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1.
Otolaryngol Head Neck Surg ; : 194599821989637, 2021 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-33618570

RESUMO

OBJECTIVE: Pathologic extranodal extension (ENE) is an important adverse feature for human papillomavirus (HPV)-negative head and neck squamous cell carcinoma (HNSCC), but the prognostic significance of microscopic ENE (ENEmi) and role of adjuvant concurrent chemoradiation (CRT) for ENEmi remain unclear. This study evaluates (1) the prognostic significance of ENEmi in HPV-negative HNSCC and (2) whether adjuvant CRT is associated with improved overall survival (OS) for these patients. STUDY DESIGN: Retrospective cohort study. SETTING: Commission on Cancer (CoC)-accredited facilities. METHODS: This retrospective cohort study included patients in the National Cancer Database from 2009 to 2015 with pathologic node-positive (pN+) HPV-negative HNSCC with either pathologic ENEmi or no ENE who had undergone margin-negative surgery. The association of ENEmi with OS was evaluated using Cox proportional hazard analyses. Analyses were repeated in patients with ENEmi receiving adjuvant therapy to evaluate the association of adjuvant CRT with OS. RESULTS: We included 5483 patients with pN+ HPV-negative HNSCC, of whom 24% had ENEmi. On multivariable analysis, ENEmi was associated with decreased OS relative to no ENE (adjusted hazard ratio [aHR], 1.43; 95% CI, 1.28-1.59). Among patients with ENEmi who received ≥60 Gy of adjuvant radiation therapy (RT) (n = 617), adjuvant CRT was not associated with improved OS relative to RT (aHR, 0.91; 95% CI, 0.66-1.27). CONCLUSION: For patients with HPV-negative HNSCC, pN+ with ENEmi is associated with worse OS than pN+ without ENE. However, for patients with ENEmi, concurrent CRT is not associated with improved OS relative to RT. The optimal adjuvant paradigm for ENEmi requires additional investigation.

2.
Laryngoscope ; 2021 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-33571385

RESUMO

OBJECTIVES/HYPOTHESIS: To determine the frequency and management of short- and long-term complications related to oromandibular free flap reconstruction and identify potentially predictive factors of hardware complications. STUDY DESIGN: Retrospective chart review. METHODS: A retrospective database from chart review was formed consisting of 266 oromandibular free flap reconstructions performed at a single institution over a 15-year period. Data were collected on demographics, surgical treatment, complications, and management of complications. Subgroup univariate and multivariate analyses were performed to compare patients with hardware complications and those without. RESULTS: Eighty-one of 266 patients (30.5%) that underwent oromandibular reconstruction had an early complication (<4 weeks after surgery), and the most common complications were cervical wound dehiscence (11.3%) and fistulas (9.40%). Eighty of 266 patients (30.1%) had a long-term complication (>4 weeks after surgery) and the most common complication was plate exposure (26.7%). Univariate and multivariate analyses showed no association between whether there was hardware extrusion and fibula versus scapula, smoking history, virtual surgical planning (VSP), and dental implantation (P > .05). Only early complications (OR, 3.59, 95% CI, 1.83-7.05, P < .01) and patients undergoing oromandibular reconstruction for osteoradionecrosis (OR, 2.26, 95% CI, 1.10-4.64, P = .03) were strongly and independently associated with subsequent hardware extrusion on univariate analysis. CONCLUSIONS: Both short- and long-term complications are common after oromandibular reconstruction. The most important predictive factor for a late complication is an early complication and prior radiation. There was no difference of plate complications among the various free flap types. Dental implantation and use of VSP were not associated with hardware complications. LEVEL OF EVIDENCE: 4 Laryngoscope, 2021.

3.
Head Neck ; 2021 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-33620125

RESUMO

BACKGROUND: Race has been shown to have variable prognostic importance in nasopharyngeal carcinoma (NPC). However, previous studies are limited by a lack of comprehensive treatment, epidemiologic, and comorbidity data. METHODS: This was a retrospective cohort study utilizing the National Cancer Database from 2004 to 2016. Multivariable Cox proportional hazards regressions were used to calculate adjusted hazard ratios (aHR) for overall survival. RESULTS: A cohort of 9995 patients met inclusion and exclusion criteria. Race, insurance, comorbidity, treatment, stage, age, and histology were independent prognosticators. Among patients with keratinizing NPC, Asians and Hispanics had superior survival (aHR 0.58 [95% confidence interval (CI) 0.48-0.69], aHR 0.76 [95% CI 0.61-0.96]) compared to white patients. Among patients with non-keratinizing differentiated NPC, Asians and black patients had improved survival (aHR 0.71 [95% CI 0.56-0.91], aHR 0.72 [95% CI 0.54-0.95]) compared to white patients. Race was not prognostic in non-keratinizing undifferentiated NPC. CONCLUSION: The prognostic significance of race varies across histological subtypes of NPC.

5.
Head Neck ; 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33586842

RESUMO

BACKGROUND: For human papilloma virus positive (HPV+) oropharyngeal squamous cell carcinoma (OPSCC), management recommendations for patients with a single metastatic lymph node <6 cm in diameter remain nebulous, leading to treatment heterogeneity in this common subgroup of patients. METHODS: We utilized the National Cancer Database to perform survival and multivariable analyses of patients with HPV+ OPSCC with one positive lymph node <6 cm and negative surgical margins. RESULTS: We found that 5-year survival is comparable between patients who receive surgery and adjuvant radiation versus surgery alone. In multivariable analyses, we found no significant difference in the hazard ratio of overall survival after adjusting for various potential confounders. CONCLUSIONS: These data suggest that patients with margin-negative HPV+ OPSCC with a single positive lymph node <6 cm have comparable survival with or without adjuvant radiation. Future studies exploring outcomes for this specific group in randomized-controlled trials will be critical for further evaluating these initial observations.

6.
Artigo em Inglês | MEDLINE | ID: mdl-33507208

RESUMO

Importance: Overall, the prognosis of sinonasal squamous cell carcinoma (SCC) is poor. This malignancy can arise de novo or from inverted papillomas, but it is unclear whether survival differences between the 2 pathologies exist. Objective: To assess for survival differences between patients with sinonasal de novo SCC (dnSCC) and those with inverted papilloma-associated SCC (IPSCC). Data Sources: A search of Ovid MEDLINE, Embase, Scopus, and the Cochrane Library from inception to January 23, 2020, with cross-referencing of retrieved studies, was performed. Additional data were requested from authors. Study Selection: Inclusion and exclusion criteria were designed to capture studies with survival outcomes of adults with sinonasal SCC who underwent regular treatment. Clinical trials, cohort studies, case-control studies, and case series with more than 10 adults aged 18 years or older with sinonasal SCC were included. Exclusion criteria were studies on non-SCC sinonasal neoplasms, studies without histopathologic diagnoses, non-English language articles, nonhuman animal studies, and abstract-only articles. Two blinded investigators (J.J.L., A.M.P., T.W.E., or N.S.W.) screened each abstract and full text, and a third investigator (J.J.L. or P.P.) adjudicated discrepancies. Of 729 unique citations, 26 studies of 1194 total patients were included. Data Extraction and Synthesis: Meta-Analysis of Observational Studies in Epidemiology (MOOSE) guidelines were followed. The Methodological Index for Nonrandomized Studies (MINORS) criteria were used to assess study quality. Two blinded investigators (J.J.L., A.M.P., T.W.E., or N.S.W.) independently extracted data from each study. Data were pooled using a random-effects model. Main Outcomes and Measures: The primary outcome was overall survival, and secondary outcomes were disease-free and disease-specific survival. Before data collection, it was hypothesized that the dnSCC cohort would have worse survival outcomes than the IPSCC cohort. Results: One study of patients with dnSCC, 12 studies of patients with IPSCC, and 5 studies with both cohorts were included in the meta-analysis of overall survival. The pooled 5-year overall survival rate for 255 patients with dnSCC was 56% (95% CI, 41%-71%; I2 = 83.8%) and for 475 patients with IPSCC was 65% (95% CI, 56%-73%; I2 = 75.7%). Five comparative studies of both cohorts totaling 240 patients with dnSCC and 155 patients with IPSCC were included in another meta-analysis. The pooled overall survival hazard ratio was 1.87 (95% CI, 1.24-2.84; I2 = 0%). Conclusions and Relevance: This systematic review and meta-analysis found that patients with dnSCC had almost a 2-fold increased risk of mortality compared with those with IPSCC. Large, multicenter studies are necessary to validate these findings before considering treatment alterations such as de-escalation based on histopathology.

7.
Am J Otolaryngol ; 42(3): 102915, 2021 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-33482566

RESUMO

OBJECTIVES: While smoking is associated with worse outcomes in HPV-positive oropharyngeal squamous cell carcinoma (OPSCC), the magnitude of this association is unclear given the heterogenous smoking definitions and outcomes. Our objective was to investigate the association between smoking, survival, and recurrence in HPV-related OPSCC using multiple smoking metrics reported in the literature. MATERIALS AND METHODS: This was a retrospective cohort study of 375 adults with p16+ OPSCC undergoing surgical resection (n = 272) or definitive chemoradiation (n = 103) at a tertiary academic institution from 2006 to 2017. The primary outcome was overall survival (OS). Secondary outcomes included disease-free survival (DFS), disease-specific survival (DSS), and recurrence. We used multiple smoking metrics commonly cited in previous studies, including ever versus never smokers, current versus former/never smokers, ≤10 versus >10 pack-year, ≤20 versus >20 pack-year, and continuous pack-year. RESULTS: There were 375 patients, median age 58 years, with 326 (87%) males, and median follow-up of 52 months. Of all smoking metrics, >20 pack-year history was the strongest predictor of both OS (HR 2.24, 95% CI: 1.19-4.20) and DFS (HR 1.67, 95% CI: 1.04-2.66) on univariable and multivariable analysis after adjusting for age, overall stage, and comorbidities. Patients with >20 pack-year smoking history were also more likely to have recurrence (HR 1.59, 95% CI: 0.95-2.67) after adjusting for overall stage. CONCLUSION: Heavier smoking >20 pack-years was the strongest smoking metric associated with 2-times worse survival and recurrence. Our findings suggest that >20 pack-year smoking history may be a more useful cutoff for risk stratification models but requires further validation.

8.
Head Neck ; 2021 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-33417293

RESUMO

BACKGROUND: Immunotherapy agents are used to treat advanced head and neck lesions. We aim to elucidate relationship between immunotherapy and surgical wound complications. METHODS: Retrospective multi-institutional case series evaluating patients undergoing ablative and flap reconstructive surgery and immunotherapy treatment. MAIN OUTCOME: wound complications. RESULTS: Eight-two (62%) patients received preoperative therapy, 89 (67%) postoperative, and 33 (25%) in both settings. Forty-one (31%) patients had recipient site complications, 12 (9%) had donor site. Nineteen (14%) had major recipient site complications, 22 (17%) had minor. There was no statistically significant difference in complications based on patient or tumor-specific variables. Preoperative therapy alone demonstrated increased major complications (odds ratio [OR] 3.7, p = 0.04), and trend to more donor site complications (OR 7.4, p = 0.06), however treatment in both preoperative and postoperative therapy was not. CONCLUSIONS: Preoperative immunotherapy may be associated with increased wound complications. Controlled studies are necessary to delineate this association and potential risks of therapy.

9.
Head Neck ; 43(1): 89-97, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32914515

RESUMO

BACKGROUND: This study aims to provide modern estimates of survival for untreated head and neck cancer (HNC) and to identify patient- and tumor-specific factors associated with not receiving definitive treatment. METHODS: Adults with mucosal HNC were identified from the Surveillance, Epidemiology, and End Results (SEER) database. Median overall survival of untreated patients was calculated and stratified by site and stage. Cause-specific survival and factors associated with no treatment were investigated with advanced statistics. RESULTS: The study cohort included 6477 patients who received no treatment. Overall, untreated patients had a median survival of 12 months, with significant variability by site and stage. Multivariable analysis identified advanced age, black race, unmarried status, and lack of private insurance as associated with no treatment. CONCLUSIONS: Survival of HNC without treatment is dismal, yet substantial variation exists by tumor site and stage. Higher rates of no treatment among the poor and racial minorities are potentially driven by disparities in care availability and provision.

10.
Laryngoscope ; 2020 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-33264444

RESUMO

OBJECTIVE/HYPOTHESIS: To assess whether young patients with oral cavity squamous cell carcinoma (OCSCC) demonstrate worse oncologic outcomes than older patients after definitive therapy. STUDY DESIGN: Systematic review and meta-analysis. METHODS: A medical librarian composed a search strategy to identify relevant studies in Medline, Embase, Scopus, and other major databases (Prospero registration number CRD42019127974). Inclusion criteria were adults with histologically diagnosed OCSCC that underwent treatment, comparator groups with an age cutoff of 40 years old, and reported survival outcomes. Articles were excluded if they contained patients with oropharyngeal squamous cell carcinoma or patients treated for palliative intent. Overall survival hazard ratios were analyzed with a meta-analysis. RESULTS: There were 23,382 patients with OCSCC that were treated with definitive therapy from 22 included studies. The pooled cohort contained 2,238 (10%) patients ≤40 years of age. Oral tongue was the most common subsite in both the younger (n = 1,961, 91%) and older (n = 18,047, 88%) cohorts. The majority of OCSCCs were either T1 or T2, representing 859 (80%) malignancies in younger patients and 8,126 (77%) malignancies in older patients. A meta-analysis of nine studies demonstrated that younger patients did not experience worse survival outcomes than older patients (hazard ratio = 0.97, 95% confidence interval = 0.66-1.41). CONCLUSIONS: Young adults with OCSCC experienced similar oncologic outcomes as older patients with OCSCC after definitive treatment. Until compelling evidence demonstrates clinically relevant differences between these two cohorts, their approach to management should be similar. Future studies should consider comorbidities and using age 40 as a standard age cutoff to provide more uniform data moving forward. Laryngoscope, 2020.

11.
Artigo em Inglês | MEDLINE | ID: mdl-33151273

RESUMO

Importance: Regional lymph node metastasis remains an important prognostic factor in patients with oropharyngeal squamous cell carcinoma (OPSCC). Although survival among patients with regional metastasis in human papillomavirus (HPV)-related OPSCC is more favorable compared with patients who are HPV negative, prognostic variables associated with failure in patients with single-node metastasis are not known. Objective: To evaluate recurrence and survival in patients with HPV-related OPSCC with single-lymph node metastasis treated with transoral surgery. Design, Setting, and Participants: A retrospective cohort study was conducted of 207 adults with newly diagnosed p16-positive OPSCC and pathology-confirmed single-node disease who underwent surgical resection with or without adjuvant therapy at 2 tertiary academic medical centers from January 1, 2007, to December 31, 2016. Statistical analysis was performed from September 1, 2018, to September 1, 2020. Interventions: Surgery alone (n = 59), surgery with adjuvant radiation (n = 75), or surgery with adjuvant chemoradiation (n = 73). Main Outcomes and Measures: The primary outcome was regional recurrence. Secondary outcomes included overall survival, any recurrence, and identification of factors associated with regional recurrence and overall survival. Results: Among 207 patients, 178 (86%) were men, with a median age of 57 years (range, 35-82 years) at the time of surgery. Median follow-up was 36.2 months (range, 7-127 months). Regional recurrence occurred in 11 patients (5%). Of these, 1 patient (9%) was lost to follow-up after diagnosis, 1 (9%) was treated with palliative chemotherapy, and 9 (82%) were treated with curative intent. Ultimately, 7 patients received successful salvage treatment, and 3 died with disease. Overall, there were 21 patients (10%) with any recurrence, with 4 patients (19%) experiencing local recurrence, 11 (52%) experiencing regional recurrence, and 6 (29%) experiencing distant metastasis. The 5-year overall survival was 95% (95% CI, 89%-98%) for all patients. Older age (odds ratio [OR], 1.2; 95% CI, 1.1-1.2), advanced T stage (OR, 3.5; 95% CI, 0.9-14.0), and positive margins (OR, 10.9; 95% CI, 1.8-67.5) were associated with increased regional recurrence. Extranodal extension (OR, 0.2; 95% CI, 0.04-0.8), lymph node size greater than 3 cm (OR, 0.2; 95% CI, 0.1-0.7), and adjuvant therapy (OR, 0.08; 95% CI, 0.02-0.4) were associated with decreased regional recurrence. Advanced comorbidities (hazard ratio, 6.20; 95% CI, 1.4-27.7), lymphovascular invasion (hazard ratio, 4.7; 95% CI, 1.0-21.2), and regional recurrence (hazard ratio, 16.0; 95% CI, 3.1-82.0) were associated with worse overall survival. Conclusions and Relevance: The findings of this cohort study suggest that patients with HPV-related OPSCC and single-node disease undergoing surgical resection with or without adjuvant treatment have excellent survival. Adjuvant therapy appears to improve regional control. Among patients with regional recurrence of OPSCC, there is a high rate of successful salvage treatment.

13.
Otolaryngol Head Neck Surg ; : 194599820951175, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32928026

RESUMO

OBJECTIVE: To systematically review the literature to determine the prevalence and clinical outcomes of second primary oropharyngeal squamous cell carcinoma (OPSCC). DATA SOURCES: Search strategies created with a medical librarian were implemented using multiple databases in October 2019. REVIEW METHODS: The population of interest included adults age >18 years with a p16+ or human papillomavirus-positive OPSCC. The outcome was a synchronous or metachronous second primary OPSCC. Inclusion and exclusion criteria were designed to capture all study designs. In total, 685 records were identified by the search strategy. Two reviewers independently performed the review, extracted data, and performed a quality assessment. Primary Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. A random-effects model was used for the meta-analysis. RESULTS: A total of 2470 patients with 35 second primary OPSCCs from 15 studies were identified. The pooled prevalence of second primary OPSCC was 1.4% (range, 0%-14.3%). In the random-effects model, the prevalence was estimated at 1.3% (95% CI, 0.7%-2.3%; P = .51, I2 = 52%). Of the 30 patients with treatment information, 26 (86.7%) received surgical treatment, while 4 (13.3%) underwent nonsurgical therapy. Of the 29 patients with available survival information, 22 (75.9%) had no evidence of disease at last follow-up, 5 (17.2%) ultimately died of disease, and 2 (6.9%) were alive with disease. CONCLUSION: Overall, the rate of second primary OPSCC in patients with an index p16+ OPSCC is low, and most patients are successfully treated. Insufficient evidence currently exists to recommend routine elective tonsillectomy during surgical treatment of p16+ OPSCC.

14.
Otolaryngol Head Neck Surg ; : 194599820949223, 2020 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-32838614

RESUMO

OBJECTIVE: Mandibular reconstruction for segmental defects is a well-studied topic. However, there are conflicting data on the risks of delayed plate-related complications. The objective of this systematic review and meta-analysis was to assess long-term plate-related complications following reconstruction of the mandible with soft tissue and a plate as compared with immediate vascularized bony reconstruction. DATA SOURCES: A medical librarian created search strategies with a combination of keywords and controlled vocabulary in Ovid Medline (1946-), Embase (1947-), Scopus (1960-), Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Clinicaltrials.gov. REVIEW METHODS: Candidate articles were independently reviewed by 2 authors. Inclusion/exclusion criteria were uniformly applied. Articles were considered eligible if they included adequate reporting of plate extrusion and/or fracture and had follow-up ≥12 months. RESULTS: A total of 2379 patients were included. The risk of plate fracture was low in cases of soft tissue with a plate (5%; 95% CI, 0.03-0.08) and osseous reconstruction (1%). The risk of extrusion following soft tissue and plate reconstruction was 20% (95% CI, 0.15-0.27). In the osseous reconstruction group, the risk of extrusion was 10% (95% CI, 0.06-0.18). Revision surgery was performed twice as often following soft tissue with a plate as compared with vascularized bony reconstruction (32% [95% CI, 0.25-0.40] vs 14% [95% CI, 0.09-0.21], respectively). CONCLUSION: Delayed plate-related complications remain a significant problem following segmental defect reconstruction. Soft tissue and plate reconstruction techniques may increase the risk of plate removal and revision surgery.

15.
Artigo em Inglês | MEDLINE | ID: mdl-32790830

RESUMO

Importance: The American Joint Committee on Cancer staging system (Cancer Staging Manual, 8th Edition) for head and neck squamous cell carcinoma (HNSCC) now categorizes human papillomavirus (HPV)-negative HNSCC in a single positive lymph node smaller than 3 cm with pathologic extranodal extension (ENE) as N2a. The standard of care for pathologic ENE is adjuvant chemoradiation therapy (CRT). Whether adding chemotherapy concurrent with adjuvant radiation therapy improves survival in this clinical scenario is unknown. Objective: To assess whether adjuvant CRT relative to radiation therapy alone is associated with improved survival among patients with pN2a HPV-negative HNSCC with ENE. Design, Setting, and Participants: This retrospective cohort study included 504 patients with pN2a HPV-negative HNSCC with ENE who had undergone margin-negative surgery and adjuvant therapy. The patients were identified from the National Cancer Database from January 1, 2004, to December 31, 2015. Statistical analyses were conducted from September 1, 2019, to April 16, 2020. Main Outcomes and Measures: The primary end point was overall survival. The association of adjuvant CRT with overall survival was analyzed using univariate and multivariate Cox proportional hazards regression analyses. Planned subset analyses were conducted in patients younger than 70 years with no comorbidities (the subset most likely to be eligible for a clinical trial of cisplatin-based chemoradiation) and in patients with pT3/T4 disease classification. Results: Of 504 patients (mean [SD] age, 60.5 [12.7] years; 319 [63.3%] men; 434 [86.1%] White) with pN2a HPV-negative HNSCC with ENE who had undergone margin-negative surgery and adjuvant therapy, 298 patients (59.1%) received adjuvant CRT. For the overall cohort of patients with pN2a ENE, adjuvant CRT was not associated with improved overall survival relative to adjuvant radiation therapy alone in a multivariate analysis (adjusted hazard ratio, 0.98; 95% CI, 0.74-1.30). Adjuvant CRT was still not associated with improved overall survival in a subset analysis of 304 patients younger than 70 years with no comorbidities (adjusted hazard ratio, 0.98; 95% CI, 0.66-1.45) nor in a subset of 220 patients with pT3/T4 disease classification (adjusted hazard ratio, 1.03; 95% CI, 0.70-1.54). Conclusions and Relevance: This study found that for patients with pN2a HPV-negative HNSCC with ENE who underwent margin-negative surgery and adjuvant therapy, adding chemotherapy concurrent with adjuvant radiation therapy was not associated with improved overall survival. Additional research is necessary to identify the optimal treatment paradigm for this clinical scenario.

16.
Clin Cancer Res ; 26(19): 5140-5152, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32665297

RESUMO

PURPOSE: Pembrolizumab improved survival in patients with recurrent or metastatic head and neck squamous-cell carcinoma (HNSCC). The aims of this study were to determine if pembrolizumab would be safe, result in pathologic tumor response (pTR), and lower the relapse rate in patients with resectable human papillomavirus (HPV)-unrelated HNSCC. PATIENTS AND METHODS: Neoadjuvant pembrolizumab (200 mg) was administered and followed 2 to 3 weeks later by surgical tumor ablation. Postoperative (chemo)radiation was planned. Patients with high-risk pathology (positive margins and/or extranodal extension) received adjuvant pembrolizumab. pTR was quantified as the proportion of the resection bed with tumor necrosis, keratinous debris, and giant cells/histiocytes: pTR-0 (<10%), pTR-1 (10%-49%), and pTR-2 (≥50%). Coprimary endpoints were pTR-2 among all patients and 1-year relapse rate in patients with high-risk pathology (historical: 35%). Correlations of baseline PD-L1 and T-cell infiltration with pTR were assessed. Tumor clonal dynamics were evaluated (ClinicalTrials.gov NCT02296684). RESULTS: Thirty-six patients enrolled. After neoadjuvant pembrolizumab, serious (grades 3-4) adverse events and unexpected surgical delays/complications did not occur. pTR-2 occurred in eight patients (22%), and pTR-1 in eight other patients (22%). One-year relapse rate among 18 patients with high-risk pathology was 16.7% (95% confidence interval, 3.6%-41.4%). pTR ≥10% correlated with baseline tumor PD-L1, immune infiltrate, and IFNγ activity. Matched samples showed upregulation of inhibitory checkpoints in patients with pTR-0 and confirmed clonal loss in some patients. CONCLUSIONS: Among patients with locally advanced, HPV-unrelated HNSCC, pembrolizumab was safe, and any pathologic response was observed in 44% of patients with 0% pathologic complete responses. The 1-year relapse rate in patients with high-risk pathology was lower than historical.

18.
Am J Otolaryngol ; 41(5): 102592, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32521295

RESUMO

PURPOSE: While smoking is linked to worse outcomes for human papillomavirus (HPV)-related oropharyngeal squamous cell cancer (OPSCC), the magnitude of this association and the amount of smoking exposure necessary to confer clinically significant differences in outcomes is unclear. Recent studies suggested that greater tobacco exposure results in higher risk of cancer progression and death. Our study objective was to perform a systematic review of the association between smoking and HPV-related OPSCC outcomes. MATERIALS AND METHODS: A literature search was conducted in April 2019 to identify relevant articles using Embase, Medline, Scopus, CENTRAL, and Cochrane databases. All studies were independently screened by two investigators to identify studies that assessed HPV-positive patients as an independent cohort, specified smoking measures, and reported locoregional recurrence (LRR), overall survival (OS), disease-specific survival (DSS), or disease-free survival (DFS) in association with smoking. RESULTS: Of 1130 studies identified, 10 met final inclusion criteria with 2321 total patients, mean age 57.5 years. Smoking measures included ever vs never, current vs never/former smokers, ≤10 vs >10 pack-year, and continuous pack-years. Of these studies, 8 (80%) showed a significant effect of smoking on increasing recurrence and mortality. Adjusted HRs for LRR ranged from 0.6 to 5.2, OS from 1.3 to 4.0, DSS from 2.3 to 7.2, and DFS from 1.02 to 4.2 among heavier smokers compared to lighter/non-smokers. CONCLUSIONS: While there was significant variability in smoking metrics and reported outcomes, all studies reporting statistically significant HRs showed that smoking was associated with worse outcomes. Further studies using uniform smoking measures are necessary to better understand this association.


Assuntos
Neoplasias Orofaríngeas/etiologia , Neoplasias Orofaríngeas/mortalidade , Infecções por Papillomavirus/complicações , Fumar/efeitos adversos , Carcinoma de Células Escamosas de Cabeça e Pescoço/etiologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/mortalidade , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/etiologia , Recidiva Local de Neoplasia/mortalidade , Neoplasias Orofaríngeas/virologia , Papillomaviridae , Prognóstico , Carcinoma de Células Escamosas de Cabeça e Pescoço/virologia , Taxa de Sobrevida
19.
Oral Oncol ; 108: 104819, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32485609

RESUMO

INTRODUCTION: Delays in radiation are multifactorial, frequent, and associated with poor outcomes. This study investigates the effect of both primary and adjuvant radiation therapy duration and their interaction with other measures of treatment delay on survival in head and neck squamous cell carcinoma (HNSCC). METHODS: We built a retrospective cohort using the National Cancer Database, consisting of primary oral cavity, hypopharynx, larynx and oropharynx squamous cell carcinoma without distant metastasis and with at least six weeks of radiation. The primary exposure was the duration of radiation therapy (DRT), and the primary outcome was death. We estimated the association between DRT and 5-year overall survival (OS) using Kaplan-Meier curves and hazard ratios (HRs) with Cox proportional hazard regression. RESULTS: In both primary (definitive) and adjuvant (post-surgical) radiation settings, increased DRT results in decreased survival. In the primary radiation cohort, 5-year OS was 59.7% [59.1%-60.3%] among those with 47-53 days DRT, which decreased significantly with each subsequent week to completion (81+ days: 38.4% [36.2%-40.7%]). In the surgical cohort, survival decreased 16.5% when DRT extended beyond 75 days (40-46 days: 68.2% [67.3%-69.1%] vs. 75+ days: 53.3% [50.1%-56.7%]). Multivariate analyses showed increased hazard of death with increased DRT (primary radiation: 81+ days HR: 1.69 [1.58-1.81]); surgical: 75+ days HR: 1.61 [1.37-1.88]), with effects intensifying when restricting to those receiving full-dose radiation. CONCLUSION: A prolonged DRT was associated with worse OS in head and neck cancer. Radiation treatment delays of even a week lead to a significant survival disadvantage. DRT had a stronger association with survival than time to initiation of postoperative adjuvant radiotherapy.

20.
Otolaryngol Head Neck Surg ; 163(5): 979-985, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32482151

RESUMO

OBJECTIVES: Distress with self-perceived changes in appearance and function can result in body image disturbance (BID), which is common in head and neck cancer (HNC) survivors and a major source of psychosocial morbidity. To address the lack of psychometrically sound patient-reported outcome measures (PROMs) of HNC-related BID, we aim to create and validate the Inventory to Measure and Assess imaGe disturbancE-Head & Neck (IMAGE-HN). STUDY DESIGN: Survey study. SETTING: Multiple academic centers. SUBJECTS AND METHODS: Following item development, HNC survivors from 4 academic centers completed the IMAGE-HN. Item responses were psychometrically analyzed using confirmatory factor analysis (CFA) and Rasch analysis. RESULTS: Item development resulted in a 31-item PROM consisting of 5 individual domains and a global domain. In total, 305 HNC survivors of diverse ages, HNC subsites, and reconstructive paradigms completed the initial items. After removal of 3 items for local dependence, CFA confirmed the unidimensionality and local independence (item residual correlations <|0.20|) for each domain. Rasch analysis indicated acceptable fit (infit and outfit mean squares <2.0), monotonicity of all rating scale categories, and low person misfit (<4%). Person separation indices and person reliability were adequate for each domain except appearance concealment, which was removed (4 items). This resulted in the IMAGE-HN, a psychometrically acceptable 24-item PROM of HNC-related BID consisting of a global scale and 4 subscales measuring unique constructs and comprised independent items. CONCLUSIONS: IMAGE-HN is a novel, psychometrically sound, multidomain PROM of HNC-related BID for use in clinical and research settings.

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