Temporal Lobe Toxicity Analysis After Proton Radiation Therapy for Skull Base Tumors

• Published in: International journal of radiation oncology, biology, physics Vol. 83; no. 5; pp. 1432 - 1440
• Main Authors: Pehlivan, Berrin, M.D, Ares, Carmen, M.D, Lomax, Antony J., Ph.D, Stadelmann, Otto, M.Sc, Goitein, Gudrun, M.D, Timmermann, Beate, M.D, Schneider, Ralf A., M.D, Hug, Eugen B., M.D
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.08.2012; Elsevier
• Subjects: Adolescent; Adult; Aged; Biological and medical sciences; BRAIN; Brain - radiation effects; Child; Chondrosarcoma - pathology; Chondrosarcoma - radiotherapy; Chordoma - pathology; Chordoma - radiotherapy; Ent and stomatology; Female; HEALTH HAZARDS; Hematology, Oncology and Palliative Medicine; Humans; Late effects; Male; Medical sciences; Middle Aged; NEOPLASMS; Organs at Risk - radiation effects; PATIENTS; Proton therapy; PROTONS; Protons - adverse effects; Protons - therapeutic use; Radiation Injuries - etiology; Radiation Injuries - pathology; Radiation Injuries - prevention & control; Radiology; RADIOLOGY AND NUCLEAR MEDICINE; RADIOTHERAPY; Radiotherapy Dosage; Radiotherapy. Instrumental treatment. Physiotherapy. Reeducation. Rehabilitation, orthophony, crenotherapy. Diet therapy and various other treatments (general aspects); RBE; Relative Biological Effectiveness; SKULL; Skull Base Neoplasms - pathology; Skull Base Neoplasms - radiotherapy; Skull base tumors; Spot scanning; Temporal Lobe - pathology; Temporal Lobe - radiation effects; Temporal lobe toxicity; THRESHOLD DOSE; TOLERANCE; TOXICITY; Tumor Burden; Young Adult; Temporal lobe toxicity; Skull base tumors; Late effects; Proton therapy; Spot scanning; Human; Temporal lobe; Nervous system diseases; Toxicity; Radiotherapy; Cerebral disorder; Radiobiology; Cancerology; Treatment; Central nervous system disease; Radiation injury; Complication; Tumor; Dosimetry; Base of the skull
• ISSN: 0360-3016; 1879-355X
• DOI: 10.1016/j.ijrobp.2011.10.042

Purpose Temporal lobe (TL) parenchyma toxicity constitutes one of the most frequent late adverse event in high-dose proton therapy (PT) for tumors of the skull base. We analyzed clinical events with dosimetric parameters in our patients treated for skull base tumors with spot-scanning PT. Methods and Materials Between 1998 and 2005, a total of 62 patients received PT to a median dose of 71.7 Gy (relative biologic effectiveness [RBE]) (range, 63–74 Gy). The dose–volume histogram of each TL and the entire brain parenchyma (BP) were analyzed according to maximum, mean, and minimum dose as well as doses to 0.5, 1, 2, and 3 cc of brain volume (D0.5 , D1 , D2 , D3 ) and correlated with clinical events. Generalized equivalent uniform dose (gEUD) values were calculated. Results At a mean follow-up of 38 months (range, 14–92 months), 2 patients had developed symptomatic Grade 3 and 5 patients asymptomatic Grade 1 TL toxicity. Mean doses to a 2-cc volume of BP increased from 71 ± 5 Gy (RBE) for no toxicity to 74 ± 5 Gy (RBE) for Grade 1 and to 76 ± 2 Gy (RBE) for Grade 3 toxicity. TL events occurred in 6 of 7 patients (86%) at or above dose levels of ≥64 Gy (RBE) D3 , ≥68 Gy (RBE) D2 , ≥72 Gy (RBE) D1 , and ≥73 Gy (RBE) D0.5 , respectively ( p = NS). No statistically significant dose/volume threshold was detected between patients experiencing no toxicity vs. Grade 1 or Grade 3. A strong trend for Grade 1 and 3 events was observed, when the gEUD was 60 Gy. Conclusions A statistically significant normal tissue threshold dose for BP has not been successfully defined. However, our data suggest that tolerance of TL and BP to fractionated radiotherapy appears to be correlated with tissue volume included in high-dose regions. Additional follow-up time and patient accrual is likely needed to achieve clinical significance for these dose–volume parameters investigated. Our findings support the importance of establishing an organ-at-risk maximally permissible dose for BP.