Spot scanning proton therapy for malignancies of the base of skull: treatment planning, acute toxicities, and preliminary clinical outcomes.

To describe treatment planning techniques and early clinical outcomes in patients treated with spot scanning proton therapy for chordoma or chondrosarcoma of the skull base. From June 2010 through August 2011, 15 patients were treated with spot scanning proton therapy for chordoma (n=10) or chondrosarcoma (n=5) at a single institution. Toxicity was prospectively evaluated and scored weekly and at all follow-up visits according to Common Terminology Criteria for Adverse Events, version 3.0. Treatment planning techniques and dosimetric data were recorded and compared with those of passive scattering plans created with clinically applicable dose constraints. Ten patients were treated with single-field-optimized scanning beam plans and 5 with multifield-optimized intensity modulated proton therapy. All but 2 patients received a simultaneous integrated boost as well. The mean prescribed radiation doses were 69.8 Gy (relative biological effectiveness [RBE]; range, 68-70 Gy [RBE]) for chordoma and 68.4 Gy (RBE) (range, 66-70) for chondrosarcoma. In comparison with passive scattering plans, spot scanning plans demonstrated improved high-dose conformality and sparing of temporal lobes and brainstem. Clinically, the most common acute toxicities included fatigue (grade 2 for 2 patients, grade 1 for 8 patients) and nausea (grade 2 for 2 patients, grade 1 for 6 patients). No toxicities of grades 3 to 5 were recorded. At a median follow-up time of 27 months (range, 13-42 months), 1 patient had experienced local recurrence and a second developed distant metastatic disease. Two patients had magnetic resonance imaging-documented temporal lobe changes, and a third patient developed facial numbness. No other subacute or late effects were recorded. In comparison to passive scattering, treatment plans for spot scanning proton therapy displayed improved high-dose conformality. Clinically, the treatment was well tolerated, and with short-term follow-up, disease control rates and toxicity profiles were favorable.

Grosshans DR ，Zhu XR ，Melancon A ，Allen PK ，Poenisch F ，Palmer M ，McAleer MF ，McGovern SL ，Gillin M ，DeMonte F ，Chang EL ，Brown PD ，Mahajan A ... -  《-》

Temporal lobe toxicity analysis after proton radiation therapy for skull base tumors.

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. 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 (D(0.5), D(1), D(2), D(3)) and correlated with clinical events. Generalized equivalent uniform dose (gEUD) values were calculated. 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) D(3), ≥ 68 Gy (RBE) D(2), ≥ 72 Gy (RBE) D(1), and ≥ 73 Gy (RBE) D(0.5), 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. 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.

Pehlivan B ，Ares C ，Lomax AJ ，Stadelmann O ，Goitein G ，Timmermann B ，Schneider RA ，Hug EB ... -  《-》

Spot-scanning proton radiation therapy for pediatric chordoma and chondrosarcoma: clinical outcome of 26 patients treated at paul scherrer institute.

To evaluate the clinical results of fractionated spot-scanning proton radiation therapy (PT) in 26 pediatric patients treated at Paul Scherrer Institute for chordoma (CH) or chondrosarcoma (CS) of the skull base or axial skeleton. Between June 2000 and June 2010, 19 CH and 7 CS patients with tumors originating from the skull base (17) and the axial skeleton (9) were treated with PT. Mean age at the time of PT was 13.2 years. The mean prescribed dose was 74 Gy (relative biological effectiveness [RBE]) for CH and 66 Gy (RBE) for CS, at a dose of 1.8-2.0 Gy (RBE) per fraction. Mean follow-up was 46 months. Actuarial 5-year local control (LC) rates were 81% for CH and 80% for CS. Actuarial 5-year overall survival (OS) was 89% for CH and 75% for CS. Two CH patients had local failures: one is alive with evidence of disease, while the other patient succumbed to local recurrence in the surgical pathway. One CS patient died of local progression of the disease. No high-grade late toxicities were observed. Spot-scanning PT for pediatric CH and CS patients resulted in excellent clinical outcomes with acceptable rates of late toxicity. Longer follow-up time and larger cohort are needed to fully assess tumor control and late effects of treatment.

Rombi B ，Ares C ，Hug EB ，Schneider R ，Goitein G ，Staab A ，Albertini F ，Bolsi A ，Lomax AJ ，Timmermann B ... -  《-》

Effectiveness and safety of spot scanning proton radiation therapy for chordomas and chondrosarcomas of the skull base: first long-term report.

Ares C ，Hug EB ，Lomax AJ ，Bolsi A ，Timmermann B ，Rutz HP ，Schuller JC ，Pedroni E ，Goitein G ... -  《-》

Results of spot-scanning proton radiation therapy for chordoma and chondrosarcoma of the skull base: the Paul Scherrer Institut experience.

Weber DC ，Rutz HP ，Pedroni ES ，Bolsi A ，Timmermann B ，Verwey J ，Lomax AJ ，Goitein G ... -  《INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS》