Neoadjuvant BRAF-targeted therapy for ameloblastoma of the mandible: an organ preservation approach.

BACKGROUND: Ameloblastoma is a rare odontogenic neoplasm frequently located in the mandible. Standard treatment involves radical bone resection and immediate reconstruction, causing functional, aesthetic, and psychological impairments. The BRAF V600E mutation is present in approximately 80% of mandible ameloblastomas, and BRAF inhibitors have demonstrated sustained responses in unresectable cases. METHODS: We identified ameloblastoma patients planned for ablative surgery and screened them for BRAF V600E mutation. Neoadjuvant BRAF inhibitors were offered to facilitate jaw preservation surgery. Retrospective data collection encompassed treatment regimens, tolerability, tumor response, and conversion to mandible preservation surgery. RESULTS: Between 2017 and 2022, a total of 11 patients received dabrafenib (n = 6) or dabrafenib with trametinib (n = 5). The median age was 19 (range = 10-83) years. Median treatment duration was 10 (range = 3-20) months. All (100%) patients achieved a radiological response. Ten (91%) patients successfully converted to mandible preservation surgery with residual tumor enucleation. One patient attained complete radiological response, and surgery was not performed. Among the 10 surgically treated patients, all exhibited a pathological response, with 4 achieving near complete response and 6 partial response. At a median follow-up of 14 (range = 7-37) months after surgery, 1 case of recurrence was observed. Grade 1-2 adverse effects were reported in 8 (73%) patients, with a single case of grade 3 (hepatitis). Dose modification was necessary for 3 patients, and 4 experienced treatment interruptions, while 1 patient permanently discontinued therapy. CONCLUSIONS: Neoadjuvant BRAF inhibition may offer a safe and effective strategy for organ preservation in mandible ameloblastoma treatment.

Evaluation of commotio retinae in orbital fractures / Avaliação com commotio retinae (Edema de Berlim) em fraturas orbitárias

ABSTRACT Purpose: This study aimed to evaluate the mechanisms of injury and types of orbital fractures and their relation to concurrent commotio retinae. Methods: This retrospective study evaluated the records of patients with orbital fractures whose diagnoses had been confirmed by computer tomography between July 2017 and September 2019. Patient demographics, the circumstances of injury, ophthalmic examination results, and radiological findings were tabulated. Statistical analysis of the data used two-tailed student's t-tests, chi-squared tests, and odds ratio calculations. Statistical significance was set at p<0.05. Results: Of the 204 patients with orbital fractures included in this study, 154 (75.5%) were male. The mean age was 42.1 years. Orbital fractures involving one orbital wall (58.8%) were more common than those affecting multiple walls (41.2%). The majority of fractures affected the inferior wall (60.3%), with the medial walls being the next most frequently affected (19.6%). The most common cause of injury was assault (59.3%), and the second most common was falls (24%). Commotio retinae was observed in 20.1% of orbital fracture cases and was most associated with injuries caused by assault (OR=5.22, p<0.001) and least associated with those caused by falls (OR=0.06, p<0.001). Eye movement restrictions were more common in central than peripheral commotio (OR=3.79, p=0.015) and with medial wall fractures than fractures to other orbital walls (OR=7.16, p<0.001). The odds of commotio were not found to be higher in patients with multi-walled orbital fractures than in those with single-walled fractures (p=0.967). Conclusions: In the study population, assault was the most common cause of orbital fractures and resulted in commotio retinae than other causes. Ophthalmologists should be aware of the likelihood of commotio retinae in patients with orbital fractures resulting from assault, regardless of the extent of the patient's injuries.

RESUMO Objetivo: Este estudo visou avaliar os mecanismos da lesão e os tipos de fraturas orbitárias e sua relação com commotio retinae simultânea. Métodos: Este estudo retrospectivo avaliou registros de pacientes com fraturas orbitárias cujos diagnósticos foram confirmados por tomografia computadorizada entre julho de 2017 e setembro de 2019. Foram registrados os dados demográficos, circunstâncias da lesão, os resultados do exame oftalmológico e achados radiológicos. A análise estatística dos dados usou os testes de t-Student bicaudal, qui-quadrado e cálculos de odds ratio. O significado estatístico foi fixada em p<0,05. Resultados: Dos 204 pacientes com fraturas orbitárias incluídos neste estudo, 154 (75,5%) eram sexo masculino (75,5%). A média de idade foi de 42,1 anos. As fraturas orbitárias envolvendo uma parede orbital (58,8%) foram mais comuns do que as que acometeram várias paredes (41,2%). A maioria das fraturas acometeu a parede inferior (60,3%), sendo as paredes mediais as próximas mais frequentemente afetadas (19,6%). A causda mais comum de lesão foi agressão (59,3%), e a segunda mais comum foi queda (24%). A commotio retinae foi observada em 20,1% dos casos de fratura orbital e foi mais associada a lesões causadas por agressão (OR=5,22, p<0,001) e menos associada com aquelas causadas por quedas (OR=0,06, p<0,001). As restrições de movimentos oculares eram mais comuns na comoção central do que na periférica (OR=3,79, p=0,015) e com fraturas da parede medial do que com fraturas de outras paredes orbitais (OR=7,16, p<0,001). As chances de comoção não foram maiores em pacientes com fraturas orbitais de paredes múltiplas do que naqueles com fraturas de parede simples (p=0,967). Conclusões: Na população do estudo, a agressão foi a causa mais comum de fraturas orbitais e resultou em commotio retinae mais grave do que qualquer outra causa. Os oftalmologistas devem estar cientes da probabilidade de commotio retinae em pacientes com fraturas orbitais resultantes de agressão, independentemente da extensão das lesões do paciente.

PET-CT underestimates the true pathological extent of disease at lymphadenectomy for melanoma patients after systemic therapy.

INTRODUCTION: Modern systemic therapy has revolutionized the treatment of melanoma. Currently, patients with clinically involved lymph nodes require lymphadenectomy with associated morbidities. Positron Emission Tomography - Computed Tomography (PET-CT) has demonstrated accuracy in melanoma detection and response to therapy. We aimed to identify whether a PET-CT directed lymphatic resection after systemic therapy is oncologically sound. MATERIALS AND METHODS: Retrospective review of patients who underwent lymphadenectomy after systemic therapy for melanoma with a preoperative PET-CT. Examined demographic, clinical, and perioperative parameters including extent of disease, systemic therapy and response, and PET-CT findings compared to pathological outcomes. We compared patients with "as or less than expected" outcomes on pathology against those with "more than expected" pathological outcomes. RESULTS: Thirty-nine patients met inclusion criteria. In 28 (71.8%), pathological outcomes were "as or less than expected" by PET-CT, and in 11 (28.2%) pathological outcome were "more than expected". "More than expected" occurred more frequently with advanced disease at presentation with 75% presenting with regional/metastatic disease versus only 42.9% in the "as or less than expected" group (p = 0.015). Poor response to therapy also trended towards the "more than expected" group with only 27.3% favorable response versus 53.6% favorable response in the "as or less than expected" group, not statistically significant. Extent of disease on imaging failed to predict pathological concordance. CONCLUSION: PET-CT underestimates pathological extent of disease in the lymphatic basin in 30% of patients after systemic therapy. We failed to identify predictors of more extensive disease and warn against limited PET-CT directed lymphatic resections.

Real world evidence of Lenvatinib + anti PD-1 as an advanced line for metastatic melanoma.

Introduction: Immunotherapy has revolutionized the prognosis of patients with metastatic melanoma. To date, the most active regimen is the combination of ipilimumab + nivolumab (ipi-nivo) achieving a response rate of nearly 60% and a median survival (OS) of 6 years. However, approximately 40% of patients experience primary resistance, while around 50% experience secondary resistance, highlighting the need for an effective second-line treatment option The recently published results on the use of lenvatinib + pembrolizumab in the advanced line setting led to the adoption of this regimen at our institution. Here we present our experience with this regimen, focusing on efficacy and safety. Methods: Electronic medical records of patients treated at a tertiary referral melanoma center, with at least one cycle of anti PD-1 + lenvatinib from 2020 to 2023 were analyzed for baseline demographic characteristics, disease related characteristics and treatment outcomes. Results: Forty-two patients were identified. The Response rate (RR) was 28% and the disease control rate was 38%. Responses were seen across different melanoma subtypes, including 67% in acral melanoma, 20% in uveal melanoma, and 25% in mucosal melanoma. Patients with a more aggressive disease manifested by elevated lactate dehydrogenase (LDH) achieved a RR of 26%, while patients with active central nervous system (CNS) metastases had a RR of 31%, and an intra-cranial RR of 23%. Responses were seen across lines of treatment, with a 25% RR in the second and third lines, and a 36% RR in the fourth and fifth lines. The median progression free survival was 3 months, and the median survival was 11 months. The treatment was not easily tolerated with 31% of the patients experiencing grade 3-4 toxicity, which was manageable through dose interruptions and reductions. Only 7% of patients discontinued the treatment due to toxicity. Conclusion: Lenvatinib in combination with anti-PD1 had demonstrated both relative safety and efficacy in patients with metastatic melanoma of all subtypes in the advanced line setting. We are eagerly anticipating the mature results of the LEAP-004 study hoping that this regimen will receive regulatory approval, paving the way for its widespread adoption in daily practice worldwide.

Umbilical Cord Graft for Refractory Neurotrophic Keratopathy.

PURPOSE: The purpose of this study was to evaluate whether an umbilical cord tissue graft (UCG) could promote reepithelialization in refractory cases of neurotrophic keratopathy, which failed traditional treatment modalities including amniotic membrane grafts. METHODS: This retrospective case series included 3 eyes of 3 patients who underwent UCG placement for refractory stage 3 neurotrophic keratopathy. Records were reviewed to evaluate the clinical course including previous treatments, time to UCG dissolution, time to corneal epithelialization, and recurrence of epithelial defects. RESULTS: The time of a nonhealing epithelial defect before UCG placement ranged from 7.7 to 30 weeks (mean 21.0). UCG dissolution time ranged from 1.7 to 8.1 weeks (mean 5.0) compared with the previous failed amniotic membrane dissolution time of 0.3 to 1.6 weeks (mean 0.95). The time to complete epithelialization after UCG placement was 7.7 and 8.1 weeks, respectively, for the first 2 cases, whereas the third case did not fully epithelialize. Only 1 eye did not have recurrence of an epithelial defect. The maximum time of maintained epithelialization without recurrence ranged from 5 to 86 weeks (mean 42.7). Follow-up time was 37 to 108.1 weeks (mean 62.2) after first UCG placement. CONCLUSIONS: UCG may allow for longer retention time of tissue grafts, provide a mechanical barrier for protection, and aid in regeneration of the ocular surface. UCG may be an option for re-epithelialization in recalcitrant cases of neurotrophic keratopathy, after conventional treatments such as amniotic membrane grafts have failed.

Evaluation of commotio retinae in orbital fractures.

PURPOSE: This study aimed to evaluate the mechanisms of injury and types of orbital fractures and their relation to concurrent commotio retinae. METHODS: This retrospective study evaluated the records of patients with orbital fractures whose diagnoses had been confirmed by computer tomography between July 2017 and September 2019. Patient demographics, the circumstances of injury, ophthalmic examination results, and radiological findings were tabulated. Statistical analysis of the data used two-tailed student's t-tests, chi-squared tests, and odds ratio calculations. Statistical significance was set at p<0.05. RESULTS: Of the 204 patients with orbital fractures included in this study, 154 (75.5%) were male. The mean age was 42.1 years. Orbital fractures involving one orbital wall (58.8%) were more common than those affecting multiple walls (41.2%). The majority of fractures affected the inferior wall (60.3%), with the medial walls being the next most frequently affected (19.6%). The most common cause of injury was assault (59.3%), and the second most common was falls (24%). Commotio retinae was observed in 20.1% of orbital fracture cases and was most associated with injuries caused by assault (OR=5.22, p<0.001) and least associated with those caused by falls (OR=0.06, p<0.001). Eye movement restrictions were more common in central than peripheral commotio (OR=3.79, p=0.015) and with medial wall fractures than fractures to other orbital walls (OR=7.16, p<0.001). The odds of commotio were not found to be higher in patients with multi-walled orbital fractures than in those with single-walled fractures (p=0.967). CONCLUSIONS: In the study population, assault was the most common cause of orbital fractures and resulted in commotio retinae than other causes. Ophthalmologists should be aware of the likelihood of commotio retinae in patients with orbital fractures resulting from assault, regardless of the extent of the patient's injuries.

Efficacy and toxicity of Ipilimumab-Nivolumab combination therapy in elderly metastatic melanoma patients.

Introduction: Immunotherapy has revolutionized metastatic Melanoma therapy. The most active regimen is combination therapy of Ipilimumab-Nivolumab (Ipi-Nivo) with response rates (RR) of ~60% and median overall survival (OS) of ~6 years. Immune-related adverse events (irAE) are common (~60% develop grade 3-4) and pose a challenge when treating frail patients. We sought to examine whether Ipi-Nivo therapy is feasible in elderly metastatic melanoma patients. Methods: Electronic records of patients treated at the Ella Lemelbaum Institute with Ipi-Nivo between the years 2017-2021 were screened for age. Elderly patients were defined as age 75 and older (group A) and were matched with records of patients age <75 (group B). Records were analyzed for baseline parameters, immunotherapy regimen, RR, toxicity and progression-free survival (PFS). Results: Twenty-six relevant patients age >75 (median 77) were identified and were matched to 34 younger patients (median age 57). No statistically significant differences were noted in terms of baseline parameters except for BRAF mutation status (group A 15%, group B 47%, p=0.008). Response rate in group A was 38% and is consistent with previously published data. Median PFS was the same for both groups (A = 5.5 months, B= 7.5 months, p=NS). Treatment was similarly tolerated: 35% of group A patients completed 4 cycles of therapy compared to 28% for group B (p=NS). Grade 2-4 irAE were the same (A=58%, B=66%, p=NS) and there was no difference in the need for hospitalization for G3-4 events between the groups. (A=63%, B=69%, p=NS). Further division into 4 age groups (>80 vs 75-79 in group A and 65-74 vs <65 in group B) found no difference in terms of response rate or G3-4 toxicity. Conclusion: Ipilimumab-Nivolumab combination therapy in elderly metastatic Melanoma patients seems to be well tolerated and efficient in selected elderly patients based on performance status and comorbidities, just as in younger patients. This regimen seems to be a feasible treatment option for this age group.

Cisplatinum nephrotoxicity in oncology therapeutics: retrospective review of patients treated between 2005 and 2012.

BACKGROUND: Cisplatinum (CP) is associated with acute kidney injury. The aim of this study was to define the spectrum of CP-induced nephrotoxicity in current practice. CASE-DIAGNOSIS/TREATMENT: A single-center, retrospective chart review was performed on children who received CP for treatment of a malignancy at the Hassenfeld Children's Center for Blood and Cancer Disorders of NYU Langone Medical Center between 2005 and 2012. Patients were considered to have nephrotoxicity if they had: (1) a decrease in estimated glomerular filtration rate (eGFR) of ≥30 % or (2) a decline in serum magnesium of ≥0.2 meq/L or (3) a decline in serum potassium of ≥0.2 meq/L. Thirty-two patients (mean age 8.0 ± 7.0 years) were included in this review, of whom 21 had a brain tumor (BT) and 11 had an osteosarcoma (OS); 31 (97 %) of the patients had a disturbance in renal function. The mean reduction in eGFR, serum magnesium and potassium was 37 ± 17, 30 ± 16 and 25 ± 14 %, respectively. The decline in eGFR, hypomagnesemia and hypokalemia was persistent in 38, 60 and 40 % of cases, respectively, through the short-term follow-up period. No patients required dialysis. CONCLUSIONS: Nearly all patients receiving CP in current care experience modest glomerular and tubular injury. The abnormalities persist in 40-60 % of cases during the short-term recovery period after CP treatment.

Triggered release of aqueous content from liposome-derived sol-gel nanocapsules.

Liposomes prepared from a mixture of L-alpha-dipalmitoylphosphatidylcholine and the PEGilated phospholipid N-(carbonylmethoxypoly(ethylene glycol 2000))-1,2-distearoyl-sn-glycero-3-phosphoethanolamine were used as templates for the production of silica and alkylated silica approximately 100 nm capsules, "liposils", entrapping aqueous solutions of anionic dyes. Triggered release of this content was successfully affected by either low-frequency ultrasound or by microwave treatments. Cryo-TEM was used to follow the formation process of these particles, which are aggregated in a chain-like manner. A mechanism explaining this phenomenon is suggested.