Defining the Genomic Landscape of Diffuse Sclerosing Papillary Thyroid Carcinoma: Prognostic Implications of RET Fusions.

BACKGROUND: Diffuse sclerosing papillary thyroid carcinoma (DSPTC) is an aggressive histopathologic subtype of papillary thyroid carcinoma. Correlation between genotype and phenotype has not been comprehensively described. This study aimed to describe the genomic landscape of DSPTC comprehensively using next-generation sequencing (NGS), analyze the prognostic implications of different mutations, and identify potential molecular treatment targets. METHODS: Tumor tissue was available for 41 DSPTC patients treated at Memorial Sloan Kettering Cancer Center between 2004 and 2021. After DNA extraction, NGS was performed using the Memorial Sloan Kettering Integrated Mutation Profiling of Actionable Cancer Targets platform, which sequences 505 critical cancer genes. Clinicopathologic characteristics were compared using the chi-square test. The Kaplan-Meier method and log-rank statistics were used to compare outcomes. RESULTS: The most common mutation was RET fusion, occurring in 32% (13/41) of the patients. Other oncologic drivers occurred in 68% (28/41) of the patients, including 8 BRAFV600E mutations (20%) and 4 USP8 mutations (10%), which have not been described in thyroid malignancy previously. Patients experienced RET fusion-positive tumors at a younger age than other drivers, with more aggressive histopathologic features and more advanced T stage (p = 0.019). Patients who were RET fusion-positive had a significantly poorer 5-year recurrence-free survival probability than those with other drivers (46% vs 84%; p = 0.003; median follow-up period, 45 months). In multivariable analysis, RET fusion was the only independent risk factor for recurrence (hazard ratio [HR], 7.69; p = 0.017). CONCLUSION: Gene-sequencing should be strongly considered for recurrent DSPTC due to significant prognostic and treatment implications of RET fusion identification. The novel finding of USP8 mutation in DSPTC requires further investigation into its potential as a driver mutation.

Parotidectomy for deep lobe pleomorphic adenomas is associated with higher rates of complications and recurrence.

BACKGROUND: Pleomorphic adenoma (PA) is a common parotid tumor, yet due to the relative rarity of deep lobe PA (DLPA), there is a paucity of information about its clinical presentation and surgical outcomes. METHODS: We reviewed the charts of patients with previously untreated parotid PA between the years 1990 and 2015. Clinical parameters and surgical outcomes were compared between superficial lobe PA (SLPA) and DLPA. RESULTS: The cohort comprised 147 cases of DLPA and 222 cases of SLPA. DLPA were larger (median 2.6 cm vs. 2.0 cm, p < 0.001), more often discovered incidentally on imaging (33%, n = 48) and had unique presentations (pharyngeal mass, dysphagia, otalgia). Postsurgical complications were more frequently observed in DLPA (41% vs. 30% in SLPA, p = 0.025), mainly transient facial nerve weakness. DLPA also showed higher recurrence rates (n = 6, 4.1% vs. n = 1, 0.4%, p = 0.016). CONCLUSIONS: Parotidectomy for DLPA carries a higher risk of complications and recurrence compared to SLPA.

Skull base surgery for malignant tumors: The 2nd international collaborative study (1995-2015).

BACKGROUND: The current study presents the effort of a global collaborative group to review the management and outcomes of malignant tumors of the skull base worldwide. PATIENTS AND METHODS: A total of 28 institutions contributed data on 3061 patients. Analysis evaluated clinical variables, survival outcomes, and multivariable factors associated with outcomes. RESULTS: The median age was 56 years (IQR 44-67). The open surgical approach was used in 55% (n = 1680) of cases, endoscopic resection was performed in 36% (n = 1087), and the combined approach in 9.6% (n = 294). With a median follow-up of 7.1 years, the 5-year OS DSS and RFS were 65%, 71.7% and 53%, respectively. On multivariable analysis, older age, comorbidities, histology, dural/intracranial involvement, positive margins, advanced stage, and primary site were independent prognostic factors for OS, DSS, and RFS. Adjuvant RT was a protective prognostic factor. CONCLUSION: The progress across various disciplines may have contributed to improved OS and DSS in this study compared to previous reports.

Outcomes of Conversion Surgery for Patients With Low-Risk Papillary Thyroid Carcinoma.

Importance: The outcomes of patients with low-risk thyroid cancer who undergo surgery following a period of active surveillance (AS) are not well-defined. Objective: To evaluate surgical, pathologic, and oncologic outcomes among patients undergoing conversion surgery (CS) following AS for low-risk papillary thyroid carcinoma. Design, Setting, and Participants: In this cohort study, patients who underwent CS for disease progression were compared with patients who underwent CS without disease progression and with a propensity score-matched cohort of patients who underwent initial surgery (IS). The median (IQR) postsurgical follow-up time was 40.3 (18.0-59.0) months. Patients were treated at a quaternary cancer referral center in the United States. Exposures: Surgery. Main Outcomes and Measures: Surgical complications, pathologic characteristics, overall survival (OS), and recurrence-free survival (RFS). Results: Of 550 patients who underwent AS, 55 (10.0%) had CS, of whom 39 (7.1%) had surgery due to suspected disease progression (median [IQR] age, 48 [39-56] years; 32 [82.1%] female). There were no clinically meaningful differences in rates of surgical sequalae between the progression CS group (12 of 39 [30.7%]) and the nonprogression CS group (7 of 16 [43.8%]) (Cramer V, 0.2; 95% CI, 0.01-0.5). The 5-year OS was 100% (95% CI, 100%-100%) in both the disease-progression CS cohort and the IS cohort. Although the cohort of patients undergoing CS after disease progression was by definition a subset with more aggressive tumor behavior, no clinically meaningful differences were observed in the rates of regional recurrence (2 of 39 [5.1%] vs 0 of 39 patients with IS), local recurrence (0 patients), distant metastasis (0 patients), or disease-specific mortality (0 patients) when compared with the matched IS group. Five-year RFS rates were similar: 100% in the IS group and 86% (95% CI, 70%-100%) in the CS group. Conclusions and Relevance: In this cohort study, CS for suspected disease progression was associated with surgical and oncologic outcomes similar to IS, supporting the feasibility and safety of AS for patients with low-risk papillary thyroid carcinoma.

Posttreatment complications in pediatric cervical neuroblastoma: A retrospective case series at a tertiary cancer center.

BACKGROUND: Neuroblastomas rarely occur as primary tumors in the cervical region. Therefore, very little has been reported regarding treatment strategies, complications, and outcomes of these cervical neuroblastomas. The goal of this study is to review the presentation, management, and outcomes of all primary cervical pediatric neuroblastoma cases at a single tertiary care center. METHODS: A retrospective cohort review of all neuroblastoma patients treated at a single center were performed. All patients with primary cervical neuroblastoma were reviewed for demographic information, tumor characteristics, treatment, and outcomes. RESULTS: Thirty (1.8%) patients were found to have undergone treatment for cervical neuroblastoma tumors diagnosed on average at 2.1 years old. Most presented with a swollen neck/palpable mass ± Horner's syndrome. Based on features including tumor staging, N-myc proto-oncogene protein (MYCN) amplification status, histology, most were deemed intermediate or high risk. Treatment strategies centered around chemotherapeutic regimens with surgery when possible as well as various adjuvant treatments including radiation therapy, immunotherapy, bone marrow transplant, and a neuroblastoma vaccine. Ten (33.3%) of patients experienced treatment-related complications and four (13.3%) died as a result of their disease progression. All four patients were high-risk patients, two of which had MYCN amplification. CONCLUSION: Cervical neuroblastomas generally have favorable outcomes. These tumors can be treated effectively with chemotherapy and surgical intervention with various adjuvant therapies. MYCN amplification and higher stage disease presentation contribute to worse outcomes.

Recent advances in head and neck surgical oncology.

In recent years, the field of head and neck oncology has witnessed a remarkable transformation with unprecedented advances that have revolutionized the management of complex tumors in this region. As an intricate subspecialty within oncology, head and neck surgical procedures demand detailed knowledge of the complex anatomy meticulous precision in surgical technique, and expertise to preserve vital functions while ensuring optimal oncological outcomes. With the relentless pursuit of improved patient outcomes, the integration of innovative technologies has significantly enhanced the surgical armamentarium. Robotics, endoscopic platforms, and image-guided navigation have revolutionized the surgical approach, enabling precise tumor resection and sparing healthy tissues. Furthermore, the application of advanced imaging modalities and molecular biomarker profiling has opened new avenues for personalized treatment strategies. From targeted therapies and immunotherapies to adaptive radiation techniques, clinicians are now equipped with an array of tailored options, ushering in a new era of personalized care for patients with head and neck malignancies. This article delves into the unfolding narratives of clinical triumphs, exploring the transformative potential of emerging therapies and the collaborative efforts propelling head and neck surgical oncology toward a future of hope and healing.

The medial transorbital approach in cranioendoscopic skull base tumor resections for locally advanced tumors.

BACKGROUND: Orbital structure preservation and avoidance of facial incisions without compromising oncological outcome are key to maintaining function and quality of life in locally advanced sinonasal tumor surgery. A transorbital approach at our institution has proven invaluable during cranioendoscopic skull base tumor resections and there are few descriptions of this in the literature. METHODS: An IRB-approved retrospective chart review was conducted at a tertiary cancer center for patients between 2020 and 2022 undergoing cranioendoscopic tumor resections utilizing a transorbital approach. Data collected included histopathology, sinus origin, disease extent, stage, operative details, length of stay, neo-adjuvant treatment and adjuvant treatment. Recurrence, survival, and complication rates were assessed. RESULTS: Four patients were identified for inclusion, including a SMARCB1-deficient carcinoma, esthesioneuroblastoma, squamous cell carcinoma and meningioma. All patients had resection of gross and microscopic disease with preservation of orbital contents. Post-operatively, one patient had mild diplopia on inferior gaze, all other patients had normal vision. Median follow-up was 9.5 months. One patient had recurrence of disease intracranially. CONCLUSIONS: The cranioendoscopic approach with a medial transorbital incision has multiple benefits. It avoids the need for a Weber-Ferguson incision with associated facial scar, allows for early intra-operative assessment for orbital invasion using tactile feedback and safe dissection of disease while protecting the globe and rectus muscles. This leads to preservation of eye function while ensuring an oncological resection. Other advantages include ligation of the anterior ethmoid artery and access for reconstruction of the medial orbital wall.

Radiation oncology for the rhinologist.

PURPOSE OF REVIEW: This comprehensive review explores evolving treatment strategies for sinonasal and nasopharyngeal malignancies. It analyzes the role of adjuvant radiotherapy, the potential of intensity-modulated proton therapy (IMPT), and the relevance of de-escalation strategies nasopharyngeal carcinoma (NPC). Additionally, it discusses hyperfractionation in re-irradiation in NPC. RECENT FINDINGS: Adjuvant radiotherapy remains pivotal for sinonasal tumors, improving locoregional control and survival, notably in squamous cell carcinomas, adenocarcinomas, and adenoid cystic carcinomas. IMPT promises enhanced outcomes by sparing healthy tissues, potentially improving patients' quality of life. For select stage II/T3N0 NPC, radiotherapy alone offers comparable outcomes to concurrent chemoradiotherapy, with fewer adverse events and improved quality of life. Selective neck irradiation in NPC patients with uninvolved necks maintains oncologic outcomes while reducing late toxicity. Hyperfractionation in re-irradiation shows promise in lowering late toxicities and improving overall survival, particularly in undifferentiated sinonasal carcinomas. SUMMARY: This review underscores the significance of adjuvant radiotherapy and the potential of advanced radiation techniques in optimizing sinonasal and nasopharyngeal malignancy outcomes. It emphasizes evolving de-escalation methods and individualized, evidence-based approaches. Future research will further refine strategies for these challenging malignancies.

Risk of Carcinoma in Pleomorphic Adenomas of the Parotid.

Importance: Surgery is the mainstay of treatment for pleomorphic adenomas (PAs) of the parotid to prevent further growth and potential future malignant transformation. While historical case series have reported transformation rates as high as 10%, there is a lack of contemporary methodologically sound data. Objective: To examine the rate of carcinoma ex pleomorphic adenoma (CXPA) detection in untreated PAs and investigate factors associated with malignant neoplasm. Design, Setting, and Participants: This cohort study reviewed all cases of primary PAs managed at a quaternary referral center between December 1990 and January 2015. Patients whose clinical presentation was compatible with a primary benign PA and whose history indicated tumor duration of over 1 year were included. Data were analyzed from January to April 2023. Exposure: Untreated PA. Main Outcomes and Measures: Rate of CXPA detection among untreated PAs and association of tumor duration with rates of CXPA detection. Pathology slides of patients who underwent surgery were reviewed by a single expert pathologist for the presence of CXPA. Univariable logistic regression was performed to evaluate possible factors associated with CXPA. Results: A total of 260 patients (median age, 47 years [IQR, 38-60 years]; 174 [66.9%] female) had a median tumor duration of 3.2 years (range, 1-30 years; mean [SD], 5.7 [5.5] years). Patients were divided into 4 groups by tumor duration: 1 to 4 years (158 [60.7%]), 5 to 9 years (47 [18.1%]), 10 to 14 years (27 [10.4%]), and 15 to 30 years (28 [10.8%]). In 156 of 170 patients who underwent preoperative fine-needle aspiration (91.8%), a benign tumor was diagnosed; 5 of these patients (3.2%; 95% CI, 1.4%-7.3%) were later diagnosed with CXPA on pathology after eventual excision, and the rate of high grade CXPA was 1.3%. None of the patients had permanent facial nerve paralysis. Tumor size at presentation (odds ratio [OR], 1.66; 95% CI, 1.22-2.24) and incremental (per year) increase in age (OR, 1.04; 95% CI, 1.01-1.08) were found to be associated with CXPA, whereas tumor duration was not (OR, 1.00; 95% CI, 1.00-1.01). Conclusions and Relevance: In this study, the rate of malignant neoplasm detection among initially untreated PA was 3.2%. The results suggest that tumor size and older age are associated with the development of CXPA, while tumor duration is not. Observation of PA for longer periods was not associated with serious permanent complications.

Complications of Thyroid Cancer Surgery in Pediatric Patients at a Tertiary Cancer Center.

BACKGROUND: The incidence of complications and risk factors for hypocalcemia after pediatric thyroid cancer surgery has not been clearly defined in the literature because most reports fail to distinguish between benign and malignant disease. The trend away from total thyroidectomy (TT) to thyroid lobectomy in low-risk disease means there is a need to clearly define the complication profile of malignant disease. METHODS: After institutional review board (IRB) approval, a retrospective chart review was undertaken at Memorial Sloan Kettering Cancer Center for pediatric patients undergoing surgery for well-differentiated thyroid cancer from 1986 to 2021. Clinicopathologic characteristics and complications were evaluated. Multivariable analysis was performed to identify factors independently associated with postoperative hypocalcemia. RESULTS: The study identified 307 pediatric patients with well-differentiated thyroid carcinoma (median follow-up period, 61 months). Of these patients, 69% underwent TT and 31% received a partial thyroidectomy. Among them, 40% had N0 disease, 28% had N1a disease, and 33% had N1b disease. Postoperatively, no patients experienced a neck hematoma, 1.6% had temporary unilateral vocal cord palsy (VCP), and 0.7% had permanent VCP due to recurrent laryngeal nerve (RLN) invasion. Temporary and permanent hypocalcemia occurred in respectively 32.6 % and 5.2 % of the patients. Multivariable analysis identified central neck dissection (CND) (odds ratio [OR] 3.30; p < 0.001) and N1 disease (OR 2.51; p = 0.036) as independent risk factors for temporary hypocalcemia and N stage (OR 3.64; p = 0.018) as a risk factor for permanent hypocalcemia. CONCLUSION: Pediatric thyroid cancer surgery results in low complication rates despite nodal metastases. Vocal cord paralysis is rare unless disease is found to be invading the RLN intraoperatively. Both N stage and CND are independent risk factors for hypocalcemia, helping to identify high-risk patients.

Surgical approaches for infratemporal fossa tumor resection: Fifteen years' experience of a single center.

BACKGROUND: The aims of this study were to report our center's experience with infratemporal fossa (ITF) tumors, to review the treatment modalities and outcomes. METHODS: Data of patients that underwent resection of ITF tumors in a single tertiary referral medical center were collected and analyzed. RESULTS: Sixty-three patients were included. Sarcoma was the most common pathology (18; 29%). The most common surgical approach was the preauricular-orbitozygomatic approach (24; 38%), followed by endoscopic, craniofacial resection, and combined approaches. Forty-seven patients (75%) required reconstruction, 23 (49%) involving free tissue transfer. Thirty-five patients (76%) with malignant lesions required adjuvant therapy consisting of radiotherapy, chemotherapy, or both. Thirty-three patients suffered from complications related to surgery or adjuvant therapy. The three- and five-years survival rates for malignancy were 82% and 66%, respectively. CONCLUSION: Complete surgical resection of ITF involving tumors is feasible, providing good long-term survival. Multidisciplinary approach is the key for success.