Ectopic Recurrence of Skull Base Chordoma after Proton Therapy.

Background: Chordoma are rare tumors of the axial skeleton. The treatment gold standard is surgery, followed by particle radiotherapy. Total resection is usually not achievable in skull base chordoma (SBC) and high recurrence rates are reported.

Definitive high-dose, proton-based radiation for unresected mobile spine and sacral chordomas.

Background/purpose: Treatment of spine and sacral chordoma generally involves surgical resection, usually in conjunction with radiation therapy.In certain locations, resection may result in significant neurological dysfunction, so definitive radiation has been used as an alternative to surgery. The purpose of this study is to report the results of high-dose, proton-based definitive radiotherapy for unresected spinal and sacral chordomas.

Clinical findings in families with chordoma with and without T gene duplications and in patients with sporadic chordoma reported to the Surveillance, Epidemiology, and End Results program.

Objective: To gain insight into the role of germline genetics in the development of chordoma, the authors evaluated data from 2 sets of patients with familial chordoma, those with and without a germline duplication of the T gene (T-dup+ vs T-dup-), which was previously identified as a susceptibility mechanism in some families. The authors then compared the patients with familial tumors to patients with sporadic chordoma in the US general population reported to the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program through 2015.

Methods: Evaluation of family members included review of personal and family medical history, physical and neurological examination, and pre- and postcontrast MRI of the skull base and spine.

Radiation tolerance of the optic pathway in patients treated with proton and photon radiotherapy.

Introduction: Radiation-induced optic neuropathy (RION) is a complication of radiation therapy (RT) that causes blindness. We aimed to define the tolerance of the anterior optic pathway to fractionated RT and identify risk factors for RION.

Materials/methods: Patients with chordoma or chondrosarcoma of the skull base treated with proton and photon therapy between 1983 and 2013, who received a minimum of 30 Gy (relative biologic effectiveness [RBE]) to the anterior optic pathway were assessed.

Individualization of Clinical Target Volume Delineation Based on Stepwise Spread of Nasopharyngeal Carcinoma: Outcome of More Than a Decade of Clinical Experience.

Purpose: Radiation-related toxicity in nasopharyngeal carcinoma (NPC) is common. There are no well-established guidelines for clinical target volume (CTV) delineation with long-term follow-up. Current consensus continues to rely heavily on bony landmarks and fixed margins around the gross tumor volume (GTV), an approach used to define fields in the conventional 2- and 3-dimensional radiation therapy era.

Prospective, Randomized Study of Radiation Dose Escalation With Combined Proton-Photon Therapy for Benign Meningiomas.

Purpose: To assess the outcomes of benign meningiomas (BM) treated to two radiation dose levels.

Methods And Materials: We randomly assigned patients (1:1) with incompletely resected or recurrent BM to 2 radiation doses: 55.8 Gy(relative biological effectiveness [RBE]) and 63.

Predicting Patient-specific Dosimetric Benefits of Proton Therapy for Skull-base Tumors Using a Geometric Knowledge-based Method.

Purpose: To predict the organ at risk (OAR) dose levels achievable with proton beam therapy (PBT), solely based on the geometric arrangement of the target volume in relation to the OARs. A comparison with an alternative therapy yields a prediction of the patient-specific benefits offered by PBT. This could enable physicians at hospitals without proton capabilities to make a better-informed referral decision or aid patient selection in model-based clinical trials.

Definitive proton beam therapy for adenoid cystic carcinoma of the nasopharynx involving the base of skull.

Objectives: Management of unresectable adenocystic carcinoma (ACC) of the nasopharynx is challenging given the high dose required for tumor control while respecting dose constraints. We evaluated long-term outcomes and toxicity in patients with unresectable ACC of the nasopharynx treated with definitive proton beam therapy.

Methods: Between 2000 and 2013, 14 patients with ACC of the nasopharynx were treated.

Thoracolumbar spinal cord tolerance to high dose conformal proton-photon radiation therapy.

Purpose: To evaluate and understand the tolerance of the thoracolumbar spinal cord using equivalent uniform dose (EUD) and dose volume histogram (DVH) analysis after combined high dose photon-proton radiotherapy.

Materials And Methods: A total of 68 patients were identified as having high dose radiotherapy, ⩾5900cGy (RBE) in the region of the thoracolumbar spinal cord, defined as extending inferiorly to L2. Pathological diagnosis for patients in this review included chordoma (50 patients, 53.

High-dose proton-based radiation therapy in the management of spine chordomas: outcomes and clinicopathological prognostic factors.

Object: Spinal chordomas can have high local recurrence rates after surgery with or without conventional dose radiation therapy (RT). Treatment outcomes and prognostic factors after high-dose proton-based RT with or without surgery were assessed.

Methods: The authors conducted a retrospective review of 126 treated patients (127 lesions) categorized according to disease status (primary vs recurrent), resection (en bloc vs intralesional), margin status, and RT timing.

Characterization of T gene sequence variants and germline duplications in familial and sporadic chordoma.

Chordoma is a rare bone cancer that is believed to originate from notochordal remnants. We previously identified germline T duplication as a major susceptibility mechanism in several chordoma families. Recently, a common genetic variant in T (rs2305089) was significantly associated with the risk of sporadic chordoma.

Long-term results of Phase II study of high dose photon/proton radiotherapy in the management of spine chordomas, chondrosarcomas, and other sarcomas.

Background: Negative surgical margins are uncommon for spine sarcomas; hence, adjuvant radiotherapy (RT) may be recommended but tumor dose may be constrained by spinal cord, nerve, and viscera tolerance.

Methods: Prospective Phase II clinical trial incorporating high dose RT. Eligible patients had primary or locally recurrent thoracic, lumbar, and/or sacral spine/paraspinal chordomas or sarcomas.

Proton radiotherapy for pediatric Ewing's sarcoma: initial clinical outcomes.

Purpose: Proton radiotherapy (PT) has been prescribed similarly to photon radiotherapy to achieve comparable disease control rates at comparable doses. The chief advantage of protons in this setting is to reduce acute and late toxicities by decreasing the amount of normal tissue irradiated. We report the preliminary clinical outcomes including late effects on our pediatric Ewing's sarcoma patients treated with PT at the Francis H.

Spinal instability neoplastic score: an analysis of reliability and validity from the spine oncology study group.

Purpose: Standardized indications for treatment of tumor-related spinal instability are hampered by the lack of a valid and reliable classification system. The objective of this study was to determine the interobserver reliability, intraobserver reliability, and predictive validity of the Spinal Instability Neoplastic Score (SINS).

Methods: Clinical and radiographic data from 30 patients with spinal tumors were classified as stable, potentially unstable, and unstable by members of the Spine Oncology Study Group.

Proton radiotherapy for parameningeal rhabdomyosarcoma: clinical outcomes and late effects.

Purpose: To report the clinical outcome and late side effect profile of proton radiotherapy in the treatment of children with parameningeal rhabdomyosarcoma (PM-RMS).

Methods And Materials: Seventeen consecutive children with PM-RMS were treated with proton radiotherapy at Massachusetts General Hospital between 1996 and 2005. We reviewed the medical records of all patients and asked referring physicians to report specific side effects of interest.

A novel classification system for spinal instability in neoplastic disease: an evidence-based approach and expert consensus from the Spine Oncology Study Group.

Study Design: Systematic review and modified Delphi technique.

Objective: To use an evidence-based medicine process using the best available literature and expert opinion consensus to develop a comprehensive classification system to diagnose neoplastic spinal instability.

Summary Of Background Data: Spinal instability is poorly defined in the literature and presently there is a lack of guidelines available to aid in defining the degree of spinal instability in the setting of neoplastic spinal disease.

In vivo proton beam range verification using spine MRI changes.

Purpose: In proton therapy, uncertainty in the location of the distal dose edge can lead to cautious treatment plans that reduce the dosimetric advantage of protons. After radiation exposure, vertebral bone marrow undergoes fatty replacement that is visible on magnetic resonance imaging (MRI). This presents an exciting opportunity to observe radiation dose distribution in vivo.

T (brachyury) gene duplication confers major susceptibility to familial chordoma.

Using high-resolution array-CGH, we identified unique duplications of a region on 6q27 in four multiplex families with at least three cases of chordoma, a cancer of presumed notochordal origin. The duplicated region contains only the T (brachyury) gene, which is important in notochord development and is expressed in most sporadic chordomas. Our findings highlight the value of screening for complex genomic rearrangements in searches for cancer-susceptibility genes.

Proton radiation therapy for primary sphenoid sinus malignancies: treatment outcome and prognostic factors.

Background: The purpose of this study was to determine treatment outcome and prognostic factors in patients with locally advanced primary sphenoid sinus malignancy treated with proton radiation therapy.

Methods: Between 1991 and 2005, 20 patients with primary sphenoid sinus malignancy received proton beam to a median dose of 76 Gray equivalent.

Results: With a median follow-up of 27 months, the 2-year local, regional, and freedom from distant metastasis rates were 86%, 86%, and 50%, respectively.

Phase II study of high-dose photon/proton radiotherapy in the management of spine sarcomas.

Purpose: Radiotherapy (XRT) for spine sarcomas is constrained by spinal cord, nerve, and viscera tolerance. Negative surgical margins are uncommon; hence, doses of >or=66 Gy are recommended. A Phase II clinical trial evaluated high-dose photon/proton XRT for spine sarcomas.

Proton radiation therapy for head and neck cancer.

Due to the close spatial relationship of head and neck and skull base tumors to numerous normal anatomical structures, conventional photon radiation therapy can be associated with significant acute and long-term treatment-related toxicities. Superior dose localization properties of proton radiation therapy allow smaller volumes of normal tissues to be irradiated than is feasible with any photon technique. Intensity-modulated proton therapy (IMPT) is a powerful delivery technique which results in improved dose distribution as compared to that of intensity-modulated radiation therapy (IMRT).

Anaplastic glioma after high-dose proton-photon radiation treatment for low-grade skull base chondrosarcoma.

We report the case of a 63-year-old man who developed an anaplastic oligoastrocytoma of the brain stem and midbrain 13 years after postoperative high-dose proton-photon radiation therapy for a recurrent low-grade chondrosarcoma of the skull base. To our knowledge, this is the first reported case of an anaplastic glioma after proton-photon irradiation.

Patient study of in vivo verification of beam delivery and range, using positron emission tomography and computed tomography imaging after proton therapy.

Purpose: To investigate the feasibility and value of positron emission tomography and computed tomography (PET/CT) for treatment verification after proton radiotherapy.

Methods And Materials: This study included 9 patients with tumors in the cranial base, spine, orbit, and eye. Total doses of 1.

Base of skull chordomas in children and adolescents: a clinicopathologic study of 73 cases.

Chordomas in children and adolescents comprise <5% of all chordomas and most frequently develop in the skull base. These tumors are believed to behave more aggressively than chordomas in adults and may have unusual morphology. This study examines a large series of pediatric skull base chordomas treated with a standardized protocol to characterize the behavior and morphology of these tumors.

Sacral chordomas: Impact of high-dose proton/photon-beam radiation therapy combined with or without surgery for primary versus recurrent tumor.

Purpose: To assess the efficacy of definitive treatment of sacral chordoma by high-dose proton/photon-beam radiation therapy alone or combined with surgery.

Methods And Materials: The records of 16 primary and 11 recurrent sacral chordoma patients treated from November 1982 to November 2002 by proton/photon radiation therapy alone (6 patients) or combined with surgery (21 patients) have been analyzed for local control, survival, and treatment-related morbidity. The outcome analysis is based on follow-up information as of 2005.