Faculty Bibliography

OBJECTIVES/OBJECTIVE:To examine the long-term neck failure outcome in patients with advanced head and neck cancer treated on larynx/organ preservation protocols at Memorial Sloan-Kettering Cancer Center. MATERIALS AND METHODS/METHODS:Two hundred thirteen patients were enrolled from 1983 through 1995 on larynx/organ preservation protocols receiving induction chemotherapy followed by radiotherapy alone or with concomitant chemotherapy. Eighty-six patients with node-positive disease received definitive chemoradiotherapy at Memorial Sloan-Kettering Cancer Center. A median dose of 70 Gy was delivered. The median follow-up of the surviving patients was 9 years. RESULTS:Sixty-five patients with node-positive disease achieved a clinical complete response and were observed after chemoradiation without immediate neck dissection. The crude rate of subsequent neck failure among those patients according to initial nodal classification was: N1 14% (3 of 21), N2: 15% (6 of 40), N3: 0% (0 of 4). The median overall survival of these patients was: N1: 12.2 years; N2: 6.5 years; N3: 0.8 years. Patients who experienced a complete response to induction chemotherapy in the neck had improved overall survival (53% vs. 29%; P = 0.005) and a lower incidence of neck failure (10% vs. 24%; P = 0.14) when compared with those patients who had less than a complete response. CONCLUSIONS:Our data suggests that in patients with advanced neck disease who have a clinical complete response in the neck to chemoradiation long-term neck control is 85% or greater without neck dissection. Whether functional imaging or treatment response to induction chemotherapy would provide better discrimination of the 10% to 15% who may experience neck relapse is an important question for future research initiatives.

PURPOSE/OBJECTIVE:To report prostate-specific antigen (PSA) relapse-free survival and distant metastases-free survival (DMFS) outcomes for patients with clinically localized prostate cancer treated with high-dose conformal radiotherapy. METHODS AND MATERIALS/METHODS:Between 1988 and 2004, a total of 2,047 patients with clinically localized prostate cancer were treated with three-dimensional conformal radiotherapy or intensity-modulated radiotherapy. Prescribed dose levels ranged from 66-86.4 Gy. Median follow-up was 6.6 years (range, 3-18 years). RESULTS:Although no differences were noted among low-risk patients for the various dose groups, significant improvements were observed with higher doses for patients with intermediate- and high-risk features. In patients with intermediate-risk features, multivariate analysis showed that radiation dose was an important predictor for improved PSA relapse-free survival (p < 0.0001) and improved DMFS (p = 0.04). In patients with high-risk features, multivariate analysis showed that the following variables predict for improved PSA relapse-free survival: dose (p < 0.0001); age (p = 0.0005), and neoadjuvant-concurrent androgen deprivation therapy (ADT; p = 0.01). In this risk group, only higher radiation dose was an important predictor for improved DMFS (p = 0.04). CONCLUSIONS:High radiation dose levels were associated with improved biochemical tumor control and decreased risk of distant metastases. For high-risk patients, despite the delivery of high radiation dose levels, the use of ADT conferred an additional benefit for improved tumor control outcomes. We observed a benefit for ADT in high-risk patients who received higher doses.

BACKGROUND:Our aim was to review Memorial Sloan-Kettering Cancer Center's experience with postoperative intensity-modulated radiotherapy (IMRT) for paranasal sinus, nasal cavity, and lacrimal gland cancer and report dosimetric measures, toxicity, and outcomes. METHODS:Between September 2000 and June 2006, 37 patients with paranasal sinus, nasal cavity, or lacrimal gland cancer underwent postoperative IMRT. Median values were as follows: prescription dose, 60 Gy (range, 50-70); PTV(D95), 99% (range, 79-101%); optic nerve Dmax, 53 Gy (range, 2-54); optic chiasm Dmax, 51Gy (range, 2-55). Acute and late toxicities were scored by Radiation Therapy Oncology Group morbidity criteria. RESULTS:Median follow-up was 28 months. Two-year local progression-free and overall survivals were 75% and 80%. No early- or late-grade 3/4 radiation-induced ophthalmologic toxicity occurred. CONCLUSIONS:Preliminary results show that adjuvant IMRT in these patients is feasible, allowed for excellent planning target volume (PTV) coverage, and minimized dose delivered to optic structures. Longer follow-up is warranted to assess the extent of late effects and outcomes.

PURPOSE/OBJECTIVE:To report toxicity and preliminary biochemical outcomes with high-dose intensity-modulated radiation therapy (IMRT) to a dose of 86.4 Gy for localized prostate cancer. METHODS AND MATERIALS/METHODS:Between August 1997 and March 2004, 478 patients were treated with 86.4 Gy using a 5- to 7-field IMRT technique. To adhere to normal tissue constraints, the mean D95 and V100 for the planning target volume were 83 Gy and 87%, respectively. Toxicity data were scored according to the Common Terminology Criteria for Adverse Events Version 3.0. Freedom from biochemical relapse was calculated. The median follow-up was 53 months. RESULTS:Thirty-seven patients (8%) experienced acute Grade 2 gastrointestinal (GI) toxicity. There was no acute Grade 3 or 4 GI toxicity. One hundred and five patients (22%) experienced acute Grade 2 genitourinary (GU) toxicity and three patients (0.6%) had Grade 3 GU toxicity. There was no acute Grade 4 GU toxicity. Sixteen patients (3%) developed late Grade 2 GI toxicity and two patients (<1%) developed late Grade 3 GI toxicity. Sixty patients (13%) had late Grade 2 GU toxicity and 12 (<3%) experienced late Grade 3 GU toxicity. The 5-year actuarial PSA relapse-free survival according to the nadir plus 2 ng/mL definition was 98%, 85% and 70% for the low, intermediate, and high risk NCCN prognostic groups. CONCLUSION/CONCLUSIONS:This report represents the largest data set of patients treated to ultra-high radiation dose levels of 86.4 Gy using IMRT for localized prostate cancer. Our findings indicate that this treatment is well tolerated and the early excellent biochemical control rates are encouraging.

PURPOSE/OBJECTIVE:To report tumor control and toxicity for patients treated with image-guided intensity-modulated radiotherapy (RT) for spinal metastases with high-dose single-fraction RT. METHODS AND MATERIALS/METHODS:A total of 103 consecutive spinal metastases in 93 patients without high-grade epidural spinal cord compression were treated with image-guided intensity-modulated RT to doses of 18-24 Gy (median, 24 Gy) in a single fraction between 2003 and 2006. The spinal cord dose was limited to a 14-Gy maximal dose. The patients were prospectively examined every 3-4 months with clinical assessment and cross-sectional imaging. RESULTS:The overall actuarial local control rate was 90% (local failure developed in 7 patients) at a median follow-up of 15 months (range, 2-45 months). The median time to local failure was 9 months (range, 2-15 months) from the time of treatment. Of the 93 patients, 37 died. The median overall survival was 15 months. In all cases, death was from progression of systemic disease and not local failure. The histologic type was not a statistically significant predictor of survival or local control. The radiation dose was a significant predictor of local control (p = 0.03). All patients without local failure also reported durable symptom palliation. Acute toxicity was mild (Grade 1-2). No case of radiculopathy or myelopathy has developed. CONCLUSION/CONCLUSIONS:High-dose, single-fraction image-guided intensity-modulated RT is a noninvasive intervention that appears to be safe and very effective palliation for patients with spinal metastases, with minimal negative effects on quality of life and a high probability of tumor control.

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.