CASE REPORT
Peter Andersen, MD, Section Editor
Accelerated hyperfractionated radiotherapy for small cell carcinoma of the nasopharynx Shigeo Takahashi, MD,1* Takenori Miyashita, MD, PhD,2 Hiroshi Hoshikawa, MD, PhD,2 Reiji Haba, MD, PhD,3 Taro Togami, MD, PhD,1 Toru Shibata, MD, PhD1 1
Department of Radiation Oncology, Kagawa University Hospital, Kagawa, Japan, 2Department of Otolaryngology, Head and Neck Surgery, Kagawa University Hospital, Kagawa, Japan, 3Department of Diagnostic Pathology, Kagawa University Hospital, Kagawa, Japan.
Accepted 27 September 2014 Published online 29 March 2015 in Wiley Online Library (wileyonlinelibrary.com). DOI 10.1002/hed.23888
ABSTRACT: Background. The purpose of this study was to report the treatment outcome of a patient with nasopharyngeal small cell carcinoma. Methods. The patient received concurrent chemoradiotherapy (CRT). Chemotherapy consisted of 4 cycles of cisplatin and etoposide. Accelerated hyperfractionated radiotherapy (RT) was performed with a dose of 45 Gy in 30 fractions over 3 weeks for the nasopharynx and upper neck region, whereas conventional fractionated RT was performed with a dose of 50 Gy in 25 fractions over 5 weeks for the lower neck region. Results. Complete response was achieved 1 month after the completion of CRT. Prophylactic cranial irradiation was not performed. Isolated brain metastasis was diagnosed 18 months
after the completion of CRT. Finally, the patient died because of the brain and cord metastases 32 months after the completion of CRT. Conclusion. The administration of prophylactic cranial irradiation may C 2015 Wiley be considered for nasopharyngeal small cell carcinoma. V Periodicals, Inc. Head Neck 37: E63–E65, 2015
KEY WORDS: small cell carcinoma, accelerated hyperfractionation, twice daily, cisplatin and etoposide regimen, concurrent chemoradiation
INTRODUCTION
CASE REPORT
Small cell carcinoma of the nasopharynx is a rare tumor. To the best of our knowledge, only 3 cases that have been treated using radiotherapy (RT) and have provided dose information have been reported.1–3 Extrapulmonary small cell carcinoma accounts for only 4% of all cases of small cell carcinoma,4 and appropriate treatment strategy has not been established for extrapulmonary small cell carcinoma because of its rarity. Extrapulmonary small cell carcinoma has been treated in a manner similar to small cell lung carcinoma (SCLC) because of the similarities in pathology and clinical behavior between SCLC and extrapulmonary small cell carcinoma.5 For limitedstage SCLC, chemoradiotherapy (CRT) using accelerated hyperfractionated RT with cisplatin and etoposide has been performed as a standard regimen.6 However, there have been no reports of the use of accelerated hyperfractionated RT for small cell carcinoma of the nasopharynx, and this is the first case report describing the treatment outcome of a patient who was treated with accelerated hyperfractionated RT for nasopharyngeal small cell carcinoma.
A 54-year-old man presented to the otolaryngology department of a local hospital with the gradual onset of an occlusive feeling in the nose and ear for approximately 2 months. Nasopharyngoscopy revealed a mass that was located in the inferior wall of the nasopharynx, and small cell carcinoma was suspected based on the tissue biopsy. The patient was referred to our hospital for detailed examination and treatment, and repeat biopsy was performed. Light microscopy after hematoxylin and eosin staining showed that the tumor was composed of small cells with a high nuclear-cytoplasmic ratio, oval-shaped to spindle-shaped nuclei that formed rosettes, and extensive necrosis (see Figure 1), in addition, small cell carcinoma was pathologically diagnosed. For imaging studies, CT, MRI, and fluorodeoxyglucose-18 positron emission tomography were performed. The tumor invaded the vomer and spread to the lymph nodes in the bilateral supraclavicular fossa (see Figure 2); there was no distant metastasis. Therefore, the tumor was classified as T3N3M0 according to the sixth edition of the Union for International Cancer Control TNM Classification. The patient was treated with concurrent CRT. Chemotherapy consisted of 4 cycles of cisplatin (80 mg/m2) on day 1 and etoposide (100 mg/m2) on days 1 to 3 every 4 weeks. RT was used in combination with the first cycle of chemotherapy. Accelerated hyperfractionated RT with
*Corresponding author: S. Takahashi, Department of Radiation Oncology, Kagawa University Hospital, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa 761-0793, Japan. E-mail: [email protected]
HEAD & NECK—DOI 10.1002/HED
MAY 2015
E63
TAKAHASHI ET AL.
FIGURE 1. The tumor was composed of small cells with a high nuclear–cytoplasmic ratio and oval-shaped to spindle-shaped nuclei that formed rosettes (hematoxylin and eosin stain, original magnification, 320). [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]
an interval of at least 6 hours between fractions was performed with a dose of 45 Gy in 30 fractions over 3 weeks for the nasopharynx and upper neck region, whereas conventional fractionated RT was performed with a dose of 50 Gy in 25 fractions over 5 weeks for the lower neck region. Acute adverse events according to the Common Terminology Criteria for Adverse Events (version 3.0) were as follows: leukocytes and hemoglobin, grade 3; mucositis, dermatitis, and dry mouth, grade 2. According to the Response Evaluation Criteria in
Solid Tumors (version 1.1), CT and MRI for imaging studies showed that complete response was achieved 1 month after the completion of the CRT (see Figure 3). The patient did not receive prophylactic cranial irradiation. The patient experienced a speech disorder and hemiplegia 18 months after the completion of the initial treatment, and isolated brain metastasis was diagnosed using MRI. Subtotal resection was performed for the brain metastasis, followed by postoperative local RT with a dose of 60 Gy in 30 fractions and 2 cycles of chemotherapy with carboplatin and etoposide were performed. However, the brain metastasis recurred, and new metastases appeared in the lumbar cord. Palliative RT for the metastases to the lumbar cord was performed with a dose of 20 Gy in 4 fractions. Finally, the patient died because of the brain and cord metastases 32 months after the completion of the initial treatment.
DISCUSSION To the best of our knowledge, this patient is the first reported case of nasopharyngeal small cell carcinoma who was treated with accelerated hyperfractionated RT. Only 3 cases that have been treated by RT and that have provided dose information have been reported.1–3 The clinical features of the 3 previously reported cases and the present case are summarized in Table 1. Two patients who were treated with a dose of 70 Gy survived without recurrence, but their follow-up duration was short (9 and 5 months).1,2 One patient who was treated with a dose of 62 Gy experienced regional failure 6 months after total regression of the malignancy.3 In the present case of
FIGURE 2. The tumor was located in the inferior wall of the nasopharynx (A), invaded the vomer (B), and spread to the lymph nodes in the bilateral supraclavicular fossa (C). [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]
FIGURE 3. Complete response was achieved 1 month after the completion of the chemoradiotherapy.
E64
HEAD & NECK—DOI 10.1002/HED
MAY 2015
ACCELERATED
HYPERFRACTIONATED
RT
FOR NASOPHARYNGEAL SMALL CELL CARCINOMA
TABLE 1. Clinical features of nasopharyngeal small cell carcinoma.
Age, y
Sex
Lee et al1
41
M
Hatoum et al2
80
M
Lin et al3
43
M
Present case
54
M
Case/reference
Stage
Treatment
Chemotherapy
T1N1
Concurrent Weekly CRT cisplatin T4bN2a CRT Cisplatin 1 etoposide No mention Concurrent Cisplatin 1 CRT etoposide T3N3 Concurrent Cisplatin 1 CRT etoposide
Radiation dose, Gy
70
Fraction size, Gy
PCI
Initial recurrence site (time)
No mention No mention None
70
2
62 45*
No mention None
No mention No mention Neck lymph node (6 mo) 1.5 (AHF)* None Brain (18 mo)
Follow-up, mo
Status
9
NED
5
NED
38
DOD
32
DOD
Abbreviations: PCI, prophylactic cranial irradiation; CRT, chemoradiotherapy; NED, no evidence of disease; DOD, dead of disease; AHF, accelerated hyperfractionation. * Accelerated hyperfractionation was performed with the dose of 45 Gy in 30 fractions over 3 weeks for the nasopharynx and upper neck region, while conventional fractionation was performed with the dose of 50 Gy in 25 fractions over 5 weeks for the lower neck region.
the patient who was treated with accelerated hyperfractionated RT, locoregional control was achieved. Extrapulmonary small cell carcinoma has been treated in a manner similar to SCLC.5 SCLC is considered a relatively radioresponsive tumor, and low doses of RT have been used previously.7 Meanwhile, SCLC is a rapidly growing tumor, and accelerated hyperfractionated RT has the advantage of being able to complete the delivery of a radiation dose over a shortened duration.7 Recently, the standard care regimen for limited-stage SCLC has been based on the study of Intergroup 0096 that showed that accelerated hyperfractionated RT with the dose of 45 Gy improved survival compared with conventional fractionation with the dose of 45 Gy.6 In the National Comprehensive Cancer Network guidelines for SCLC,8 in addition to accelerated hyperfractionated RT, conventional fractionation with the dose of 60 to 70 Gy has also been mentioned as a useful regimen. In small cell carcinoma of the nasopharynx cases reported to date, either accelerated hyperfractionated RT with the dose of 45 Gy or conventional daily fractionation with the dose of 70 Gy achieved locoregional control. Still, given the few cases reported, it is difficult to define an optimal RT dose and schedule for this disease. Patients with SCLC who achieved complete response can be considered for the administration of prophylactic cranial irradiation because a meta-analysis evaluating the usefulness of prophylactic cranial irradiation in such patients reported an improvement in brain metastasis recurrence, disease-free survival, and overall survival.9 Prophylactic cranial irradiation for the 3 previously reported cases was not mentioned, but they did not experience metastases to the central nervous system (CNS). The present case without prophylactic cranial irradiation suffered from distant metastases to the CNS. If nasopha-
ryngeal small cell carcinoma is treated in a manner similar to SCLC, it may be appropriate to deliver prophylactic cranial irradiation, recognizing the dosimetric challenge of matching the nasopharynx/neck field to the whole brain prophylactic cranial irradiation field. In conclusion, a patient with small cell carcinoma of the nasopharynx was treated with concurrent CRT using accelerated hyperfractionated RT without prophylactic cranial irradiation. Locoregional control was achieved, but recurrence in the CNS occurred. Thus, the administration of prophylactic cranial irradiation may be considered for nasopharyngeal small cell carcinoma.
REFERENCES 1. Lee LY, Chang KP, Hsu CL, Chen TC, Kuo TT. Small-cell neuroendocrine carcinoma of the nasopharynx: report of a rare case lacking association with Epstein–Barr virus. Int J Surg Pathol 2011;19:199–202. 2. Hatoum GF, Patton B, Takita C, et al. Small cell carcinoma of the head and neck: the university of Miami experience. Int J Radiat Oncol Biol Phys 2009;74:477–481. 3. Lin IH, Hwang CF, Huang HY, Chien CY. Small cell carcinoma of the nasopharynx. Acta Otolaryngol 2007;127:206–208. 4. Levenson RM Jr, Ihde DC, Matthews MJ, et al. Small cell carcinoma presenting as an extrapulmonary neoplasm: sites of origin and response to chemotherapy. J Natl Cancer Inst 1981;67:607–612. 5. Walenkamp AM, Sonke GS, Sleijfer DT. Clinical and therapeutic aspects of extrapulmonary small cell carcinoma. Cancer Treat Rev 2009;35:228– 236. 6. Turrisi AT III, Kim K, Blum R, et al. Twice-daily compared with oncedaily thoracic radiotherapy in limited small cell lung cancer treated concurrently with cisplatin and etoposide. N Engl J Med 1999;340:265–271. 7. Schild SE, Curran WJ Jr. Small cell lung cancer. In: Gunderson LL, Tepper JE, editors. Clinical radiation oncology. Philadelphia, PA: Elsevier; 2012. pp 795–804. 8. National Comprehensive Cancer Network. Small cell lung cancer, NCCN clinical practice guidelines in oncology: version 2.2014. Available at: http://www.nccn.org/professionals/physician_gls/pdf/sclc.pdf. Accessed December 23, 2013. 9. Auperin A, Arriagada R, Pignon JP, et al. Prophylactic cranial irradiation for patients with small cell lung cancer in complete remission. Prophylactic Cranial Irradiation Overview Collaborative Group. N Engl J Med 1999; 341:476–484.
HEAD & NECK—DOI 10.1002/HED
MAY 2015
E65
Peter Andersen, MD, Section Editor
Accelerated hyperfractionated radiotherapy for small cell carcinoma of the nasopharynx Shigeo Takahashi, MD,1* Takenori Miyashita, MD, PhD,2 Hiroshi Hoshikawa, MD, PhD,2 Reiji Haba, MD, PhD,3 Taro Togami, MD, PhD,1 Toru Shibata, MD, PhD1 1
Department of Radiation Oncology, Kagawa University Hospital, Kagawa, Japan, 2Department of Otolaryngology, Head and Neck Surgery, Kagawa University Hospital, Kagawa, Japan, 3Department of Diagnostic Pathology, Kagawa University Hospital, Kagawa, Japan.
Accepted 27 September 2014 Published online 29 March 2015 in Wiley Online Library (wileyonlinelibrary.com). DOI 10.1002/hed.23888
ABSTRACT: Background. The purpose of this study was to report the treatment outcome of a patient with nasopharyngeal small cell carcinoma. Methods. The patient received concurrent chemoradiotherapy (CRT). Chemotherapy consisted of 4 cycles of cisplatin and etoposide. Accelerated hyperfractionated radiotherapy (RT) was performed with a dose of 45 Gy in 30 fractions over 3 weeks for the nasopharynx and upper neck region, whereas conventional fractionated RT was performed with a dose of 50 Gy in 25 fractions over 5 weeks for the lower neck region. Results. Complete response was achieved 1 month after the completion of CRT. Prophylactic cranial irradiation was not performed. Isolated brain metastasis was diagnosed 18 months
after the completion of CRT. Finally, the patient died because of the brain and cord metastases 32 months after the completion of CRT. Conclusion. The administration of prophylactic cranial irradiation may C 2015 Wiley be considered for nasopharyngeal small cell carcinoma. V Periodicals, Inc. Head Neck 37: E63–E65, 2015
KEY WORDS: small cell carcinoma, accelerated hyperfractionation, twice daily, cisplatin and etoposide regimen, concurrent chemoradiation
INTRODUCTION
CASE REPORT
Small cell carcinoma of the nasopharynx is a rare tumor. To the best of our knowledge, only 3 cases that have been treated using radiotherapy (RT) and have provided dose information have been reported.1–3 Extrapulmonary small cell carcinoma accounts for only 4% of all cases of small cell carcinoma,4 and appropriate treatment strategy has not been established for extrapulmonary small cell carcinoma because of its rarity. Extrapulmonary small cell carcinoma has been treated in a manner similar to small cell lung carcinoma (SCLC) because of the similarities in pathology and clinical behavior between SCLC and extrapulmonary small cell carcinoma.5 For limitedstage SCLC, chemoradiotherapy (CRT) using accelerated hyperfractionated RT with cisplatin and etoposide has been performed as a standard regimen.6 However, there have been no reports of the use of accelerated hyperfractionated RT for small cell carcinoma of the nasopharynx, and this is the first case report describing the treatment outcome of a patient who was treated with accelerated hyperfractionated RT for nasopharyngeal small cell carcinoma.
A 54-year-old man presented to the otolaryngology department of a local hospital with the gradual onset of an occlusive feeling in the nose and ear for approximately 2 months. Nasopharyngoscopy revealed a mass that was located in the inferior wall of the nasopharynx, and small cell carcinoma was suspected based on the tissue biopsy. The patient was referred to our hospital for detailed examination and treatment, and repeat biopsy was performed. Light microscopy after hematoxylin and eosin staining showed that the tumor was composed of small cells with a high nuclear-cytoplasmic ratio, oval-shaped to spindle-shaped nuclei that formed rosettes, and extensive necrosis (see Figure 1), in addition, small cell carcinoma was pathologically diagnosed. For imaging studies, CT, MRI, and fluorodeoxyglucose-18 positron emission tomography were performed. The tumor invaded the vomer and spread to the lymph nodes in the bilateral supraclavicular fossa (see Figure 2); there was no distant metastasis. Therefore, the tumor was classified as T3N3M0 according to the sixth edition of the Union for International Cancer Control TNM Classification. The patient was treated with concurrent CRT. Chemotherapy consisted of 4 cycles of cisplatin (80 mg/m2) on day 1 and etoposide (100 mg/m2) on days 1 to 3 every 4 weeks. RT was used in combination with the first cycle of chemotherapy. Accelerated hyperfractionated RT with
*Corresponding author: S. Takahashi, Department of Radiation Oncology, Kagawa University Hospital, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa 761-0793, Japan. E-mail: [email protected]
HEAD & NECK—DOI 10.1002/HED
MAY 2015
E63
TAKAHASHI ET AL.
FIGURE 1. The tumor was composed of small cells with a high nuclear–cytoplasmic ratio and oval-shaped to spindle-shaped nuclei that formed rosettes (hematoxylin and eosin stain, original magnification, 320). [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]
an interval of at least 6 hours between fractions was performed with a dose of 45 Gy in 30 fractions over 3 weeks for the nasopharynx and upper neck region, whereas conventional fractionated RT was performed with a dose of 50 Gy in 25 fractions over 5 weeks for the lower neck region. Acute adverse events according to the Common Terminology Criteria for Adverse Events (version 3.0) were as follows: leukocytes and hemoglobin, grade 3; mucositis, dermatitis, and dry mouth, grade 2. According to the Response Evaluation Criteria in
Solid Tumors (version 1.1), CT and MRI for imaging studies showed that complete response was achieved 1 month after the completion of the CRT (see Figure 3). The patient did not receive prophylactic cranial irradiation. The patient experienced a speech disorder and hemiplegia 18 months after the completion of the initial treatment, and isolated brain metastasis was diagnosed using MRI. Subtotal resection was performed for the brain metastasis, followed by postoperative local RT with a dose of 60 Gy in 30 fractions and 2 cycles of chemotherapy with carboplatin and etoposide were performed. However, the brain metastasis recurred, and new metastases appeared in the lumbar cord. Palliative RT for the metastases to the lumbar cord was performed with a dose of 20 Gy in 4 fractions. Finally, the patient died because of the brain and cord metastases 32 months after the completion of the initial treatment.
DISCUSSION To the best of our knowledge, this patient is the first reported case of nasopharyngeal small cell carcinoma who was treated with accelerated hyperfractionated RT. Only 3 cases that have been treated by RT and that have provided dose information have been reported.1–3 The clinical features of the 3 previously reported cases and the present case are summarized in Table 1. Two patients who were treated with a dose of 70 Gy survived without recurrence, but their follow-up duration was short (9 and 5 months).1,2 One patient who was treated with a dose of 62 Gy experienced regional failure 6 months after total regression of the malignancy.3 In the present case of
FIGURE 2. The tumor was located in the inferior wall of the nasopharynx (A), invaded the vomer (B), and spread to the lymph nodes in the bilateral supraclavicular fossa (C). [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]
FIGURE 3. Complete response was achieved 1 month after the completion of the chemoradiotherapy.
E64
HEAD & NECK—DOI 10.1002/HED
MAY 2015
ACCELERATED
HYPERFRACTIONATED
RT
FOR NASOPHARYNGEAL SMALL CELL CARCINOMA
TABLE 1. Clinical features of nasopharyngeal small cell carcinoma.
Age, y
Sex
Lee et al1
41
M
Hatoum et al2
80
M
Lin et al3
43
M
Present case
54
M
Case/reference
Stage
Treatment
Chemotherapy
T1N1
Concurrent Weekly CRT cisplatin T4bN2a CRT Cisplatin 1 etoposide No mention Concurrent Cisplatin 1 CRT etoposide T3N3 Concurrent Cisplatin 1 CRT etoposide
Radiation dose, Gy
70
Fraction size, Gy
PCI
Initial recurrence site (time)
No mention No mention None
70
2
62 45*
No mention None
No mention No mention Neck lymph node (6 mo) 1.5 (AHF)* None Brain (18 mo)
Follow-up, mo
Status
9
NED
5
NED
38
DOD
32
DOD
Abbreviations: PCI, prophylactic cranial irradiation; CRT, chemoradiotherapy; NED, no evidence of disease; DOD, dead of disease; AHF, accelerated hyperfractionation. * Accelerated hyperfractionation was performed with the dose of 45 Gy in 30 fractions over 3 weeks for the nasopharynx and upper neck region, while conventional fractionation was performed with the dose of 50 Gy in 25 fractions over 5 weeks for the lower neck region.
the patient who was treated with accelerated hyperfractionated RT, locoregional control was achieved. Extrapulmonary small cell carcinoma has been treated in a manner similar to SCLC.5 SCLC is considered a relatively radioresponsive tumor, and low doses of RT have been used previously.7 Meanwhile, SCLC is a rapidly growing tumor, and accelerated hyperfractionated RT has the advantage of being able to complete the delivery of a radiation dose over a shortened duration.7 Recently, the standard care regimen for limited-stage SCLC has been based on the study of Intergroup 0096 that showed that accelerated hyperfractionated RT with the dose of 45 Gy improved survival compared with conventional fractionation with the dose of 45 Gy.6 In the National Comprehensive Cancer Network guidelines for SCLC,8 in addition to accelerated hyperfractionated RT, conventional fractionation with the dose of 60 to 70 Gy has also been mentioned as a useful regimen. In small cell carcinoma of the nasopharynx cases reported to date, either accelerated hyperfractionated RT with the dose of 45 Gy or conventional daily fractionation with the dose of 70 Gy achieved locoregional control. Still, given the few cases reported, it is difficult to define an optimal RT dose and schedule for this disease. Patients with SCLC who achieved complete response can be considered for the administration of prophylactic cranial irradiation because a meta-analysis evaluating the usefulness of prophylactic cranial irradiation in such patients reported an improvement in brain metastasis recurrence, disease-free survival, and overall survival.9 Prophylactic cranial irradiation for the 3 previously reported cases was not mentioned, but they did not experience metastases to the central nervous system (CNS). The present case without prophylactic cranial irradiation suffered from distant metastases to the CNS. If nasopha-
ryngeal small cell carcinoma is treated in a manner similar to SCLC, it may be appropriate to deliver prophylactic cranial irradiation, recognizing the dosimetric challenge of matching the nasopharynx/neck field to the whole brain prophylactic cranial irradiation field. In conclusion, a patient with small cell carcinoma of the nasopharynx was treated with concurrent CRT using accelerated hyperfractionated RT without prophylactic cranial irradiation. Locoregional control was achieved, but recurrence in the CNS occurred. Thus, the administration of prophylactic cranial irradiation may be considered for nasopharyngeal small cell carcinoma.
REFERENCES 1. Lee LY, Chang KP, Hsu CL, Chen TC, Kuo TT. Small-cell neuroendocrine carcinoma of the nasopharynx: report of a rare case lacking association with Epstein–Barr virus. Int J Surg Pathol 2011;19:199–202. 2. Hatoum GF, Patton B, Takita C, et al. Small cell carcinoma of the head and neck: the university of Miami experience. Int J Radiat Oncol Biol Phys 2009;74:477–481. 3. Lin IH, Hwang CF, Huang HY, Chien CY. Small cell carcinoma of the nasopharynx. Acta Otolaryngol 2007;127:206–208. 4. Levenson RM Jr, Ihde DC, Matthews MJ, et al. Small cell carcinoma presenting as an extrapulmonary neoplasm: sites of origin and response to chemotherapy. J Natl Cancer Inst 1981;67:607–612. 5. Walenkamp AM, Sonke GS, Sleijfer DT. Clinical and therapeutic aspects of extrapulmonary small cell carcinoma. Cancer Treat Rev 2009;35:228– 236. 6. Turrisi AT III, Kim K, Blum R, et al. Twice-daily compared with oncedaily thoracic radiotherapy in limited small cell lung cancer treated concurrently with cisplatin and etoposide. N Engl J Med 1999;340:265–271. 7. Schild SE, Curran WJ Jr. Small cell lung cancer. In: Gunderson LL, Tepper JE, editors. Clinical radiation oncology. Philadelphia, PA: Elsevier; 2012. pp 795–804. 8. National Comprehensive Cancer Network. Small cell lung cancer, NCCN clinical practice guidelines in oncology: version 2.2014. Available at: http://www.nccn.org/professionals/physician_gls/pdf/sclc.pdf. Accessed December 23, 2013. 9. Auperin A, Arriagada R, Pignon JP, et al. Prophylactic cranial irradiation for patients with small cell lung cancer in complete remission. Prophylactic Cranial Irradiation Overview Collaborative Group. N Engl J Med 1999; 341:476–484.
HEAD & NECK—DOI 10.1002/HED
MAY 2015
E65
