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1.
Anticancer Res ; 39(9): 4885-4890, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31519591

RESUMO

BACKGROUND/AIM: This study aimed to evaluate the outcomes of patients with head and neck squamous cell carcinoma (HNSCC) who underwent resection and refused the recommended adjuvant therapy. PATIENTS AND METHODS: Locoregional recurrence-free survival (LRRFS) and time to progression (TTP) were assessed in HNSCC patients treated with surgery who declined some or all adjuvant therapy (refusal group (RG)) compared to those who received the recommended adjuvant therapy (TG). RESULTS: With a median follow-up of 23 months, the 2-year LRRFS was significantly lower in the 17 patients from the RG compared to the 152 patients from the TG: 23.1% vs. 69%, HR=0.30, 95% confidence incidence (CI)=0.15-0.59; p<0.001. The mean TTP was 12 months in the RG and was not reached in the TG (p<0.001). CONCLUSION: Patients with HNSCC who declined the recommended adjuvant therapy had a recurrence rate of 50% within a year.


Assuntos
Neoplasias de Cabeça e Pescoço/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais , Terapia Combinada , Gerenciamento Clínico , Feminino , Neoplasias de Cabeça e Pescoço/diagnóstico , Neoplasias de Cabeça e Pescoço/mortalidade , Neoplasias de Cabeça e Pescoço/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Recidiva , Estudos Retrospectivos , Terapia de Salvação , Análise de Sobrevida , Resultado do Tratamento
3.
Clin Cancer Res ; 25(11): 3430-3442, 2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-30755439

RESUMO

PURPOSE: Human papillomavirus (HPV)-negative head and neck squamous cell carcinomas (HNSCC) commonly bear disruptive mutations in TP53, resulting in treatment resistance. In these patients, direct targeting of p53 has not been successful, but synthetic lethal approaches have promise. Although Aurora A kinase (AURKA) is overexpressed and an oncogenic driver, its inhibition has only modest clinical effects in HPV-negative HNSCC. We explored a novel combination of AURKA and WEE1 inhibition to overcome intrinsic resistance to AURKA inhibition.Experimental Design: AURKA protein expression was determined by fluorescence-based automated quantitative analysis of patient specimens and correlated with survival. We evaluated treatment with the AURKA inhibitor alisertib (MLN8237) and the WEE1 inhibitor adavosertib (AZD1775), alone or in combination, using in vitro and in vivo HNSCC models. RESULTS: Elevated nuclear AURKA correlated with worse survival among patients with p16(-) HNSCC. Alisertib caused spindle defects, G2-M arrest and inhibitory CDK1 phosphorylation, and cytostasis in TP53 mutant HNSCC FaDu and UNC7 cells. Addition of adavosertib to alisertib instead triggered mitotic entry and mitotic catastrophe. Moreover, in FaDu and Detroit 562 xenografts, this combination demonstrated synergistic effects on tumor growth and extended overall survival compared with either vehicle or single-agent treatment. CONCLUSIONS: Combinatorial treatment with adavosertib and alisertib leads to synergistic antitumor effects in in vitro and in vivo HNSCC models. These findings suggest a novel rational combination, providing a promising therapeutic avenue for TP53-mutated cancers.

4.
Oncogene ; 38(18): 3475-3487, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30647454

RESUMO

Recent studies have revealed the mutational signatures underlying the somatic evolution of cancer, and the prevalences of associated somatic genetic variants. Here we estimate the intensity of positive selection that drives mutations to high frequency in tumors, yielding higher prevalences than expected on the basis of mutation and neutral drift alone. We apply this approach to a sample of 525 head and neck squamous cell carcinoma exomes, producing a rank-ordered list of gene variants by selection intensity. Our results illustrate the complementarity of calculating the intensity of selection on mutations along with tallying the prevalence of individual substitutions in cancer: while many of the most prevalently-altered genes were heavily selected, their relative importance to the cancer phenotype differs from their prevalence and from their P value, with some infrequent variants exhibiting evidence of strong positive selection. Furthermore, we extend our analysis of effect size by quantifying the degree to which mutational processes (such as APOBEC mutagenesis) contributes mutations that are highly selected, driving head and neck squamous cell carcinoma. We calculate the substitutions caused by APOBEC mutagenesis that make the greatest contribution to cancer phenotype among patients. Lastly, we demonstrate via in vitro biochemical experiments that the APOBEC3B protein can deaminate the cytosine bases at two sites whose mutant states are subject to high net realized selection intensities-PIK3CA E545K and E542K. By quantifying the effects of mutations, we deepen the molecular understanding of carcinogenesis in head and neck squamous cell carcinoma.


Assuntos
Citidina Desaminase/genética , Neoplasias de Cabeça e Pescoço/genética , Antígenos de Histocompatibilidade Menor/genética , Mutação , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Carcinogênese/genética , Classe I de Fosfatidilinositol 3-Quinases/genética , Exoma , Humanos , Mutagênese , Fenótipo , Fosfatidilinositol 3-Quinases/genética
5.
Laryngoscope ; 129(8): 1844-1855, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30575965

RESUMO

OBJECTIVES: To compare long-term oncologic outcomes and adjuvant therapies for patients treated with transoral robotic surgery (TORS), nonrobotic surgery, or transoral laser microsurgery (TLM). STUDY DESIGN: A retrospective analysis of the National Cancer Database (2010-2014). METHODS: Patients with clinical tumor (T)1 and T2 oropharyngeal squamous cell carcinomas (OPSCC) were classified into those receiving TORS versus nonrobotic surgery versus TLM. Univariate and multivariate survival analyses were conducted with chi-square tests; Kaplan-Meier log-rank test; and Cox multivariate, logistic regression, and multinomial regression modeling. RESULTS: We identified 2,224 OPSCC TORS patients; 6,697 nonrobotic surgery patients; and 333 TLM patients. The majority of patients were white males with a mean age of approximately 59 years. No significant difference was noted between the cohorts in tumor stage; however, TORS patients were more likely to have nodal (N)1 to N3 disease than nonrobotic surgery and TLM patients, respectively (69.8% vs. 62.0% vs. 59.7%, P < 0.001). TORS was associated with a lower likelihood of positive margins when compared to nonrobotic surgery, although not TLM (nonrobotic surgery: hazard ratio [HR] 1.51, P < 0.001, TLM: HR 1.13, P = 0.582). TORS was associated with lower likelihood of postsurgical chemoradiotherapy (TLM: HR 2.07, P < 0.001, nonrobotic surgery: 1.65, P < 0.001) but not adjuvant radiotherapy alone (TLM: HR 1.06, P = 0.569, nonrobotic surgery: 0.96, P = 0.655). On multivariate Cox analysis of overall survival, the use of TORS was not associated with increased survival (TLM: HR 1.31, P = 0.233, nonrobotic surgery: HR 1.12, P < 0.303). CONCLUSION: The advantages of TORS for early-stage OPSCC may be a lower likelihood of postsurgical positive margins and subsequent need for adjuvant chemoradiotherapy. LEVEL OF EVIDENCE: NA Laryngoscope, 129:1844-1855, 2019.


Assuntos
Carcinoma de Células Escamosas/terapia , Cirurgia Endoscópica por Orifício Natural/mortalidade , Neoplasias Orofaríngeas/terapia , Procedimentos Cirúrgicos Robóticos/mortalidade , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Quimiorradioterapia Adjuvante/mortalidade , Distribuição de Qui-Quadrado , Terapia Combinada , Bases de Dados Factuais , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Margens de Excisão , Pessoa de Meia-Idade , Análise Multivariada , Cirurgia Endoscópica por Orifício Natural/métodos , Estadiamento de Neoplasias , Neoplasias Orofaríngeas/mortalidade , Neoplasias Orofaríngeas/patologia , Modelos de Riscos Proporcionais , Análise de Regressão , Estudos Retrospectivos , Procedimentos Cirúrgicos Robóticos/métodos , Resultado do Tratamento , Estados Unidos
6.
Cell Rep ; 25(5): 1332-1345.e5, 2018 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-30380422

RESUMO

Cell lines are important tools for biological and preclinical investigation, and establishing their relationship to genomic alterations in tumors could accelerate functional and therapeutic discoveries. We conducted integrated analyses of genomic and transcriptomic profiles of 15 human papillomavirus (HPV)-negative and 11 HPV-positive head and neck squamous cell carcinoma (HNSCC) lines to compare with 279 tumors from The Cancer Genome Atlas (TCGA). We identified recurrent amplifications on chromosomes 3q22-29, 5p15, 11q13/22, and 8p11 that drive increased expression of more than 100 genes in cell lines and tumors. These alterations, together with loss or mutations of tumor suppressor genes, converge on important signaling pathways, recapitulating the genomic landscape of aggressive HNSCCs. Among these, concurrent 3q26.3 amplification and TP53 mutation in most HPV(-) cell lines reflect tumors with worse survival. Our findings elucidate and validate genomic alterations underpinning numerous discoveries made with HNSCC lines and provide valuable models for future studies.

7.
Sci Rep ; 8(1): 14036, 2018 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-30232350

RESUMO

Identification of nodal metastasis and tumor extranodal extension (ENE) is crucial for head and neck cancer management, but currently only can be diagnosed via postoperative pathology. Pretreatment, radiographic identification of ENE, in particular, has proven extremely difficult for clinicians, but would be greatly influential in guiding patient management. Here, we show that a deep learning convolutional neural network can be trained to identify nodal metastasis and ENE with excellent performance that surpasses what human clinicians have historically achieved. We trained a 3-dimensional convolutional neural network using a dataset of 2,875 CT-segmented lymph node samples with correlating pathology labels, cross-validated and fine-tuned on 124 samples, and conducted testing on a blinded test set of 131 samples. On the blinded test set, the model predicted ENE and nodal metastasis each with area under the receiver operating characteristic curve (AUC) of 0.91 (95%CI: 0.85-0.97). The model has the potential for use as a clinical decision-making tool to help guide head and neck cancer patient management.

8.
Otolaryngol Head Neck Surg ; : 194599818779052, 2018 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-30060700

RESUMO

Objective To characterize treatment delays in surgically treated oropharyngeal cancer, identify factors associated with delays, and associate delays with survival. Study Design Retrospective cross-sectional analysis. Setting Commission on Cancer-accredited institutions. Subjects and Methods We identified patients in the National Cancer Database with surgically treated oropharyngeal cancer. We characterized the durations of diagnosis-to-treatment initiation, surgery-to-radiation treatment, radiation treatment duration, total treatment package, and diagnosis-to-treatment end intervals as medians. We associated delays with patient, tumor, and treatment factors via multivariable logistic regression analysis and with overall survival by Cox proportional hazards regression. Results In total, 3708 patients met inclusion criteria. Median durations of diagnosis-to-treatment initiation, surgery-to-radiation treatment, radiation treatment duration, total treatment package, and diagnosis-to-treatment end intervals were 27, 42, 47, 90, and 106 days, respectively. Medicaid and human papillomavirus (HPV) negativity were associated with delays. Delayed total treatment package and diagnosis-to-treatment end intervals were associated with decreased survival (hazard ratio [HR] = 1.81 [1.29-2.54], P = .001 and HR = 1.97 [1.39-2.78], P < .001, respectively); this was maintained following HPV stratification. Delays in the surgery-to-radiation treatment interval were associated with decreased overall survival in HPV-negative but not HPV-positive patients (HR = 2.05 [1.19-3.52], P = .010 and HR = 1.15 [0.74-1.80], P = .535, respectively). Diagnosis-to-treatment initiation and radiation treatment duration were not associated with overall survival in the overall cohort (HR = 1.21 [0.86-1.72], P = .280 and HR = 1.40 [0.99-1.99], P = .061, respectively); however, following stratification, delayed radiation treatment duration approached significance in HPV-negative but not HPV-positive patients (HR = 1.60 [0.96-2.68], P = .072 and HR = 1.35 [0.84-2.18], P = .220). Conclusion Treatment durations identified here can serve as national benchmarks and for institutions to compare quality to their peers. Distinct benchmarks should be applied to HPV-negative and HPV-positive patients.

9.
Otolaryngol Head Neck Surg ; : 194599818782404, 2018 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-30060705

RESUMO

Objective To design and implement a postoperative clinical care pathway designed to reduce intensive care usage on length of stay, readmission rates, and surgical complications in head and neck free flap patients. Methods A postoperative clinical care pathway detailing timelines for patient care was developed by a multispecialty team. In total, 108 matched patients receiving free tissue transfer for reconstruction of head and neck defects in the year before (prepathway), year after (early pathway), and second year after (late pathway) pathway implementation were compared based on postoperative length of stay, 30-day readmission rate, intensive care unit (ICU) admission, and rates of medical/surgical complications. Results Median length of stay decreased from 10 to 7.5 and 7 days in the pre-, early, and late-pathway groups, respectively ( P = .012). Readmission rate decreased from 16% in the prepathway group to 0% and 3% in the early and late-pathway groups. The number of patients admitted to the ICU postoperatively decreased from 100% to 36% and 6% in the pre-, early, and late-pathway groups, respectively ( P = .025). The rates of surgical and medical complications were equivalent. Discussion This pathway effectively reduced ICU admission, length of stay, and readmission rates, without increasing postoperative complications. These outcomes were sustainable over 2 years. Implications for Practice Free flap patients may not require routine ICU admission and may be taken off ventilatory support in the operating room. This effectively reduces costly resource use in this patient population. Similar pathways could be introduced at other institutions.

10.
Laryngoscope ; 2018 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-30151832

RESUMO

OBJECTIVES: Approximately 3% to 9% of head and neck cancer presents with a metastatic node and no identifiable primary tumor. These cases of head and neck carcinoma of unknown primary (HNCUP) present a therapeutic challenge. Therapy of this disease varies based on factors such as institutional, surgeon, and patient preference. Evidence demonstrating the outcomes associated with these therapies for HNCUP is limited, and among the available series, the tumor human papillomavirus (HPV) status is often ignored. Treatment deintensification has been proposed for a subset of these patients. We aim to evaluate the treatment-related outcomes for HPV-associated and HPV-negative HNCUP. METHODS: A retrospective study of 978 adult HNCUP diagnosed from 2010 to 2013 in the NCDB was conducted. Multivariate Cox survival regressions as well as univariate Kaplan-Meier analyses were conducted. RESULTS: Patients with HPV-associated disease had superior survival, with a 3-year survival of 94.8% (standard error [SE]: 1.0), compared with 80.3% (SE: 2.9) among those with HPV-negative disease. Among HPV-negative patients with clinical nodal classification (cN)2/cN3 disease, treatment with definitive radiotherapy alone compared to definitive chemoradiotherapy was associated with diminished survival (hazard ratio 5.507, P = 0.005). Among patients with HPV-associated cancer and cN2/cN3 disease, all treatments (surgery alone, surgery with adjuvant radiotherapy, surgery with adjuvant chemoradiotherapy, definitive chemoradiotherapy, definitive radiotherapy) resulted in statistically equivalent survival. CONCLUSION: Tumor HPV status has a significant prognostic value for HNCUP and should be considered in future studies of treatment deintensification in this group. Treatment deintensification to radiotherapy alone in cN2/cN3 cases may result in poorer patient survival for HPV-negative patients, whereas it may be a promising option for further investigation in HPV-positive patients. LEVEL OF EVIDENCE: 4.

11.
Laryngoscope ; 2018 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-30151947

RESUMO

OBJECTIVE: Salivary squamous cell carcinomas (SCCs) represent a unique disease entity because many are thought to represent metastases from primary cutaneous malignancies. Nevertheless, they represent a significant proportion of parotid gland cancers and have a notably poor prognosis. Recently, there has been controversy regarding the utility of adjuvant chemotherapy in the treatment of these malignancies, with most studies concluding that there is no survival benefit. We aim to determine the outcomes associated with the use of adjuvant radiotherapy and chemoradiotherapy in the treatment of early- and late-stage salivary SCC. METHODS: A retrospective study of 2,285 of surgically resected adult salivary SCC diagnosed from 2004 to 2014 in the National Cancer Database was conducted. Patients were divided into early- (I/II) and late-stage (III/IV) groups. Demographic, facility, tumor, and survival variables were included in the analyses. Multivariate Cox survival regressions, propensity-score matched analyses, and univariate Kaplan-Meier analyses were conducted. RESULTS: The use of adjuvant chemoradiotherapy for late-stage patients was associated with improved survival compared to the use of adjuvant radiotherapy alone (hazard ratio [HR] 0.774, P = 0.026). Five-year survival for late-stage patients treated with surgery alone, surgery with adjuvant radiotherapy, and surgery with adjuvant chemoradiotherapy was 31.1% (standard error [SE]: 2.5), 45.6% (SE: 2.2), and 58.9% (SE: 3.4). Use of adjuvant therapy (either chemoradiotherapy or radiotherapy alone) was associated with improved survival for early-stage patients (HR 0.746, P = 0.037). CONCLUSION: The addition of chemotherapy to the adjuvant therapy of late-stage patients with salivary SCC may result in improved long-term survival. Expanded use of adjuvant therapy for early-stage disease may also improve patient outcomes. LEVEL OF EVIDENCE: 4. Laryngoscope, 2018.

13.
Cancer Res ; 78(16): 4613-4626, 2018 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-29921694

RESUMO

Human papilloma viruses (HPV) are linked to an epidemic increase in oropharyngeal head and neck squamous cell carcinomas (HNSCC), which display viral inactivation of tumor suppressors TP53 and RB1 and rapid regional spread. However, the role of genomic alterations in enabling the modulation of pathways that promote the aggressive phenotype of these cancers is unclear. Recently, a subset of HPV+ HNSCC has been shown to harbor novel genetic defects or decreased expression of TNF receptor-associated factor 3 (TRAF3). TRAF3 has been implicated as a negative regulator of alternative NF-κB pathway activation and activator of antiviral type I IFN response to other DNA viruses. How TRAF3 alterations affect pathogenesis of HPV+ HNSCC has not been extensively investigated. Here, we report that TRAF3-deficient HPV+ tumors and cell lines exhibit increased expression of alternative NF-κB pathway components and transcription factors NF-κB2/RELB. Overexpression of TRAF3 in HPV+ cell lines with decreased endogenous TRAF3 inhibited NF-κB2/RELB expression, nuclear localization, and NF-κB reporter activity, while increasing the expression of IFNA1 mRNA and protein and sensitizing cells to its growth inhibition. Overexpression of TRAF3 also enhanced TP53 and RB tumor suppressor proteins and decreased HPV E6 oncoprotein in HPV+ cells. Correspondingly, TRAF3 inhibited cell growth, colony formation, migration, and resistance to TNFα and cisplatin-induced cell death. Conversely, TRAF3 knockout enhanced colony formation and proliferation of an HPV+ HNSCC line expressing higher TRAF3 levels. Together, these findings support a functional role of TRAF3 as a tumor suppressor modulating established cancer hallmarks in HPV+ HNSCC.Significance: These findings report the functional role of TRAF3 as a tumor suppressor that modulates the malignant phenotype of HPV+ head and neck cancers. Cancer Res; 78(16); 4613-26. ©2018 AACR.

14.
Head Neck ; 40(7): 1343-1355, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29756412

RESUMO

BACKGROUND: Evidence surrounding the effect of adjuvant treatment in salivary gland cancers is limited. The benefit of adding chemotherapy to adjuvant treatment is also of interest. We investigated the association of these treatments with survival and whether this differed by stage or the presence of adverse features. METHODS: A retrospective study of adult salivary gland cancer cases diagnosed from 2004 to 2013 in the National Cancer Data Base (NCDB) was conducted. RESULTS: Treatment with adjuvant radiotherapy was associated with improved survival for both patients with early-stage (hazard ratio [HR] 0.744; P = .004) and late-stage (HR 0.688; P < .001) disease with adverse features. Further addition of chemotherapy to the adjuvant treatment of patients with late-stage disease with adverse features was not associated with a survival benefit (HR 1.028; P = .705). CONCLUSION: Adjuvant radiotherapy is associated with improved survival for patients with adverse features, regardless of stage. The addition of chemotherapy to the adjuvant treatment of patients with late-stage disease with adverse features is not associated with improved outcomes.

15.
JAMA Otolaryngol Head Neck Surg ; 144(6): 519-525, 2018 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-29801040

RESUMO

Importance: Data are limited on the prognostic value of human papillomavirus (HPV) status for head and neck carcinoma subsites. Objective: To determine whether HPV positivity at each head and neck subsite is associated with improved overall survival. Design, Setting, and Participants: This retrospective population-based cohort study used the National Cancer Database to identify patients diagnosed with head and neck squamous cell carcinomas from January 1, 2010, to December 31, 2014. Patients were classified according to the location of their primary malignancy into 1 of the 6 main subsites of the upper aerodigestive tract: oral cavity, oropharynx, nasopharynx, hypopharynx, larynx, and sinonasal tract. Patients were also classified by their HPV status. Data collection for this study took place from January 1, 2010, to December 31, 2014. Data analysis was conducted from August 1, 2017, to September 30, 2017. Main Outcomes and Measures: The difference in 5-year overall survival between patients with HPV-positive status and those with HPV-negative status in various head and neck carcinoma subsites; the role of HPV status in an unadjusted Cox multivariate regression model. Results: Of the 175 223 total number of patients identified (129 634 [74.0%] male; 45 589 [26.0%] female; mean [SD] age, 63.1 [11.9] years), 133 273 (76.1%) were ineligible and 41 950 (23.9%) were included in the sample. This sample included 16 644 patients (39.7%) with HPV-positive tumors and 25 306 (60.3%) with HPV-negative tumors. Patients with an HPV-positive status were more likely to be younger, be white, be male, present with local T category tumors, and have poor differentiation on histologic examination. HPV-positive status was associated with survival at 4 tumor subsites: oral cavity (hazard ratio [HR], 0.76; 95% CI, 0.66-0.87), oropharynx (HR, 0.44; 95% CI, 0.41-0.47), hypopharynx (HR, 0.59; 95% CI, 0.45-0.77), and larynx (HR, 0.71; 95% CI, 0.59-0.85). The HPV status was the greatest factor in survival outcome between the HPV-positive and -negative cohorts at the oropharynx subsite (77.6% vs 50.7%; survival difference, 26.9%; 95% CI, 25.6%-28.2%) and hypopharynx subsites (52.2% vs 28.8%; survival difference, 23.4%; 95% CI, 17.5%-29.3%). For the nasopharynx (HR, 1.03; 95% CI, 0.75-1.42) and sinonasal tract (HR, 0.63; 95% CI, 0.39-1.01) subsites, HPV-positive status was not an independent prognostic factor. Conclusions and Relevance: Human papillomavirus positivity was associated with improved survival in 4 subsites (oropharynx, hypopharynx, oral cavity, and larynx), and the largest survival difference was noted in the oropharynx and hypopharynx subsites. In the nasopharynx and sinonasal tract subsites, HPV positivity had no association with overall survival. Given these results, routine testing for HPV at the oropharynx, hypopharynx, oral cavity, and larynx subsites may be warranted.

16.
Oral Oncol ; 79: 64-70, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29598952

RESUMO

OBJECTIVES: Currently, human papillomavirus-associated oropharyngeal squamous cell carcinoma (HPV-A OPC) is managed with either primary surgery or definitive chemoradiotherapy (CRT), despite the lack of supporting randomized prospective data. We therefore assessed the outcomes of each treatment strategy using the National Cancer Database (NCDB). METHODS: The NCDB was used to identify patients diagnosed with cT1 N2a-2b or cT2 N1-2b HPV-A OPC from 2010 to 2013 who underwent treatment with primary surgery or CRT. Demographic and clinicopathologic predictors of treatment were analyzed by the chi-square test and logistic regression. Overall survival (OS) was evaluated using multivariable Cox proportional hazard regression, Kaplan-Meier, log-rank test, and propensity score-matched analysis. RESULTS: We identified 3063 patients; 1576 (51.5%) received CRT and 1487 (48.5%) underwent primary surgery. Median follow up was 32 months. 972 (65.4%) surgical patients received adjuvant CRT. On multivariable Cox regression, 3-year OS was comparable between surgery and CRT (hazard ratio [HR] 1.08, 95% confidence interval [CI] 0.83-1.41, P = 0.58). Inferior OS was significantly associated with increasing clinical T and N stage, older age, and non-private insurance. Propensity score-matching yielded a 2526 patient cohort and redemonstrated similar OS (HR, 1.09; 95% CI 0.81-1.47; P = 0.55). Comparable outcomes persisted in a subset analysis of patients with margin-negative resection, with 3-year OS 90.8% in CRT patients vs. 93.6% in surgery patients (log-rank P = 0.27). CONCLUSIONS: Upfront surgery and CRT yielded comparable 3-year OS outcomes in this cohort. In this national sample, 65.4% of surgical patients received trimodal therapy with adjuvant CRT, highlighting the need for improved patient selection for primary surgery.

17.
Otolaryngol Head Neck Surg ; 158(3): 497-504, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29292665

RESUMO

Objective After radiation failure for early T-stage larynx cancer, national guidelines recommend salvage surgery. Total laryngectomy and conservation laryngeal surgery with an open or endoscopic approach are both used. Beyond single-institution studies, there is a lack of evidence concerning the outcomes of these procedures. We aim to study whether treatment with conservation laryngeal surgery is associated with poorer outcomes than treatment with total laryngectomy as salvage surgery after radiation failure for T1/T2 larynx cancers. Study Design A retrospective study was conducted of adult squamous cell larynx cancer cases in the National Cancer Database diagnosed from 2004 to 2012. Setting Commission on Cancer cancer programs in the United States. Methods Demographic, facility, tumor, and survival variables were included in the analyses. Multivariate survival regressions as well as univariate Kaplan-Meier analyses were conducted. Results Slightly more than 7% of patients receiving radiotherapy for T1/T2 larynx cancers later received salvage surgery. Salvage with partial laryngectomy was not associated with diminished survival as compared with total laryngectomy. However, positive surgical margins were associated with worse outcomes (hazard ratio, 1.782; P = .001), and a larger percentage of patients receiving partial laryngectomy had positive margins than those receiving total laryngectomy. Facility characteristics were not associated with differences in salvage surgery type or outcomes. Conclusion In recognition of the inherent selection bias, patients who experienced recurrences after radiation for T1/T2 larynx cancer and underwent conservation salvage laryngeal surgery demonstrated clinical outcomes similar to those of patients undergoing salvage total laryngectomy. Increased rates of positive surgical margins were observed among patients undergoing salvage conservation surgery.

18.
19.
Laryngoscope ; 128(3): 664-669, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-28865100

RESUMO

OBJECTIVE: Oral cavity cancer is the most common malignant disease of the head and neck. The natural course of the disease is poorly characterized and unavailable for patient consideration during initial treatment planning. Our primary objective was to outline this natural history, with a secondary aim of identifying predictors of treatment refusal. STUDY DESIGN: Retrospective review of adult patients with oral cavity cancer who refused surgery that was recommended by their physician in the National Cancer Database. METHODS: Demographic, tumor, and survival variables were included in the analyses. Multivariate Cox regressions as well as univariate Kaplan-Meier analyses were conducted. RESULTS: Patients who were older, uninsured, had government insurance, or had more advanced disease were more likely to go untreated. Survival among untreated patients was poor, but there was a small proportion of patients surviving long term. Five-year survival rates ranged from 31.1% among early-stage patients to 12.6% among stage 4 patients. CONCLUSION: Although the natural course of oral cavity cancer carries a poor prognosis, there are a number of patients with longer-than-expected survival. The survival estimates may provide supplemental information for patients deciding whether to pursue treatment. In addition to age and extent of disease, system factors such as insurance status and facility case volume are associated with a patient's likelihood of refusing treatment. LEVEL OF EVIDENCE: 4. Laryngoscope, 128:664-669, 2018.


Assuntos
Neoplasias Bucais/mortalidade , Boca/patologia , Recusa do Paciente ao Tratamento/estatística & dados numéricos , Idoso , Bases de Dados Factuais , Intervalo Livre de Doença , Feminino , Humanos , Cobertura do Seguro , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/diagnóstico , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida/tendências , Estados Unidos/epidemiologia
20.
Cancer ; 124(4): 717-726, 2018 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-29243245

RESUMO

BACKGROUND: The growing epidemic of human papillomavirus-positive (HPV+) oropharyngeal cancer and the favorable prognosis of this disease etiology have led to a call for deintensified treatment for some patients with HPV+ cancers. One of the proposed methods of treatment deintensification is the avoidance of chemotherapy concurrent with definitive/adjuvant radiotherapy. To the authors' knowledge, the safety of this form of treatment de-escalation is unknown and the current literature in this area is sparse. The authors investigated outcomes after various treatment combinations stratified by American Joint Committee on Cancer (AJCC) eighth edition disease stage using patients from the National Cancer Data Base. METHODS: A retrospective study of 4443 patients with HPV+ oropharyngeal cancer in the National Cancer Data Base was conducted. Patients were stratified into AJCC eighth edition disease stage groups. Multivariate Cox regressions as well as univariate Kaplan-Meier analyses were conducted. RESULTS: For patients with stage I disease, treatment with definitive radiotherapy was associated with diminished survival compared with chemoradiotherapy (hazard ratio [HR], 1.798; P = .029), surgery with adjuvant radiotherapy (HR, 2.563; P = .002), or surgery with adjuvant chemoradiotherapy (HR, 2.427; P = .001). For patients with stage II disease, compared with treatment with chemoradiotherapy, patients treated with a single-modality (either surgery [HR, 2.539; P = .009] or radiotherapy [HR, 2.200; P = .030]) were found to have poorer survival. Among patients with stage III disease, triple-modality therapy was associated with improved survival (HR, 0.518; P = .024) compared with treatment with chemoradiotherapy. CONCLUSIONS: Deintensification of treatment from chemoradiotherapy to radiotherapy or surgery alone in cases of HPV+ AJCC eighth edition stage I or stage II disease may compromise patient safety. Treatment intensification to triple-modality therapy for patients with stage III disease may improve survival in this group. Cancer 2018;124:717-26. © 2017 American Cancer Society.

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