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Title: Intensity-modulated radiation therapy (IMRT) for nasopharynx cancer: Update of the Memorial Sloan-Kettering experience

Abstract

Purpose: We previously demonstrated that intensity-modulated radiation therapy (IMRT) significantly improves radiation dose distribution over three-dimensional planning for nasopharynx cancer and reported positive early clinical results. We now evaluate whether IMRT has resulted in improved outcomes for a larger cohort of patients with longer follow-up. Methods and Materials: Since 1998, all 74 patients with newly diagnosed, nonmetastatic nasopharynx cancer were treated with IMRT using accelerated fractionation to 70 Gy; 59 received a hyperfractionated concomitant boost, and more recently 15 received once-daily treatment with dose painting. With the exception of Stage I disease (n = 5) and patient preference (n = 1), 69 patients received concurrent and adjuvant platinum-based chemotherapy similar to that in the Intergroup 0099 trial. Results: Patient characteristics: median age 45; 32% Asian; 72% male; 65% World Health Organization III; 6% Stage I, 16% Stage II, 30% Stage III, 47% Stage IV. Median follow-up is 35 months. The 3-year actuarial rate of local control is 91%, and regional control is 93%; freedom from distant metastases, progression-free survival, and overall survival at 3 years are 78%, 67%, and 83%, respectively. There was 100% local control for Stage T1/T2 disease, compared to 83% for T3/T4 disease (p = 0.01). Sixmore » patients failed at the primary site, with median time to local tumor progression 16 months; 5 were exclusively within the 70 Gy volume, and 1 was both within and outside the target volume. There is a trend for improved local control with IMRT when compared to local control of 79% for 35 patients treated before 1998 with three-dimensional planning and chemotherapy (p 0.11). Six months posttherapy, 21%, 13%, 15%, and 0% of patients with follow-up audiograms (n = 24 patients) had Grade 1, 2, 3, and 4 sensorineural hearing loss, respectively. For patients with >1 year follow-up (n = 59), rates of long-term xerostomia were as follows: 26% none, 42% Grade 1, 32% Grade 2, and zero Grade 3. Conclusions: The pattern of primary site failure within the target volume suggests locally advanced T stage disease may require a higher biologic dose to gross tumor. Rates of severe (Grade 3-4) ototoxicity and xerostomia are low with IMRT as a result of normal-tissue protection. Distant metastases are now the dominant form of failure, emphasizing the need for improved systemic therapy.« less

Authors:
 [1];  [2];  [3];  [4];  [2];  [2]
  1. Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY (United States). E-mail: woldens@mskcc.org
  2. Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY (United States)
  3. Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY (United States)
  4. Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY (United States)
Publication Date:
OSTI Identifier:
20788266
Resource Type:
Journal Article
Resource Relation:
Journal Name: International Journal of Radiation Oncology, Biology and Physics; Journal Volume: 64; Journal Issue: 1; Other Information: DOI: 10.1016/j.ijrobp.2005.03.057; PII: S0360-3016(05)00592-4; Copyright (c) 2006 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; CHEMOTHERAPY; FAILURES; FRACTIONATED IRRADIATION; METASTASES; NEOPLASMS; PATIENTS; PHARYNX; PLANNING; RADIATION DOSE DISTRIBUTIONS; RADIATION DOSES; RADIOTHERAPY

Citation Formats

Wolden, Suzanne L., Chen, William C., Pfister, David G., Kraus, Dennis H., Berry, Sean L., and Zelefsky, Michael J. Intensity-modulated radiation therapy (IMRT) for nasopharynx cancer: Update of the Memorial Sloan-Kettering experience. United States: N. p., 2006. Web. doi:10.1016/J.IJROBP.2005.0.
Wolden, Suzanne L., Chen, William C., Pfister, David G., Kraus, Dennis H., Berry, Sean L., & Zelefsky, Michael J. Intensity-modulated radiation therapy (IMRT) for nasopharynx cancer: Update of the Memorial Sloan-Kettering experience. United States. doi:10.1016/J.IJROBP.2005.0.
Wolden, Suzanne L., Chen, William C., Pfister, David G., Kraus, Dennis H., Berry, Sean L., and Zelefsky, Michael J. Sun . "Intensity-modulated radiation therapy (IMRT) for nasopharynx cancer: Update of the Memorial Sloan-Kettering experience". United States. doi:10.1016/J.IJROBP.2005.0.
@article{osti_20788266,
title = {Intensity-modulated radiation therapy (IMRT) for nasopharynx cancer: Update of the Memorial Sloan-Kettering experience},
author = {Wolden, Suzanne L. and Chen, William C. and Pfister, David G. and Kraus, Dennis H. and Berry, Sean L. and Zelefsky, Michael J.},
abstractNote = {Purpose: We previously demonstrated that intensity-modulated radiation therapy (IMRT) significantly improves radiation dose distribution over three-dimensional planning for nasopharynx cancer and reported positive early clinical results. We now evaluate whether IMRT has resulted in improved outcomes for a larger cohort of patients with longer follow-up. Methods and Materials: Since 1998, all 74 patients with newly diagnosed, nonmetastatic nasopharynx cancer were treated with IMRT using accelerated fractionation to 70 Gy; 59 received a hyperfractionated concomitant boost, and more recently 15 received once-daily treatment with dose painting. With the exception of Stage I disease (n = 5) and patient preference (n = 1), 69 patients received concurrent and adjuvant platinum-based chemotherapy similar to that in the Intergroup 0099 trial. Results: Patient characteristics: median age 45; 32% Asian; 72% male; 65% World Health Organization III; 6% Stage I, 16% Stage II, 30% Stage III, 47% Stage IV. Median follow-up is 35 months. The 3-year actuarial rate of local control is 91%, and regional control is 93%; freedom from distant metastases, progression-free survival, and overall survival at 3 years are 78%, 67%, and 83%, respectively. There was 100% local control for Stage T1/T2 disease, compared to 83% for T3/T4 disease (p = 0.01). Six patients failed at the primary site, with median time to local tumor progression 16 months; 5 were exclusively within the 70 Gy volume, and 1 was both within and outside the target volume. There is a trend for improved local control with IMRT when compared to local control of 79% for 35 patients treated before 1998 with three-dimensional planning and chemotherapy (p 0.11). Six months posttherapy, 21%, 13%, 15%, and 0% of patients with follow-up audiograms (n = 24 patients) had Grade 1, 2, 3, and 4 sensorineural hearing loss, respectively. For patients with >1 year follow-up (n = 59), rates of long-term xerostomia were as follows: 26% none, 42% Grade 1, 32% Grade 2, and zero Grade 3. Conclusions: The pattern of primary site failure within the target volume suggests locally advanced T stage disease may require a higher biologic dose to gross tumor. Rates of severe (Grade 3-4) ototoxicity and xerostomia are low with IMRT as a result of normal-tissue protection. Distant metastases are now the dominant form of failure, emphasizing the need for improved systemic therapy.},
doi = {10.1016/J.IJROBP.2005.0},
journal = {International Journal of Radiation Oncology, Biology and Physics},
number = 1,
volume = 64,
place = {United States},
year = {Sun Jan 01 00:00:00 EST 2006},
month = {Sun Jan 01 00:00:00 EST 2006}
}
  • Purpose: To review the Memorial Sloan-Kettering Cancer Center's experience in using intensity-modulated radiation therapy (IMRT) for the treatment of oropharyngeal cancer. Methods and Materials: Between September 1998 and June 2004, 50 patients with histologically confirmed cancer of the oropharynx underwent IMRT at our institution. There were 40 men and 10 women with a median age of 56 years (range, 28-78 years). The disease was Stage I in 1 patient (2%), Stage II in 3 patients (6%), Stage III in 7 (14%), and Stage IV in 39 (78%). Forty-eight patients (96%) received definitive treatment, and 2 (4%) were treated in themore » postoperative adjuvant setting. Concurrent chemotherapy was used in 43 patients (86%). Patients were treated using three different IMRT approaches: 76% dose painting, 18% concomitant boost with IMRT in both am and pm deliveries, and 6% concomitant boost with IMRT only in pm delivery. Regardless of the approach, the average prescription dose to the gross tumor planning target volume was 70 Gy, while the average dose delivered to the subclinical volume was 59.4 Gy in the dose painting group and 54 Gy in the concomitant boost group. Percutaneous endoscopic gastrostomy feeding tubes (PEGs) were placed before the beginning of treatment in 84% of the patients. Acute and late toxicity were graded according to the Radiation Therapy Oncology Group (RTOG) radiation morbidity scoring criteria. Toxicity was also evaluated using subjective criteria such as the presence of esophageal stricture, and the need for PEG usage. The local progression-free, regional progression-free, and distant metastases-free rates, and overall survival were calculated using the Kaplan-Meier method. Results: Three patients had persistent locoregional disease after treatment. The 2-year estimates of local progression-free, regional progression-free, distant metastases-free, and overall survival were 98%, 88%, 84%, and 98%, respectively. The worst acute mucositis experienced was Grade 1 in 4 patients (8%), Grade 2 in 27 (54%), and Grade 3 in 19 (38%). Xerostomia decreased with increasing time interval from the end of radiotherapy, and among the patients with at least 9 months of follow-up there was 67% Grade 0-1 and 33% Grade 2 toxicity. Of the 42 patients who required upfront PEG placement, 6 were still using PEG for nutrition at the time of this analysis. Three patients had cervical esophageal strictures, and of these, 1 was still PEG dependent 1 year after treatment. Two of these patients were treated with the IMRT concomitant boost am and pm approach, whereas the other was treated with the dose painting technique. Conclusions: Intensity-modulated radiotherapy achieved encouraging local control rates in patients with oropharyngeal carcinoma. Treatment toxicity was acceptable even in the setting of concurrent chemotherapy. Long-term follow-up is needed to confirm these preliminary findings.« less
  • Purpose: To update the Memorial Sloan-Kettering Cancer Center's experience with intensity-modulated radiotherapy (IMRT) in the treatment of oropharyngeal cancer (OPC). Methods and Materials: Between September 1998 and April 2009, 442 patients with histologically confirmed OPC underwent IMRT at our center. There were 379 men and 63 women with a median age of 57 years (range, 27-91). The disease was Stage I in 2%, Stage II in 4%, Stage III in 21%, and Stage IV in 73% of patients. The primary tumor subsite was tonsil in 50%, base of tongue in 46%, pharyngeal wall in 3%, and soft palate in 2%.more » The median prescription dose to the planning target volume of the gross tumor was 70 Gy for definitive (n = 412) cases and 66 Gy for postoperative cases (n = 30). A total 404 patients (91%) received chemotherapy, including 389 (88%) who received concurrent chemotherapy, the majority of which was platinum-based. Results: Median follow-up among surviving patients was 36.8 months (range, 3-135). The 3-year cumulative incidence of local failure, regional failure, and distant metastasis was 5.4%, 5.6%, and 12.5%, respectively. The 3-year OS rate was 84.9%. The incidence of late dysphagia and late xerostomia {>=}Grade 2 was 11% and 29%, respectively. Conclusions: Our results confirm the feasibility of IMRT in achieving excellent locoregional control and low rates of xerostomia. According to our knowledge, this study is the largest report of patients treated with IMRT for OPC.« less
  • Purpose: Desmoplastic small round cell tumor (DSRCT) is a rare malignancy typically involving the peritoneum in young men. Whole abdominopelvic radiation therapy (WAP-RT) using conventional 2-dimensional (2D) radiation therapy (RT) is used to address local recurrence but has been limited by toxicity. Our objectives were to assess the benefit of intensity modulated radiation therapy (IMRT) on toxicity and to update the largest series on radiation for DSRCT. Methods and Materials: The records of 31 patients with DSRCT treated with WAP-RT (22 with 2D-RT and 9 with IMRT) between 1992 and 2011 were retrospectively reviewed. All received multi-agent chemotherapy and maximalmore » surgical debulking followed by 30 Gy of WAP-RT. A further focal boost of 12 to 24 Gy was used in 12 cases. Boost RT and autologous stem cell transplantation were nearly exclusive to patients treated with 2D-RT. Toxicities were assessed with the Common Terminology Criteria for Adverse Events. Dosimetric analysis compared IMRT and simulated 2D-RT dose distributions. Results: Of 31 patients, 30 completed WAP-RT, with a median follow-up after RT of 19 months. Acute toxicity was reduced with IMRT versus 2D-RT: P=.04 for gastrointestinal toxicity of grade 2 or higher (33% vs 77%); P=.02 for grade 4 hematologic toxicity (33% vs 86%); P=.01 for rates of granulocyte colony-stimulating factor; and P=.04 for rates of platelet transfusion. Post treatment red blood cell and platelet transfusion rates were also reduced (P=.01). IMRT improved target homogeneity ([D05-D95]/D05 of 21% vs 46%) and resulted in a 21% mean bone dose reduction. Small bowel obstruction was the most common late toxicity (23% overall). Updated 3-year overall survival and progression-free survival rates were 50% and 24%, respectively. Overall survival was associated with distant metastasis at diagnosis on multivariate analysis. Most failures remained intraperitoneal (88%). Conclusions: IMRT for consolidative WAP-RT in DSRCT improves hematologic toxicity in particular. Although the long-term efficacy of current treatment options remains disappointing, the improved therapeutic index of IMRT may aid in generalizing its use and allowing the addition of novel approaches such as intraperitoneal immunotherapy.« less
  • Purpose: External beam radiotherapy (EBRT) plays a controversial role in the management of nonanaplastic thyroid cancer. We reviewed our institution's outcomes in patients treated with EBRT for advanced or recurrent nonanaplastic thyroid cancer. Methods and Materials: Between April 1989 and April 2006, 76 patients with nonanaplastic thyroid cancer were treated with EBRT. The median follow-up for the surviving patients was 35.3 months (range, 4.2-178.4). The lesions were primarily advanced and included Stage T2 in 5 (7%), T3 in 5 (7%), and T4 in 64 (84%) patients. Stage N1 disease was present in 60 patients (79%). Distant metastases before EBRT weremore » identified in 27 patients (36%). The median total EBRT dose delivered was 6,300 cGy. The histologic features examined included medullary in 12 patients (16%) and nonmedullary in 64 (84%). Of the 76 patients, 71 (93%) had undergone surgery before RT, and radioactive iodine treatment was used in 56 patients (74%). Results: The 2- and 4-year overall locoregional control rate for all histologic types was 86% and 72%, respectively, and the 2- and 4-year overall survival rate for all patients was 74% and 55%, respectively. No significant differences were found in locoregional control, overall survival, or distant metastases-free survival for patients with complete resection, microscopic residual disease, or gross residual disease. Grade 3 acute mucositis and dysphagia occurred in 14 (18%) and 24 (32%) patients, respectively. Late adverse toxicity was notable for percutaneous endoscopic gastrostomy tube use in 4 patients (5%). Conclusion: The results of our study have shown that EBRT is effective for locoregional control of selected locally advanced or recurrent nonanaplastic thyroid malignancies, with acceptable acute toxicity.« less
  • With traditional photon therapy to treat large postoperative pancreatic target volume, it often leads to poor tolerance of the therapy delivered and may contribute to interrupted treatment course. This study was performed to evaluate the potential advantage of using passive-scattering (PS) and modulated-scanning (MS) proton therapy (PT) to reduce normal tissue exposure in postoperative pancreatic cancer treatment. A total of 11 patients with postoperative pancreatic cancer who had been previously treated with PS PT in University of Pennsylvania Roberts Proton Therapy Center from 2010 to 2013 were identified. The clinical target volume (CTV) includes the pancreatic tumor bed as wellmore » as the adjacent high-risk nodal areas. Internal (iCTV) was generated from 4-dimensional (4D) computed tomography (CT), taking into account target motion from breathing cycle. Three-field and 4-field 3D conformal radiation therapy (3DCRT), 5-field intensity-modulated radiation therapy, 2-arc volumetric-modulated radiation therapy, and 2-field PS and MS PT were created on the patients’ average CT. All the plans delivered 50.4 Gy to the planning target volume (PTV). Overall, 98% of PTV was covered by 95% of the prescription dose and 99% of iCTV received 98% prescription dose. The results show that all the proton plans offer significant lower doses to the left kidney (mean and V{sub 18} {sub Gy}), stomach (mean and V{sub 20} {sub Gy}), and cord (maximum dose) compared with all the photon plans, except 3-field 3DCRT in cord maximum dose. In addition, MS PT also provides lower doses to the right kidney (mean and V{sub 18} {sub Gy}), liver (mean dose), total bowel (V{sub 20} {sub Gy} and mean dose), and small bowel (V{sub 15} {sub Gy} absolute volume ratio) compared with all the photon plans and PS PT. The dosimetric advantage of PT points to the possibility of treating tumor bed and comprehensive nodal areas while providing a more tolerable treatment course that could be used for dose escalation and combining with radiosensitizing chemotherapy.« less