Skull Base Cancer Research Articles

Late toxicity of proton beam therapy for patients with the nasal cavity, para-nasal sinuses, or involving the skull base malignancy: importance of long-term follow-up.

Although several reports have shown that proton beam therapy (PBT) offers promise for patients with skull base cancer, little is known about the frequency of late toxicity in clinical practice when PBT is used for these patients. Here, we conducted a retrospective analysis to clarify the late toxicity profile of PBT in patients with malignancies of the nasal cavity, para-nasal sinuses, or involving the skull base. Entry to this retrospective study was restricted to patients with (1) malignant tumors of the nasal cavity, para-nasal sinuses, or involving the skull base; (2) definitive or postoperative PBT (>50 GyE) from January 1999 through December 2008; and (3) more than 1 year of follow-up. Late toxicities were graded according to the common terminology criteria for adverse events v4.0 (CTCAE v4.0). From January 1999 through December 2008, 90 patients satisfied all criteria. Median observation period was 57.5 months (range, 12.4-162.7 months), median time to onset of grade 2 or greater late toxicity except cataract was 39.2 months (range, 2.7-99.8 months), and 3 patients had toxicities that occurred more than 5 years after PBT. Grade 3 late toxicities occurred in 17 patients (19%), with 19 events, and grade 4 late toxicities in 6 patients (7%), with 6 events (encephalomyelitis infection 2, optic nerve disorder 4). In conclusion, the late toxicity profile of PBT in patients with malignancy involving the nasal cavity, para-nasal sinuses, or skull base malignancy was partly clarified. Because late toxicity can still occur at 5 years after treatment, long-term follow-up is necessary.

CRISPS – An Easy Acronym to Interpreting Metastatic Neck Lymphadenopathy

Purpose: To present a pictorial review showing the various radiologic features of metastatic lymphadenopathy in skull base cancer.

Quality of life following endoscopic endonasal resection of anterior skull base cancers

For several decades, the exclusive purpose in the management of anterior skull base malignancies has been to increase survival rates. Recently, given the improved prognosis achieved, more attention has been focused on quality of life (QOL) as well. Producing data on QOL in anterior skull base cancers is hampered by the rarity of the neoplasm and the lack of specific questionnaires. The purpose of this study was to assess health-related QOL in a large and homogeneous cohort of patients affected by anterior skull base cancers who had undergone endoscopic endonasal resection. The authors conducted a retrospective review of patients treated for sinonasal and skull base cancers via an endoscopic endonasal approach at two Italian tertiary care referral centers. All patients were asked to complete the Anterior Skull Base Surgery Questionnaire to evaluate their QOL before and 1 month and 1 year after surgical treatment. To assess which parameters affect QOL, the study population was divided into subgroups according to age, sex, stage of disease, surgical approach, and adjuvant therapy. One hundred fifty-three patients were enrolled in this study according to the adopted inclusion criteria. Overall QOL started at a score of 4.68 for the preoperative period, sharply decreased as far as a score of 4.03 during the 1st postoperative month, and rose again to a score of 4.59 over the course of 1 year after treatment, with a significant difference among the 3 values (p < 0.05). The specific symptoms and physical status domains registered poorer results at the 1-year assessment (4.00 and 4.71, respectively) than at the preoperative assessment (both domains 4.86), with a statistically significant reduction in scores (p < 0.05). Worse outcomes were associated with several variables: age > 60 years (difference of 0.21 points between the preoperative and 1-year period, p < 0.05), expanded surgical approaches with transnasal craniectomy (decrease of 0.20 points between the preoperative and 1-year period, p < 0.05), and postoperative radiotherapy (score of 4.53 at the 1-year period vs. 4.70 in patients without any adjuvant treatment, p < 0.05). No statistically significant differences were found when analyzing the study population according to sex (p > 0.1) and T classification of disease at presentation (p > 0.05). Radical endoscopic endonasal resection led to either complete or at least partial recovery of patient QOL within the 1st postoperative year.

Transoral robotic surgery to resect skull base tumors via transpalatal and lateral pharyngeal approaches

Robot-assisted surgery in the field of head and neck has been gaining popularity due to appeal in using minimally invasive approaches, obtaining excellent visualization, and overall low risk. Reports among multiple different specialties have also shown reduction in surgery duration, recovery time in the intensive care unit, and overall time of hospitalization stays when compared to classic open procedures [1]. Techniques for resecting skull base cancers are traditionally performed through large incisions and require mobilization of large amounts of tissue. Transoral robotic surgery (TORS) may provide a more accurate means to treat head and neck and skull base cancer, while allowing for decreased levels of morbidity and decreased levels of adjuvant radiation and chemotherapy. Reports on the development of TORS application to anterior skull base masses have previously described in small case descriptions in preclinical experimental canine and cadaver models using transcervical or suprahyoid ports [2–4]. Subsequently, TORS was applied to a small case series and feasible in 9 of 10 patients with parapharyngeal space tumors with no carotid encasement or bone erosion [5]. The objective of this study is to discuss feasible approaches using transoral robotic surgery (TORS) to access the anterior and lateral skull base and describe a novel approach for nodal dissection in the retropharyngeal space.

Improving Tertiary Center Skull Base Cancer Outcomes: A Story of Missed Opportunity in Primary and Secondary Care

Objective: To describe the extent of benefit, in terms of survival, of patients undergoing radical skull base resective surgery for cancers in a single UK center; in particular to explore the impact of delayed referral and salvage surgery on outcome.

Improvement in survival during the past 4 decades among patients with anterior skull base cancer

The aims of this study were to determine the trends in survival of patients with anterior skull base cancer over several decades and to identify time-related changes in the demographic and clinical characteristics of this population. In all, 282 patients who underwent craniofacial resection at Memorial Sloan-Kettering Cancer Center and Tel Aviv Medical Center were studied. Patients were categorized in accord with the period of surgery: early (1973-1984, n = 34), intermediate (1985-1996, n = 72), and later (1997-2008, n = 176). Patients operated after 1996 had higher rates of comorbidity, dural and pterygopalatine invasion, and multicompartmental involvement than those operated before 1996 (p ≤ .001). There was a significant improvement in 5-year overall and disease-specific survival, from 55% and 57%, respectively, for patients operated before 1996, to 66% and 70%, respectively, for those operated after 1996 (p = .02 and p = .006, respectively). On multivariate analysis, surgery after 1996 was an independent predictor of outcome (HR, 0.39, p < .001). The survival of patients with anterior skull base cancer is improving. Surgery after 1996 is an independent prognostic factor for an improved outcome.

On-Board Imaging Validation of Optically Guided Stereotactic Radiosurgery Positioning System for Conventionally Fractionated Radiotherapy for Paranasal Sinus and Skull Base Cancer

To evaluate the positioning accuracy of an optical positioning system for stereotactic radiosurgery in a pilot experience of optically guided, conventionally fractionated, radiotherapy for paranasal sinus and skull base tumors. Before each daily radiotherapy session, the positioning of 28 patients was set up using an optical positioning system. After this initial setup, the patients underwent standard on-board imaging that included daily orthogonal kilovoltage images and weekly cone beam computed tomography scans. Daily translational shifts were made after comparing the on-board images with the treatment planning computed tomography scans. These daily translational shifts represented the daily positional error in the optical tracking system and were recorded during the treatment course. For 13 patients treated with smaller fields, a three-degree of freedom (3DOF) head positioner was used for more accurate setup. The mean positional error for the optically guided system in patients with and without the 3DOF head positioner was 1.4 ± 1.1 mm and 3.9 ± 1.6 mm, respectively (p <.0001). The mean positional error drifted 0.11 mm/wk upward during the treatment course for patients using the 3DOF head positioner (p = .057). No positional drift was observed in the patients without the 3DOF head positioner. Our initial clinical experience with optically guided head-and-neck fractionated radiotherapy was promising and demonstrated clinical feasibility. The optically guided setup was especially useful when used in conjunction with the 3DOF head positioner and when it was recalibrated to the shifts using the weekly portal images.

Heavy ion radiotherapy during pregnancy

To provide a safe particle therapy treatment for a pregnant woman with skull-base cancer. Case report. University clinic. A 27-year-old woman diagnosed for a skull-base chordoma and whose pregnancy was found during the course of radiotherapy with accelerated carbon ions. Therapy was continued as scheduled, and fetal dose produced by photons and neutrons was measured at each radiotherapy fraction using passive and active monitors. Radiation dose to the uterus. Health of the mother and the newborn. Total dose to the uterus was <0.2 mSv. About 30% of this dose was caused by neutrons. Magnetic resonance imaging of the skull base showed no evidence of recurrent disease in the mother. The child was healthy with normal development. Heavy ion cancer therapy produces a very low dose in distal organs.

Anomalous phosphenes in ocular protontherapy

We have undertaken a clinical ground study of proton-induced light flashes (phosphenes). Patients treated at the Institut Curie – Centre de Protonthérapie in Orsay, France, received radiation therapy to cure ocular and skull-base cancers. Sixty percent of the patients treated for choroidal melanomas using 73 MeV protons report anomalous phosphenes. Delivering a radiation dose on the retina only is not sufficient to trigger the light flash. The present study may be the first indication of phosphenes triggered by protons of few tens of MeV.

Outcome of craniofacial surgery in children and adolescents with malignant tumors involving the skull base: An international collaborative study

The aim of the study was to characterize the distribution of anterior skull base (ASB) cancers in the pediatric population and to identify predictors of outcome. This was an international study of 1307 patients undergoing craniofacial surgery for malignant tumors; 6.4% (n = 84) among these were <or=21 years old. The most common histologic type was sarcoma (40%), followed by squamous cell carcinoma (14%). Higher incidence of tumors was found in older children (7.5-21 years) compared to younger children. The 5-year disease-specific and overall survival rates were 61% and 55%, respectively (median follow-up of 30 months). The best prognosis was associated with low-grade sarcomas and the worst with salivary and squamous cell carcinomas. High-grade sarcoma represented an intermediate risk group. On multivariate analysis, prior radiotherapy and histology were independent predictors of survival. Surgery for malignant tumors involving the ASB is feasible and safe in children. Histology is significant determinant of poor outcome in this population.

Minimally invasive endoscopic pericranial flap: A new method for endonasal skull base reconstruction

One of the major challenges of cranial base surgery is reconstruction of the dural defect. Following a craniofacial resection, the standard reconstructive technique is direct suture repair of the dural defect with a fascial graft and rotation of an anteriorly based pericranial scalp flap to cover the dura. The introduction of endoscopic techniques and an endonasal approach to the ventral skull base has created new challenges for reconstruction. The nasoseptal flap has become the workhorse for vascularized endoscopic skull base reconstruction; however at times, the septal mucosal flap may be unavailable for reconstruction. This can be due to prior surgical resection or involvement of the nasal septum by sinonasal cancer. We have developed a minimally invasive endoscopic pericranial flap for endoscopic skull base reconstruction. The use of a pericranial scalp flap for reconstruction during endonasal skull base surgery using minimally invasive techniques has not been previously reported. We performed cadaveric studies to illustrate feasibility of an endoscopic pericranial flap for endonasal skull base reconstruction, then applied this novel technique to an elderly patient after endonasal skull base and dural resection of an esthesioneuroblastoma. The technical report of the minimally invasive pericranial flap is outlined and the advantages and limitations during endonasal skull base reconstruction are discussed. The patient had excellent healing of her skull base and had no evidence of any postoperative cerebrospinal fluid leak. The minimally invasive endoscopic pericranial flap provides another option for endonasal reconstruction of cranial base defects. There is minimal donor site morbidity, and it provides a large flap that can cover the entire ventral skull base. The issues of intranasal tissue tumor involvement and the need for radiotherapy make the endoscopic pericranial flap an ideal reconstruction for anterior cranial base defects resulting from endonasal sinonasal and skull base cancer resections.

The Role of Palliative Radiosurgery When Cancer Invades the Cavernous Sinus

Involvement of the cavernous sinus by direct invasion from skull base cancer or from metastatic spread of cancers is a challenging problem. We evaluated the role of stereotactic radiosurgery (SRS) in the treatment of patients who developed cavernous sinus metastases or direct invasion. We retrospectively reviewed the data from 37 patients who had cavernous sinus metastases or had cavernous sinus invasion from adjacent skull base cancers and who underwent SRS between 1992 and 2006 at the University of Pittsburgh Medical Center. The median patient age was 57.8 years. Previous adjuvant management included fractionated radiotherapy in 8, chemotherapy in 16, and both radiotherapy and chemotherapy in 5. The primary sites of metastases or invasion were nasopharyngeal carcinoma (n = 7), parotid gland carcinoma (n = 7), and metastases from systemic cancer (n = 23). The median target volume was 6.3 cm(3) (range, 0.3-33.6), and the median margin dose was 14 Gy (range, 12-20). At a mean of 12.9 months (range, 0.8-63.9), 32 patients had died and 5 were living. The overall survival rate after SRS was 36.6% and 19.4% at 1 and 2 years, respectively. Progression-free survival was related to a greater marginal dose. After SRS, 12 (35.3%) of 34 patients with neurologic symptoms exhibited improvement. SRS early after diagnosis was significantly associated with improvement of cranial nerve dysfunction. SRS is a minimally invasive palliative option for patients whose cancer has invaded the cavernous sinus. The benefits for cranial nerve deficits are best when SRS is performed early.

Incidence and Prognostic Significance of Perineural Invasion in Patients with Paranasal Sinuses and Skull Base Cancer

Incidence and Prognostic Significance of Perineural Invasion in Patients with Paranasal Sinuses and Skull Base Cancer

Evaluation of quality of life and psychiatric morbidity in patients with malignant tumours of the skull base

In general, patients with malignant tumours of the skull base have a poor prognosis. Treatment may have a disfiguring physical and disabling mental effect on patients. To evaluate the effect of treatment on physical and mental quality of life in patients with skull base malignancy, we conducted a cross-sectional patient survey of 18 patients treated for such tumours, using the University of Washington (version 4) quality of life questionnaire and the hospital anxiety and depression scale. The total quality of life score (median value) was 980 (550-1125). Patients with anterior skull base malignancy scored lower than those with lateral skull base malignancy (p=0.003). In general, the worst individual domain scores were: mood (64 per cent); activity (69 per cent); and, specifically for patients with anterior skull base malignancy, taste (54 per cent, p=0.004) and anxiety (60 per cent, p=0.034). One-third of skull base cancer patients were at risk of suffering from mental distress and psychiatric morbidity (indicated as a score of more than seven on the hospital anxiety and depression scale).

Malignant tumors of the anterior skull base.

Cancers of the paranasal sinuses or nasal cavity are the most common malignant tumors of the anterior skull base. Several types of tumors occur in this location, including cancers of endodermal, mesodermal, and epidermal origins. Although anterior skull base surgery is a relatively recent approach in treating these tumors, widespread changes have already occurred in procedural methods and treatment goals. We review the tumor types that occur in the anterior skull base and discuss the current treatment options, including multimodal therapy and the team approach to surgery. Surgical techniques are also described. Management of anterior skull base cancer is complex due to the anatomic detail of the region and the variety of cancers that occur in this area. Currently, the "gold standard" for surgery is the anterior craniofacial approach. Combined with adjuvant radiation therapy, 5-year disease-free survival rates have increased to 50%, with some tumors such as adenocarcinomas and esthesioneuroblastomas reaching up to 80% 5-year survival rates. Potential complications include cerebrospinal fluid leakage, meningitis, abscess formation, and pneumocephalus. Treatment of anterior skull base cancer is complex due to the significant anatomic detail of the region and the variety of cancers that occur in this area. Multimodal therapy through a team approach is the optimal management approach for these tumors.

Chemotherapy for skull base cancers

This article focuses on treatment options for select skull base problems that have decreased post-treatment morbidity and, in many cases, improved survival. The select skull base cancers covered include nasopharyngeal carcinoma, squamous cell carcinoma of the paranasal sinuses, sinonasal undifferentiated carcinoma, neuroendocrine carcinoma, esthesioneuroblastoma, and salivary gland carcinoma.

Medial antebrachial cutaneous nerve: a new donor graft for repair of facial nerve defects at the skull base.

When grafting a facial nerve defect after resection of a skull base cancer, the use of the greater auricular nerve is generally contraindicated because of concern of malignant involvement. In the past, the sural nerve was used as a donor graft for reconstruction of the facial nerve. We have found a sensory branch of the median nerve of the upper arm, the medial antebrachial cutaneous (MAC) nerve, to be a suitable option for facial nerve grafting. The MAC nerve provides a good diameter match for the facial nerve and has branching to allow reconstruction of the distal facial nerve in the parotid bed. The length is adequate to graft from the brainstem to the distal facial branches. Loss of sensation is limited and well tolerated by the patient. The MAC nerve has been used in grafting in 15 patients with skull base disease and facial nerve defects. No complications have been encountered, and the functional return appears to be similar to other grafts. In our practice the MAC nerve is a valuable option for facial nerve repair at the skull base.

Proton and neutron radiation in cancer treatment: clinical and economic outcomes

The French National Agency for Medical Evaluation (ANDEM) was requested to assess the effectiveness of proton and neutron beam therapy in cancer treatment compared to conventional radiotherapy. This task was accomplished by a critical appraisal of the clinical and economic literature. According to the published economic literature and the capital and staffing cost analysis, it appears that the costs of proton therapy are likely to be two or three times greater than those of photon conformal therapy. According to the published clinical literature, proton beam therapy should be proposed as a routine treatment only for uveal melanoma and skull base cancers. Neutron beam therapy should be proposed as a routine treatment for inoperable salivary gland tumors; its use may be also discussed in cases of stage C-D1 prostate cancers and soft tissue sarcomas. Based on the current scientific evidence and given the incidence rate of these tumors, the time and material requirements, the current French proton/neutron beam facilities are able to meet the current demand. For other cancers the medical and economic potential of proton therapy is still an open question.

Intraoperative radiotherapy of skull base cancer

As the head and neck surgeon expands the boundaries of resectability into the skull base, the margin of tumor clearance diminishes. Intraoperative radiotherapy (IORT) can be used as an adjunct to skull base surgery and external beam radiation to enhance local control in areas with close margins or remaining microscopic disease. During the period from May 1982 to May 1988, 25 patients underwent IORT of the skull base following resection and prior to closure to treat microscopic disease in 9 patients, sterilize close margins in 14 patients, and attempt to eliminate remaining gross disease in 2 patients. The types of tumors treated were 13 squamous cell carcinomas, 4 adenoid cystic carcinomas, 3 high-grade mucoepidermoid carcinomas, 3 sarcomas, 1 malignant mixed tumor, and an oncocytic adenocarcinoma. The majority of the tumors either originated in the sinuses or were skull base extensions of oral cavity or oropharyngeal cancers. In 22 patients with 1-year follow-up, IORT prevented local recurrence in 14 (64%) patients. This may represent improved control of local disease in patients who historically have a very dismal prognosis. The indications, techniques, and complications of this exciting therapeutic modality are also reviewed.