The aim of this treatment planning study was to investigate the potential advantages of intensity-modulated (IM) proton therapy (IMPT) compared with IM photon therapy (IMRT) in nasopharyngeal carcinoma (NPC). Eight NPC patients were chosen. The dose prescriptions in cobalt Gray equivalent (GyE) for gross tumor volumes of the primary tumor (GTV-T), planning target volumes of GTV-T and metastatic (PTV-TN) and elective (PTV-N) lymph node stations were 72.6 GyE, 66 GyE, and 52.8 GyE, respectively. For each patient, nine coplanar fields IMRT with step-and-shoot technique and 3D spot-scanned three coplanar fields IMPT plans were prepared. Both modalities were planned in 33 fractions to be delivered with a simultaneous integrated boost technique. All plans were prepared and optimized by using the research version of the inverse treatment planning system KonRad (DKFZ, Heidelberg). Both treatment techniques were equal in terms of averaged mean dose to target volumes. IMPT plans significantly improved the tumor coverage and conformation (P < 0.05) and they reduced the averaged mean dose to several organs at risk (OARs) by a factor of 2–3. The low-to-medium dose volumes (0.33–13.2 GyE) were more than doubled by IMRT plans. In radiotherapy of NPC patients, three-field IMPT has greater potential than nine-field IMRT with respect to tumor coverage and reduction of the integral dose to OARs and non-specific normal tissues. The practicality of IMPT in NPC deserves further exploration when this technique becomes available on wider clinical scale.

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Intensity-modulated radiotherapy of nasopharyngeal carcinoma: a comparative treatment planning study of photons and protons

Background

Nasopharyngeal carcinoma (NPC) is a rare malignancy in the United States, which is considered a low-risk country.



Methods

We searched the surveillance, epidemiology, and end results (SEER) database for patients with NPC who were diagnosed from 1988 to 2006. We compared the clinical features and outcomes of children and adolescents (<20 years old) and adults.



Results

The incidence for children and adolescents was 0.5 per million person-years versus 8.4 in adults. NPC was less rare in black children and adolescents (incidence, 1.5 per million person-years). Our search criteria retrieved 129 children and adolescents and 5,885 adults. Black children and adolescents represented 34.9% of patients below the age of 20 years. Younger patients had distinct features with advanced stages more frequently observed (31% and 46% of children and adolescents had stages III and IV, respectively) and 87% had WHO type III histology. Outcome was better in children and adolescents with 5-year NPC-specific survival of 83% ± 3.9% compared to 62% ± 0.8% in adults (P < 0.001). In a multivariate model, the following factors affected the outcome: age, race, stage, and histologic type. Young adults (20–45 years old) had almost double the risk of NPC-specific mortality when compared to children and adolescents [hazards ratio (HR), 1.93; P = 0.0077]. Children and adolescents with NPC were at higher risk of getting second cancer than adults (observed-to-expected ratio of 4.36 in children and adolescents; vs. 1.41 in adults; both were significantly higher than general population).



Conclusion

Despite the use of similar treatment approaches, NPC in children and adolescents may have different biologic features. Young patients are at higher risk of developing therapy related complications, including second cancer. Pediatr Blood Cancer. 2010;55:279–284. © 2010 Wiley–Liss, Inc.

Differential features of nasopharyngeal carcinoma in children and adults: A SEER study

BACKGROUND:

Nasopharyngeal carcinoma (NPC) is very rare in childhood. It differs from its adult counterpart in the prevalence of the nonkeratinizing, undifferentiated subtype and by an advanced clinical stage at onset and better chances of survival. The risk of long-term treatment-related toxicity also may be a more important issue in younger individuals.



METHODS:

A prospective chemoradiotherapy protocol for pediatric NPC was started in Italy in 2000 within the framework of the Rare Tumors in Pediatric Age (TREP) project. Three courses of cisplatin/5-fluorouracil induction chemotherapy were followed by radiotherapy (doses up to 65 grays) with concomitant cisplatin.



RESULTS:

Forty-six patients (ages 9-17 years) were considered eligible for the study over a 10-year period. The ratio of observed to expected cases based on epidemiological data was approximately 1 for both children and adolescents. All but 1 patient had lymph node involvement, and 5 patients had distant metastases. The rate of response to primary chemotherapy was 90%. The 5-year overall and progression-free survival rates were 80.9% and 79.3%, respectively (median follow-up, 62 months). The only statistically significant prognostic variable was the presence or absence of distant metastases. A 65% incidence of late sequelae was reported.



CONCLUSIONS:

This study demonstrates the feasibility and efficacy of a prospective protocol even for such rare tumors as pediatric NPC. The use of lower radiotherapy doses than those used in adults did not affect locoregional failure rates. Long-term follow-up will be needed to obtain more information on both survival and treatment sequelae. The next objective will be to establish broader, international prospective cooperation schemes. Cancer 2011. © 2011 American Cancer Society.

A prospective protocol for nasopharyngeal carcinoma in children and adolescents: the Italian Rare Tumors in Pediatric Age (TREP) project.

Purpose To evaluate the efficacy of intensity-modulated radiotherapy (IMRT) in reducing the acute toxicities associated with conventional RT (CRT) in children with nasopharyngeal carcinoma. Patients and Methods A total of 36 children with nonmetastatic nasopharyngeal carcinoma, treated at the Tata Memorial Hospital between June 2003 and December 2006, were included in this study. Of the 36 patients, 28 were boys and 8 were girls, with a median age of 14 years; 4 (11%) had Stage II and 10 (28%) Stage III disease at presentation. All patients had undifferentiated carcinoma and were treated with a combination of chemotherapy and RT. Of the 36 patients, 19 underwent IMRT and 17 underwent CRT. Results After a median follow-up of 27 months, the 2-year locoregional control, disease-free, and overall survival rate was 76.5%, 60.6%, and 71.3%, respectively. A significant reduction in acute Grade 3 toxicities of the skin ( p = 0.006), mucous membrane ( p = 0.033), and pharynx ( p = 0.035) was noted with the use of IMRT. The median time to the development of Grade 2 toxicity was delayed with IMRT (skin, 35 vs. 25 days, p = 0.016; mucous-membrane, 39 vs. 27 days, p = 0.002; and larynx, 50 vs. 28 days, p = 0.009). The duration of RT significantly influenced disease-free survival on multivariate analysis (RT duration >52 days, hazard ratio=5.49, 95% confidence interval, 1.14–26.45, p = 0.034). The average mean dose to the first and second planning target volume was 71.8 Gy and 62.5 Gy with IMRT compared with 66.3 Gy ( p = 0.001) and 64.4 Gy ( p = 0.046) with CRT, respectively. Conclusion The results of our study have shown that IMRT significantly reduces and delays the onset of acute toxicity, resulting in improved tolerance and treatment compliance for children with nasopharyngeal carcinoma. Also, IMRT provided superior target coverage and normal tissue sparing compared with CRT.

Eva Szutowicz

Papers

Treatment results of 165 pediatric patients with non-metastatic nasopharyngeal carcinoma: A rare cancer network study