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Franco DeMonte and Ehab Hanna

Object

Achieving microscopically tumor-free margins during resection of skull base malignancies has consistently been identified as a positive prognostic factor for patient survival. When malignancies extend perineurally into the major nerves traversing the skull base and entering the cavernous sinus, achieving tumor-free margins can be challenging and typically necessitates performing a craniotomy to access the lateral wall of the cavernous sinus. This report describes a novel technique used to access and resect malignancy extending perineurally into the intracranial portion of V2 via the maxillary sinus.

Methods

Seven patients with maxillary sinus tumors and perineural extensions along V2, who underwent resection of the primary tumor and transmaxillary intracranial exposure and dissection of the maxillary nerve to achieve maximal tumor resection, were analyzed. Prospectively collected data, including symptoms, clinical signs, diagnostic imaging data, pathological diagnosis, incidence and nature of complications, adjuvant therapies, and oncological outcomes, were retrospectively analyzed.

Results

All patients in this cohort had trigeminal nerve symptomatology as well as abnormal enhancement in the pterygopalatine fissure as noted on magnetic resonance imaging. The transmaxillary exploration of the maxillary nerve technique was used in all seven patients, resulting in gross-total resection of the tumors in every patient. At the last follow-up (mean 30 months, range 13–58 months, in four of seven patients for > 2 years), six patients were alive without evidence of local disease. One patient with squamous cell carcinoma died of progressive infratemporal fossa and regional neck disease 26 months after resection. No intracranial or cavernous sinus disease was present.

Conclusions

This technique extended the limits of resection without the need for a craniotomy and improved local tumor control in this patient cohort.

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Rohan Ramakrishna, Shaan M. Raza, Michael Kupferman, Ehab Hanna and Franco DeMonte

OBJECT

Adenoid cystic carcinoma (ACC) is a locally aggressive tumor of salivary gland origin. Little data exist to guide treatment when this tumor extends to involve the structures of the skull base.

METHODS

Fifty-one patients with a diagnosis of ACC affecting the skull base were identified from a prospective database at MD Anderson Cancer Center (from 1992 to 2010).

RESULTS

Median follow-up for study patients was 6.75 years. The 5- and 10-year overall survival (OS) rates were 78% and 50%, respectively. Sixty-six percent of patients had progression of their disease. The 5- and 10-year progression-free survival (PFS) rates were 46.7% and 21.0%, respectively. Gross-total resection was achieved in 75% of patients, with 49% having microscopically negative margins at the time of first operation. On univariate analysis, resections with microscopically negative margins were associated with a significant OS advantage (20.1 ± 3.3 years) compared with resections that left residual disease, even if microscopic (10.3 ± 1.6 years, p = 0.035). In patients who underwent reoperation, the effect persisted, with improved OS in those with negative margins (21.4 ± 0.0 vs 16.7 ± 4.0 years, p = 0.06). The use of adjuvant radiotherapy was associated with an OS advantage (16.2 ± 2.5 vs 5.5 ± 2.2 years, p = 0.03) at initial diagnosis and improved PFS (7.8 ± 1.0 vs 2.1 ± 0.62 years, p = 0.005), whereas repeat irradiation provided no benefit. The use of adjuvant chemotherapy at diagnosis or at recurrence was not associated with any significant advantage. Multivariate analysis revealed margin-negative resection at initial operation and at recurrence retained OS significance, even after controlling for age, radiation therapy, and T stage.

CONCLUSIONS

ACC of the skull base is best treated with a multidisciplinary approach aimed at maximal, safe resection. Adjuvant radiotherapy should be offered, whereas chemotherapy does not confer benefit.

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Gautam U. Mehta, Franco DeMonte, Shirley Y. Su, Michael E. Kupferman, Ehab Y. Hanna and Shaan M. Raza

Chondrosarcomas of the skull base are malignant tumors for which surgery is the primary therapeutic option. Gross-total resection has been demonstrated to improve survival in patients with these tumors. Chondrosarcomas arising from the petroclival synchondrosis harbor particularly unique anatomical considerations that have long been a barrier to achieving such a resection. Endoscopic endonasal transpterygoid approaches have been recently used to gain improved access to such lesions; however, these approaches have classically relied on a medial to lateral transclival trajectory, which provides limited exposure for complete resection of lateral disease. In this paper the authors describe an endoscopic endonasal transpterygoid transnasopharyngeal approach that provides comprehensive access to the petroclival region through dissection of the eustachian tube with resection of the cartilaginous torus tubarius. Of note, the authors have previously demonstrated the superior outcomes and validity of this approach relative to other cranial base techniques for petroclival chondrosarcomas. Surgical outcomes in 5 cases of chondrosarcoma without medial extension are detailed. Gross-total resection was achieved in 4 of 5 patients. Postoperative complications included transient palatal numbness in all patients and eustachian tube dysfunction due to the approach. With tympanostomy tube placement, no patient had persistent hearing loss. Overall, this approach appears to be a safe and effective technique for resection of petroclival chondrosarcomas.

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Shaan M. Raza, Rohan Ramakrishna, Randal S. Weber, Michael E. Kupferman, Paul W. Gidley, Ehab Y. Hanna and Franco DeMonte

OBJECT

A relative paucity of information exists regarding outcomes from craniofacial resection for advanced nonmelanoma skin cancers involving the skull base. In light of advances in surgical technique and adjuvant therapy protocols, the authors reviewed their surgical experience to determine disease control rates, overall survival (OS), morbidity, and mortality.

METHODS

A retrospective review of 24 patients with nonmelanoma cutaneous cancers with skull base involvement treated with craniofacial resection at The University of Texas MD Anderson Cancer Center from 1994 to 2012 was performed. Of these patients, 19 (79%) had squamous cell carcinoma (SCC), 4 (17%) had basosquamous carcinoma (BSCC), and 1 patient (4%) had adenocarcinoma. Factors as assessed were prior treatment, TNM staging, tumor involvement, extent of intracranial extension, margin status, postoperative complications, recurrence, disease status at last follow-up, and long-term survival. The majority of tumors were T4 (67%) according to the TNM classification; perineural extension was noted in 58%, cavernous sinus involvement in 25%, and dural involvement in 29%.

RESULTS

Postoperative complications occurred in 4 patients (17%) including 1 death. Kaplan-Meier estimates were calculated for OS and progression-free survival (PFS). Median OS was 43.2 months with an 82% 1-year OS and 37% 5-year OS; the median PFS was 91.2 months. Margin status was positively associated with median OS in SCC (91 months [for negative margins] vs 57 months, p = 0.8) and in BSCC (23.7 vs 3.2 months, p < 0.05). Postoperative radiotherapy was associated with improved median OS (43.2 vs 22 months, p = 0.6). Brain involvement was uniformly fatal after 1 year, while cavernous sinus involvement (31 vs 43 months, p = 0.82), perineural disease (31 vs 54 months, p = 0.30), and T4 stage (22 vs 91.2 months, p = 0.09) were associated with worsened OS. Similar associations were found with median PFS.

CONCLUSIONS

Aggressive multimodality management with surgery and postoperative radiotherapy can positively impact locoregional control and OS. With improvements in technique and adjuvant therapy protocols, treatment can still be considered in situations of perineural disease and cavernous sinus involvement and as a salvage option for patients in whom prior treatment has failed. As patients with advanced NMSCs often have few options, craniofacial resection, as part of a coordinated multimodal management plan, is justified if it can be performed safely.

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Moran Amit, Diana Bell, Patrick J. Hunt, Ehab Hanna, Shirley Y. Su, Michael Kupferman, Mohamed Aashiq, Hideaki Takahashi, Paul W. Gidley, Marc-Elie Nader, Franco DeMonte and Shaan M. Raza

OBJECTIVE

Infratemporal fossa (ITF) tumors are unique in histological characteristics and difficult to treat. Predictors of patient outcomes in this context are not known. The objective of this study was to identify independent predictors of outcome and to characterize patterns of failure in patients with ITF carcinoma.

METHODS

All patients who had been surgically treated for anterolateral skull base malignancy between 1999 and 2017 at the authors’ institution were retrospectively reviewed. Patient demographics, preoperative performance status, tumor stage, tumor characteristics, treatment modalities, and pathological data were collected. Primary outcomes were disease-specific survival (DSS) and local progression-free survival (LPFS) rates. Overall survival (OS) and patterns of progression were secondary outcomes.

RESULTS

Forty ITF malignancies with skull base involvement were classified as carcinoma. Negative margins were achieved in 23 patients (58%). Median DSS and LPFS were 32 and 12 months, respectively. Five-year DSS and OS rates were 55% and 36%, respectively. The 5-year LPFS rate was 69%. The 5-year overall PFS rate was 53%. Disease recurrence was noted in 28% of patients. Age, preoperative performance status, and margin status were statistically significant prognostic factors for DSS. Lower preoperative performance status and positive surgical margins increased the probability of local recurrence.

CONCLUSIONS

The ability to achieve negative margins was significantly associated with improved tumor control rates and DSS. Cranial base surgical approaches must be considered in multimodal treatment regimens for anterolateral skull base carcinomas.

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Jack Phan, Courtney Pollard III, Paul D. Brown, Nandita Guha-Thakurta, Adam S. Garden, David I. Rosenthal, Clifton D. Fuller, Steven J. Frank, G. Brandon Gunn, William H. Morrison, Jennifer C. Ho, Jing Li, Amol J. Ghia, James N. Yang, Dershan Luo, He C. Wang, Shirley Y. Su, Shaan M. Raza, Paul W. Gidley, Ehab Y. Hanna and Franco DeMonte

OBJECTIVE

The objective of this study was to assess outcomes after Gamma Knife radiosurgery (GKRS) re-irradiation for palliation of patients with trigeminal pain secondary to recurrent malignant skull base tumors.

METHODS

From 2009 to 2016, 26 patients who had previously undergone radiation treatment to the head and neck received GKRS for palliation of trigeminal neuropathic pain secondary to recurrence of malignant skull base tumors. Twenty-two patients received single-fraction GKRS to a median dose of 17 Gy (range 15–20 Gy) prescribed to the 50% isodose line (range 43%–55%). Four patients received fractionated Gamma Knife Extend therapy to a median dose of 24 Gy in 3 fractions (range 21–27 Gy) prescribed to the 50% isodose line (range 45%–50%). Those with at least a 3-month follow-up were assessed for symptom palliation. Self-reported pain was evaluated by the numeric rating scale (NRS) and MD Anderson Symptom Inventory–Head and Neck (MDASI-HN) pain score. Frequency of as-needed (PRN) analgesic use and opioid requirement were also assessed. Baseline opioid dose was reported as a fentanyl-equivalent dose (FED) and PRN for breakthrough pain use as oral morphine-equivalent dose (OMED). The chi-square and Student t-tests were used to determine differences before and after GKRS.

RESULTS

Seven patients (29%) were excluded due to local disease progression. Two experienced progression at the first follow-up, and 5 had local recurrence from disease outside the GKRS volume. Nineteen patients were assessed for symptom palliation with a median follow-up duration of 10.4 months (range 3.0–34.4 months). At 3 months after GKRS, the NRS scores (n = 19) decreased from 4.65 ± 3.45 to 1.47 ± 2.11 (p < 0.001); MDASI-HN pain scores (n = 13) decreased from 5.02 ± 1.68 to 2.02 ± 1.54 (p < 0.01); scheduled FED (n = 19) decreased from 62.4 ± 102.1 to 27.9 ± 45.5 mcg/hr (p < 0.01); PRN OMED (n = 19) decreased from 43.9 ± 77.5 to 10.9 ± 20.8 mg/day (p = 0.02); and frequency of any PRN analgesic use (n = 19) decreased from 0.49 ± 0.55 to 1.33 ± 0.90 per day (p = 0.08). At 6 months after GKRS, 9 (56%) of 16 patients reported being pain free (NRS score 0), with 6 (67%) of the 9 being both pain free and not requiring analgesic medications. One patient treated early in our experience developed a temporary increase in trigeminal pain 3–4 days after GKRS requiring hospitalization. All subsequently treated patients were given a single dose of intravenous steroids immediately after GKRS followed by a 2–3-week oral steroid taper. No further cases of increased or new pain after treatment were observed after this intervention.

CONCLUSIONS

GKRS for palliation of trigeminal pain secondary to recurrent malignant skull base tumors demonstrated a significant decrease in patient-reported pain and opioid requirement. Additional patients and a longer follow-up duration are needed to assess durability of symptom relief and local control.