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Three-dimensional conformal radiotherapy for paranasal sinus carcinoma: Clinical results for 25 patients
Int. J. Radiation Oncology Biol. Phys., Vol. 56, No. 1, pp. 169 –176, 2003 Copyright © 2003 Elsevier Inc. Printed in the USA. All rights reserved 0360-3016/03/$–see front matter
doi:10.1016/S0360-3016(03)00078-6
3D-CRT
THREE-DIMENSIONAL CONFORMAL RADIOTHERAPY FOR PARANASAL SINUS CARCINOMA: CLINICAL RESULTS FOR 25 PATIENTS LAETITIA PADOVANI, M.D.,* PASCAL POMMIER, M.D.,* SE´ BASTIEN CLIPPE, M.D.,* ISABELLE MARTEL-LAFAY, M.D.,* CLAUDE MALET, PH.D.,* MARC POUPART, M.D.,† PHILIPPE ZROUNBA, M.D.,‡ PHILIPPE CERUSE, M.D.,§ SOPHIE DESMES, M.D.,¶ CHRISTIAN CARRIE, M.D.,* XAVIER MONTBARBON, M.D.,* AND CHANTAL GINESTET, PH.D.* Departments of *Radiation Oncology, ‡Head and Neck Oncology, and ¶Statistics, Centre Le´on Be´rard, Lyon, France; †Department of Head and Neck Oncology, Hoˆpital de la Croix Rousse, Lyon, France; §Department of Head and Neck Oncology, Hoˆpital E. Herriot, Lyon, France Purpose: To assess local control, survival, and clinical and dosimetric prognostic factors in 25 patients with locally advanced maxillary or ethmoid sinus carcinoma treated by three-dimensional conformal radiotherapy (RT). Methods and Materials: Surgery was performed in 22 patients and was macroscopically complete in 16. Seven patients received chemotherapy (concomitant with RT in four). The following quality indexes were defined for the 95% and 90% isodoses: tumor conformity index, normal tissue conformity index, and global conformity index. Results: The median radiation dose to the planned treatment volume was 63 Gy, with a minimal dose of 60 Gy, except in 2 patients whose cancer progressed during RT. The maximal doses tolerated by the structures involved in vision were respected, except for tumors that involved the optic nerve. After a median follow-up of 25 months, 14 local tumor recurrences developed. The major prognostic factors were central nervous system involvement by disease and the presence of nonresectable tumors. The radiation dose and tumor conformity index value were not significant prognostic indicators. Two patients died of acute infectious toxicity, and two developed late ipsilateral ocular toxicity. Conclusion: Improving local control remains the main challenge in RT for paranasal tumors. © 2003 Elsevier Inc. Conformal radiotherapy, Paranasal sinus, Quality index, Local control, Carcinoma.
In 1995, the Department of Radiation Oncology at the Le´on Be´rard Anticancer Center (Lyon, France) developed a technique of three-dimensional conformal RT (CRT) with individually shaped, multiple isocentric noncoplanar field arrangements for paranasal sinus and nasal cavity tumors. The details of the technique and preliminary results have been previously published (11). The clinical and dosimetric results after a median follow-up of 25 months for 25 patients who had locally advanced carcinoma of the maxillary and ethmoid sinus are reported here.
INTRODUCTION Paranasal sinus and nasal cavity carcinoma represent 3– 4% of head-and-neck cancers. A 3-year overall survival rate of 50% has been reported for patients with all stages of disease, and the main cause of treatment failure was local recurrence (1, 2). Complete resection represents the major prognostic factor for survival (3–5). When radiotherapy (RT) is used alone or postoperatively to treat macroscopic residual disease, dose escalation ⬎65 Gy has been reported to correlate with improvement in local control (5, 6). Advances in radiation technology and imaging techniques have led to major improvements in the quality of dose delivery to the paranasal sinus. These improvements have led to a decrease in ocular complications, but local control remains poor (4, 7–10).
METHODS AND MATERIALS Between January 1995 and July 2001, 25 consecutive patients (6 women, 19 men) with paranasal sinus carcinoma 2001, Nagoya, Japan. Acknowledgments—We thank Margaret Haugh for reviewing the English in this manuscript. Received Feb 18, 2002, and in revised form Jul 12, 2002. Accepted for publication Oct 14, 2002.
Reprint requests to: Pascal Pommier, M.D., Department of Radiation Oncology, Centre Le´on Be´rard, 28 rue Lae¨nnec, Lyon cedex 08 69373 France. Tel: ⫹33-4-78-78-26-48; Fax: ⫹33-4-7878-26-26; E-mail: [email protected] Presented at the 3rd S. Takahashi Memorial International Workshop on 3-Dimensional Conformal Radiotherapy, December 8 –10, 169
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received CRT in the Department of Radiation Oncology of the Le´ on Be´ rard Anticancer Center. Clinical features The median age of the patients was 67 years (range 34 – 86). The study involved a group of 25 paranasal sinus tumors, including 13 adenocarcinomas and 12 squamous cell carcinomas. Seven patients were treated for maxillary sinus tumor and 18 for ethmoid sinus tumor. The extent of disease was assessed by physical examination and CT or MRI. Most of the paranasal sinus tumors were diagnosed at an advanced stage: T4 in 17 patients, T3 in 4, and T2 in 4. Three patients had brain involvement by tumor and eight presented with involvement of the base of the skull or dura mater, or both. Five patients had lymph node involvement at diagnosis. The disease was recurrent in 4 patients (T4 ethmoid carcinoma in all cases), with an interval of 2–11 months from the first treatment completion. No patient had previously undergone RT. Surgery Surgery was performed in 22 patients. Sixteen underwent macroscopically complete tumor removal and five macroscopically incomplete tumor resection. Data were not available for 1 patient, and the surgery was considered to be incomplete for treatment planning. One patient developed a relapse just after surgery (macroscopically incomplete), before RT began. Three patients had tumors that were nonresectable because of their large size (two with a T4 tumor of the ethmoid and one with a T4 tumor of the maxillary sinus). Chemotherapy Seven patients received chemotherapy. The general practice was to use neoadjuvant chemotherapy in an effort to shrink nonresectable tumors and thereby permit surgical resection. Cisplatin-based regimens for squamous cell carcinoma (2 patients) and a combination of cyclophosphamide, cisplatin, and doxorubicin for adenocarcinoma (1 patient) were performed. Success was obtained for only 1 patient. Concomitant cisplatin-based chemotherapy was delivered to patients who had progressive disease after surgery or who had undifferentiated carcinoma (3 patients) and to 1 patient who had a good partial response to neoadjuvant chemotherapy. One patient received postoperative adjuvant chemotherapy for undifferentiated squamous cell carcinoma. CRT procedures The details of the technique have been previously described (11). The clinical target volume (CTV) was defined as the pretreatment gross tumor volume and microscopic extension, taking into account the initial imaging findings, surgery report, and biopsy and postoperative histologic examination findings. The planning target volume (PTV) included the CTV plus an additional uniform 5-mm expan-
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sion, not taking into account the organs at risk (OARs) or the potential reduction of the treatment volume because of dosimetric constraints. The choice of portal incidence was determined first by the maximal dose tolerated by the OARs and second by the minimal dose (60 Gy) to be delivered to the PTV. The maximal dose was limited to 54 Gy and 60 Gy, respectively, to the chiasma and central nervous system (CNS). The dose to the ipsilateral optic nerve and retina was limited to 60 Gy, except in the case of definitive RT for tumors that involved the optic nerve. In all patients, the choice of portal incidence was made with the aim of sparing the contralateral eye. The goal was to deliver 66 –70 Gy to the PTV in the case of incomplete or no surgery and 64 – 66 Gy in the case of complete resection. Dose–volume histograms were calculated for the PTV, ipsilateral and contralateral eyes, lens, and optic nerve. Radiation was delivered in doses of 2 Gy/fraction at five fractions weekly. When lymph node RT was required, the primary tumor and cervix were included in the AP and lateral beams up to a minimal dose of 30 Gy to limit overdosage or underdosage due to matching of radiation fields. The inferior cervical regions, to which a boost with electrons was delivered, received a total dose of 50 Gy. The junction was selected to be in a region that received prophylactic RT (50 Gy). Thus, the risk of overdosage or underdosage was mitigated by treatment design: the maximal dose that could be delivered was 70 Gy and the minimal dose was 30 Gy. The electron field at the skin junction with the photon field and the electron field tilt were also calculated using the treatment planning system. Noncoplanar fields were used only for the tumor CTV. Thus, there were no problems in matching the photon fields with the electron boost.
RESULTS The median dose delivered to the PTV was 63 Gy (range 30 –70). The minimal dose was 60 Gy, except for 2 patients who received 30 Gy and 50 Gy because of disease progression during RT. These 2 patients were excluded from the analysis of the dosimetric prognostic factors. The median dose was 63 Gy (range 30 –70) and 64 Gy (range 50 – 68) for patients who had undergone complete tumor resection and incomplete or no tumor resection, respectively. Five patients with clinically and histologically demonstrated lymph node involvement (four with maxillary sinus tumors and one with an ethmoid sinus tumor), three of whom had squamous cell carcinoma and two who had adenocarcinoma, received 60 Gy to the ipsilateral side of the neck. The contralateral side of the neck was irradiated in 1 case of ethmoid sinus tumor because of major node involvement in the ipsilateral side of the neck and capsular invasion. In 3 patients with locally advanced T4N0 tumors, prophylactic RT of the ipsilateral side of the neck was given. The median number of fields was 10 (range 6 to 12).
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Table 1. Prescribed doses and does distribution in PTV
Average (SD) Range
Prescribed dose (Gy)
Mean dose (Gy)
Maximal dose (Gy)
63.2 (3.2) 60.0–70.0
60.7 (3.6) 55.9–68.3
67.1 (4.3) 61.3–76.2
Abbreviations: PTV ⫽ planning target volume; SD ⫽ standard deviation.
Dosimetric results The dosimetric results for the 25 patients, according to the prescribed dose, are shown in Tables 1 through 4. They do not take into account the doses that have indeed been delivered. Dose distribuitons to the optic pathways are shown in Table 2 and 3. The quality of RT was assessed by the tumor conformity index (TCI), normal tissue conformity index (NTCI), and global conformity index (GCI) for the 90% and 95% isodoses (Table 4). The values were defined as follows: 95% (90%) TCI ⫽ PTV volume in the 95% (90%) isodose/PTV volume; 95% (90%) NTCI ⫽ PTV volume in the 95% (90%) isodose/95% (90%) isodose volume; and 95% (90%) GCI ⫽ [95% (90%) TCI ⫻ 95% (90%) NTCI]1/2. Progression-free survival The progression-free survival curves are shown in Fig. 1. The median follow-up time was 25 months (range 4 –51). For 1 patient with a nonresectable tumor extending to the base of the skull, residual tumor was observed on CT 2 months after RT. The patient died and was considered to have had local disease progression. Two patients had local and regional tumor progression during RT. One of these patients had a T3 nonresectable adenocarcinoma of the ethmoid sinus involving the dura mater. Neoadjuvant chemotherapy failed to reduce the volume, and RT was stopped at 50 Gy because of progression. The other patient developed local tumor progression during RT, despite initial surgery considered to be macroscopically complete, for a T2N1 squamous cell carcinoma of the maxillary sinus. Fourteen local relapses occurred. Nine recurrences were local only, three were associated with relapses in the cervical lymph nodes, and two were associated with distant metastases. All 3 patients with brain involvement, including 2 patients who underwent complete tumor resection, died of local recurrence 3– 8 months after treatment completion
(tumor extension to the brain in 2 patients and to the base of the skull in 1 patient). The site of recurrence relative to the PTV could not be assessed. Local recurrences occurred within the PTV in 8 patients 2–36 months after RT completion. Four of these patients had base of the skull and/or dura mater tumor involvement. The recurrence was documented for 6 patients and suspected for 2 patients. One patient had T3 and seven had T4 tumors; 6 patients had adenocarcinoma. Seven patients underwent surgery, which was considered macroscopically complete in five. The radiation dose ranged from 60 to 66 Gy (median 64). Local recurrence was associated with relapse in the lymph nodes in 1 patient and with metastasis in 2 patients. Two patients developed local involvement in the vicinity of the PTV because the CTV had been inadequately defined. The first patient had T3 squamous cell carcinoma of the maxillary sinus. The tumor encompassed the internal corner of the maxillary sinus, left nasal fossa, internal wall of the ethmoid sinus, and internal corner of the left orbital cavity. After neoadjuvant chemotherapy, limited but macroscopically complete, surgery was performed. However, the sphenoid sinus was not examined. The CTV was limited to the initially involved anatomic structures. Postoperative chemoradiotherapy delivered 70 Gy of radiation plus weekly platinum-based chemotherapy. Eleven months later, the patient experienced bilateral recurrence in the cervical lymph nodes, along with a large local recurrence including the sphenoid sinus. The second patient, who had T2 adenocarcinoma of the ethmoid sinus that extended to the ipsilateral nasal cavity, underwent macroscopically complete surgery. Because of the limited initial tumor and its complete resection, the postoperative RT dose was only 60 Gy. To protect the contralateral optic nerve, the dose to the top of the contralateral ethmoid sinus was limited to 50 Gy. Nine months later, local recurrence developed, probably from this site, and extended to the orbital cavity.
Table 2. Dose distributions in ipsilateral and contralateral eye Eyes receiving isodose (%)
Ipsilateral eye Average (SD) Range Contralateral eye Average (SD) Range
Mean dose (Gy)
40 Gy
50 Gy
43.0 (12.7) 12.7–61.5
61.3 (28.6) 13.0–100.0
42.5 (27.9) 6.0–99.0
14.6 (6.7) 2.7–25.9
4.1 (6.0) 0.0–21.0
1.2 (2.2) 0.0–8.0
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Table 3. Dose distribution for chiasma and ipsilateral and contralateral lenses and optic nerves Lens
Optic nerve
Dose (Gy)
Chiasma
Ipsilateral
Contralateral
Ipsilateral
Contralateral
Average (SD) Range
46.1 (14.7) 1.4–62.7
36.5 (14.0) 1.4–53.7
7.1 (4.7) 0.7–19.5
50.1 (15.6) 2.7–71.7
24.4 (10.4) 1.9–46.0
Four patients developed recurrent disease in the lymph nodes (this was associated with local recurrence in 2 patients), and 1 patient experienced local and nodal disease progression during RT. Histologic features, primary tumor site, initial node status, and management data are given in Table 5. Three patients developed metastases that were associated with local tumor relapse in two. One patient had T4 undifferentiated squamous cell carcinoma of the maxillary sinus. The treatment consisted of incomplete surgery, RT (68 Gy) plus three concomitant courses of 5-fluorouracil and cisplatinum, and prophylactic RT to the ipsilateral cervical lymph nodes. This patient developed isolated liver metastases 27 months after the end of RT. Two patients who had T4 adenocarcinoma of the ethmoid sinus and base of the skull or dura mater involvement experienced local failure contemporaneous with pleural and brain metastases 3 months after the end of RT. All patients with metastases died of disease progression. No statistically significant difference was found in local or nodal disease-free survival between patients with adenocarcinoma and those with squamous cell carcinoma (p ⫽ 0.7). Overall survival The overall survival curves are shown in Fig. 2. Six patients were alive with their cancer in complete remission at last follow-up. The other 19 patients died, 2 of acute toxicity (1–3 months after RT completion), 9 of exclusive local relapse (including 1 who had disease progression during RT), and 8 of disease in the lymph nodes or metastases, either alone (3 patients) or associated with local recurrence (5 patients). All 3 patients who did not undergo surgery, and 2 of the 6 patients in whom tumor resection was uncompleted (or unknown) died of local progressive disease (86%). All 3
patients with brain involvement and 5 of 7 available patients with base of the skull or dura mater involvement died of local relapse. Two of the latter 5 patients, who had initial lymph node involvement, but in whom local control was achieved, died of ipsilateral lymph node relapse within the radiation fields. One patient who did not undergo prophylactic neck RT died of exclusive nodal disease progression, despite salvage surgery and RT. Toxicity Two patients died of acute infectious complications. The first had T3 squamous cell carcinoma of the maxillary sinus, with macroscopically incomplete surgery that required orbital floor reconstruction using a prosthesis. During RT, this patient developed a regressive corneal abscess, and, despite antibiotic treatment, the operative site became infected and the prosthesis had to be removed. Three months after the end of RT, the patient died of sepsis, after having developed pneumopathy and reinfection of the operative site. The second patient, who had T4 adenocarcinoma of the ethmoid sinus and meninges involvement requiring reconstruction using fascia lata, developed a frontal sinocutaneous fistula during RT. A purulent exudate oozed from the scar at the beginning of RT, and bone infection developed. Despite antibiotic treatment, a major local infection occurred 1 month after the end of RT, leading to the patient’s death. Two patients experienced complete regressive purulent keratoconjunctivitis during RT. Late toxic effects occurred in 3 patients. Two patients with T4 adenocarcinoma of the ethmoid sinus that extended to the ipsilateral orbital contents developed ipsilateral uveitis and retinopathy 17 and 23 months after RT completion. In 1 patient, the uveitis was associated with local recurrence inside the CTV, which included the internal part of the ipsilateral orbital cavity and optic nerve. The doses deliv-
Table 4. TCI, NTCI, and GCI values for 95% and 90% isodoses
Isodose 95% Average (SD) Range Isodose 90% Average (SD) Range
TCI
NTCI
GCI
0.69 (0.18) 0.32–0.95
0.81 (0.13) 0.36–0.97
0.74 (0.11) 0.51–0.86
0.86 (0.11) 0.61–0.99
0.76 (0.11) 0.45–0.94
0.80 (0.06) 0.64–0.90
Abbreviations: TCI ⫽ tumor conformity index; NTCI ⫽ normal tissue conformity index; GCI ⫽ global conformity index.
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Fig. 1. Progression-free survival.
ered to the PTV were 60 and 64 Gy. Limited necrosis of the nose cartilage requiring surgical resection was found in the third patient 2 years after the end of treatment. This patient was treated by incomplete surgery and had received an irradiation dose of 60 Gy for T4 ethmoid carcinoma that invaded the nose cartilage. DISCUSSION Because of the wide heterogeneity in the tumor histologic features, surgical and radiotherapeutic techniques, and the small sample size of most reported series, clinical data remain relatively scarce for carcinoma of the paranasal sinuses. The present series included 25 patients with locally advanced maxillary or ethmoid sinus carcinoma (squamous Table 5. Characteristics of patients who had disease recurrence in lymph nodes Histologic subtype Adenocarcinoma Squamous cell Location Maxillary sinus Ethmoid sinuc Node and radiation status N0 with radiation N0 without radiation N1 with radiation
1/13 4/12 4/7 1/18 0/3 2/17 3/5
cell carcinoma or adenocarcinoma) for which homogeneous conformal RT was administered. This series represents one of the most extensive experiences reported. Although local treatment modalities were considered optimal, the local control in our series was poor (14 patients had local tumor recurrence or progression). The major adverse prognostic factor was the initial involvement of the CNS (frontal parenchyma; 3 patients) or the base of the skull or dura mater (8 patients). Five of the available 7 patients with base of the skull or meninges involvement died of local relapse, including 1 patient who had tumor progression during RT and 2 patients who had concomitant metastases. The site of recurrence was considered to be in the PTV for 3 patients, but it could not be determined for 1 patient. The unfavorable nature of CNS involvement has been described by several authors, and it is possible that patients with tumors affecting the CNS are unsuitable for curative RT (4, 9). Nevertheless, selected patients should be considered for palliative treatment to prevent painful local tumor evolution without impairing the patient’s quality of life. Published guidelines state that, whenever possible, surgery should be performed to improve local control (3–5). Despite the initial gross tumor volume, 22 patients (88%) underwent surgery. All 3 patients who had nonresectable tumors died of local disease progression or recurrence, and 2 of the 4 patients who underwent surgical tumor debulking experienced local recurrence. However, 9 of the available
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Fig. 2. Overall survival.
16 patients with macroscopically complete resection experienced local progression. Thus, no conclusions on the role of surgery can be drawn from our series. The role of chemotherapy for paranasal sinus carcinoma remains unclear. Several authors (12, 13) reported that concomitant cisplatin-based chemotherapy and hyperfractionated or accelerated RT achieved excellent local control for advanced paranasal tumors in small series. In our series, only 7 patients received chemotherapy, which was neoadjuvant in 3 patients and concomitant with RT in 4. The aim of neoadjuvant chemotherapy was to reduce the gross tumor volume so that surgery could be performed. However, surgery was possible for only 1 patient. Despite concomitant chemotherapy, 3 of the 4 patients experienced local tumor recurrence. Because of the poor prognosis factors for our patients treated with chemotherapy, our observations yielded no conclusions or recommendations about chemotherapy for paranasal sinus carcinoma. Rasch et al. (14) have recently reported the influence of both observer and treatment planner on the calculated CTV and the dose delivered to OARs. Nevertheless, these data could not be correlated to clinical features. In our series, two tumor recurrences occurred at the limit of the radiation field. In all patients, surgery was considered to be complete, but this consisted of limited resection. The volume of the CTV was delineated, taking into account the tumor location indicated on preoperative images and the postoperatively established tumor histologic features. Surgery was probably insufficient to screen the microscopic extent of the disease, and the CTV did not encompass adjoining structures. Image
fusion of preoperative CT or MRI and postoperative treatment planning using CT and positron emission tomography images should improve the accuracy of the CTV delineation, prevent ballistic miss fields, and decrease toxic effects (15–17). Despite using CT-based three-dimensional RT, Roa et al. (4) reported that 17 of their 39 patients had local disease recurrence within the irradiation fields. In our series, 14 local tumor recurrences developed. The site of recurrence was within the fields in 8 patients and suspected to be within them in 2. For patients whose cancer involved the brain, the exact location of the recurrence relative to the PTV could not be determined. No radiation dose effect was observed in our series. The median dose for patients who had tumor recurrence within the CTV was 64 Gy (range 60 – 66) and was not significantly different statistically from that of the whole population. The optimal dose after macroscopically complete tumor resection is not available. At least 66 –70 Gy of radiation is necessary to control the tumor when surgery is not done or when macroscopic residual disease remains (4 – 6, 18). In this series, the median radiation dose for these patients was probably kept too low, so as not to exceed the maximal tolerated dose for the OARs. No prognostic factors were found using the 95% and 90% TCIs. The 95% TCI for patients with in-field recurrences and other available patients was, respectively, 0.79 (range 0.46 – 0.95) and 0.74 (range 0.32– 0.86); the corresponding 90% TCIs were 0.94 (range 0.65– 0.99) and 0.90 (range 0.61– 0.97). The GCI results were satisfactory, taking into account the vicinity of
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the OARs, with average GCIs of 74% and 81%, respectively, for the 95% and 90% isodoses. Our results suggest the need to increase the total radiation dose in the PTV, with respect to the OARs. Intensitymodulated RT (IMRT) should improve conformal dose administration to the target tissues while decreasing the radiation dose to the normal tissues (19 –21). Hunt et al. (22) and Wolden et al. (23) demonstrated that IMRT for nasopharynx cancer led to an improvement in local control compared with CRT, respecting the dose tolerated by the OARs. Ion-beam therapy, and notably, intensity-modulated proton therapy, has been reported to be a useful technique for the treatment of tumors surrounded by OARs (24). Another cause of failure was metastasis to the lymph nodes. The risk failure in the lymph nodes has been reported to be as high as 8 –29% for patients with squamous cell carcinoma of the maxillary sinus (5, 25). In our series, 5 patients (3 with squamous cell carcinoma and 2 with adenocarcinoma) had cervical lymph node involvement at the time of initial staging (20%). Five patients experienced recurrent disease in the cervical nodes. This recurrence was bilateral for 1 patient. Three patients of the five previously irradiated for N1 disease developed relapses in the ipsilateral irradiated cervical chains. For patients who did not receive prophylactic RT to the cervical nodes, salvage surgery and RT were not effective. Several authors, on the basis of the results of retrospectively analyzed series, proposed prophylactic cervical lymph node RT in two high-risk groups of patients: those with T3 and T4 paranasal sinus carcinoma and those with squamous cell carcinoma (26, 27). At the beginning of our experience, 2 patients with Stage T3N0 and T2N0 squamous cell carcinoma of the maxillary sinus developed tumor recurrences in the lymph nodes. We decided to perform prophylactic ipsilateral cervical chain RT for large-volume tumors (T4), regardless of
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their histologic features, and for squamous cell carcinomas involving the infrastructure of the maxillary sinus. No tumor recurrences in the ipsilateral or contralateral lymph nodes have been observed for the N0 patients who received prophylactic node irradiation. We have not observed any acute or late toxic effects of Grade 2 or greater toxicity related to this irradiation. We observed good results for radiation toxicity, with the exception of two toxic deaths attributed to postoperative severe infection. The average value of the 95% NTCI was very good. For the 2 patients who experienced ocular complications, the mean radiation dose to the ipsilateral eye was 53 and 48.7 Gy (maximal dose 67 and 64.8), respectively. These results were greater than the averages for the whole population (mean dose 43 Gy, and maximal dose 63), because of the PTV delineation that included the OARs. However, these patients’ values for 95% NTCI (0.81 and 0.87) and 95% GCI (0.83 and 0.75) greater higher than the population mean values. These results suggest that these complications would have been difficult to avoid, even with more advanced technology such as IMRT or proton therapy. CONCLUSION Although local CRT modalities are considered to be optimal in paranasal sinus carcinoma, the major cause of failure remains a lack of local control. Several local recurrences could have been avoided by a better delineation of the PTV, with better surgical procedures and imaging fusion. New irradiation techniques such as IMRT and ion beam therapy, should allow increases in the radiation dose delivered to the PTV, while respecting the maximal dose tolerated by the OARs. An ongoing French multicentric study is evaluating the dosimetric, clinical, and economic aspects of IMRT compared with CRT.
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doi:10.1016/S0360-3016(03)00078-6
3D-CRT
THREE-DIMENSIONAL CONFORMAL RADIOTHERAPY FOR PARANASAL SINUS CARCINOMA: CLINICAL RESULTS FOR 25 PATIENTS LAETITIA PADOVANI, M.D.,* PASCAL POMMIER, M.D.,* SE´ BASTIEN CLIPPE, M.D.,* ISABELLE MARTEL-LAFAY, M.D.,* CLAUDE MALET, PH.D.,* MARC POUPART, M.D.,† PHILIPPE ZROUNBA, M.D.,‡ PHILIPPE CERUSE, M.D.,§ SOPHIE DESMES, M.D.,¶ CHRISTIAN CARRIE, M.D.,* XAVIER MONTBARBON, M.D.,* AND CHANTAL GINESTET, PH.D.* Departments of *Radiation Oncology, ‡Head and Neck Oncology, and ¶Statistics, Centre Le´on Be´rard, Lyon, France; †Department of Head and Neck Oncology, Hoˆpital de la Croix Rousse, Lyon, France; §Department of Head and Neck Oncology, Hoˆpital E. Herriot, Lyon, France Purpose: To assess local control, survival, and clinical and dosimetric prognostic factors in 25 patients with locally advanced maxillary or ethmoid sinus carcinoma treated by three-dimensional conformal radiotherapy (RT). Methods and Materials: Surgery was performed in 22 patients and was macroscopically complete in 16. Seven patients received chemotherapy (concomitant with RT in four). The following quality indexes were defined for the 95% and 90% isodoses: tumor conformity index, normal tissue conformity index, and global conformity index. Results: The median radiation dose to the planned treatment volume was 63 Gy, with a minimal dose of 60 Gy, except in 2 patients whose cancer progressed during RT. The maximal doses tolerated by the structures involved in vision were respected, except for tumors that involved the optic nerve. After a median follow-up of 25 months, 14 local tumor recurrences developed. The major prognostic factors were central nervous system involvement by disease and the presence of nonresectable tumors. The radiation dose and tumor conformity index value were not significant prognostic indicators. Two patients died of acute infectious toxicity, and two developed late ipsilateral ocular toxicity. Conclusion: Improving local control remains the main challenge in RT for paranasal tumors. © 2003 Elsevier Inc. Conformal radiotherapy, Paranasal sinus, Quality index, Local control, Carcinoma.
In 1995, the Department of Radiation Oncology at the Le´on Be´rard Anticancer Center (Lyon, France) developed a technique of three-dimensional conformal RT (CRT) with individually shaped, multiple isocentric noncoplanar field arrangements for paranasal sinus and nasal cavity tumors. The details of the technique and preliminary results have been previously published (11). The clinical and dosimetric results after a median follow-up of 25 months for 25 patients who had locally advanced carcinoma of the maxillary and ethmoid sinus are reported here.
INTRODUCTION Paranasal sinus and nasal cavity carcinoma represent 3– 4% of head-and-neck cancers. A 3-year overall survival rate of 50% has been reported for patients with all stages of disease, and the main cause of treatment failure was local recurrence (1, 2). Complete resection represents the major prognostic factor for survival (3–5). When radiotherapy (RT) is used alone or postoperatively to treat macroscopic residual disease, dose escalation ⬎65 Gy has been reported to correlate with improvement in local control (5, 6). Advances in radiation technology and imaging techniques have led to major improvements in the quality of dose delivery to the paranasal sinus. These improvements have led to a decrease in ocular complications, but local control remains poor (4, 7–10).
METHODS AND MATERIALS Between January 1995 and July 2001, 25 consecutive patients (6 women, 19 men) with paranasal sinus carcinoma 2001, Nagoya, Japan. Acknowledgments—We thank Margaret Haugh for reviewing the English in this manuscript. Received Feb 18, 2002, and in revised form Jul 12, 2002. Accepted for publication Oct 14, 2002.
Reprint requests to: Pascal Pommier, M.D., Department of Radiation Oncology, Centre Le´on Be´rard, 28 rue Lae¨nnec, Lyon cedex 08 69373 France. Tel: ⫹33-4-78-78-26-48; Fax: ⫹33-4-7878-26-26; E-mail: [email protected] Presented at the 3rd S. Takahashi Memorial International Workshop on 3-Dimensional Conformal Radiotherapy, December 8 –10, 169
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received CRT in the Department of Radiation Oncology of the Le´ on Be´ rard Anticancer Center. Clinical features The median age of the patients was 67 years (range 34 – 86). The study involved a group of 25 paranasal sinus tumors, including 13 adenocarcinomas and 12 squamous cell carcinomas. Seven patients were treated for maxillary sinus tumor and 18 for ethmoid sinus tumor. The extent of disease was assessed by physical examination and CT or MRI. Most of the paranasal sinus tumors were diagnosed at an advanced stage: T4 in 17 patients, T3 in 4, and T2 in 4. Three patients had brain involvement by tumor and eight presented with involvement of the base of the skull or dura mater, or both. Five patients had lymph node involvement at diagnosis. The disease was recurrent in 4 patients (T4 ethmoid carcinoma in all cases), with an interval of 2–11 months from the first treatment completion. No patient had previously undergone RT. Surgery Surgery was performed in 22 patients. Sixteen underwent macroscopically complete tumor removal and five macroscopically incomplete tumor resection. Data were not available for 1 patient, and the surgery was considered to be incomplete for treatment planning. One patient developed a relapse just after surgery (macroscopically incomplete), before RT began. Three patients had tumors that were nonresectable because of their large size (two with a T4 tumor of the ethmoid and one with a T4 tumor of the maxillary sinus). Chemotherapy Seven patients received chemotherapy. The general practice was to use neoadjuvant chemotherapy in an effort to shrink nonresectable tumors and thereby permit surgical resection. Cisplatin-based regimens for squamous cell carcinoma (2 patients) and a combination of cyclophosphamide, cisplatin, and doxorubicin for adenocarcinoma (1 patient) were performed. Success was obtained for only 1 patient. Concomitant cisplatin-based chemotherapy was delivered to patients who had progressive disease after surgery or who had undifferentiated carcinoma (3 patients) and to 1 patient who had a good partial response to neoadjuvant chemotherapy. One patient received postoperative adjuvant chemotherapy for undifferentiated squamous cell carcinoma. CRT procedures The details of the technique have been previously described (11). The clinical target volume (CTV) was defined as the pretreatment gross tumor volume and microscopic extension, taking into account the initial imaging findings, surgery report, and biopsy and postoperative histologic examination findings. The planning target volume (PTV) included the CTV plus an additional uniform 5-mm expan-
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sion, not taking into account the organs at risk (OARs) or the potential reduction of the treatment volume because of dosimetric constraints. The choice of portal incidence was determined first by the maximal dose tolerated by the OARs and second by the minimal dose (60 Gy) to be delivered to the PTV. The maximal dose was limited to 54 Gy and 60 Gy, respectively, to the chiasma and central nervous system (CNS). The dose to the ipsilateral optic nerve and retina was limited to 60 Gy, except in the case of definitive RT for tumors that involved the optic nerve. In all patients, the choice of portal incidence was made with the aim of sparing the contralateral eye. The goal was to deliver 66 –70 Gy to the PTV in the case of incomplete or no surgery and 64 – 66 Gy in the case of complete resection. Dose–volume histograms were calculated for the PTV, ipsilateral and contralateral eyes, lens, and optic nerve. Radiation was delivered in doses of 2 Gy/fraction at five fractions weekly. When lymph node RT was required, the primary tumor and cervix were included in the AP and lateral beams up to a minimal dose of 30 Gy to limit overdosage or underdosage due to matching of radiation fields. The inferior cervical regions, to which a boost with electrons was delivered, received a total dose of 50 Gy. The junction was selected to be in a region that received prophylactic RT (50 Gy). Thus, the risk of overdosage or underdosage was mitigated by treatment design: the maximal dose that could be delivered was 70 Gy and the minimal dose was 30 Gy. The electron field at the skin junction with the photon field and the electron field tilt were also calculated using the treatment planning system. Noncoplanar fields were used only for the tumor CTV. Thus, there were no problems in matching the photon fields with the electron boost.
RESULTS The median dose delivered to the PTV was 63 Gy (range 30 –70). The minimal dose was 60 Gy, except for 2 patients who received 30 Gy and 50 Gy because of disease progression during RT. These 2 patients were excluded from the analysis of the dosimetric prognostic factors. The median dose was 63 Gy (range 30 –70) and 64 Gy (range 50 – 68) for patients who had undergone complete tumor resection and incomplete or no tumor resection, respectively. Five patients with clinically and histologically demonstrated lymph node involvement (four with maxillary sinus tumors and one with an ethmoid sinus tumor), three of whom had squamous cell carcinoma and two who had adenocarcinoma, received 60 Gy to the ipsilateral side of the neck. The contralateral side of the neck was irradiated in 1 case of ethmoid sinus tumor because of major node involvement in the ipsilateral side of the neck and capsular invasion. In 3 patients with locally advanced T4N0 tumors, prophylactic RT of the ipsilateral side of the neck was given. The median number of fields was 10 (range 6 to 12).
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Table 1. Prescribed doses and does distribution in PTV
Average (SD) Range
Prescribed dose (Gy)
Mean dose (Gy)
Maximal dose (Gy)
63.2 (3.2) 60.0–70.0
60.7 (3.6) 55.9–68.3
67.1 (4.3) 61.3–76.2
Abbreviations: PTV ⫽ planning target volume; SD ⫽ standard deviation.
Dosimetric results The dosimetric results for the 25 patients, according to the prescribed dose, are shown in Tables 1 through 4. They do not take into account the doses that have indeed been delivered. Dose distribuitons to the optic pathways are shown in Table 2 and 3. The quality of RT was assessed by the tumor conformity index (TCI), normal tissue conformity index (NTCI), and global conformity index (GCI) for the 90% and 95% isodoses (Table 4). The values were defined as follows: 95% (90%) TCI ⫽ PTV volume in the 95% (90%) isodose/PTV volume; 95% (90%) NTCI ⫽ PTV volume in the 95% (90%) isodose/95% (90%) isodose volume; and 95% (90%) GCI ⫽ [95% (90%) TCI ⫻ 95% (90%) NTCI]1/2. Progression-free survival The progression-free survival curves are shown in Fig. 1. The median follow-up time was 25 months (range 4 –51). For 1 patient with a nonresectable tumor extending to the base of the skull, residual tumor was observed on CT 2 months after RT. The patient died and was considered to have had local disease progression. Two patients had local and regional tumor progression during RT. One of these patients had a T3 nonresectable adenocarcinoma of the ethmoid sinus involving the dura mater. Neoadjuvant chemotherapy failed to reduce the volume, and RT was stopped at 50 Gy because of progression. The other patient developed local tumor progression during RT, despite initial surgery considered to be macroscopically complete, for a T2N1 squamous cell carcinoma of the maxillary sinus. Fourteen local relapses occurred. Nine recurrences were local only, three were associated with relapses in the cervical lymph nodes, and two were associated with distant metastases. All 3 patients with brain involvement, including 2 patients who underwent complete tumor resection, died of local recurrence 3– 8 months after treatment completion
(tumor extension to the brain in 2 patients and to the base of the skull in 1 patient). The site of recurrence relative to the PTV could not be assessed. Local recurrences occurred within the PTV in 8 patients 2–36 months after RT completion. Four of these patients had base of the skull and/or dura mater tumor involvement. The recurrence was documented for 6 patients and suspected for 2 patients. One patient had T3 and seven had T4 tumors; 6 patients had adenocarcinoma. Seven patients underwent surgery, which was considered macroscopically complete in five. The radiation dose ranged from 60 to 66 Gy (median 64). Local recurrence was associated with relapse in the lymph nodes in 1 patient and with metastasis in 2 patients. Two patients developed local involvement in the vicinity of the PTV because the CTV had been inadequately defined. The first patient had T3 squamous cell carcinoma of the maxillary sinus. The tumor encompassed the internal corner of the maxillary sinus, left nasal fossa, internal wall of the ethmoid sinus, and internal corner of the left orbital cavity. After neoadjuvant chemotherapy, limited but macroscopically complete, surgery was performed. However, the sphenoid sinus was not examined. The CTV was limited to the initially involved anatomic structures. Postoperative chemoradiotherapy delivered 70 Gy of radiation plus weekly platinum-based chemotherapy. Eleven months later, the patient experienced bilateral recurrence in the cervical lymph nodes, along with a large local recurrence including the sphenoid sinus. The second patient, who had T2 adenocarcinoma of the ethmoid sinus that extended to the ipsilateral nasal cavity, underwent macroscopically complete surgery. Because of the limited initial tumor and its complete resection, the postoperative RT dose was only 60 Gy. To protect the contralateral optic nerve, the dose to the top of the contralateral ethmoid sinus was limited to 50 Gy. Nine months later, local recurrence developed, probably from this site, and extended to the orbital cavity.
Table 2. Dose distributions in ipsilateral and contralateral eye Eyes receiving isodose (%)
Ipsilateral eye Average (SD) Range Contralateral eye Average (SD) Range
Mean dose (Gy)
40 Gy
50 Gy
43.0 (12.7) 12.7–61.5
61.3 (28.6) 13.0–100.0
42.5 (27.9) 6.0–99.0
14.6 (6.7) 2.7–25.9
4.1 (6.0) 0.0–21.0
1.2 (2.2) 0.0–8.0
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Table 3. Dose distribution for chiasma and ipsilateral and contralateral lenses and optic nerves Lens
Optic nerve
Dose (Gy)
Chiasma
Ipsilateral
Contralateral
Ipsilateral
Contralateral
Average (SD) Range
46.1 (14.7) 1.4–62.7
36.5 (14.0) 1.4–53.7
7.1 (4.7) 0.7–19.5
50.1 (15.6) 2.7–71.7
24.4 (10.4) 1.9–46.0
Four patients developed recurrent disease in the lymph nodes (this was associated with local recurrence in 2 patients), and 1 patient experienced local and nodal disease progression during RT. Histologic features, primary tumor site, initial node status, and management data are given in Table 5. Three patients developed metastases that were associated with local tumor relapse in two. One patient had T4 undifferentiated squamous cell carcinoma of the maxillary sinus. The treatment consisted of incomplete surgery, RT (68 Gy) plus three concomitant courses of 5-fluorouracil and cisplatinum, and prophylactic RT to the ipsilateral cervical lymph nodes. This patient developed isolated liver metastases 27 months after the end of RT. Two patients who had T4 adenocarcinoma of the ethmoid sinus and base of the skull or dura mater involvement experienced local failure contemporaneous with pleural and brain metastases 3 months after the end of RT. All patients with metastases died of disease progression. No statistically significant difference was found in local or nodal disease-free survival between patients with adenocarcinoma and those with squamous cell carcinoma (p ⫽ 0.7). Overall survival The overall survival curves are shown in Fig. 2. Six patients were alive with their cancer in complete remission at last follow-up. The other 19 patients died, 2 of acute toxicity (1–3 months after RT completion), 9 of exclusive local relapse (including 1 who had disease progression during RT), and 8 of disease in the lymph nodes or metastases, either alone (3 patients) or associated with local recurrence (5 patients). All 3 patients who did not undergo surgery, and 2 of the 6 patients in whom tumor resection was uncompleted (or unknown) died of local progressive disease (86%). All 3
patients with brain involvement and 5 of 7 available patients with base of the skull or dura mater involvement died of local relapse. Two of the latter 5 patients, who had initial lymph node involvement, but in whom local control was achieved, died of ipsilateral lymph node relapse within the radiation fields. One patient who did not undergo prophylactic neck RT died of exclusive nodal disease progression, despite salvage surgery and RT. Toxicity Two patients died of acute infectious complications. The first had T3 squamous cell carcinoma of the maxillary sinus, with macroscopically incomplete surgery that required orbital floor reconstruction using a prosthesis. During RT, this patient developed a regressive corneal abscess, and, despite antibiotic treatment, the operative site became infected and the prosthesis had to be removed. Three months after the end of RT, the patient died of sepsis, after having developed pneumopathy and reinfection of the operative site. The second patient, who had T4 adenocarcinoma of the ethmoid sinus and meninges involvement requiring reconstruction using fascia lata, developed a frontal sinocutaneous fistula during RT. A purulent exudate oozed from the scar at the beginning of RT, and bone infection developed. Despite antibiotic treatment, a major local infection occurred 1 month after the end of RT, leading to the patient’s death. Two patients experienced complete regressive purulent keratoconjunctivitis during RT. Late toxic effects occurred in 3 patients. Two patients with T4 adenocarcinoma of the ethmoid sinus that extended to the ipsilateral orbital contents developed ipsilateral uveitis and retinopathy 17 and 23 months after RT completion. In 1 patient, the uveitis was associated with local recurrence inside the CTV, which included the internal part of the ipsilateral orbital cavity and optic nerve. The doses deliv-
Table 4. TCI, NTCI, and GCI values for 95% and 90% isodoses
Isodose 95% Average (SD) Range Isodose 90% Average (SD) Range
TCI
NTCI
GCI
0.69 (0.18) 0.32–0.95
0.81 (0.13) 0.36–0.97
0.74 (0.11) 0.51–0.86
0.86 (0.11) 0.61–0.99
0.76 (0.11) 0.45–0.94
0.80 (0.06) 0.64–0.90
Abbreviations: TCI ⫽ tumor conformity index; NTCI ⫽ normal tissue conformity index; GCI ⫽ global conformity index.
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Fig. 1. Progression-free survival.
ered to the PTV were 60 and 64 Gy. Limited necrosis of the nose cartilage requiring surgical resection was found in the third patient 2 years after the end of treatment. This patient was treated by incomplete surgery and had received an irradiation dose of 60 Gy for T4 ethmoid carcinoma that invaded the nose cartilage. DISCUSSION Because of the wide heterogeneity in the tumor histologic features, surgical and radiotherapeutic techniques, and the small sample size of most reported series, clinical data remain relatively scarce for carcinoma of the paranasal sinuses. The present series included 25 patients with locally advanced maxillary or ethmoid sinus carcinoma (squamous Table 5. Characteristics of patients who had disease recurrence in lymph nodes Histologic subtype Adenocarcinoma Squamous cell Location Maxillary sinus Ethmoid sinuc Node and radiation status N0 with radiation N0 without radiation N1 with radiation
1/13 4/12 4/7 1/18 0/3 2/17 3/5
cell carcinoma or adenocarcinoma) for which homogeneous conformal RT was administered. This series represents one of the most extensive experiences reported. Although local treatment modalities were considered optimal, the local control in our series was poor (14 patients had local tumor recurrence or progression). The major adverse prognostic factor was the initial involvement of the CNS (frontal parenchyma; 3 patients) or the base of the skull or dura mater (8 patients). Five of the available 7 patients with base of the skull or meninges involvement died of local relapse, including 1 patient who had tumor progression during RT and 2 patients who had concomitant metastases. The site of recurrence was considered to be in the PTV for 3 patients, but it could not be determined for 1 patient. The unfavorable nature of CNS involvement has been described by several authors, and it is possible that patients with tumors affecting the CNS are unsuitable for curative RT (4, 9). Nevertheless, selected patients should be considered for palliative treatment to prevent painful local tumor evolution without impairing the patient’s quality of life. Published guidelines state that, whenever possible, surgery should be performed to improve local control (3–5). Despite the initial gross tumor volume, 22 patients (88%) underwent surgery. All 3 patients who had nonresectable tumors died of local disease progression or recurrence, and 2 of the 4 patients who underwent surgical tumor debulking experienced local recurrence. However, 9 of the available
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Fig. 2. Overall survival.
16 patients with macroscopically complete resection experienced local progression. Thus, no conclusions on the role of surgery can be drawn from our series. The role of chemotherapy for paranasal sinus carcinoma remains unclear. Several authors (12, 13) reported that concomitant cisplatin-based chemotherapy and hyperfractionated or accelerated RT achieved excellent local control for advanced paranasal tumors in small series. In our series, only 7 patients received chemotherapy, which was neoadjuvant in 3 patients and concomitant with RT in 4. The aim of neoadjuvant chemotherapy was to reduce the gross tumor volume so that surgery could be performed. However, surgery was possible for only 1 patient. Despite concomitant chemotherapy, 3 of the 4 patients experienced local tumor recurrence. Because of the poor prognosis factors for our patients treated with chemotherapy, our observations yielded no conclusions or recommendations about chemotherapy for paranasal sinus carcinoma. Rasch et al. (14) have recently reported the influence of both observer and treatment planner on the calculated CTV and the dose delivered to OARs. Nevertheless, these data could not be correlated to clinical features. In our series, two tumor recurrences occurred at the limit of the radiation field. In all patients, surgery was considered to be complete, but this consisted of limited resection. The volume of the CTV was delineated, taking into account the tumor location indicated on preoperative images and the postoperatively established tumor histologic features. Surgery was probably insufficient to screen the microscopic extent of the disease, and the CTV did not encompass adjoining structures. Image
fusion of preoperative CT or MRI and postoperative treatment planning using CT and positron emission tomography images should improve the accuracy of the CTV delineation, prevent ballistic miss fields, and decrease toxic effects (15–17). Despite using CT-based three-dimensional RT, Roa et al. (4) reported that 17 of their 39 patients had local disease recurrence within the irradiation fields. In our series, 14 local tumor recurrences developed. The site of recurrence was within the fields in 8 patients and suspected to be within them in 2. For patients whose cancer involved the brain, the exact location of the recurrence relative to the PTV could not be determined. No radiation dose effect was observed in our series. The median dose for patients who had tumor recurrence within the CTV was 64 Gy (range 60 – 66) and was not significantly different statistically from that of the whole population. The optimal dose after macroscopically complete tumor resection is not available. At least 66 –70 Gy of radiation is necessary to control the tumor when surgery is not done or when macroscopic residual disease remains (4 – 6, 18). In this series, the median radiation dose for these patients was probably kept too low, so as not to exceed the maximal tolerated dose for the OARs. No prognostic factors were found using the 95% and 90% TCIs. The 95% TCI for patients with in-field recurrences and other available patients was, respectively, 0.79 (range 0.46 – 0.95) and 0.74 (range 0.32– 0.86); the corresponding 90% TCIs were 0.94 (range 0.65– 0.99) and 0.90 (range 0.61– 0.97). The GCI results were satisfactory, taking into account the vicinity of
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the OARs, with average GCIs of 74% and 81%, respectively, for the 95% and 90% isodoses. Our results suggest the need to increase the total radiation dose in the PTV, with respect to the OARs. Intensitymodulated RT (IMRT) should improve conformal dose administration to the target tissues while decreasing the radiation dose to the normal tissues (19 –21). Hunt et al. (22) and Wolden et al. (23) demonstrated that IMRT for nasopharynx cancer led to an improvement in local control compared with CRT, respecting the dose tolerated by the OARs. Ion-beam therapy, and notably, intensity-modulated proton therapy, has been reported to be a useful technique for the treatment of tumors surrounded by OARs (24). Another cause of failure was metastasis to the lymph nodes. The risk failure in the lymph nodes has been reported to be as high as 8 –29% for patients with squamous cell carcinoma of the maxillary sinus (5, 25). In our series, 5 patients (3 with squamous cell carcinoma and 2 with adenocarcinoma) had cervical lymph node involvement at the time of initial staging (20%). Five patients experienced recurrent disease in the cervical nodes. This recurrence was bilateral for 1 patient. Three patients of the five previously irradiated for N1 disease developed relapses in the ipsilateral irradiated cervical chains. For patients who did not receive prophylactic RT to the cervical nodes, salvage surgery and RT were not effective. Several authors, on the basis of the results of retrospectively analyzed series, proposed prophylactic cervical lymph node RT in two high-risk groups of patients: those with T3 and T4 paranasal sinus carcinoma and those with squamous cell carcinoma (26, 27). At the beginning of our experience, 2 patients with Stage T3N0 and T2N0 squamous cell carcinoma of the maxillary sinus developed tumor recurrences in the lymph nodes. We decided to perform prophylactic ipsilateral cervical chain RT for large-volume tumors (T4), regardless of
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their histologic features, and for squamous cell carcinomas involving the infrastructure of the maxillary sinus. No tumor recurrences in the ipsilateral or contralateral lymph nodes have been observed for the N0 patients who received prophylactic node irradiation. We have not observed any acute or late toxic effects of Grade 2 or greater toxicity related to this irradiation. We observed good results for radiation toxicity, with the exception of two toxic deaths attributed to postoperative severe infection. The average value of the 95% NTCI was very good. For the 2 patients who experienced ocular complications, the mean radiation dose to the ipsilateral eye was 53 and 48.7 Gy (maximal dose 67 and 64.8), respectively. These results were greater than the averages for the whole population (mean dose 43 Gy, and maximal dose 63), because of the PTV delineation that included the OARs. However, these patients’ values for 95% NTCI (0.81 and 0.87) and 95% GCI (0.83 and 0.75) greater higher than the population mean values. These results suggest that these complications would have been difficult to avoid, even with more advanced technology such as IMRT or proton therapy. CONCLUSION Although local CRT modalities are considered to be optimal in paranasal sinus carcinoma, the major cause of failure remains a lack of local control. Several local recurrences could have been avoided by a better delineation of the PTV, with better surgical procedures and imaging fusion. New irradiation techniques such as IMRT and ion beam therapy, should allow increases in the radiation dose delivered to the PTV, while respecting the maximal dose tolerated by the OARs. An ongoing French multicentric study is evaluating the dosimetric, clinical, and economic aspects of IMRT compared with CRT.
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