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OPINION STATEMENT: Salivary gland tumors represent a heterogeneous group of neoplasms characterized by varied histologies and disease outcomes. Initial treatment for the primary and gross nodal disease is usually surgery. Management of the clinically node-negative neck depends upon the risk of lymph nodal involvement. This is usually determined by the AJCC "T" stage and histology. Both surgery and radiation may be utilized to address the lymph nodes at risk. This is especially important for minor salivary gland tumors. Radiation plays an important role in the adjuvant management of salivary gland tumors by reducing the risk of locoregional recurrence. Certain histologies like adenoid cystic carcinoma have a predilection for neurotropic spread to the skull base. Radiation is particularly important in controlling disease at the skull base. The role of concurrent chemotherapy in the adjuvant treatment of salivary gland tumors is not established and remains an area of active research. Certain histologies like salivary duct carcinoma exhibit readily identifiable molecular targets amenable to targeted therapy. Finally, advanced testing of these tumors using next-generation sequencing can also potentially identify molecular targets amenable to therapy. While useful in the management of metastatic disease, the role of these therapies in the adjuvant setting remains unknown.
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Cuidados Pós-Operatórios , Neoplasias das Glândulas Salivares/diagnóstico , Neoplasias das Glândulas Salivares/terapia , Quimioterapia Adjuvante , Tomada de Decisão Clínica , Terapia Combinada/efeitos adversos , Terapia Combinada/métodos , Gerenciamento Clínico , Humanos , Cuidados Pós-Operatórios/métodos , Prognóstico , Radioterapia Adjuvante/efeitos adversos , Radioterapia Adjuvante/métodos , Recidiva , Retratamento , Neoplasias das Glândulas Salivares/mortalidade , Neoplasias das Glândulas Salivares/cirurgia , Resultado do TratamentoRESUMO
BACKGROUND: De-intensified treatment strategies for early human papillomavirus-positive (HPV+) oropharynx cancer (OPC) rely on selecting patients with an excellent prognosis. The criterion for enrollment in current de-intensification trials is ≤10 pack-years. More nuance to the pack-year criteria may expand enrollment, improve patient outcomes, and prevent overtreatment. It was hypothesized that patients with more than 10 pack-years may experience favorable outcomes if smoking cessation has been achieved. METHODS: From an institutional review board-approved database, patients with HPV+ oropharyngeal squamous carcinoma treated definitively with radiation with or without chemotherapy were retrospectively identified. Patients with a history of smoking who were eligible for national de-intensification trials were included (cT1-2N1-2b or T3N0-2b [American Joint Committee on Cancer, seventh edition]). Cox regression with penalized smoothing splines was used to evaluate nonlinear effects of cessation. Recursive partitioning analysis (RPA) was used to objectively search for relationships between the 2 colinear variables (pack-years and time since cessation). RESULTS: Among 330 patients meeting the inclusion criteria, 130 (40%) were never smokers, 139 (42%) were former smokers, and 61 (18%) were current smokers. With standard therapy, all former smokers achieved a progression-free survival (PFS) rate higher than 91%, regardless of pack-year exposure. Nonlinear Cox regression demonstrated that more recent cessation was associated with significantly worse PFS even among those with ≤20 pack-years. RPA demonstrated that only current smokers experienced a 2-year PFS rate lower than 91%; former smokers, regardless of pack-years, experienced a 2-year PFS rate higher than 91%. CONCLUSIONS: The 10-pack-year rule may not apply to all early HPV+ OPCs, particularly for former smokers. Future randomized de-intensification trials should consider a broader and more nuanced approach until the predictive role of smoking status is established.
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Neoplasias Orofaríngeas/virologia , Infecções por Papillomavirus/complicações , Fumar/efeitos adversos , Carcinoma de Células Escamosas de Cabeça e Pescoço/virologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Neoplasias Orofaríngeas/mortalidade , Neoplasias Orofaríngeas/terapia , Papillomaviridae/patogenicidade , Prognóstico , Abandono do Hábito de Fumar , Carcinoma de Células Escamosas de Cabeça e Pescoço/mortalidade , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia , Fatores de TempoRESUMO
BACKGROUND: Cutaneous angiosarcoma (CAS) is a rare, malignant tumor of vascular mesenchymal origin accounting for less than 1% of all sarcomas. OBJECTIVE: To examine epidemiologic trends and outcomes in CAS. METHODS: In this retrospective, population-based study, patients with CAS were identified from the Surveillance Epidemiology and End Results database. Age, sex, and race-standardized incidence rates (IRs) were calculated. Survival was assessed with Kaplan-Meier curves and Cox proportional hazards models. RESULTS: Of 811 patients with CAS, 43% had a prior primary cancer. CAS IR for patients without prior primary cancers dropped from 5.88 per 100,000 in 1973 to 1984 to 2.87 per 100,000 in 2005 to 2014. In those with prior primary cancers, IR rose from 0.03 per 100,000 in 1973 to 1984 to 2.25 per 100,000 in 2005 to 2014. On multivariate analysis, patients older than 70 years of age had a higher risk of death compared with those younger than 50 years (hazard ratio, 2.16; 95% confidence interval 1.33-3.57; P = .002), and distant disease was associated with increased risk of death compared with localized disease (hazard ratio, 1.50; 95% confidence interval, 1.11-2.03; P = .008). Receipt of surgery and/or radiation therapy was not associated with survival. LIMITATIONS: Potential selection and miscoding bias, retrospective nature. CONCLUSION: CAS rates are rising among those with other prior primary cancers. Survival is not affected by current therapeutic strategies, highlighting the need for additional treatment options.
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Hemangiossarcoma/epidemiologia , Segunda Neoplasia Primária/epidemiologia , Neoplasias Cutâneas/epidemiologia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Quimiorradioterapia Adjuvante/estatística & dados numéricos , Quimioterapia Adjuvante/métodos , Quimioterapia Adjuvante/estatística & dados numéricos , Procedimentos Cirúrgicos Dermatológicos/estatística & dados numéricos , Feminino , Hemangiossarcoma/terapia , Humanos , Incidência , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante/métodos , Terapia Neoadjuvante/estatística & dados numéricos , Segunda Neoplasia Primária/terapia , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Programa de SEER/estatística & dados numéricos , Neoplasias Cutâneas/terapia , Taxa de Sobrevida , Estados Unidos/epidemiologiaRESUMO
Importance: Intensity-modulated radiation therapy (IMRT) reirradiation of nonmetastatic recurrent or second primary head and neck squamous cell carcinoma (HNSCC) results in poor progression-free survival (PFS) and overall survival (OS). Objective: To investigate the tolerability, PFS, OS, and patient-reported outcomes with nivolumab (approved standard of care for patients with HNSCC) during and after IMRT reirradiation. Design, Setting, and Participants: In this multicenter nonrandomized phase 2 single-arm trial, the treatment outcomes of patients with recurrent or second primary HNSCC who satisfied recursive partitioning analysis class 1 and 2 definitions were evaluated. Between July 11, 2018, and August 12, 2021, 62 patients were consented and screened. Data were evaluated between June and December 2023. Intervention: Sixty- to 66-Gy IMRT in 30 to 33 daily fractions over 6 to 6.5 weeks with nivolumab, 240 mg, intravenously 2 weeks prior and every 2 weeks for 5 cycles during IMRT, then nivolumab, 480 mg, intravenously every 4 weeks for a total nivolumab duration of 52 weeks. Main Outcomes and Measures: The primary end point was PFS. Secondary end points included OS, incidence, and types of toxic effects, including long-term treatment-related toxic effects, patient-reported outcomes, and correlatives of tissue and blood biomarkers. Results: A total of 62 patients were screened, and 51 were evaluable (median [range] age was 62 [56-67] years; 42 [82%] were male; 6 [12%] had p16+ disease; 38 [75%] had salvage surgery; and 36 [71%.] had neck dissection). With a median follow-up of 24.5 months (95% CI, 19.0-25.0), the estimated 1-year PFS was 61.7% (95% CI, 49.2%-77.4%), rejecting the null hypothesis of 1-year PFS rate of less than 43.8% with 1-arm log-rank test P = .002 within a 1-year timeframe. The most common treatment-related grade 3 or higher adverse event (6 [12%]) was lymphopenia with 2 patients (4%) and 1 patient each (2%) exhibiting colitis, diarrhea, myositis, nausea, mucositis, and myasthenia gravis. Functional Assessment of Cancer Therapy-General and Functional Assessment of Cancer Therapy-Head and Neck Questionnaire quality of life scores remained stable and consistent across all time points. A hypothesis-generating trend favoring worsening PFS and OS in patients with an increase in blood PD1+, KI67+, and CD4+ T cells was observed. Conclusions and Relevance: This multicenter nonrandomized phase 2 trial of IMRT reirradiation therapy and nivolumab suggested a promising improvement in PFS over historical controls. The treatment was well tolerated and deserves further evaluation. Trial Registration: ClinicalTrials.gov Identifier: NCT03521570.
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Neoplasias de Cabeça e Pescoço , Recidiva Local de Neoplasia , Nivolumabe , Radioterapia de Intensidade Modulada , Carcinoma de Células Escamosas de Cabeça e Pescoço , Humanos , Nivolumabe/uso terapêutico , Nivolumabe/efeitos adversos , Masculino , Feminino , Carcinoma de Células Escamosas de Cabeça e Pescoço/radioterapia , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/mortalidade , Radioterapia de Intensidade Modulada/métodos , Radioterapia de Intensidade Modulada/efeitos adversos , Pessoa de Meia-Idade , Idoso , Recidiva Local de Neoplasia/radioterapia , Neoplasias de Cabeça e Pescoço/radioterapia , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/terapia , Neoplasias de Cabeça e Pescoço/mortalidade , Reirradiação/métodos , Reirradiação/efeitos adversos , Antineoplásicos Imunológicos/uso terapêutico , Antineoplásicos Imunológicos/efeitos adversos , Segunda Neoplasia Primária , Intervalo Livre de Progressão , AdultoRESUMO
Giant cell tumour (GCT) constitutes about 5 % of all skeletal tumors. They rarely occur in the skull. When involved, they preferentially involve the sphenoid or temporal bones. Skull-base GCTs generally present with multiple cranial nerves involvement, most commonly sixth followed by the third cranial nerve. We describe a case of clival GCT presenting with an isolated trigeminal nerve involvement in a 19-year-old man which was managed by surgery and adjuvant radiation. At 18 months of follow-up, the patient is clinically asymptomatic. Clival GCT should also be considered in the differential diagnosis of any isolated trigeminal nerve palsy. Adjuvant radiation has an important role to play in managing this tumour.
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Tumor de Células Gigantes do Osso/complicações , Neoplasias da Base do Crânio/complicações , Doenças do Nervo Trigêmeo/etiologia , Fossa Craniana Posterior , Humanos , Masculino , Adulto JovemRESUMO
OBJECTIVE: Organ preservation (OP) treatment for advanced laryngeal cancer has increased compared to primary total laryngectomy. Our study compares oncologic and functional outcomes between these approaches. STUDY DESIGN: Retrospective cohort study. SETTING: Single tertiary care institution. METHODS: Retrospective review of patients receiving primary total laryngectomy or OP for laryngeal cancer between 1/1/2000 and 12/31/2018. RESULTS: A total of 118 patients received primary total laryngectomy and 119 received OP. Overall survival was similar between total laryngectomy and OP. When stratified by T stage, disease-free survival was worse among T3 patients receiving OP versus total laryngectomy. In T3 patients, 28 OP patients experienced local recurrence (28.9%) compared to 3 total laryngectomy patients (7.1%; p < 0.01). In total, 20 OP patients with local recurrence received salvage surgery. These patients had similar overall survival to patients who underwent initial total laryngectomy (TL). About 14 OP patients with local recurrence did not receive salvage surgery. About 89 (75.4%) TL patients achieved normal diet as compared to 64 (53.8%) OP patients (p < 0.001). In TL patients, 106 (89.8%) received primary or secondary tracheoesophageal-prosthesis, 82 (77.4%) of whom achieved completely understandable speech. CONCLUSIONS: There was no difference in survival by treatment in T4 patients, possibly because of strict patient selection. However, disease-free survival was worse in T3 patients receiving OP, likely due to a high local recurrence rate. Approximately 40% of patients with local recurrence were not eligible for salvage laryngectomy. TL patients had comparable swallowing and speech outcomes with OP patients. LEVEL OF EVIDENCE: 3 Laryngoscope, 133:1122-1131, 2023.
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Neoplasias Laríngeas , Laringe , Humanos , Laringectomia/efeitos adversos , Neoplasias Laríngeas/patologia , Preservação de Órgãos , Estudos Retrospectivos , Laringe/patologia , Estadiamento de Neoplasias , Resultado do TratamentoRESUMO
Aim: The aim of the study was to determine the effect of different anterior reference points during facebow transfer, on sagittal inclination of occlusal plane (SIOP) and horizontal condylar guidance (HCG) values obtained on arcon and nonarcon articulators. Materials and Methods: Facebow records of 25 participants were made and transferred to Hanau Wide-Vue (WV) and Hanau H2 (H2) articulators using conventional indirect transfer (CIT), superior annular groove (SAG), and inferior annular groove (IAG) as anterior reference points. Maxillary casts were mounted on each articulator followed by mandibular mountings. Protrusive interocclusal record was used to determine HCG, and SIOP was measured as an angle between the occlusal plane of mounted maxillary cast and upper member of the articulator. Both, HCG and SIOP were measured on a digital lateral cephalogram and the values obtained were compared with previously determined values from both the articulators. Intergroup comparison was done by analysis of variance and pair-wise comparison by Tukey post hoc test. Results: Values of SIOP significantly (P = 0.00) changed on both the articulators when CIT, SAG, and IAG were the anterior reference points. The ratio of SIOP and HCG on both articulators was comparable to that of the cephalogram for CIT, IAG, but it was substantially low for SAG. Conclusions: The variation of anterior reference point changes the value of SIOP recorded on Hanau WV and H2 articulators; however, it had no effect on HCG values recorded on both the articulators. The angle between SIOP and HCG changed with variations in superior-inferior position of the mountings on both articulators.
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BACKGROUND/AIM: Definitive treatment for locally advanced head and neck squamous cell carcinoma (LAHNSCC) is often compromised in older adults due to concerns about potential treatment toxicity intolerance. We reviewed our institutional experience with definitive management of older adults with LAHNSCC. PATIENTS AND METHODS: From our Institutional Review Board-approved registry, we identified patients aged >60 years with stage III-IV, M0 LAHNSCC (seventh/earlier editions of the American Joint Committee on Cancer classification) treated with definitive radiotherapy from 1993-2019. Indications for concurrent chemotherapy included T3-4 or N2-3 disease. Multivariable analysis using Fine and Gray regression was performed to identify risk factors associated with recurrence. The cumulative incidence method was used to calculate recurrence rates. RESULTS: Overall, 350 patients were identified: 223 aged 60-69, 82 aged 70-74, and 45 aged ≥75 years. Median follow-up was 36.3 months. Two-year recurrence rates were 13.7%, 20.2% and 34.8%, respectively; human papillomavirus-positive disease was present in 190 (85%), 44 (54%), and 25 (56%), respectively; and systemic therapy was given to 194 (87%), 64 (88%), and 23 (56%) patients, respectively. Factors significantly associated with increased risk of recurrence included age ≥75 years, Karnofsky performance status 70-80, clinical N2c-N3, and Charlson score 2-3. CONCLUSION: Patients aged ≥75 years received less aggressive therapy and experienced increased recurrence compared to younger patients. Outcomes for those aged 70-74 years were similar to younger patients treated with aggressive therapy, despite their inferior performance status/comorbidity, and such patients should not routinely be excluded from standard-of-care therapy. Further study is needed to optimize therapy for a redefined older adult (age ≥75 years) population.
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Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Infecções por Papillomavirus , Idoso , Carcinoma de Células Escamosas/patologia , Quimiorradioterapia/efeitos adversos , Quimiorradioterapia/métodos , Cisplatino/uso terapêutico , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Humanos , Papillomaviridae , Infecções por Papillomavirus/complicações , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológicoRESUMO
BACKGROUND/AIM: Hypofractionated radiation therapy is not commonly used in head and neck cancers (HNC) due to increased toxicity observed in historical cohorts. This study reviews our institutional experience using hypofractionated intensity modulated radiation therapy (H-IMRT) for HNC. PATIENTS AND METHODS: A retrospective cohort study of 56 patients with HNC treated with H-IMRT with ≥50 Gy in 20 fractions was conducted. The primary outcomes were acute and late toxicity. RESULTS: Two-year locoregional control was 87% and median overall survival was 46 months. There were no acute or late grade 4 or 5 toxicities. Acute grade 2 and 3 toxicity was seen in 79% (N=44) and 25% (N=14), respectively. Late grade 2 toxicity was seen in 9% (N=5). No patients required the placement of a feeding tube or tracheostomy. CONCLUSION: H-IMRT for the definitive or post-operative treatment of HNC using ≥50 Gy in 20 fractions appears safe and well tolerated with modest toxicity.
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Neoplasias de Cabeça e Pescoço , Radioterapia de Intensidade Modulada , Nutrição Enteral , Neoplasias de Cabeça e Pescoço/etiologia , Neoplasias de Cabeça e Pescoço/radioterapia , Humanos , Hipofracionamento da Dose de Radiação , Radioterapia de Intensidade Modulada/efeitos adversos , Estudos RetrospectivosRESUMO
BACKGROUND: We sought to determine whether detection of cartilage invasion (CI) by computed tomography predicts oncologic outcomes after primary total laryngectomy. METHODS: Retrospective cohort study comparing oncologic outcomes between radiologic versus pathologic diagnosis. RESULTS: Assessment of clear CI versus gestalt CI resulted in 84% versus 48% specificity, 90.9% versus 80.3% positive predictive value (PPV), 60.6% versus 80.3% sensitivity, 44.7% versus 48% negative predictive value (NPV), respectively. Disease-free survival (DFS) was similar between cT4a and cT3/cT2 patients (p = 0.87). DFS trended towards superiority among pT3/pT2 versus pT4a patients (p = 0.18). DFS was similar among patients with CI on radiologist gestalt versus no CI (p = 0.94). Histologically confirmed CI was associated with a hazard ratio (HR) of 1.46 (p = 0.27), gestalt CI 1.13 (p = 0.70), and clear CI 1.61 (p = 0.10) for DFS. CONCLUSION: Gestalt determination of CI results in high sensitivity but low specificity, while clear determination of CI results in moderate sensitivity and high specificity.
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Carcinoma de Células Escamosas , Neoplasias Laríngeas , Carcinoma de Células Escamosas/patologia , Cartilagem/patologia , Humanos , Neoplasias Laríngeas/diagnóstico por imagem , Neoplasias Laríngeas/patologia , Neoplasias Laríngeas/cirurgia , Laringectomia/métodos , Invasividade Neoplásica/patologia , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Tomografia Computadorizada por Raios XRESUMO
OBJECTIVES: To explore the influence of treatment package time(TPT) in high-risk oral cavity squamous cell carcinoma(OCSCC) receiving adjuvant radiotherapy with concurrent chemotherapy(CRT). MATERIALS AND METHODS: We queried our multi-institutional OCSCC collaborative database for cases diagnosed between 2005 and 2015 who underwent surgery followed by adjuvant CRT. All patients had high-risk features: extranodal extension(ENE) and/or positive surgical margin(PM). TPT was days between surgery to last radiotherapy fraction. Kaplan-Meier curves, log-rank p-values and multivariate analysis(MVA) were used to investigate the impact of TPT on overall(OS), disease-free(DFS), locoregional failure-free(LRFS) and distant metastases-free(DMFS) survival. RESULTS: We identified 187 cases: median age 58 (range, 24-87 years), males 66%, and ever smokers 69%. ENE and PM were detected in 85% and 32%, and oral tongue and floor of the mouth constituted 49% and 18%, respectively. Median radiotherapy and cisplatin doses received were 66 Gy and 200 mg/m2. Overall, median TPT was 98 (range, 63-162 days). OS was worse for TPT > 90-days (n = 134) than TPT ≤ 90 (n = 53) at two-(65% vs. 71%) and five-years (45% vs. 62%); p = 0.05, with similar results for DFS. No influence on LRFS or DMFS was noted. More lymph nodes(LN) dissected(P = 0.039), T3-4 disease(P = 0.017), and unplanned reoperations(P = 0.037) occurred with TPT > 90-days. On MVA, TPT in 10-day increments was independently detrimental for OS (Hazard Ratio: 1.14; 95 %Confidence Interval [1-1.28]; P = 0.043), perineural invasion, age and positive LN (p < 0.05 for all). CONCLUSION: In one of the largest multi-institutional cohorts, TPT > 90-days predicted worse OS for high-risk OCSCC receiving adjuvant CRT. All efforts are needed to optimize perioperative care and baseline conditions for favorable outcomes.
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Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/radioterapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/tratamento farmacológico , Neoplasias Bucais/radioterapia , Radioterapia Adjuvante , Adulto JovemRESUMO
Rationale: Achieving predictable aesthetic results of large craniofacial defects has always been difficult, and it requires a multidisciplinary approach. Patient Concern: The chief concern of the patient was poor aesthetics due to a congenital craniofacial defect. Diagnosis: The patient was a known case of plexiform neurofibromatosis and had a congenital temporo-orbital bone defect of unknown origin. Treatment: The reconstruction of the defect was done using rapid prototyping (RPT) and iliac crest graft. Three-dimensional computed tomography imaging and RPT were used to obtain a customized titanium prosthesis to rehabilitate the temporal defect and the defect lateral to the orbit was reconstructed using an iliac crest graft. Outcome: Postoperative results were satisfactory and predictable. The positive change in appearance has improved the psychological well-being of the patient. Take-away Lessons: A multidisciplinary approach, use of advanced and improved technology helps in better treatment planning and achieving desired aesthetic results.
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Adjuvant chemoradiation (CRT), with high-dose cisplatin remains standard treatment for oral cavity squamous cell carcinoma (OCSCC) with high-risk pathologic features. We evaluated outcomes associated with different cisplatin dosing and schedules, concurrent with radiation (RT), and the effect of cumulative dosing of cisplatin. An IRB-approved collaborative database of patients (pts) with primary OCSCC (Stage I-IVB AJCC 7th edition) treated with primary surgical resection between January 2005 and January 2015, with or without adjuvant therapy, was established from six academic institutions. Patients were categorized by cisplatin dose and schedule, and resultant groups compared for demographic data, pathologic features, and outcomes by statistical analysis to determine disease free survival (DFS) and freedom from metastatic disease (DM). From a total sample size of 1282 pts, 196 pts were identified with high-risk features who were treated with adjuvant CRT. Administration schedule of cisplatin was not significantly associated with DFS. On multivariate (MVA), DFS was significantly better in patients without perineural invasion (PNI) and in those receiving ≥200 mg/m2 cisplatin dose (p < 0.001 and 0.007). Median DFS, by cisplatin dose, was 10.5 (<200 mg/m2) vs. 20.8 months (≥200 mg/m2). Our analysis demonstrated cumulative cisplatin dose ≥200 mg/m2 was associated with improved DFS in high-risk resected OCSCC pts.
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Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Carcinoma de Células Escamosas/patologia , Quimiorradioterapia , Humanos , Estadiamento de Neoplasias , Carcinoma de Células Escamosas de Cabeça e PescoçoRESUMO
The anti-PD1 monoclonal antibody pembrolizumab improves survival in recurrent/metastatic head and neck squamous cell carcinoma (HNSCC). Patients with locoregional, pathologically high-risk HNSCC recur frequently despite adjuvant cisplatin-radiation therapy (CRT). Targeting PD1 may reverse immunosuppression induced by HNSCC and CRT. We conducted a phase I trial with an expansion cohort (n = 20) to determine the recommended phase II schedule (RP2S) for adding fixed-dose pembrolizumab to standard adjuvant CRT. Eligible patients had resected HPV-negative, stage III-IV oral cavity, pharynx, or larynx HNSCC with extracapsular nodal extension or positive margin. RP2S was declared if three or fewer dose-limiting toxicities (DLT) occurred in a cohort of 12. DLT was defined as grade 3 or higher non-hematologic adverse event (AE) related to pembrolizumab, immune-related AE requiring over 2 weeks of systemic steroids, or unacceptable RT delay. A total of 34 patients enrolled at 23 NRG institutions. During the first cohort, only one DLT was observed (fever), thus RP2S was declared as pembrolizumab 200 mg every 3 weeks for eight doses, starting one week before CRT. During expansion, three additional DLTs were observed (wound infection, diverticulitis, nausea). Of the 34 patients, 28 (82%) received five or more doses of pembrolizumab. This regimen was safe and feasible in a cooperative group setting. Further development is warranted.
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BACKGROUND/AIM: Head and neck cancers are often treated with extended courses of radiotherapy (RT), which may prove excessively toxic for frail patients. Split course RT (SCRT) delivers two courses of RT separated by 4-6 weeks, personalizing treatment intensity based on response. In this study, we present our updated experience using this technique. PATIENTS AND METHODS: From a single institution database, we identified patients considered for SCRT. For patients undergoing a second course of RT, cumulative incidence of locoregional recurrence (LRR) and overall survival (OS) are reported. RESULTS: A total of 98 patients were included, of whom seventy-five percent underwent a second course of RT. The most common fractionation was 30 Gy in 10 fractions for each course, with a median cumulative dose of 60 Gy. In those undergoing a second course of RT, median OS was 9.7 months and cumulative incidence of LRR at 6, 12, and 24 months was 17.0%, 23.1%, and 29.4%, respectively. CONCLUSION: SCRT offers an attractive treatment paradigm to personalize radiation intensity based on patient tolerance, while maintaining reasonable safety and efficacy in those unfit for standard full course RT.
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Neoplasias de Cabeça e Pescoço/mortalidade , Recidiva Local de Neoplasia/mortalidade , Radioterapia/mortalidade , Idoso , Fracionamento da Dose de Radiação , Feminino , Seguimentos , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/radioterapia , Humanos , Masculino , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/radioterapia , Prognóstico , Taxa de SobrevidaRESUMO
OBJECTIVES: Patients with human papillomavirus (HPV) associated squamous cell carcinoma of the oropharynx (SCC-OP) have improved overall survival (OS) after distant metastasis (DM) compared to HPV negative patients. These patients may be appropriate candidates for enrollment on clinical trials evaluating the efficacy of metastasis-directed therapy (MDT). This study seeks to identify prognostic factors associated with OS after DM, which could serve as enrollment criteria for such trials. MATERIALS AND METHODS: From an IRB approved multi-institutional database, we retrospectively identified patients with HPV/p16 positive SCC-OP diagnosed between 2001 and 2018. Patterns of distant failure were assessed, including number of lesions at diagnosis and sites of involvement. The primary outcome was OS after DM. Prognostic factors for OS after DM were identified with Cox proportional hazards. Stepwise approach was used for multivariable analysis. RESULTS: We identified 621 patients with HPV-associated SCC-OP, of whom 82 (13.2%) were diagnosed with DM. Median OS after DM was 14.6 months. On multivariable analysis, smoking history and number of lesions were significantly associated with prolonged OS. Median OS after DM by smoking (never vs ever) was 37.6 vs 11.2 months (p = 0.006), and by lesion number (1 vs 2-4 vs 5 or more) was 41.2 vs 17.2 vs 10.8 months (p = 0.007). CONCLUSION: Among patients with newly diagnosed metastatic HPV-associated SCC-OP, lesion number and smoking status were associated with significantly prolonged overall survival. These factors should be incorporated into the design of clinical trials investigating the utility of MDT, with or without systemic therapy, in this population.
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Papillomavirus Humano 16 , Neoplasias Orofaríngeas/virologia , Infecções por Papillomavirus/complicações , Fenótipo , Carcinoma de Células Escamosas de Cabeça e Pescoço/virologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Ósseas/secundário , Neoplasias Encefálicas/secundário , Ensaios Clínicos como Assunto , Feminino , Humanos , Neoplasias Hepáticas/secundário , Neoplasias Pulmonares/secundário , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Metástase Neoplásica , Neoplasias Orofaríngeas/mortalidade , Neoplasias Orofaríngeas/patologia , Neoplasias Orofaríngeas/terapia , Cuidados Pós-Operatórios , Modelos de Riscos Proporcionais , Radioterapia , Projetos de Pesquisa , Estudos Retrospectivos , Fumar/epidemiologia , Fumar/mortalidade , Carcinoma de Células Escamosas de Cabeça e Pescoço/mortalidade , Carcinoma de Células Escamosas de Cabeça e Pescoço/secundário , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia , Fatores de TempoRESUMO
BACKGROUND: Process-related measures have been proposed as quality metrics in head and neck cancer care. A recent single-institution study identified four key metrics associated with increased survival. This study sought to validate the association of these quality metrics with survival in a multi-institutional cohort. METHODS: Multicenter retrospective study of patients with oral cavity squamous cell (1/2005-1/2015). Baseline patient and disease characteristics and compliance with quality metrics was evaluated. Association between compliance with quality metrics with overall survival (OS), disease-free survival (DFS), and disease-specific survival (DSS) was evaluated using Cox proportional hazards models. RESULTS: Failure to comply with two or more of the quality metrics was associated with worse OS, DFS, and DSS. Adherence to all or all but one of the quality metrics was found to be associated with improved survival. CONCLUSIONS: Process-related quality metrics are associated with increased survival in patients with oral cavity squamous cell carcinoma in a multi-institutional cohort.
Assuntos
Benchmarking , Neoplasias de Cabeça e Pescoço , Intervalo Livre de Doença , Neoplasias de Cabeça e Pescoço/terapia , Humanos , Boca , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Carcinoma de Células Escamosas de Cabeça e PescoçoRESUMO
Molecular dynamics simulations with many-body interatomic potentials are used to study melting of Ni and Fe nanoparticles with diameters that range between 2 and 12 nm. Two different embedded-atom method interatomic potentials are used for each element. The capability of each interatomic potential to model (i) size-dependent melting in nanoparticles and (ii) the bulk melting temperature of Ni or Fe is explored. In agreement with existing theory, molecular dynamics simulations show that the melting temperature of non-supported nanoparticles decreases with decreasing nanoparticle size, displaying a linear relationship with the inverse of nanoparticle diameter. However, molecular dynamics simulations using the interatomic potentials considered in this work provide a lower estimate than existing theory for the sensitivity of the melting temperature to nanoparticle size (slope of linear relationship). Molecular dynamics simulations demonstrate that melting is surface initiated and that a finite temperature range exists in which partial melting of the nanoparticle occurs. This observation is very important in the development of advanced vapor-liquid-solid models for catalyst-assisted single-walled carbon nanotube synthesis.
RESUMO
OBJECTIVE: To investigate the association between tumor volume and locoregional failure (LRF) after concurrent chemoradiation (CCRT) for locally advanced larynx cancer (LC). METHODS: This is a retrospective cohort study from 2009 to 2014 identified from an institutional review board-approved registry. Fifty-nine of 68 patients with locally advanced larynx cancer treated with definitive CCRT who had available imaging for review were identified. The main endpoint to be assessed was the association between gross tumor volumes (GTV; T = total, P = primary, N = nodal) and LRF. Receiver operative characteristic (ROC) curves were used to investigate diagnostic accuracy. RESULTS: Twenty LRFs were observed, resulting in a 2-year LRF rate of 39% (95% CI, 23-52%). On UVA, the GTV-T (P = .01), GTV-P (P = .05), and GTV-N (P = .04) were statistically significant predictors of LRF. Furthermore, age, smoking status, N-stage, larynx subsite, and tracheostomy/feeding tube dependence were potentially associated with LRF (P < .3), whereas T-stage (T3-4 vs. T2) was not (HR 1.05, 95% CI, 0.38-2.91, P = .92). In the multivariable model, GTV-P (HR 1.022, 95% CI, 0.999-1.046, P = .07) and GTV-N (HR 1.053, 95% CI, 1.0004-1.108, P = .05) were the two most impactful covariates on the model's R2 . ROC analysis suggested an optimal cut point of 12 cc in the GTV-T. The 2-year LRF for GTV-T > 12 cc was 64.2% and ≤ 12 cc was 16.4%, P = .006. CONCLUSION: GTV is associated with LRF after definitive CCRT for LC. Patients with bulky primary and/or nodal tumors may be better served with upfront surgical resection regardless of T-stage. Further investigation into the safety of larynx preservation for low-volume T4 tumors can be considered. LEVEL OF EVIDENCE: 4 Laryngoscope, 130:2372-2377, 2020.
Assuntos
Carcinoma de Células Escamosas/terapia , Neoplasias Laríngeas/terapia , Carcinoma de Células Escamosas/diagnóstico por imagem , Carcinoma de Células Escamosas/patologia , Quimiorradioterapia/métodos , Feminino , Humanos , Neoplasias Laríngeas/diagnóstico por imagem , Neoplasias Laríngeas/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Seleção de Pacientes , Sistema de Registros , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Carga TumoralRESUMO
OBJECTIVES: This study examines the utility of surveillance imaging in detecting locoregional failures (LRF), distant failures (DF) and second primary tumors (SPT) in patients with human papillomavirus (HPV) associated oropharyngeal cancer (OPC) after definitive chemoradiotherapy (CRT). METHODS AND MATERIALS: An institutional database identified 225 patients with biopsy proven, non- metastatic HPV+ OPC treated with definitive CRT between 2004 and 2015, whose initial post-treatment imaging was negative for disease recurrence (DR). Two groups were defined: patients with <2 scans/year Group 1 and patients with ≥2 scans/year Group 2. The Mann-Whitney test or Chi-square was used to determine differences in baseline characteristics between groups. Fine & Gray regression was used to detect an association between imaging frequency, DR and diagnosis of SPT. RESULTS: Median follow up was 40.8 months. 30% of patients had ≥T3 disease and 90% had ≥ N2 disease (AJCC 7th edition). Twenty one failures (9.3%) were observed, 7 LRF and 15 DF. Six LRF occurred within 24 months and 14 DF occurred within 36 months of treatment completion. Regression analysis showed Group 2 had increased risk of DR compared to Group1 (HR 10.3; p = 0.002) albeit with more advanced disease at baseline. Five SPT were found (2 lung, 2 esophagus, and 1 oropharynx) between 4.5 and 159 months post-CRT. CONCLUSION: Surveillance imaging seems most useful in the first 2-3 years post treatment, and is particularly important in detecting DF. Surveillance scans for SPT has a low yield, but should be considered for those meeting lung cancer screening guidelines.