Extracranial temporal bone paragangliomas: Re-defining the role of otologic surgery within the scope of function-preserving multimodal concepts.

INTRODUCTION: The aim of this study was to present our concept in the management of extracranial temporal bone paragangliomas and demonstrate the outcome after primary surgical management of the middle ear component, with an individualized indication for adjuvant radiotherapy. MATERIALS AND METHODS: The records of all patients treated for extracranial jugulotympanic paragangliomas by means of primary surgical management between 2010 and 2021 were studied retrospectively. RESULTS: Twenty-nine patients made up our study sample (mean age 58.8 years). 15 cases were managed solely by means of surgery. Out of the remaining 14 cases with reduction of the middle ear component, adjuvant irradiation was performed in 11 cases, whereas a wait-and-scan strategy was adopted at the patient's request in three cases. No further growth was detected in our study cases. CONCLUSION: Our protocol seems to be associated with an acceptable quality of life and a satisfactory oncologic outcome.

[Proposal for the delineation of postoperative primary clinical target volumes in ethmoid cancers]. / Proposition de délinéation des volumes cibles anatomocliniques postopératoires de la tumeur primitive des cancers de l'ethmoïde.

It is proposed to delineate the anatomo-clinical target volumes of primary tumor (CTV-P) in ethmoid cancers treated with post-operative radiotherapy. This concept is based on the use of radioanatomy and the natural history of cancer. It is supported by the repositioning of the planning scanner with preoperative imaging for the replacement of the initial GTV and the creation of margins around it extended to the microscopic risk zones according to the anatomical concept. This article does not discuss the indications of external radiotherapy but specifies the volumes to be delineated if radiotherapy is considered.

Leptomeningeal Metastases in Renal Cell Carcinoma at Initial Diagnosis: 2 Case Reports and Literature Review.

Leptomeningeal metastasis (LM) in solid tumors are rare, even more in renal cell carcinoma (RCC). To date there is a lack of consensual treatment modalities of leptomeningeal metastasis. Furthermore, with the improvement of outcomes and more effective systemic targeted therapies, the management of leptomeningeal metastasis becomes a real challenge. We here report two cases of RCC with leptomeningeal metastasis at initial diagnosis. Both patients had concurrent adjacent skull bone metastasis. Therapeutic management of both patients consisted in surgical resection, followed by radiotherapy in one case. Systemic treatment was delayed according to current recommendations for the management of metastatic RCC. The aim of this work is to report the therapeutic approach and related outcomes and also provide a review of the currently available literature on leptomeningeal disease in renal cell carcinoma. Indeed, local treatment with curative outcome of meningeal location in RCC should be performed specially in LM at initial diagnosis.

The Role of Radiotherapy in Skull Metastasis of Thyroid Follicular Carcinoma.

INTRODUCTION: Bone metastasis is seen in 2.3-12.7% of thyroid follicular carcinomas. Bone metastasis most commonly occurs in the vertebrae, costas and hip bones. In this report we discuss the diagnosis and treatment of a patient followed up due to skull metastasis of thyroid follicular carcinoma in light of literature. CASE REPORT: A 51-year-old female patient underwent surgery due a mass in the scalp. The histopathological examination was reported as metastasis of follicular thyroid carcinoma. No radiotherapy was indicated because of the total excision of the mass and the benign surgical margins. The patient, in whom fine needle aspiration biopsy showed the result of follicular carcinoma underwent a total bilateral thyroidectomy. Whole-body I-131 scintigraphy revealed diffuse activity involvement in the thyroid gland, and lung and bone (skull, sacrum, right acetabulum) metastasis. The patient was scheduled for radioactive iodine therapy. CONCLUSION: Total/near total thyroidectomy and metastasectomy should be the treatment of choice in skull metastasis. Postoperative radioactive iodine and radiotherapy should be offered. Radiotherapy should be reserved for inoperable and residual tumour cases.

Cryopreserved amniotic membrane and umbilical cord for a radiation-induced wound with exposed dura: a case report.

An 87-year old male received surgical excision of scalp melanoma and subsequent radiotherapy due to metastasis to the skull. A radiation-induced wound developed with osteoradionecrosis that required necrotic bone excision resulting in a 7.5x8.5cm wound over the exposed dura, which remained non-healing despite many attempts by local wound care management. Due to the refractory nature of the wound, strips of cryopreserved umbilical cord (cUC) allograft were applied over the exposed dura resulting in significant vascular granulation tissue formation in the central wound bed within four weeks. Re-epithelialisation around the wound perimeter was further promoted by injection of particulate amniotic membrane umbilical cord matrix (AMUC) at the 16th week, and completed by another application of cUC strips and injection of AMUC proximal to the necrotic bone at the 21st week. Vascularisation of the necrotic bone was further promoted by application of cUC and AMUC injection directly into the bony margins at 29 weeks and 34 weeks, respectively, followed by application with an AMUC-hydrogel paste, applied four times over an eight week interval. By 96 weeks, healthy re-epithelialised tissue had formed under the necrotic bony margins. This report highlights the unique regenerative capabilities of cUC and AMUC in promoting wound healing over exposed dura in a long-standing full-thickness, radiation-induced scalp and skull wound.

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. Optic neuropathy with radiographic correlation occurring ≥6 months after completion of RT in the absence of tumor recurrence or other probable cause was diagnosed as RION. RESULTS: Of 514 patients, 17 developed RION. With median follow-up of 4.8 years, cumulative incidence of RION was 1% among patients receiving <59 Gy (RBE) and 5.8% among patients receiving ≥60 Gy (RBE) to the optic pathway. Higher maximum point dose to the optic pathway (subhazard ratio [SHR] = 1.2, 95% CI 1.05-1.2, p = 0.001), older age (SHR = 1.1, 95% CI 1.02-1.08, p < 0.0005), and female sex (SHR = 16.3, 95% CI 2.2-122.4, p = 0.007) were statistically significant risk factors for RION in multivariate analysis. CONCLUSION: In our study cohort, rates of RION were very low with conventionally fractionated RT up to 59 Gy. At doses ≥60 Gy, there is an increased risk of RION, with greater risk for women and older patients.

Radiation-Induced Moyamoya Syndrome After Proton Therapy in Child with Clival Chordoma: Natural History and Surgical Treatment.

BACKGROUND: Proton therapy has proven to be effective and safe in the treatment of radioresistant skull base tumors such as chordomas. Thanks to the peculiar physical properties of the proton beam, radiation energy is delivered in a narrow space called the Bragg peak and the surrounding normal tissues receive a minimal amount of the radiation dose. This is important to lower the risk of radiation-induced damage, especially in children. However, local adverse effects in proximity to the target volume may occur. In particular, the development of moyamoya syndrome (MMS) has been rarely reported in children receiving proton beam therapy for brain tumors. CASE DESCRIPTION: We report on a child who developed rapidly progressive MMS after proton beam therapy for a clivus chordoma. A combined indirect revascularization procedure by encephalo-duro-arterio-synangiosis and encephalo-myo-synangiosis was performed with good neuroradiologic and clinical outcome. CONCLUSIONS: Regardless of the presence of known risk factors for MMS, strict neuroimaging surveillance is indicated in all patients treated with radiotherapy including those receiving proton beam therapy. We suggest that an early revascularization procedure should be considered in patients with worsening symptoms and/or sign of neuroradiologic progression of cerebral vasculopathy. This management of MMS could lower the risk of permanent neurologic deficits and improve patients' quality of life.

Whole-brain Radiation Therapy for Breast Cancer Patients with Dural Metastasis Without Concomitant Brain Metastasis and Leptomeningeal Metastasis.

AIM: To evaluate outcomes of breast cancer patients with confirmed dural metastasis (DM) alone who received whole-brain radiation therapy (WBRT). PATIENTS AND METHODS: The medical records of thirty-three breast cancer patients who received WBRT to treat intracranial metastasis were retrospectively reviewed. The clinical presentation of DM-only was compared with that of brain metastasis (BM)/leptomeningeal metastasis (LM). RESULTS: Eight patients had DM and 25 patients had BM/LM. Median survival was 12 months in patients with DM and 7 months in those with BM/LM. Multivariate analysis found that only a Karnofsky performance status of ≥70 was significantly associated with improved OS. DM did not cause the death of any patient. Symptoms did not worsen in any DM patient. CONCLUSION: WBRT can be considered for patients with DM alone for symptom improvement and preventing DM-related death.

Metastatic craniocervical hemangiopericytoma presenting with hydrocephalus and papilledema - Case review.

Hemangiopericytomas are rare mesenchymal tumors with propensity to recur locally and metastasize. We report the unique case of a fifty-five-year-old male with recurrence of a previously resected craniocervical hemangiopericytoma presenting with obstructive hydrocephalus secondary to new metastatic cerebellar deposits. Emergent surgical resection of the cerebellar hemangiopericytomas was performed prior to adjuvant radiotherapy. Hemangiopericytomas are rare but important differentials for craniocervical junction lesions. Gross total resection remains the cornerstone of management with post-operative radiotherapy and chemotherapy as potential adjuncts. Tumors located in deep regions pose complex management challenges as safe maximal excision may be limited by proximal eloquent structures.

Extra-articular tenosynovial giant cell tumor of diffuse type in the temporal area with brain parenchymal invasion: a case report.

Tenosynovial giant cell tumor of diffuse type is a locally aggressive neoplasm that most commonly arises in the lower extremities. Herein, we report for the first time a case of an extra-articular tenosynovial giant cell tumor of diffuse type in the temporal region with brain parenchymal invasion. Imaging studies revealed an intracranial expansile mass in the temporal bone without involvement of the temporomandibular joint. The unusual location of the tumor without involvement of the joint and the presence of brain parenchymal invasion made this case challenging to diagnose.

Outcomes of stereotactic radiosurgery for foramen magnum meningiomas: an international multicenter study.

OBJECTIVE Meningiomas are the most common benign extramedullary lesions of the foramen magnum; however, their optimal management remains undefined. Given their location, foramen magnum meningiomas (FMMs) can cause significant morbidity, and complete microsurgical removal can be challenging. Anterior and anterolateral FMMs carry greater risks with surgery, but they comprise the majority of these lesions. As an alternative to resection, stereotactic radiosurgery (SRS) has been used to treat FMMs in small case series. To more clearly define the outcomes of SRS and to delineate a rational management paradigm for these lesions, the authors analyzed the safety and efficacy of SRS for FMM in an international multicenter trial. METHODS Seven medical centers participating in the International Gamma Knife Research Foundation (IGKRF) provided data for this retrospective cohort study. Patients who were treated with Gamma Knife radiosurgery and whose clinical and radiological follow-up was longer than 6 months were eligible for study inclusion. Data from pre- and post-SRS radiological and clinical evaluations were analyzed. Stereotactic radiosurgery treatment variables were recorded. RESULTS Fifty-seven patients (39 females and 18 males, with a median age of 64 years) met the study inclusion criteria. Thirty-two percent had undergone prior microsurgical resection. Patients most frequently presented with cranial neuropathy (39%), headache (35%), numbness (32%), and ataxia (30%). Median pre-SRS tumor volume was 2.9 cm3. Median SRS margin dose was 12.5 Gy (range 10-16 Gy). At the last follow-up after SRS, 49% of tumors were stable, 44% had regressed, and 7% had progressed. Progression-free survival rates at 5 and 10 years were each 92%. A greater margin dose was associated with a significantly increased likelihood of tumor regression, with 53% of tumors treated with > 12 Gy regressing. Fifty-two percent of symptomatic patients noted some clinical improvement. Adverse radiation effects were limited to hearing loss and numbness in 1 patient (2%). CONCLUSIONS Stereotactic radiosurgery for FMM frequently results in tumor control or tumor regression, as well as symptom improvement. Margin doses > 12 Gy were associated with increased rates of tumor regression. Stereotactic radiosurgery was generally safe and well tolerated. Given its risk-benefit profile, SRS may be particularly useful in the management of small- to moderate-volume anterior and anterolateral FMMs.

A radiobiological Markov simulation tool for aiding decision making in proton therapy referral.

PURPOSE: Proton therapy can be a highly effective strategy for the treatment of tumours. However, compared with X-ray therapy it is more expensive and has limited availability. In addition, it is not always clear whether it will benefit an individual patient more than a course of traditional X-ray therapy. Basing a treatment decision on outcomes of clinical trials can be difficult due to a shortage of data. Predictive modelling studies are becoming an attractive alternative to supplement clinical decisions. The aim of the current work is to present a Markov framework that compares clinical outcomes for proton and X-ray therapy. METHODS: A Markov model has been developed which estimates the radiobiological effect of a given treatment plan. This radiobiological effect is estimated using the tumour control probability (TCP), normal tissue complication probability (NTCP) and second primary cancer induction probability (SPCIP). These metrics are used as transition probabilities in the Markov chain. The clinical outcome is quantified by the quality adjusted life expectancy. To demonstrate functionality, the model was applied to a 6-year-old patient presenting with skull base chordoma. RESULTS: The model was successfully developed to compare clinical outcomes for proton and X-ray treatment plans. For the example patient considered, it was predicted that proton therapy would offer a significant advantage compared with volumetric modulated arc therapy in terms of survival and mitigating injuries. CONCLUSIONS: The functionality of the model was demonstrated using the example patient. The proposed Markov method may be a useful tool for deciding on a treatment strategy for individual patients.

Sparsity constrained split feasibility for dose-volume constraints in inverse planning of intensity-modulated photon or proton therapy.

A split feasibility formulation for the inverse problem of intensity-modulated radiation therapy treatment planning with dose-volume constraints included in the planning algorithm is presented. It involves a new type of sparsity constraint that enables the inclusion of a percentage-violation constraint in the model problem and its handling by continuous (as opposed to integer) methods. We propose an iterative algorithmic framework for solving such a problem by applying the feasibility-seeking CQ-algorithm of Byrne combined with the automatic relaxation method that uses cyclic projections. Detailed implementation instructions are furnished. Functionality of the algorithm was demonstrated through the creation of an intensity-modulated proton therapy plan for a simple 2D C-shaped geometry and also for a realistic base-of-skull chordoma treatment site. Monte Carlo simulations of proton pencil beams of varying energy were conducted to obtain dose distributions for the 2D test case. A research release of the Pinnacle 3 proton treatment planning system was used to extract pencil beam doses for a clinical base-of-skull chordoma case. In both cases the beamlet doses were calculated to satisfy dose-volume constraints according to our new algorithm. Examination of the dose-volume histograms following inverse planning with our algorithm demonstrated that it performed as intended. The application of our proposed algorithm to dose-volume constraint inverse planning was successfully demonstrated. Comparison with optimized dose distributions from the research release of the Pinnacle 3 treatment planning system showed the algorithm could achieve equivalent or superior results.

Comparison of linear and nonlinear programming approaches for "worst case dose" and "minmax" robust optimization of intensity-modulated proton therapy dose distributions.

Robust optimization of intensity-modulated proton therapy (IMPT) takes uncertainties into account during spot weight optimization and leads to dose distributions that are resilient to uncertainties. Previous studies demonstrated benefits of linear programming (LP) for IMPT in terms of delivery efficiency by considerably reducing the number of spots required for the same quality of plans. However, a reduction in the number of spots may lead to loss of robustness. The purpose of this study was to evaluate and compare the performance in terms of plan quality and robustness of two robust optimization approaches using LP and nonlinear programming (NLP) models. The so-called "worst case dose" and "minmax" robust optimization approaches and conventional planning target volume (PTV)-based optimization approach were applied to designing IMPT plans for five patients: two with prostate cancer, one with skull-based cancer, and two with head and neck cancer. For each approach, both LP and NLP models were used. Thus, for each case, six sets of IMPT plans were generated and assessed: LP-PTV-based, NLP-PTV-based, LP-worst case dose, NLP-worst case dose, LP-minmax, and NLP-minmax. The four robust optimization methods behaved differently from patient to patient, and no method emerged as superior to the others in terms of nominal plan quality and robustness against uncertainties. The plans generated using LP-based robust optimization were more robust regarding patient setup and range uncertainties than were those generated using NLP-based robust optimization for the prostate cancer patients. However, the robustness of plans generated using NLP-based methods was superior for the skull-based and head and neck cancer patients. Overall, LP-based methods were suitable for the less challenging cancer cases in which all uncertainty scenarios were able to satisfy tight dose constraints, while NLP performed better in more difficult cases in which most uncertainty scenarios were hard to meet tight dose limits. For robust optimization, the worst case dose approach was less sensitive to uncertainties than was the minmax approach for the prostate and skull-based cancer patients, whereas the minmax approach was superior for the head and neck cancer patients. The robustness of the IMPT plans was remarkably better after robust optimization than after PTV-based optimization, and the NLP-PTV-based optimization outperformed the LP-PTV-based optimization regarding robustness of clinical target volume coverage. In addition, plans generated using LP-based methods had notably fewer scanning spots than did those generated using NLP-based methods.

Metástasis asintomáticas de la base craneal: evolución clínica y alternativas terapéuticas / Asymptomatic skull base metastases: clinical course and therapeutic alternatives

Introducción. Las metástasis sintomáticas de la base craneal (MBC) son una progresión infrecuente, tardía y de mal pronóstico en pacientes con tumores sólidos. Sus manifestaciones clínicas pueden agruparse en cinco síndromes característicos, y su tratamiento más frecuente es la radioterapia. Gracias a los progresos tecnológicos en las pruebas de imagen y al seguimiento estrecho de los pacientes con cáncer, las MBC pueden diagnosticarse incidentalmente. En este subgrupo no se conoce la evolución clínica ni se ha establecido la mejor modalidad de tratamiento. Objetivo. Analizar las características clínicas y la evolución de los pacientes diagnosticados incidentalmente de MBC. Pacientes y métodos. Entre enero de 2012 y diciembre de 2015, 31 pacientes con una neoplasia sólida diagnosticados de MBC fueron valorados por nuestro servicio. Resultados. Las MBC se diagnosticaron por la presencia de un síndrome de base craneal (n = 24) o incidentalmente (n = 7). Los pacientes sintomáticos fueron tratados con radioterapia. Todos los pacientes diagnosticados incidentalmente permanecieron sin síntomas relacionados con la afectación de la base craneal hasta la fecha del fallecimiento, aunque frecuentemente presentaron de forma concomitante otros tipos de progresión intracraneal de mal pronóstico. Se observó una diferencia estadísticamente significativa en la supervivencia a favor de los pacientes sintomáticos (p = 0,001). Conclusiones. Las MBC diagnosticadas incidentalmente se asociaron frecuentemente a otros tipos de progresión intracraneal, limitando las opciones terapéuticas (AU)

Introduction. Skull base metastases (SBM) are an infrequent and late type of cancer progression that are associated to poor prognosis. Its clinical manifestations may be grouped in fi ve clinical syndromes and radiotherapy is its more frequent treatment. Because of the improvement in imaging tests and the close follow up of cancer patients, SBM can be diagnosed incidentally. In this group the best option of treatment has not been established. Aim. To analyze the clinical features and outcomes of patients with SBM diagnosed incidentally. Patients and methods. Between January 2012 and December 2015, 31 patients with diagnoses of SBM from solid primary tumor were reviewed. Results. SBM were diagnosed due to skull base syndromes (n = 24) or incidentally (n = 7). Symptomatic patients were treated with radiotherapy. Patients diagnosed incidentally remained without symptoms of craneal base involvement during the follow up, although they frequently had other types of intracranial progression. A statistically significant difference in survival was observed between symptomatic and asymptomatic patients (p = 0.001). Conclusions. The incidentally diagnosed SBM were frequently associated to other types of intracranial progression, limiting the options of treatment (AU)

[Primary lymphoma of the skull: Case report and literature review]. / Lymphome primitif de la voûte crânienne : cas clinique et revue de la littérature.

Primitive lymphomas of the bone are exceptional tumors, representing 4% of all non-Hodgkin lymphomas. The location at the skull remains the rarest. We report the case of a 56 year old patient with lytic lesions in the skull of a small cell lymphoma B, treated with primary chemotherapy and intensity-modulated radiotherapy in arctherapy with a dose of 30Gy in 15 fractions. With a follow-up time of 18 months after the end of treatment, the patient has no sign of disease evolution.

Spot scanning proton therapy minimizes neutron dose in the setting of radiation therapy administered during pregnancy.

This is a real case study to minimize the neutron dose equivalent (H) to a fetus using spot scanning proton beams with favorable beam energies and angles. Minimum neutron dose exposure to the fetus was achieved with iterative planning under the guidance of neutron H measurement. Two highly conformal treatment plans, each with three spot scanning beams, were planned to treat a 25-year-old pregnant female with aggressive recurrent chordoma of the base of skull who elected not to proceed with termination. Each plan was scheduled for delivery every other day for robust target coverage. Neutron H to the fetus was measured using a REM500 neutron survey meter placed at the fetus position of a patient simulating phantom. 4.1 and 44.1 µSv/fraction were measured for the two initial plans. A vertex beam with higher energy and the fetal position closer to its central axis was the cause for the plan that produced an order higher neutron H. Replacing the vertex beam with a lateral beam reduced neutron H to be comparable with the other plan. For a prescription of 70 Gy in 35 fractions, the total neutron H to the fetus was estimated to be 0.35 mSv based on final measurement in single fraction. In comparison, the passive scattering proton plan and photon plan had an estimation of 26 and 70 mSv, respectively, for this case. While radiation therapy in pregnant patients should be avoided if at all possible, our work demonstrated spot scanning beam limited the total neutron H to the fetus an order lower than the suggested 5 mSv regulation threshold. It is far superior than passive scattering beam and careful beam selection with lower energy and keeping fetus further away from beam axis are essential in minimizing the fetus neutron exposure.

Fractionated stereotactic radiotherapy of benign skull-base tumors: a dosimetric comparison of volumetric modulated arc therapy with Rapidarc® versus non-coplanar dynamic arcs.

BACKGROUND: Benign tumors of the skull base are a challenge when delivering radiotherapy. An appropriate choice of radiation technique may significantly improve the patient's outcomes. Our study aimed to compare the dosimetric results of fractionated stereotactic radiotherapy between non-coplanar dynamic arcs and coplanar volumetric modulated arctherapy (Rapidarc®). METHODS: Thirteen patients treated with Novalis TX® were analysed: six vestibular schwannomas, four pituitary adenomas and three meningioma. Two treatment plans were created for each case: dynamic arcs (4-5 non coplanar arcs) and Rapidarc® (2 coplanar arcs). All tumors were >3 cm and accessible to both techniques. Patients had a stereotactic facemask (Brainlab) and were daily repositioned by Exactrac®. GTV and CTV were contoured according to tumor type. A 1-mm margin was added to the CTV to obtain PTV. Radiation doses were 52.2-54 Gy, using 1.8 Gy per fraction. Treatment time was faster with Rapidarc®. RESULTS: The mean PTV V95 % was 98.8 for Rapidarc® and 95.9 % for DA (p = 0.09). Homogeneity index was better with Rapidarc®: 0.06 vs. 0.09 (p = 0.01). Higher conformity index values were obtained with Rapidarc®: 75.2 vs. 67.9 % (p = 0.04). The volume of healthy brain that received a high dose (V90 %) was 0.7 % using Rapidarc® vs. 1.4 % with dynamic arcs (p = 0.05). Rapidarc® and dynamic arcs gave, respectively, a mean D40 % of 10.5 vs. 18.1 Gy (p = 0.005) for the hippocampus and a Dmean of 25.4 vs. 35.3 Gy (p = 0.008) for the ipsilateral cochlea. Low-dose delivery with Rapidarc® and dynamic arcs were, respectively, 184 vs. 166 cm(3) for V20 Gy (p = 0.14) and 1265 vs. 1056 cm(3) for V5 Gy (p = 0.67). CONCLUSIONS: Fractionated stereotactic radiotherapy using Rapidarc® for large benign tumors of the skull base provided target volume coverage that was at least equal to that of dynamics arcs, with better conformity and homogeneity and faster treatment time. Rapidarc® also offered better sparing of the ipsilateral cochlea and hippocampus. Low-dose delivery were similar between both techniques.