of disease progression after SRT in a multi-institutional cohort of 1,540 patients. RESULTS:The 6-year progression-free probability was 32% (95% CI, 28% to 35%) overall. Forty-eight percent (95% CI, 40% to 56%) of patients treated with SRT alone at PSA levels of 0.50 ng/mL or lower were disease free at 6 years, including 41% (95% CI, 31% to 51%) who also had a PSA doubling time of 10 months or less or poorly differentiated (Gleason grade 8 to 10) cancer. Significant variables in the model were PSA level before SRT (P < .001), prostatectomy Gleason grade (P < .001), PSA doubling time (P < .001), surgical margins (P < .001), androgen-deprivation therapy before or during SRT (P < .001), and lymph node metastasis (P = .019). The resultant nomogram was internally validated and had a concordance index of 0.69. CONCLUSION/CONCLUSIONS:Nearly half of patients with recurrent prostate cancer after radical prostatectomy have a long-term PSA response to SRT when treatment is administered at the earliest sign of recurrence. The nomogram we developed predicts the outcome of SRT and should prove valuable for medical decision making for patients with a rising PSA level.

PURPOSE: Although high-dose-rate brachytherapy (HDRBT) offers significant advantages over low dose rate brachytherapy, there are scant data on improved local control (LC) and treatment-related complications in patients with recurrent head and neck (H&N) cancers. We report our preliminary results in patients with recurrent H&N cancers treated with interstitial HDRBT. METHODS AND MATERIALS: Thirty patients with recurrent H&N cancers were treated with HDRBT between September 2003 and October 2005. Seventy-seven percent (23/30) of the patients had either local or regional recurrence in the area of previous external beam radiation therapy. The treatment sites were oral cavity/oropharynx (11/30), neck (10/30), face/nasal cavity (6/30), and parotid bed (3/30). Whereas 18 patients underwent surgical resection followed by HDRBT, 3 patients were treated with combined external beam radiation and HDRBT, and the remaining 9 were treated with HDRBT alone. The dose and fractionation schedules used were 3.4Gy twice per day (b.i.d.) to 34Gy for postoperative cases, 4Gy b.i.d. to 20Gy when combined with 40-50Gy external beam, and 4Gy b.i.d. to 40Gy for definitive treatment. HDRBT was initiated 5 days after catheter placement to allow for tissue healing. RESULTS: With a median followup of 12 months, 6 local recurrences were observed 1-10 months after the procedure. The 2-year LC and overall survival outcomes for the entire group were 71% and 63%, respectively. Patients treated with surgical resection and HDRBT had an improved 2-year LC compared to the patients treated with HDRBT+/-external beam radiation alone (88% vs. 40%, p=0.05). Six Grade II and four Grade III complications were noted in five patients, all observed in the postoperative HDRBT group. CONCLUSION: The preliminary results of HDRBT indicate an acceptable LC and morbidity in recurrent H&N cancers. A planned surgical resection followed by HDRBT is associated with improved tumor control in these high-risk patients. Based on these encouraging results, prospective clinical trials are warranted using HDRBT in recurrent H&N cancers to decrease late toxicity

In this paper we put forward the claim that the combination of low dose-rate brachytherapy (BRT) and fractionated external-beam radiotherapy (EBRT) may, when planned to take advantage of the relative advantages of each of these two modalities, result in enhanced tumor dose with no penalties to organs at risk. The concept of iso-effective dose (IED) serves the role of common currency for fusing BRT and EBRT and, for evaluation purposes, converting back the resulting IED distribution into a biologically equivalent plan delivered by any single modality. If we accept this view, there are further questions that must be answered regarding practical matters. We show how to deal with these questions by describing an actual patient plan.

PURPOSE/OBJECTIVE:To perform a retrospective analysis of patients with paranasal sinus (PNS) cancer treated with postoperative radiotherapy (RT) at Memorial Sloan-Kettering Cancer Center. METHODS AND MATERIALS/METHODS:Between January 1987 and July 2005, 85 patients with PNS and nasal cavity cancer underwent postoperative RT. Most patients had squamous cell carcinoma (49%; n = 42), T4 tumors (52%; n = 36), and the maxillary sinus (53%; n = 45) as the primary disease site. The median radiation dose was 63 Gy. Of the 85 patients, 76 underwent CT simulation and 53 were treated with either three-dimensional conformal RT (27%; n = 23) or intensity-modulated RT (35%; n = 30). Acute and late toxicities were scored according to the Radiation Therapy Oncology Group radiation morbidity scoring criteria. RESULTS:With a median follow-up for surviving patients of 60 months, the 5-year estimates of local progression-free, regional progression-free, distant metastasis-free, disease-free, and overall survival rates were 62%, 87%, 82%, 55%, and 67%, respectively. On multivariate analysis, squamous cell histology and cribriform plate involvement predicted for an increased likelihood of local recurrence, and squamous cell histologic features predicted for worse overall survival. None of the patients who underwent CT simulation and were treated with modern techniques developed a Grade 3-4 late complication of the eye. CONCLUSION/CONCLUSIONS:Complete surgical resection followed by adjuvant RT is an effective and safe approach in the treatment of PNS cancer. Emerging tools, such as three-dimensional conformal treatment and, in particular, intensity-modulated RT for PNS tumors, may minimize the occurrence of late complications associated with conventional RT techniques. Local recurrence remains a significant problem.

PURPOSE/OBJECTIVE:To assess long-term prostate-specific antigen (PSA) outcome after permanent prostate brachytherapy (BT) and identify predictors of improved disease-free survival. METHODS AND MATERIALS/METHODS:Eleven institutions combined data on 2,693 patients treated with permanent interstitial BT monotherapy for T1-T2 prostate cancer. Of these patients, 1,831 (68%) were treated with I-125 (median dose, 144 Gy) and 862 (32%) were treated with Pd-103 (median dose, 130 Gy). Criteria for inclusion were: available pre-BT PSA, BT > or =5 years before data submission, BT between 1988-1998, and no androgen deprivation before failure. The median follow-up was 63 months. RESULTS:Among patients where the I-125 dose to 90% of the prostate (D90) was > or =130 Gy, the 8-year PSA relapse-free survival (PRFS) was 93% compared with 76% for those with lower D90 dose levels (p < 0.001). A multivariable analysis identified tumor stage (p = 0.002), Gleason score (p < 0.001), pretreatment PSA level (p < 0.001), treatment year (p = 0.001), and the isotope used (p = 0.004) as pretreatment and treatment variables associated with PRFS. When restricted to patients with available postimplantation dosimetric information, D90 emerged as a significant predictor of biochemical outcome (p = 0.01), and isotope was not significant. The 8-year PRFS was 92%, 86%, 79%, and 67%, respectively, for patients with PSA nadir values of 0-0.49, 0.5-0.99, 1.0-1.99, and >2.0 ng/mL (p < 0.001). Among patients free of biochemical relapse at 8 years, the median nadir level was 0.1 ng/mL, and 90% of these patients achieved a nadir PSA level <0.6 ng/mL. CONCLUSIONS:Outcome after permanent BT for prostatic cancer relates to tumor stage, Gleason score, pretreatment PSA, BT year, and post-BT dosimetric quality. PSA nadir < or =0.5 ng/mL was particularly associated with durable long-term PSA disease-free survival. The only controllable factor to impact on long-term outcome was the D90 which is a reflection of implant quality.

PURPOSE/OBJECTIVE:To report the 5-year tumor control and toxicity outcomes for patients with localized prostate treated with I-125 permanent implantation using an intraoperative real-time conformal planning technique. METHODS AND MATERIALS/METHODS:Between January 1998 and June 2002, 367 patients with prostate cancer were treated with I-125 permanent interstitial implantation using a transrectal ultrasound-guided approach. Real-time intraoperative treatment planning which incorporated inverse planning optimization was used. The median follow-up time was 63 months. RESULTS:The median V100 and D90 were 96% and 173 Gy, respectively. In 96% of cases a D90 of >140 Gy was achieved. The median urethral and rectal doses were 100% and 33% of the prescription doses, respectively. The 5-year PSA relapse-free survival outcomes for favorable and intermediate risk patients according to the ASTRO definition were 96% and 89%, respectively. In these patients no dosimetric parameter was identified which influenced the biochemical outcome. Of 38% who developed acute Grade 2 urinary symptoms, 63% had resolution of their symptoms within a median time of 6 months. The incidence of late rectal and urinary Grade 3 or higher toxicities were 1% and 4%, respectively. Seven percent (n = 27) developed late rectal bleeding (Grade 2) and 19% experienced late Grade 2 urinary symptoms. CONCLUSION/CONCLUSIONS:Real-time intraoperative planning consistently achieved optimal coverage of the prostate with the prescription dose with concomitant low doses delivered to the urethra and rectum. Biochemical control outcomes were excellent at 5 years and late toxicity was unusual. These data demonstrate that real-time planning methods can consistently and reliably deliver the intended dose distribution to achieve an optimal therapeutic ratio between the target and normal tissue structures.