Original Article Radiat Oncol J 2013;31(3):118-124 http://dx.doi.org/10.3857/roj.2013.31.3.118 pISSN 2234-1900 · eISSN 2234-3156
Neoadjuvant intra-arterial chemotherapy combined with radiotherapy and surgery in patients with advanced maxillary sinus cancer Won Taek Kim, MD1, Jiho Nam, MD2, Yong Kan Ki, MD1, Ju Hye Lee, MD1, Dong Hyun Kim, MD1, Dahl Park, PhD1, Kyu Sup Cho, MD3, Hwan Jung Roh, MD4, Dong Won Kim, MD, PhD1 1
Department of Radiation Oncology, Biomedical Research Institute, Pusan National University Hospital, Pusan National University School of Medicine, Busan; 2Department of Radiation Oncology, Pusan National University Yangsan Hospital, Yangsan; 3Department of Otolaryngology, Biomedical Research Institute, Pusan National University Hospital, Pusan National University School of Medicine, Busan; 4Department of Otolaryngology, Pusan National University Yangsan Hospital, Pusan National University School of Medicine, Yangsan, Korea
Purpose: The optimal treatment of advanced maxillary sinus cancer has been challenging for several decades. Intra-arterial chemotherapy (IAC) for head and neck cancer has been controversial. We have analyzed the long-term outcome of neoadjuvant IAC followed by radiation therapy (RT) and surgery. Materials and Methods: Twenty-seven patients with advanced maxillary sinus cancer were treated between 1989 and 2002. Five-fluorouracil (5-FU, 500 mg/m2) was infused intra-arterially, and followed by RT (total 50.4 Gy/28 fractions). A planned surgery was performed 3 to 4 weeks after completion of IAC and RT. Results: At a median follow-up of 77 months (range, 12 to 169 months), the 5-year rates of overall survival in all patients were 63%. The 5-year rates of overall survival of stage T3/T4 patients were 70.0% and 58.8%, respectively. Seven of fourteen patients with disease recurrence had a local recurrence alone. The 5-year actuarial local control rates in patients with stage T3/T4, and in all patients were 20.0%, 32.3%, and 27.4%, respectively. Overall response rate after the completion of IAC and RT was 70.3%. During the follow-up, seven patients (25.9%) showed mild to moderate late complications. The tumor extent (i.e., the involvement of either orbit and/or base of skull) appeared to be related with local recurrence. Conclusion: Neoadjuvant IAC with 5-FU followed by RT and surgery may be effective to improve local tumor control in the patients with advanced maxillary sinus cancer. However, local failure was still the major cause of death. Further investigations are required to determine the optimal treatment schedule, radiotherapy techniques and chemotherapy regimens. Keywords: Maxillary sinus neoplasms, Intra-arterial infusion, Radiation therapy, Surgery
Introduction Malignant tumor of maxillary sinus is an uncommon neoplasm. It accounts for less than 0.5% of all cancers [1]. The majority
of these tumors are diagnosed at locally advanced stage. The optimal treatment of locally advanced maxillary sinus cancer has been challenging for several decades. Extensive surgical resection including orbital exenteration was occasionally
Received 2 April 2013, Revised 1 June 2013, Accepted 21 June 2013. Correspondence: Jiho Nam, MD, Department of Radiation Oncology, Pusan National University Yangsan Hospital, 20 Geumo-ro, Yangsan 626-787, Korea. Tel: +82-55-360-3453, Fax: +82-55-360-2449, E-mail: [email protected] CC This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/ licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
www.e-roj.org 118
Copyright © 2013. The Korean Society for Radiation Oncology
Combined therapy of maxillary sinus cancer required to achieve complete resection of the tumor. However, these tumors are usually located in the vicinity of the critical organs, therefore, extensive surgery alone usually results in various complications and/or poor cosmetic outcomes. Radiation therapy (RT) alone, often performed in medically inoperable patients, was less effective than surgery alone or combined surgery and RT [2]. In spite of extensive surgical resection with or without RT, the majority of treatment failure was local recurrence [2,3]. Although the studies of combined modality approaches in patients with locally advanced maxillary sinus cancer have reported improved survival outcomes, however, combined chemotherapy may also increase the incidence of various adverse events. To minimize these adverse effects of che motherapeutic agents, several studies of intra-arterial che motherapy (IAC) combined-multimodal approaches have been performed in locally advanced maxillary cancer. However, the optimal treatment sequences and combinations still remain controversial. Since 1989 we have treated patients with locally advanced maxillary sinus cancer using sequential multimodal therapy which consisted of neoadjuvant IAC, sequentially combined RT, and surgery. This study is an analysis of long-term followup data to evaluate the clinical outcomes of this combined modality approach in patients with non-metastatic locally advanced maxillary sinus cancer.
Materials and Methods This retrospective study was performed by reviewing the patients’ medical records and radiographic imaging data of the patients who had been diagnosed with locally advanced maxillary sinus cancer and then treated with multimodal therapy of IAC between November 1989 and December 2002. 1. Patients Patients with locally advanced, non-metastatic cancer (cT34N0M0) of the maxillary sinus were analyzed for this study. All patients underwent pretreatment staging workup of a complete history and physical examination with clinical staging, complete blood cell count, liver function tests, renal function tests, chest X-ray, computed tomography (CT) scan, and ultrasonography of liver. Patients with the Eastern Cooperative Oncology Group (ECOG) performance status 0–2, no previous treatment, normal blood cell count, normal or less than 50% increased level of liver and renal function test, and
http://dx.doi.org/10.3857/roj.2013.31.3.118
no other medical condition were combined. Written informed consents before treatment were provided by all of the patients. 2. Intra-arterial chemotherapy Chemotherapy was administered intra-arterially. The intraarterial infusion was performed with the catheterization of superficial temporal artery. Through the skin incision in the preauricular region, the superficial temporal artery was exposed and the tip of the catheter was inserted into the internal maxillary artery. To identify the proper location of the feeding artery, Indigo carmine dye was infused, and then the catheter was advanced to the feeding artery. After the location was confirmed, the catheter was fixed. Chemotherapeutic agent of 5-fluorouracil (5-FU, 500 mg/ m2) was infused at the rate of 1 mg/m2 per minute (8 hours per day) through the catheter. This was repeated every 4 to 6 days per week for 1 to 2 weeks. According to the tolerance and toxicity of the treatment, chemotherapy dose was reduced gradually by 25% to 50%. 3. Radiation therapy RT was started 1 to 2 weeks after the last course of the chemotherapy (IAC). All patients were treated with externalbeam RT using a 6-megavolt X-ray of linear accelerator. Either parallel opposed lateral fields or anteroposterior fields were used to treat the primary tumor area with a dose of 50.4 Gy at 1.8 Gy/fraction to the isocenter. Wedges or tissue compensators were used to maintain dose homogeneity within 10% of the prescribed dose. RT was delivered with a continuous course of once-daily, 5 days-per-week treatment for all patients. The initial treatment volume was designed to encompass the primary tumor site with median 2 cm (range, 1 to 3 cm) margins depending on CT or endoscopic findings and the proximity of critical structures. Elective neck irradiation to the ipsilateral neck was performed using anteroposteriorposteroanterior photon fields in patients with T4 stage, poor responders to chemotherapy (i.e.,
Neoadjuvant intra-arterial chemotherapy combined with radiotherapy and surgery in patients with advanced maxillary sinus cancer Won Taek Kim, MD1, Jiho Nam, MD2, Yong Kan Ki, MD1, Ju Hye Lee, MD1, Dong Hyun Kim, MD1, Dahl Park, PhD1, Kyu Sup Cho, MD3, Hwan Jung Roh, MD4, Dong Won Kim, MD, PhD1 1
Department of Radiation Oncology, Biomedical Research Institute, Pusan National University Hospital, Pusan National University School of Medicine, Busan; 2Department of Radiation Oncology, Pusan National University Yangsan Hospital, Yangsan; 3Department of Otolaryngology, Biomedical Research Institute, Pusan National University Hospital, Pusan National University School of Medicine, Busan; 4Department of Otolaryngology, Pusan National University Yangsan Hospital, Pusan National University School of Medicine, Yangsan, Korea
Purpose: The optimal treatment of advanced maxillary sinus cancer has been challenging for several decades. Intra-arterial chemotherapy (IAC) for head and neck cancer has been controversial. We have analyzed the long-term outcome of neoadjuvant IAC followed by radiation therapy (RT) and surgery. Materials and Methods: Twenty-seven patients with advanced maxillary sinus cancer were treated between 1989 and 2002. Five-fluorouracil (5-FU, 500 mg/m2) was infused intra-arterially, and followed by RT (total 50.4 Gy/28 fractions). A planned surgery was performed 3 to 4 weeks after completion of IAC and RT. Results: At a median follow-up of 77 months (range, 12 to 169 months), the 5-year rates of overall survival in all patients were 63%. The 5-year rates of overall survival of stage T3/T4 patients were 70.0% and 58.8%, respectively. Seven of fourteen patients with disease recurrence had a local recurrence alone. The 5-year actuarial local control rates in patients with stage T3/T4, and in all patients were 20.0%, 32.3%, and 27.4%, respectively. Overall response rate after the completion of IAC and RT was 70.3%. During the follow-up, seven patients (25.9%) showed mild to moderate late complications. The tumor extent (i.e., the involvement of either orbit and/or base of skull) appeared to be related with local recurrence. Conclusion: Neoadjuvant IAC with 5-FU followed by RT and surgery may be effective to improve local tumor control in the patients with advanced maxillary sinus cancer. However, local failure was still the major cause of death. Further investigations are required to determine the optimal treatment schedule, radiotherapy techniques and chemotherapy regimens. Keywords: Maxillary sinus neoplasms, Intra-arterial infusion, Radiation therapy, Surgery
Introduction Malignant tumor of maxillary sinus is an uncommon neoplasm. It accounts for less than 0.5% of all cancers [1]. The majority
of these tumors are diagnosed at locally advanced stage. The optimal treatment of locally advanced maxillary sinus cancer has been challenging for several decades. Extensive surgical resection including orbital exenteration was occasionally
Received 2 April 2013, Revised 1 June 2013, Accepted 21 June 2013. Correspondence: Jiho Nam, MD, Department of Radiation Oncology, Pusan National University Yangsan Hospital, 20 Geumo-ro, Yangsan 626-787, Korea. Tel: +82-55-360-3453, Fax: +82-55-360-2449, E-mail: [email protected] CC This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/ licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
www.e-roj.org 118
Copyright © 2013. The Korean Society for Radiation Oncology
Combined therapy of maxillary sinus cancer required to achieve complete resection of the tumor. However, these tumors are usually located in the vicinity of the critical organs, therefore, extensive surgery alone usually results in various complications and/or poor cosmetic outcomes. Radiation therapy (RT) alone, often performed in medically inoperable patients, was less effective than surgery alone or combined surgery and RT [2]. In spite of extensive surgical resection with or without RT, the majority of treatment failure was local recurrence [2,3]. Although the studies of combined modality approaches in patients with locally advanced maxillary sinus cancer have reported improved survival outcomes, however, combined chemotherapy may also increase the incidence of various adverse events. To minimize these adverse effects of che motherapeutic agents, several studies of intra-arterial che motherapy (IAC) combined-multimodal approaches have been performed in locally advanced maxillary cancer. However, the optimal treatment sequences and combinations still remain controversial. Since 1989 we have treated patients with locally advanced maxillary sinus cancer using sequential multimodal therapy which consisted of neoadjuvant IAC, sequentially combined RT, and surgery. This study is an analysis of long-term followup data to evaluate the clinical outcomes of this combined modality approach in patients with non-metastatic locally advanced maxillary sinus cancer.
Materials and Methods This retrospective study was performed by reviewing the patients’ medical records and radiographic imaging data of the patients who had been diagnosed with locally advanced maxillary sinus cancer and then treated with multimodal therapy of IAC between November 1989 and December 2002. 1. Patients Patients with locally advanced, non-metastatic cancer (cT34N0M0) of the maxillary sinus were analyzed for this study. All patients underwent pretreatment staging workup of a complete history and physical examination with clinical staging, complete blood cell count, liver function tests, renal function tests, chest X-ray, computed tomography (CT) scan, and ultrasonography of liver. Patients with the Eastern Cooperative Oncology Group (ECOG) performance status 0–2, no previous treatment, normal blood cell count, normal or less than 50% increased level of liver and renal function test, and
http://dx.doi.org/10.3857/roj.2013.31.3.118
no other medical condition were combined. Written informed consents before treatment were provided by all of the patients. 2. Intra-arterial chemotherapy Chemotherapy was administered intra-arterially. The intraarterial infusion was performed with the catheterization of superficial temporal artery. Through the skin incision in the preauricular region, the superficial temporal artery was exposed and the tip of the catheter was inserted into the internal maxillary artery. To identify the proper location of the feeding artery, Indigo carmine dye was infused, and then the catheter was advanced to the feeding artery. After the location was confirmed, the catheter was fixed. Chemotherapeutic agent of 5-fluorouracil (5-FU, 500 mg/ m2) was infused at the rate of 1 mg/m2 per minute (8 hours per day) through the catheter. This was repeated every 4 to 6 days per week for 1 to 2 weeks. According to the tolerance and toxicity of the treatment, chemotherapy dose was reduced gradually by 25% to 50%. 3. Radiation therapy RT was started 1 to 2 weeks after the last course of the chemotherapy (IAC). All patients were treated with externalbeam RT using a 6-megavolt X-ray of linear accelerator. Either parallel opposed lateral fields or anteroposterior fields were used to treat the primary tumor area with a dose of 50.4 Gy at 1.8 Gy/fraction to the isocenter. Wedges or tissue compensators were used to maintain dose homogeneity within 10% of the prescribed dose. RT was delivered with a continuous course of once-daily, 5 days-per-week treatment for all patients. The initial treatment volume was designed to encompass the primary tumor site with median 2 cm (range, 1 to 3 cm) margins depending on CT or endoscopic findings and the proximity of critical structures. Elective neck irradiation to the ipsilateral neck was performed using anteroposteriorposteroanterior photon fields in patients with T4 stage, poor responders to chemotherapy (i.e.,
