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1.
Head Neck ; 2020 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-32383550

RESUMO

BACKGROUND: The COVID-19 pandemic has significantly impacted medical training. Here we assess its effect on head and neck surgical education. METHODS: Surveys were sent to current accredited program directors and trainees to assess the impact of COVID-19 on the fellow's experience and employment search. Current fellows' operative logs were compared with those of the 2018 to 2019 graduates. RESULTS: Despite reduction in operative volume, 82% of current American Head and Neck Society fellows have reached the number of major surgical operations to support certification. When surveyed, 86% of program directors deemed their fellow ready to enter practice. The majority of fellows felt prepared to practice ablative (96%), and microvascular surgery (73%), and 57% have secured employment to follow graduation. Five (10%) had a pending job position put on hold due to the pandemic. CONCLUSIONS: Despite the impact of the COVID-19 pandemic, current accredited trainees remain well-positioned to obtain proficiency and enter the work-force.

2.
J Aging Soc Policy ; : 1-7, 2020 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-32418475

RESUMO

COVID-19 has taken a terrible toll on the nursing home population. Yet, there are five times the number of seniors living in the community who are also extremely vulnerable because they suffer from respiratory illnesses. Using the 2018 wave of the Health and Retirement Study we analyze this group of roughly 7 million seniors living in the community and find that they have multiple risk factors that make them particularly exposed. We also show how current strategies for protecting this population may be exacerbating risks and suggest concrete steps for better protecting this group.

3.
J Surg Oncol ; 121(7): 1167-1168, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32153021
4.
Oral Oncol ; 104: 104641, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32182548

RESUMO

OBJECTIVES: Patients with prior irradiated head and neck cancer (HNC) who are ineligible for definitive retreatment have limited local palliative options. We report the largest series of the use of the Quad Shot (QS) regimen as a last-line local palliative therapy. MATERIALS AND METHODS: We identified 166 patients with prior HN radiation therapy (RT) treated with QS regimen (3.7 Gy twice daily over 2 consecutive days at 4 weeks intervals per cycle, up to 4 cycles). Palliative response defined by symptom(s) relief or radiographic tumor reduction, locoregional progression free survival (LPFS), overall survival (OS) and radiation-related toxicity were assessed. RESULTS: Median age was 66 years. Median follow-up for all patients was 6.0 months and 9.7 months for living patients. Overall palliative response rate was 66% and symptoms improved in 60% of all patients. Predictors of palliative response were > 2 year interval from prior RT and 3-4 QS cycles. Median LPFS was 5.1 months with 1-year LPFS 17.7%, and median OS was 6.4 months with 1-year OS 25.3%. On multivariate analysis, proton RT, KPS > 70, presence of palliative response and 3-4 QS cycles were associated with improved LPFS and improved OS. The overall Grade 3 toxicity rate was 10.8% (n = 18). No Grade 4-5 toxicities were observed. CONCLUSION: Palliative QS is an effective last-line local therapy with minimal toxicity in patients with previously irradiated HNC. The administration of 3-4 QS cycles predicts palliative response, improved PFS, and improved OS. KPS > 70 and proton therapy are associated with survival improvements.

5.
Cancer ; 126(10): 2153-2162, 2020 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-32097509

RESUMO

BACKGROUND: Distant metastases (DMs) are the primary cause of treatment failure in patients with salivary gland carcinoma. There is no consensus on the standard treatment. METHODS: Patients with DMs were identified from an institutional database of 884 patients with salivary gland cancer who underwent resection of the primary tumor between 1985 and 2015. Survival outcomes for patients with DMs were determined with the Kaplan-Meier method. Univariate and multivariate analyses were performed to identify factors associated with DM. RESULTS: Of the 884 patients identified, 137 (15%) developed DMs during follow-up. Most of the primary tumors (n = 77 [56%]) were located in a major salivary gland. At clinical presentation, 53% of the tumors were classified as T3 or T4, and 32% had clinical node metastases. The median time to DM was 20.3 months. The factors associated with shorter distant recurrence-free survival were male sex, high-risk tumor histology, and advanced pathological T and N classifications. Patients with bone metastases had a lower survival rate than patients with lung metastases. The total number of DMs in a patient was inversely associated with survival. Patients who underwent surgical resection of DMs had a significantly higher 5-year rate of metastatic disease-specific survival than patients who underwent observation or nonsurgical treatment (44%, 29%, and 19%, respectively; P = .003). CONCLUSIONS: In patients with DMs of salivary gland carcinoma, survival is negatively associated with high-grade histology, bone DMs, and the total number of DMs. Metastasectomy can help to lengthen disease-free survival.

6.
Cancer ; 126(9): 1905-1916, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-32097507

RESUMO

BACKGROUND: Proton therapy (PT) improves outcomes in patients with nasal cavity (NC) and paranasal sinus (PNS) cancers. Herein, the authors have reported to their knowledge the largest series to date using intensity-modulated proton therapy (IMPT) in the treatment of these patients. METHODS: Between 2013 and 2018, a total of 86 consecutive patients (68 of whom were radiation-naive and 18 of whom were reirradiated) received PT to median doses of 70 grays and 67 grays relative biological effectiveness, respectively. Approximately 53% received IMPT. RESULTS: The median follow-up was 23.4 months (range, 1.7-69.3 months) for all patients and 28.1 months (range, 2.3-69.3 months) for surviving patients. The 2-year local control (LC), distant control, disease-free survival, and overall survival rates were 83%, 84%, 74%, and 81%, respectively, for radiation-naive patients and 77%, 80%, 54%, and 66%, respectively for reirradiated patients. Among radiation-naive patients, when compared with 3-dimensional conformal proton technique, IMPT significantly improved LC (91% vs 72%; P < .01) and independently predicted LC (hazard ratio, 0.14; P = .01). Sixteen radiation-naive patients (24%) experienced acute grade 3 toxicities; 4 (6%) experienced late grade 3 toxicities (osteoradionecrosis, vision loss, soft-tissue necrosis, and soft tissue fibrosis) (grading was performed according to the National Cancer Institute Common Terminology Criteria for Adverse Events [version 5.0]). Slightly inferior LC was noted for patients undergoing reirradiation with higher complications: 11% experienced late grade 3 toxicities (facial pain and brain necrosis). Patients treated with reirradiation had more grade 1 to 2 radionecrosis than radiation-naive patients (brain: 33% vs 7% and osteoradionecrosis: 17% vs 3%). CONCLUSIONS: PT achieved remarkable LC for patients with nasal cavity and paranasal sinus cancers with lower grade 3 toxicities relative to historical reports. IMPT has the potential to improve the therapeutic ratio in these malignancies and is worthy of further investigation.

8.
Oncologist ; 2019 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-31784491

RESUMO

BACKGROUND: Patients with pituitary metastasis (PM) have a relatively poor prognosis. We describe the presentation, management, and outcomes of patients with PM. SUBJECTS, MATERIALS, AND METHODS: We performed a retrospective review of patients diagnosed with PM at a single institution from 1996 to 2015. Eighty-five patients diagnosed with metastasis to the pituitary or sella turcica by pathology or based on a combination of neuroimaging and clinical findings were included. Univariate and multivariable Cox regressions evaluated associations between clinical factors and overall survival. RESULTS: The most frequent sites of primary malignancies resulting in PM were lung (26%) and breast (26%). Median age at diagnosis was 60 years (range, 18-95). The most common complaints at diagnosis included visual deficits (62%), headache (47%), and cranial nerve palsy (31%). Seventy percent of patients had pituitary insufficiency-adrenal insufficiency (59%), hypothyroidism (59%), or diabetes insipidus (28%). Management of PM included radiation therapy (76%), chemotherapy (68%), surgical resection (21%), or combination therapy (71%). Fifty percent and 52% of patients who received surgical treatment and irradiation, respectively, reported symptomatic improvement. Median overall survival (OS) was 16.5 months (95% confidence interval: 10.7-25.4). On multivariable analysis, a primary cancer site other than lung or breast (p = .020), age <60 years (p = .030), and surgical resection (p = .016) were associated with longer OS. CONCLUSION: Patients <60 years of age, those with primary tumor sites other than lung or breast, and those who undergo surgical resection of the pituitary lesion may have prolonged survival. Surgical resection and radiation treatment resulted in symptomatic improvement in ~50% of patients. IMPLICATIONS FOR PRACTICE: This study is the largest original series of patients with metastatic disease to the sella. In patients with pituitary metastasis, younger age, primary site other than lung or breast, and metastatic resection may prolong survival. Resection and radiation led to symptomatic improvement in ∼50% of patients. Seventy percent of patients had hypopituitarism. These hormonal deficiencies can be life threatening and can result in substantial morbidity if left untreated. Patients should be treated using a multimodality approach-including a potential role for surgery, radiation, chemotherapy, and hormone replacement-with the goal of improving survival and quality of life.

9.
J Surg Oncol ; 120(8): 1456-1461, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31680250

RESUMO

BACKGROUND AND OBJECTIVES: Remifentanil infusion is used as an intraoperative anesthetic for thyroidectomy, but has been associated with acute opioid tolerance and hyperalgesia. A national shortage of remifentanil provided an opportunity to study postoperative pain in patients undergoing thyroidectomy. METHODS: Retrospective review of prospectively collected data from an outpatient surgery center. Primary analysis compared patients treated before and after remifentanil shortage. RESULTS: Median postoperative opioid consumption was 20 morphine milligram equivalents (MMEs) among those treated in the high-dose period and 15 MMEs in the low-dose period. Remifentanil/weight received was a significant predictor of requiring a postoperative narcotic (P = .006). Total non-remifentanil narcotics administered were equivalent but patients in the low dose period received higher amounts of intraoperative long-acting narcotics. CONCLUSIONS: Remifentanil infusion for thyroid surgery is associated with higher postoperative pain and postoperative narcotics requirement. While a hyperalgesia state is possible, shifting of longer-acting narcotics from intraoperative to postoperatively is also supported.


Assuntos
Analgésicos Opioides/administração & dosagem , Uso de Medicamentos/estatística & dados numéricos , Dor Pós-Operatória/tratamento farmacológico , Remifentanil/administração & dosagem , Tireoidectomia , Adulto , Procedimentos Cirúrgicos Ambulatórios , Feminino , Humanos , Infusões Intravenosas , Cuidados Intraoperatórios , Masculino , Pessoa de Meia-Idade , Medição da Dor , Alta do Paciente , Período Pós-Operatório , Estudos Retrospectivos
10.
J Endocr Soc ; 3(9): 1693-1706, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31528829

RESUMO

Context: Pituitary adenomas (PA) are often irregularly shaped, particularly posttreatment. There are no standardized radiographic criteria for assessing treatment response, substantially complicating interpretation of prospective outcome data. Existing imaging frameworks for intracranial tumors assume perfectly spherical targets and may be suboptimal. Objective: To compare a three-dimensional (3D) volumetric approach against accepted surrogate measurements to assess PA posttreatment response (PTR). Design: Retrospective review of patients with available pre- and postradiotherapy (RT) imaging. A neuroradiologist determined tumor sizes in one dimensional (1D) per Response Evaluation in Solid Tumors (RECIST) criteria, two dimensional (2D) per Response Assessment in Neuro-Oncology (RANO) criteria, and 3D estimates assuming a perfect sphere or perfect ellipsoid. Each tumor was manually segmented for 3D volumetric measurements. The Hakon Wadell method was used to calculate sphericity. Setting: Tertiary cancer center. Patients or Other Participants: Patients (n = 34, median age = 50 years; 50% male) with PA and MRI scans before and after sellar RT. Interventions: Patients received sellar RT for intact or surgically resected lesions. Main Outcome Measures: Radiographic PTR, defined as percent tumor size change. Results: Using 3D volumetrics, mean sphericity = 0.63 pre-RT and 0.60 post-RT. With all approaches, most patients had stable disease on post-RT scan. PTR for 1D, 2D, and 3D spherical measurements were moderately well correlated with 3D volumetrics (e.g., for 1D: 0.66, P < 0.0001) and were superior to 3D ellipsoid. Intraclass correlation coefficient demonstrated moderate to good reliability for 1D, 2D, and 3D sphere (P < 0.001); 3D ellipsoid was inferior (P = 0.009). 3D volumetrics identified more potential partially responding and progressive lesions. Conclusions: Although PAs are irregularly shaped, 1D and 2D approaches are adequately correlated with volumetric assessment.

11.
J Surg Oncol ; 120(7): 1259-1265, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31549410

RESUMO

BACKGROUND AND OBJECTIVES: The reported risk of nodal metastasis in hard palate and upper gingival squamous cell carcinoma (SCC) has been inconsistent with inadequate consensus regarding the utility of neck dissection in the clinically negative (cN0) neck. MATERIALS AND METHODS: Using the National Cancer Database, cN0 patients diagnosed with SCC of the head and neck with the subsites of the hard palate and upper gingiva were identified from 2004 to 2014. RESULTS: A total of 1830 patients were identified, and END was performed on 422 patients with cN0 tumors. Pathologically positive nodes occurred in 14% (59/422) of patients in this cohort. Higher tumor stage, academic hospital type, and large hospital volume (>28 cancer-specific cases/year) were associated with a higher likelihood of END both in univariate and multivariate analyses (P < .05). Patients >80 years of age were less likely to receive END on multivariate analysis (OR 0.52, 0.32-0.84). No variables, including advanced T stage, predicted occult metastases. Cox proportional hazards regression analysis showed that patients who underwent END demonstrated improved OS over an 11-year period (hazard ratio 0.75, P = .002). On subgroup analysis, this improvement was significant in patients with both stage T1 and T4 tumors. CONCLUSIONS: Tumor stage, hospital type, and hospital volume were associated with higher rates of END for patients with cN0 hard palate SCC and after controlling for clinical factors, END was associated with improved overall survival.


Assuntos
Carcinoma de Células Escamosas/mortalidade , Procedimentos Cirúrgicos Eletivos/mortalidade , Neoplasias Gengivais/mortalidade , Neoplasias Maxilares/mortalidade , Esvaziamento Cervical/mortalidade , Palato Duro/cirurgia , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/cirurgia , Bases de Dados Factuais , Feminino , Seguimentos , Neoplasias Gengivais/patologia , Neoplasias Gengivais/cirurgia , Humanos , Masculino , Neoplasias Maxilares/patologia , Neoplasias Maxilares/cirurgia , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Palato Duro/patologia , Estudos Retrospectivos , Taxa de Sobrevida
12.
Head Neck ; 41(11): 3906-3915, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31433540

RESUMO

BACKGROUND: Despite advances in treatment, the recurrence rates for laryngeal cancer range from 16% to 40%. METHODS: Patients with recurrent laryngeal cancer treated at Memorial Sloan Kettering (MSK) from 1999 to 2016 were reviewed. Survival outcomes were analyzed. RESULTS: Of 241 patients, 88% were male; the median age was 67 years; 71% had primary glottic tumors. At initial treatment, 72% of patients were seen with early stage disease; primary treatment was radiation (68%), chemoradiation (29%), and surgery (3%). The most common salvage surgery was total laryngectomy (74%). Forty-seven percentage were upstaged at salvage surgery. The 2- and 5-year disease-specific survival (DSS) was 74% and 57%, respectively. Patients with cT4 disease treated with nonsurgical primary management had a 0% 5-year DSS. Independent predictors of DSS were tumor location, perineural invasion, margin, and stage. CONCLUSIONS: Salvage surgery results in acceptable oncologic outcomes. Stage, disease site, perineural invasion, and margins are associated with inferior DSS.

13.
Oral Oncol ; 95: 52-58, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31345394

RESUMO

OBJECTIVE: Polymorphous adenocarcinoma of salivary gland (PAC) is rare. Despite being described as a low risk histology, some patients develop regional and distant metastasis. More aggressive behavior has been attributed to a PAC subcategory called cribriform adenocarcinoma of minor salivary glands (CAMSG). We examined oncological outcomes of PAC. PATIENTS AND METHODS: Fifty-seven patients with PAC were identified from an institutional database of 884 patients surgically treated for salivary gland malignancies from 1985 to 2015. Detailed histopathological analysis was performed. Survival outcomes were calculated using the Kaplan-Meier method. Factors predictive of recurrence were identified using the Cox proportional hazard method. RESULTS: Fifty-four (95%) had tumors of minor salivary gland origin; the most frequent location was the oral cavity in 41 (76%), specifically the hard palate in 32 (55%). Forty-six patients (81%) were clinical T1-T2; 3 (5%) had a clinically positive neck. Thirty-two patients (56%) were classified as PAC and 14 (25%) as CAMSG. Forty-four patients (77%) had surgery alone; 13 (23%) had surgery and postoperative radiotherapy. The 5- and 10-year overall survival and disease-specific survival were 88% and 79% and 98% and 94%, respectively (median follow up 84 [1-159] months); 5- and 10-year recurrence-free survival were 93% and 88%, respectively. Univariate analysis showed male sex, III/IV stage, and CASMG variant had increased incidence of recurrence but were not statistically significant. CONCLUSION: PAC of the salivary glands is an indolent disease with good survival outcomes. Recurrence is uncommon and tends to occur late. Long-term follow-up is indicated in patients with this disease.

14.
J Neurol Surg B Skull Base ; 80(4): 371-379, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31316883

RESUMO

Objectives Determining surgical trends and outcomes for sinonasal tumors is challenging given their low incidence and heterogeneous pathology. This study utilized the National Cancer Database (NCDB) to identify trends and outcomes associated with surgical management of sinonasal tumors. Design Retrospective database analysis. Setting National Cancer Database. Participants Patients with sinonasal malignancies identified from the NCDB between 2010 and 2015. Main Outcome Measures The primary outcome was the choice of surgical therapy used for sinonasal tumor resection: endoscopic versus open approach. Each was cohort analyzed with respect to various demographic and clinicopathologic factors. A treatment effect model was used to identify potential differences between surgical approaches. Survival was evaluated using Kaplan-Meier analysis. Results A total of 10,193 patients with sinonasal malignancies were identified in the NCDB database; of these, 2,292 had a documented subsite, histology, and definitive surgical treatment with documented surgical approach and were included in the analysis. About 71.9% of patients had an open approach and 28.1% a purely endoscopic procedures. Tumor histology, treatment facility type, margin status, and length of stay were all variables that were associated with significant differences between the open and endoscopic cohort. Five-year survival rates for the open and endoscopic cohorts were not significantly different (59.6 and 60.8%, respectively). Conclusions Assessment of the NCDB revealed that 28% patients with sinonasal malignancy were selected for endoscopic surgery. These patients had comparable oncologic outcomes to open resection.

15.
Head Neck ; 41(10): 3551-3563, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31294897

RESUMO

BACKGROUND: Timely postoperative radiation therapy (RT) within 50 days of surgery for head and neck cancers provides a survival advantage. METHODS: Using the National Cancer Database, we performed a propensity score-matched analysis comparing patients undergoing open or endoscopic surgery for squamous cell carcinoma (SCC) of the nasal cavity and paranasal sinuses from 2010 to 2015. RESULTS: Among 168 pairs, patients undergoing endoscopic surgery had shorter time to surgery (24.2 vs 36.7 days, P < .001) and shorter postoperative time to RT (PTTR, 51.2 vs 58.4 days, P = .02). On multivariable linear regression, endoscopic surgery predicted shorter PTTR (ß = -7.6, P = .01). Using the Kaplan-Meier method, patients in the longest PTTR quartile had decreased overall survival (OS; Q1 vs Q4, 3-year OS 76.5% vs 53.3%, P = .007), a durable finding when adjusted for covariates (Q1 vs Q4, HR 0.50, P = .008). CONCLUSIONS: Patients undergoing endoscopic surgery for sinonasal SCC experience shorter PTTR. Shorter PTTR is associated with extended OS.

16.
Oral Oncol ; 94: 86-92, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31178218

RESUMO

OBJECTIVE: Previous population-based studies in salivary gland carcinomas have described a relationship between female sex and superior oncological outcome. PATIENTS AND METHODS: Our institutional database of 884 surgically treated patients with salivary gland malignancies from 1985 to 2015 was analyzed for the impact of sex on oncological outcomes. Histologies were classified in three risk groups, low, intermediate and high. Survival outcomes were determined using the Kaplan-Meier method. Hazard ratios for male sex were determined using the Cox proportional hazards model. RESULTS: Eight hundred sixty-seven patients were identified; median age was 59 years, and 51% had a minor salivary gland malignancy. Female patients were younger (58 versus 60 years; p = 0.040) and had a lower incidence of high-risk histologies (25% versus 40%, p < 0.001) and T3-T4 tumors compared to men (23% versus 31%, p < 0.001). With a median follow-up of 57 months, female patients had a superior 5-year disease-specific survival (DSS) (90% versus 79%; p < 0.001). The unadjusted hazard ratio showed male patients had a 2.15-fold increased risk of death (HR 2.15; 95% CI, 1.50-3.06, p < 0.001). After adjusting for Charlson comorbidity index, tobacco use, histological risk group, and overall pathological stage, males still had a statistically significant increased risk of death (HR 1.48; 95% CI 1.05-2.17; p = 0.047). Subgroup analysis showed DSS for females was significantly better in the high-risk histological group (5-year 68% versus 49%, p = 0.007). CONCLUSION: Our study shows that sex has an impact on cancer-specific survival and that female sex favors improved survival.

17.
Mod Pathol ; 32(10): 1447-1459, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31186531

RESUMO

Sinonasal undifferentiated carcinoma (SNUC) is an aggressive malignancy harboring IDH2 R172 mutations in >80% cases. We explored the potential of genome-wide DNA methylation profiling to elucidate tumor biology and improve the diagnosis of sinonasal undifferentiated carcinoma and its histologic mimics. Forty-two cases, including sinonasal undifferentiated, large cell neuroendocrine, small cell neuroendocrine, and SMARCB1-deficient carcinomas and olfactory neuroblastoma, were profiled by Illumina Infinium Methylation EPIC array interrogating >850,000 CpG sites. The data were analyzed using a custom bioinformatics pipeline. IDH2 mutation status was determined by the targeted exome sequencing (MSK-IMPACTTM) in most cases. H3K27 methylation level was assessed by the immunohistochemistry-based H-score. DNA methylation-based semi-supervised hierarchical clustering analysis segregated IDH2 mutants, mostly sinonasal undifferentiated (n = 10) and large cell neuroendocrine carcinomas (n = 4), from other sinonasal tumors, and formed a single cluster irrespective of the histologic type. t-distributed stochastic neighbor embedding dimensionality reduction analysis showed no overlap between IDH2 mutants, SMARCB1-deficient carcinoma and olfactory neuroblastoma. IDH2 mutants demonstrated a global methylation phenotype and an increase in repressive trimethylation of H3K27 in comparison to IDH2 wild-type tumors (p < 0.001). Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed no difference in pathway activation between IDH2-mutated sinonasal undifferentiated and large cell neuroendocrine carcinomas. In comparison to SMARCB1-deficient, IDH2-mutated carcinomas were associated with better disease-free survival (p = 0.034) and lower propensity for lung metastasis (p = 0.002). ARID1A mutations were common in small cell neuroendocrine carcinoma but not among IDH2 mutants (3/3 versus 0/18 and p < 0.001). IDH2 mutations in sinonasal carcinomas induce a hypermethylator phenotype and define a molecular subgroup of tumors arising in this location. IDH2-mutated sinonasal undifferentiated carcinoma and large cell neuroendocrine carcinoma likely represent a phenotypic spectrum of the same entity, which is distinct from small cell neuroendocrine and SMARCB1-deficient sinonasal carcinomas. DNA methylation-based analysis of the sinonasal tumors has potential to improve the diagnostic accuracy and classification of tumors arising in this location.

18.
Am J Manag Care ; 25(6): e165-e166, 2019 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-31211547

RESUMO

Medicare's star rating system for Medicare Advantage health plans is a powerful tool for driving plan behavior and, beginning in 2019, CMS is providing new weight to patient access and experience measures. As the shift begins, a recent analysis of person-centered care measures in the star rating system conducted by the Center for Consumer Engagement in Health Innovation found ample room for improving both plan performance and how the ratings measure patient-centeredness. Although from 2010 to 2017, plans performed better on person-centered measures compared with the other measures in the star rating set (3.4 vs 3.0), our analysis also shows that performance on patient-centered measures has not comparatively budged appreciably over time. This may indicate that improvement initiatives focused on non-person-centered star measures have not had a spillover effect on the person-centered measures, or that plans may feel that once a minimum threshold on person-centered measures is met, they need not focus attention on further improvements. At the same time, we need a more comprehensive assessment of person-centeredness. The CMS star measures classified as person-centered are limited in scope and do not constitute a comprehensive view of what it actually means to be person-centered. The new weighting of patient access and experience measures in the CMS star rating system will press plans to refocus their managerial attention, allocate internal assets, and improve their performance, but we also need new measures that are more closely aligned with the domains that describe person-centered care.

19.
Head Neck ; 41(8): 2741-2747, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30933393

RESUMO

BACKGROUND: Standard treatment of squamous cell carcinoma (SCC) of the anterior nasal mucosa is surgical resection with or without postoperative radiation. METHODS: Retrospective review of patients diagnosed with SCC of the nasal cavity between January 2000 and July 2018 who refused total rhinectomy and who were treated with radiation with or without chemotherapy with curative intent. RESULTS: Eleven patients were identified, 73% had stage III or stage IV disease. Four patients were treated with intensity-modulated radiotherapy and seven with intensity-modulated proton radiotherapy. Concurrent chemoradiotherapy was used in nine patients (82%). With a median follow-up of 15 months (3-124 months), two patients experienced recurrence and one developed distant metastasis and died from disease. The 2-year rhinectomy-free survival rate was 88%. Two-year overall survival and recurrence-free survival were 100% and 75%, respectively. CONCLUSION: A radiation-based approach for SCC of the nasal cavity mucosa is a valid option for selected patients who refuse up-front surgery.

20.
Nat Med ; 25(5): 767-775, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31011208

RESUMO

Anti-tumor immunity is driven by self versus non-self discrimination. Many immunotherapeutic approaches to cancer have taken advantage of tumor neoantigens derived from somatic mutations. Here, we demonstrate that gene fusions are a source of immunogenic neoantigens that can mediate responses to immunotherapy. We identified an exceptional responder with metastatic head and neck cancer who experienced a complete response to immune checkpoint inhibitor therapy, despite a low mutational load and minimal pre-treatment immune infiltration in the tumor. Using whole-genome sequencing and RNA sequencing, we identified a novel gene fusion and demonstrated that it produces a neoantigen that can specifically elicit a host cytotoxic T cell response. In a cohort of head and neck tumors with low mutation burden, minimal immune infiltration and prevalent gene fusions, we also identified gene fusion-derived neoantigens that generate cytotoxic T cell responses. Finally, analyzing additional datasets of fusion-positive cancers, including checkpoint-inhibitor-treated tumors, we found evidence of immune surveillance resulting in negative selective pressure against gene fusion-derived neoantigens. These findings highlight an important class of tumor-specific antigens and have implications for targeting gene fusion events in cancers that would otherwise be less poised for response to immunotherapy, including cancers with low mutational load and minimal immune infiltration.


Assuntos
Antígenos de Neoplasias/genética , Imunoterapia/métodos , Neoplasias/imunologia , Neoplasias/terapia , Linfócitos T Citotóxicos/imunologia , Proteínas Cromossômicas não Histona/genética , Proteínas Cromossômicas não Histona/imunologia , Fusão Gênica , Neoplasias de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/imunologia , Neoplasias de Cabeça e Pescoço/terapia , Humanos , Fatores de Transcrição NFI/genética , Fatores de Transcrição NFI/imunologia , Neoplasias/genética , Proteínas Nucleares/genética , Proteínas Nucleares/imunologia , Proteínas Oncogênicas/genética , Proteínas Oncogênicas/imunologia , Proteínas de Ligação a Poli-ADP-Ribose/genética , Proteínas de Ligação a Poli-ADP-Ribose/imunologia , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-myb/genética , Proteínas Proto-Oncogênicas c-myb/imunologia , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/imunologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/imunologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia , Sequenciamento Completo do Genoma
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