Induction Chemotherapy and Involved-Field Radiotherapy for Intracranial Germinoma
Authors: Arnold C. Paulino, Hidefumi Aoyama, Hiroki Shirato, Masaaki Kashiwamura, Jun Ikeda, Yutaka Sawamura
Journal: Journal of Clinical Oncology (2002)

Article Tools SPECIAL DEPARTMENTS Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2002.20.12.2911 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 12065573 Induction Chemotherapy and Involved-Field Radiotherapy for Intracranial Germinoma Arnold C. PaulinoxArnold C. PaulinoSearch for articles by this author Hidefumi AoyamaxHidefumi AoyamaSearch for articles by this author , Hiroki ShiratoxHiroki ShiratoSearch for articles by this author , Masaaki KashiwamuraxMasaaki KashiwamuraSearch for articles by this author , Jun IkedaxJun IkedaSearch for articles by this author , Yutaka SawamuraxYutaka SawamuraSearch for articles by this author Show More Emory Clinic and Emory University, Atlanta, GAHokkaido University Graduate School of Medicine, Sapporo, Japan https://doi.org/10.1200/JCO.2002.20.12.2911 First Page Full Text PDF Figures and Tables © 2002 by American Society of Clinical OncologyjcoJ Clin OncolJournal of Clinical OncologyJCO0732-183X1527-7755American Society of Clinical OncologyResponse15062002In Reply:We appreciate the opportunity to respond to the letter authored by Dr Paulino, who raised an important question regarding the ototoxicity associated with the use of cisplatin and radiation. Because excellent survival was achieved, any early or late morbidity is a matter of serious concern. We reported in the original article1 that the effect of the treatment on the neurocognitive and pituitary functions was minimal in a long follow-up. Ototoxicity is an important issue as well, although we did not mention it in the article. Sensorineural hearing loss (SNHL) has been frequently documented after the combination of radiation and cisplatin-containing chemotherapy, especially in medulloblastoma series. The radiation dose to cochlea, the cumulative cisplatin dose, and the combination of radiation and cisplatin are known to be risk factors for the development of SNHL.2-4 Radiation-induced SNHL is caused by ischemic change of the cochlea vessel and usually appears over 1 year after the radiation. It usually involves middle frequencies (speech ranges, 1 to 2 kHz) and is progressive from the onset. Once it occurs, it is usually resistant to any medications.5 A cumulative radiation dose to cochlea of over 50 to 60 Gy is considered to be a significant risk factor.2 Cisplatin-induced SNHL occurs primarily at high frequencies, especially at 4 and 8 kHz, and then gradually affects middle frequencies (speech ranges) with increasing amounts of cisplatin dosage. An adequate dose reduction of cisplatin is recommended if a hearing loss of 40dB develops at a 4 kHz or lower frequency.6 Schell et al3 reported that the risk to develop hearing loss at the speech frequencies was zero at a cisplatin dose of between 90 to 360 mg/m2 and 10% to 28% at a dose of between 450 to 750 mg/m2.To detect possible hearing loss during treatment, we conducted audiologic assessment before each cycle of chemotherapy in the protocol. All the patients were examined as planned. We had aimed to reduce the cisplatin dose if the patient developed hearing loss at the middle frequency. However, no one expressed hearing loss at the middle frequencies (less than 4 kHz) during treatment, and thus the reduction of cisplatin dosage because of ototoxicity was not commenced. Six (18%) of 33 patients were detected to have hearing loss greater than 40 dB at 8 kHz during or after the course of chemotherapy. One of them had a hearing loss more than 40 dB at 4 kHz after the completion of three cycles of cisplatin and etoposide (cumulative cisplatin dose, 300 mg/m2). The audiograms of the six patients showing hearing loss at high frequencies showed stable hearing function after the treatment with a median audiologic follow-up of 65 months (range, 3 to 108 months). Two other patients showed hearing loss at 18 and 31 months after the initiation of the treatment, but neither was caused by the initial treatment. One patient showed a hearing loss of 55 dB at 8 kHz, which occurred after four cycles of salvage chemotherapy consisting of ifosfamide, etoposide, and cisplatin for a recurrence of disease. This patient initially received four cycles of ifosfamide, etoposide, and cisplatin followed by local irradiation with 24 Gy, and no decline of hearing function had been observed until the time of recurrence. Therefore, we considered that this example of hearing loss was caused by salvage treatment. The other patient had symptomatic hearing loss involving low and middle frequencies (60 to 80 dB at 500 Hz to 2 kHz). This hearing loss was attributed to disseminated disease involving bilateral cerebello-pontine regions. With a median follow-up of 58 months for all 33 patients, no one except the one patient described above has complained of difficulties in daily conversation. None are using a hearing aid.Three factors may have contributed to this favorable result in terms of ototoxicity. First is the location of intracranial germ cell tumors, which predominantly involve neurohypophysis and the pineal gland, and otic organs are not always located in the irradiated volume. Second, we have reduced the radiation dose to the cochlea by using small-field and low-dose radiation, and the use of a three-dimensional radiation treatment planning system. In our series, the radiation dose to the cochlea was estimated to be 10.5 Gy in average (range, 0 to 36 Gy; median, 7.2 Gy), which would be far below the threshold radiation dose to develop radiation-induced SNHL.1-4 Third, the cisplatin dosage used in our series was relatively small; only five patients (15%) received cumulative cisplatin dose over 400 mg/m2 as an initial treatment.In conclusion, treatment-related symptomatic hearing loss was not observed in the follow-up period. Audiometric toxicity was observed only at high frequencies above the speech range in 18% of the patients without apparent impairment in quality of life. However, because the number of patients in our study is too small to verify a general conclusion, we recommend audiologic assessment before each cycle of chemotherapy. Every effort to reduce the radiation dose to the otic organs using image-guided radiotherapy is recommended. 1. Aoyama H, Shirato H, Ikeda J, et al: Induction chemotherapy followed by low-dose involved-field radiotherapy for intracranial germ cell tumors. J Clin Oncol 20:: 857,2002-865, Link, Google Scholar2. Huang E, Ten BS, Strother DR, et al: Intensity-modulated radiation therapy for pediatric medulloblastoma: Early report on the reduction of ototoxicity. Int J Radiat Oncol Biol Phys 52:599-605, 2002 Google Scholar3. Schell MJ, McHaney VA, Green AA, et al: Hearing loss in children and young adults receiving cisplatin with or without prior cranial irradiation. J Clin Oncol 7:: 754,1989-760, Link, Google Scholar4. Grau C, Overgaard J: Postirradiation sensorineural hearing loss: A common but ignored late radiation complication. Int J Radiat Oncol Biol Phys 36:: 515,1996-517, Crossref, Medline, Google Scholar5. Kashiwamura M, Fukuda S, Chida E, et al: Sensorineural hearing loss induced by radiation as a late effect: Five cases followed by audiogram. Auris Nasus Larynx 28:: 111,2001-115, Crossref, Google Scholar6. Sawamura Y, Ikeda J, Ishii N, et al: Combined irradiation and chemotherapy using ifosfamide, cisplatin, and etoposide for children with medulloblastoma/posterior fossa primitive neuroectodermal tumor: Results of a pilot study. Neurol Med Chir 36:: 632,1996-638, Crossref, Medline, Google Scholar