Janus, Jeffrey R.

OBJECTIVE This study aimed to provide data on extended outcomes in primary clival chordomas, focusing on progression-free survival (PFS) and overall survival (OS). METHODS A retrospective single-center analysis was conducted on patients with clival chordoma treated between 1987 and 2022 using surgery, stereotactic radiosurgery, or proton radiation therapy (PRT). RESULTS The study included 100 patients (median age 44 years, 51% male). Surgery was performed using the endoscopic endonasal approach in 71 patients (71%). Gross-total resection (GTR) or near-total resection (NTR) was attained in 39 patients (39%). Postoperatively, new cranial nerve deficits occurred in 7%, CSF leak in 4%, and meningitis in none of the patients. Radiation therapy was performed in 79 patients (79%), with PRT in 50 patients (50%) as the primary treatment. During the median follow-up period of 73 (interquartile range [IQR] 38–132) months, 41 recurrences (41%) and 31 deaths (31%) were confirmed. Patients with GTR/NTR had a median PFS of 41 (IQR 24–70) months. Patients with subtotal resection or biopsy had a median PFS of 38 (IQR 16–97) months. The median PFS of patients who received radiation therapy was 43 (IQR 26–86) months, while that of patients who did not receive radiation therapy was 18 (IQR 5–62) months. The Kaplan-Meier method showed that patients with GTR/NTR (p = 0.007) and those who received radiation therapy (p < 0.001) had longer PFS than their counterparts. The PFS rates following primary treatment at 5, 10, 15, and 20 years were 51%, 25%, 17%, and 7%, respectively. The OS rates at the same intervals were 84%, 60%, 42%, and 34%, respectively. Multivariate Cox regression analysis showed that age < 44 years (p = 0.02), greater extent of resection (EOR; p = 0.03), and radiation therapy (p < 0.001) were associated with lower recurrence rates. Another multivariate analysis showed that age < 44 years (p = 0.01), greater EOR (p = 0.04), and freedom from recurrence (p = 0.02) were associated with lower mortality rates. Regarding pathology data, brachyury was positive in 98%, pan-cytokeratin in 93%, epithelial membrane antigen in 85%, and S100 in 74%. No immunohistochemical markers were associated with recurrence. CONCLUSIONS In this study, younger age, maximal safe resection, and radiation therapy were important factors for longer PFS in patients with primary clival chordomas. Preventing recurrences played a crucial role in achieving longer OS.

OBJECTIVE The objective of this study was to clarify the detailed clinical course of recurrent clival chordoma and the outcomes of each treatment modality. METHODS A single-center retrospective analysis was conducted on patients seen for recurrent clival chordoma. The cohort was identified from those who underwent surgery, stereotactic radiosurgery, or proton therapy at the authors’ institution between 1990 and 2022. RESULTS A total of 95 recurrences in 40 patients with a median (interquartile range [IQR]) follow-up of 43 (18–79) months were identified. The median (IQR) age at the time of diagnosis was 48 (36–62) years, and 55% of patients were male. Twenty-three patients were treated with surgery followed by adjuvant radiation before the first recurrence. The median (range) number of recurrences per patient was 2 (1–8), and the median (IQR) time to the first recurrence was 29 (9–51) months. The recurrences were treated with one or more of the following therapies: surgery, radiation, systemic therapy, and laser interstitial thermal therapy (LITT). Surgery was performed for 44 recurrences in 25 patients. Radiation was used to treat 42 recurrences in 28 patients. Patients with recurrences treated with surgery plus radiation had the longest progression-free survival (PFS) (median [95% CI] overall survival [OS] 120 [0–245] months, p < 0.01, log-rank test). Patients with recurrences but without prior radiation had longer PFS than those patients with prior radiation. The median (95% CI) OS after the first recurrence was 68 (54–82) months, 5-year OS after the first recurrence was 48%, and 10-year OS was 27%. Multivariate Cox regression analysis showed that mortality after the first recurrence was significantly associated with no adjuvant radiation (HR 0.149, 95% CI 0.038–0.59, p = 0.0067), older age at the time of the first recurrence (HR 1.04, 95% CI 1.01–1.08, p = 0.021), and total number of recurrences (p = 0.032). Seven patients received systemic therapy, and the median (95% CI) OS of these patients since initiation of systemic therapy was 31 (11–51) months. Imatinib and/or nivolumab were used in 6 patients (15%). One patient (3%) was treated with LITT for his fourth recurrence. CONCLUSIONS Despite the aggressive nature of recurrent chordoma, 14 of 29 patients (48%) survived for more than 5 years after the initial recurrence using combined therapies. Multiple treatment options may contribute to the long-term survival of patients with this intractable tumor.

BACKGROUND: Anterior approaches to the cervical spine are among the most common exposures by which neurosurgeons and orthopedic surgeons access the prevertebral space and ultimately the cervical disk and vertebral bodies. There is a paucity of literature describing the microanatomic fascial planes of the neck with respect to anterior cervical approaches. OBJECTIVE: To delineate the microanatomic connections of the cervical fascial planes pertinent to anterior cervical exposure. METHODS: Using a cadaveric model, original illustrations, the Visible Human Project, and an original surgical video, we demonstrate a stepwise method for identifying the correct planes for anterior cervical exposure. RESULTS: A step-by-step method for identifying the anterior cervical fascial planes intraoperatively is demonstrated. CONCLUSION: A comprehensive understanding of anterior cervical microsurgical anatomy is vital for performing a methodical yet efficient approach to the prevertebral space while minimizing retraction and iatrogenic injury to the surrounding neurovascular structures.

Pleomorphic liposarcomas (PLS) are the rarest subtype of liposarcomas, representing only 5–10% of liposarcomas. Pleomorphic liposarcomas are extremely aggressive and have a poor prognosis. Here, we present the case of a 66-year-old female who presented with difficulty swallowing, talking, and hearing. An extensive investigation revealed the presence of an aggressively growing parapharyngeal space mass. The patient underwent a left parapharyngeal space exploration and left deep lobe parotidectomy by the cervicoparotid approach. Histopathological evaluation of the surgical specimen further confirms the presence of pleomorphic subtype of liposarcoma. The patient received adjuvant radiotherapy following the procedure. At 6 months postop, the patient is in good health and shows no evidence of recurrence. In addition to this treatment, we discuss the radiologic and histologic findings of this current case.

The management of clival chordoma in our group shifted around 2013 to mostly endoscopic, and proton beam was introduced for our multidisciplinary team. Consecutive patients who had surgical resection from 1987 to 2021 were reviewed. A total of 58 patients (39 patients after 2013) were analyzed. The mean tumor size was 3.7 cm, and the most common location was the upper clivus (43%). Compared to before 2013, after 2013, the endoscopic endonasal approach was more common (90%, p < 0.001), and more gross or near total resections (64%, p = 0.002) were attained. Ten cases (17%) were revision surgeries referred from elsewhere, and three cases (5%) underwent additional surgery elsewhere before adjuvant radiation. The postoperative cerebrospinal fluid leak occurred in 7%. Post-operative new cranial nerve deficits occurred in 32% before 2013, compared to 2.6% after 2013 (p = 0.004). For cases before 2013, 10 patients (53%) recurred during the median follow-up of 144 months (mean, 142 months), whereas for cases after 2013, seven patients (18%) recurred with a median follow-up of 35 months (mean, 42 months). 5-year progression-free survival was 58%, and 5-year overall survival was 87%. A specialized multidisciplinary team improved the resection rate compared to a historical cohort with an excellent morbidity profile.

Salivary lymphadenoma is an extremely rare neoplasm that is usually seen in the older patient population, arising sporadically on one side and almost exclusive to the parotid gland. Imaging and pathology findings can mimic both benign and malignant tumors, and therefore, this lesion may be misdiagnosed if not on the differential diagnosis. This article reviews the clinical presentation, as well as the pathology and imaging findings of salivary lymphadenoma in the setting of Sjogren’s syndrome.

e18055 Background: Entrectinib, a TRK kinase inhibitor, has been approved for the treatment of tissue agnostic rare tumors positive for TRK fusions. A very low frequency molecular subset of TRK fusion tumors dubbed as secretory carcinoma (SC) are characterized by organ-agnostic epithelial origin, ETV6-NTRK3 (EN) fusion and distinguishable secretory-type tumor cells. These tumors have been frequently miscategorized as acinic cell carcinoma or adenocarcinoma. A previous mouse study identified EGF dependent epithelial progenitors as putative cell-of-origin for SC. Methods: To test the role of EGFR signaling in EN mediated transformation and therapy resistance, we expressed EN, kinase-dead EN-K380M, and drug-resistant EN-G623R in human epithelial MCF10A cells with EGF-dependent primitive function and investigated their ability to grow in the presence and absence of EGF and/or entrectinib. To understand the significance of findings based on our model, we analyzed a total of 22 ‘rare’ patients from Mayo Clinic Tissue Registry and analyzed TCGA PanCan datasets. Results: We report herein that EGF signaling is essential for normal growth but dispensable during EN driven transformation. Our findings suggest that levels equivalent to circulating EGF (0.5-1ng/ml) is sufficient to drive 100% resistance to entrectinib in vitro. Three different strategies to blockade EGF/EGFR axis including depletion of EGF in culture system, genetic depletion of EGFR using shRNA as well as cetuximab antibody-based EGFR neutralization potentiated oncogene-addiction and hypersensitivity to entrectinib in our models. As predicted, models with G623R mutation in EN was refractory to entrectinib under all experimental conditions. Further omics analysis of TCGA PanCan suggested that EN and EGFR mutations are mutually exclusive and entrectinib-resistant G623R mutation were uncommon. Interestingly, nearly all EN tumors from Mayo Clinic Tissue Registry immunostained weakly or strongly for EGFR and showed perfect concordance with pEGFR suggesting pathway activation. Conclusions: Together, these findings raise an important question whether blockade of ‘wildtype’ EGFR signaling could improve medical intervention in SC patients presenting with wildtype EGFR and no drug-resistant mutation in entrectinib, by improving oncogene-addiction and attendant hypersensitization of transformed cells to entrectinib.

AbstractBackgroundParotid gland mucoepidermoid carcinoma (MEC) has published five‐year cancer‐specific survival (CSS) rates of 77%–97%, with variance related to grade.MethodsPatients receiving primary surgery for parotid gland MEC from 1995 to 2014 at a tertiary medical center underwent clinical review, histopathologic review, and cytogenetic analysis. Survival outcomes were evaluated.ResultsAmong 58 patients, T/N/M classification was as follows: T1 in 35 patients, T2 in 14, T4a in 9, N0 in 53, N1 in 2, N2b in 3. Histologic grade was low in 27, intermediate in 17, and high in 12 patients with 98% MAML2 positivity. All patients underwent parotidectomy, and seven patients received adjuvant radiation therapy. CSS was 100% at 5 years and 94.1% at 10 and 15 years. Two patients experienced locoregional recurrence.ConclusionsTreatment with adequate surgical resection and adjuvant radiation therapy for high‐grade or advanced‐stage tumors yields excellent survival, independent of clinical stage or pathologic grade.