Delay to surgery after neoadjuvant chemotherapy in head and neck squamous cell carcinoma affects oncologic outcomes.

BACKGROUND: Neoadjuvant chemotherapy (NAC) is used in head and neck squamous cell carcinoma (HNSCC) for downstaging advanced disease and decreasing distant metastasis (DM). To the authors' knowledge, no study has specifically examined the impact of a delayed time to surgery (TTS) after NAC on oncologic outcomes. They thus aimed to identify a cutoff for TTS after NAC and its effect on survival indices. METHODS: This was a retrospective review of all patients with HNSCC receiving NAC followed by surgery with curative intent between March 2016 and March 2019 at the MD Anderson Cancer Center. Receiver operating characteristic analysis was used to identify a cutoff for TTS, and this cutoff was used to analyze the overall survival (OS), locoregional recurrence rate, DM-free rate, and disease-free survival (DFS). A multivariate Cox regression analysis was performed. RESULTS: One hundred one patients were analyzed with a median follow-up of 24.7 months. The 3-year OS and locoregional recurrence rates did not differ with a TTS ≥ 34 days. However, the 3-year DM-free rate was significantly worse (56% vs 90%; P = .001) in the group with a TTS ≥ 34 days, and the 3-year DFS was significantly lower (26% vs 64%; P = .006). In a multivariate analysis, a TTS ≥ 34 days (hazard ratio [HR], 4.92; 95% confidence interval [CI], 1.84-13.13) and extracapsular extension (HR, 3.01; 95% CI, 1.13-8.00) were significant independent predictors of a poorer DM-free rate. Weight loss > 10% (HR, 5.53; 95% CI, 1.02-30.24) was the only independent predictor for a TTS ≥ 34 days. CONCLUSIONS: Emphasis should be placed on early definitive locoregional treatment after NAC, particularly in patients who do not respond to NAC. There is a need to validate these findings and establish new benchmarks for the interval between NAC and surgery.

Impact of provider type and number of providers on surveillance testing among survivors of head and neck cancers.

BACKGROUND: Guidelines for follow-up after head and neck cancer (HNC) treatment recommend frequent clinical examinations and surveillance testing. Here, the authors describe real-world follow-up care for HNC survivors and variations in surveillance testing. METHODS: Using Surveillance, Epidemiology, and End Results (SEER)-Medicare data, this study examined a population-based cohort of HNC survivors between 2001 and 2011 Usage of cross-sectional head and neck imaging (CHNI), chest imaging (CI), positron emission tomography (PET), fiberoptic nasopharyngolaryngoscopy (FNPL), and, in irradiated patients, thyroid function testing (TFT) was captured over 2 consecutive surveillance years. Multivariate modeling with logistic regression analyses was used to assess variations by clinical factors, nonclinical factors, number and types of providers seen and their evolution over time. RESULTS: Among 13,836 HNC survivors, the majority saw a medical, radiation, or surgical oncologist and a primary care provider (PCP; 81.7%) in their first year of surveillance. However, only 58.1% underwent either PET or CHNI, 47.8% underwent CHNI, 64.1% underwent CI, 32.5% underwent PET scans, 55.0% underwent FNPL, and 55.9% underwent TFT. In multivariate analyses, patients who followed up with more providers and those who followed up with both a PCP and an oncologist were more likely to undergo surveillance testing (P < .007). However, adjusting for providers seen did not explain the variations in surveillance testing rates based on age, race, education, income level, and place of residence. Over time, there was a gradual increase in the use of PET scans and TFT during surveillance years. CONCLUSIONS: In this large SEER-Medicare data study, only half of HNC survivors received the recommended testing, and greater compliance was seen in those who followed up with both an oncologist and a PCP. More attention is needed to minimize variations in surveillance testing across sociodemographic groups.

Outcomes of patients with oropharyngeal squamous cell carcinoma treated with induction chemotherapy followed by concurrent chemoradiation compared with those treated with concurrent chemoradiation.

BACKGROUND: Induction chemotherapy (IC) has been associated with a decreased risk of distant metastasis in locally advanced head and neck squamous cell carcinoma. However, its role in the treatment of oropharyngeal squamous cell carcinoma (OPSCC) is not well established. METHODS: The outcomes of patients with OPSCC treated with IC followed by concurrent chemoradiation (CRT) were compared with the outcomes of those treated with CRT alone. The primary outcome was overall survival (OS), and the secondary end points were the times to locoregional and distant recurrence. RESULTS: In an existing database, 585 patients met the inclusion criteria: 137 received IC plus CRT, and 448 received CRT. Most patients were positive for human papillomavirus (HPV; 90.9%). Patients receiving IC were more likely to present with a higher T stage, a higher N stage, and low neck disease. The 3-year OS rate was significantly lower in patients receiving IC (75.7%) versus CRT alone (92.9%). In a multicovariate analysis, receipt of IC (adjusted hazard ratio [aHR], 3.4; P < .001), HPV tumor status (aHR, 0.36; P = .002), and receipt of concurrent cetuximab (aHR, 2.7; P = .002) were independently associated with OS. The risk of distant metastasis was also significantly higher in IC patients (aHR, 2.8; P = .001), whereas an HPV-positive tumor status (aHR, 0.44; P = .032) and completion of therapy (aHR, 0.51; P = .034) were associated with a lower risk of distant metastasis. In HPV-positive patients, IC remained associated with distant metastatic progression (aHR, 2.6; P = .004) but not OS. CONCLUSIONS: In contrast to prior studies, IC was independently associated with worse OS and a higher risk of distant metastasis in patients with OPSCC. Future studies are needed to validate these findings.

Enhanced Recovery After Surgery (ERAS) in Head and Neck Oncologic Surgery: A Case-Matched Analysis of Perioperative and Pain Outcomes.

BACKGROUND: Enhanced recovery after surgery (ERAS) pathways are well established in certain surgical specialties because findings have shown significant improvements in outcomes. Convincing literature in head and neck cancer (HNC) surgery is lacking. This study aimed to assess the effect of an ERAS pathway on National Surgical Quality Improvement Program (NSQIP)-based occurrences and pain-related outcomes in HNC surgery. METHODS: The study matched 200 patients undergoing head and neck oncologic surgery on an ERAS pathway between 1 March 2016 and 31 March 2019 with control subjects (1:1 ratio) during the same period. Demographic and perioperative data collected from the NSQIP database were extracted. Pain scores and medication usage were electronically extracted from our electronic medical record system and compared. Risk factors for high opioid usage also were assessed. RESULTS: Both groups were statistically similar in baseline characteristics. The ERAS group had fewer planned intensive care unit (ICU) admissions (4% vs. 14%; p < 0.001), a shorter mean hospital stay (7.2 ± 2.3 vs. 8.7 ± 4.2 days; p < 0.001), and fewer overall complications (18.6% vs. 27.0%; p = 0.045). Morphine milligram equivalent requirements over 72 h were significantly reduced during 72 h in the ERAS group (138.8 ± 181.5 vs. 207.9 ± 205.5; p < 0.001). In the multivariate analysis, the risk factors for high opioid analgesic usage included preoperative opioid usage, age younger than 65 years, race, patient-controlled analgesia use, and ICU admission. CONCLUSION: The study findings showed that ERAS in HNC surgery can result in improved outcomes and resource use, and that these results are sustainable. The outcomes described in this report can be further used to optimize ERAS pathways.

Impact of neoadjuvant chemotherapy on perioperative morbidity after major surgery for head and neck cancer.

BACKGROUND: Neoadjuvant chemotherapy (NAC) has been used in patients with advanced head and neck cancers (HNCs) with the intent of downstaging tumors and suppressing distant metastases. However, to the authors' knowledge, the perioperative impact of NAC has not been systematically explored in patients with HNC. The objective of the current study was to compare perioperative outcomes with surgery upfront compared with patients treated with NAC. METHODS: Between March 1, 2016, and March 31, 2019, patients undergoing surgery for HNC with flap reconstruction at The University of Texas MD Anderson Cancer Center in Houston were included. Data were extracted from the prospectively maintained National Surgical Quality Improvement Program database. Postoperative complications, return to operating room, and readmission rates were compared. Univariate and multivariate analyses of length of stay and overall and wound complications were performed. RESULTS: A total of 834 patients were analyzed, 687 of whom (82.4%) underwent surgery upfront and 147 of whom (17.6%) received NAC. A total of 631 cases (75.7%) involved the upper aerodigestive tract whereas 203 cases (24.3%) were cutaneous. A total of 317 patients (38.0%) had recurrent disease. The NAC group was younger (P < .001) and had less hypertension (P = .011), but had more advanced clinical stage tumors (P < .001) and surgeries with multiple flap reconstruction (P = .007). Patient groups did not differ with regard to wound complications (P = .47), return to operating room (P = .31), or readmission rates (P = .49). The NAC group received more blood transfusions (P < .001) but was found to have a lower risk of overall complications on multivariate analysis (odds ratio, 0.50; 95% CI, 0.30-0.83). The overall complication rate was unchanged with surgery performed ≤21 days after the last chemotherapy cycle. CONCLUSIONS: Patients undergoing NAC appear to have a higher disease burden but tend to be younger and healthier. Within the context of this inherent selection bias, NAC does not appear to increase perioperative morbidity among patients undergoing surgery for HNC.

Feasibility of an Enhanced Recovery After Surgery (ERAS) pathway for major head and neck oncologic surgery.

OBJECTIVES: Enhanced Recovery After Surgery (ERAS) protocols are gaining traction in the field of head and neck surgery following success in other specialties. Various institutions have reported on the feasibility of implementation and early outcomes in their centers. We report our experience of setting up an ERAS program in a high-volume tertiary cancer care center, including the challenges faced and overcome. METHODS: With multidisciplinary input, an ERAS protocol was developed consisting of pre-, intra-, and post-operative interventions based on current evidence. We then assessed an initial series of 104 patients on the ERAS protocol and tracked the compliance rates for various interventions. RESULTS: Compliance rates to interventions including pre-operative medication (84.6%), multimodal analgesia (84.6%95.1%), early removal of urinary catheters (76.0%) and early mobilization (56.7%) show a wide variation. However, response rates in the assessment of patient-reported outcomes are low. We discuss factors surrounding the feasibility of implementing an ERAS protocol and tracking outcomes in a diverse, high volume center. DISCUSSION: While there are challenges in implementation, results indicate that a successful ERAS pathway in major head and neck oncologic surgery is feasible. Engaging shareholders and making full use of technology in the form of electronic medical systems are essential to this success. IMPLICATIONS FOR PRACTICE: ERAS pathways should be encouraged in head and neck surgery, given their proven feasibility in a range of institutions. Further study is needed to confirm this program's impact on outcomes.

Modern treatment of sinonasal undifferentiated carcinoma.

PURPOSE OF REVIEW: Sinonasal undifferentiated carcinomas are rare aggressive tumours with traditionally poor outcomes. Although multimodality treatment has been recommended by most centres, the ideal treatment sequence or regimen has not been established. RECENT FINDINGS: Recent evidence suggests that induction chemotherapy may be used for chemoselection and cytoreduction prior to definitive chemoradiotherapy. Where there is a favourable response, concurrent chemoradiotherapy is favoured, with an improved overall survival and improved rates of organ preservation. SUMMARY: Induction chemotherapy may be a useful guide for selection of patients for chemoradiotherapy or surgery and has shown encouraging results. Further research is required to establish the ideal induction chemotherapy regimen for this rare group of tumours.

Enhanced recovery after surgery (ERAS) in head and neck oncologic surgery: Impact on return to intended oncologic therapy (RIOT) and survival.

BACKGROUND: Enhanced Recovery After Surgery (ERAS) pathways in head and neck cancer (HNC) have shown to improve perioperative outcomes and reduce complications. The longer term implications on adjuvant treatment and survival have not been studied. We hereby report the first study on the impact of an ERAS pathway on return to intended oncologic treatment (RIOT) and overall survival (OS) in HNC. METHODS: 200 patients undergoing head and neck oncologic surgery on an ERAS pathway between March 1, 2016 and March 31, 2019 were matched to controls over the same interval. Demographic, tumor and adjuvant therapy-related data were collected, including time to adjuvant therapy(TAT) and treatment package time(TPT). Risk factors for TAT > 42 days and TPT ≥ 85 days were assessed. OS was compared and risk factors for inferior OS determined. RESULTS: Baseline characteristics including co-morbidities and tumor stage were similar. Of 179 patients planned for adjuvant treatment, there was no difference in RIOT rate (89.0% vs 87.5%, p = 0.753), proportion of TAT > 42 days of surgery (55.6% vs 59.7%, p = 0.642), or TPT ≥ 85 days (48.1% vs 57.1, p = 0.258), for the ERAS and control groups, respectively. On multivariate analysis, alcohol use (OR 3.58; 95 %CI 1.11-11.52) and recurrent disease status (OR 2.88; 95 %CI 1.40-5.93) were independently associated with prolonged TAT. Three-year OS was similar between the ERAS and control groups (73% vs 76%, p = 0.521). CONCLUSION: ERAS has not shown to improve RIOT or OS in the current study. However, its benefit for perioperative outcomes is undeniable and further studies are required on longer term quality and survival outcomes.

Multifocal regression and pathologic response predicts recurrence after neoadjuvant chemotherapy in head and neck squamous cell carcinoma.

OBJECTIVES: Complete pathological response after neoadjuvant chemotherapy (NAC) in head and neck squamous cell carcinomas (HNSCC) is a good prognostic factor. Multifocal regression post-NAC in breast cancer has proven to impact locoregional control (LRC) but has not been evaluated in HNSCC. We evaluate the impact of multifocal regression and major pathologic response (MPR) on survival indices in HNSCC. MATERIALS AND METHODS: Retrospective review of HNSCC patients receiving NAC followed by surgery with curative intent between March 2016 to March 2019 at MD Anderson Cancer Center. Tumor focality (uni- or multifocal), pathologic response and other pathologic data were collected. MPR was defined as ≤ 10% residual tumor. Overall survival (OS) and LRC were analyzed and multivariate Cox regression analysis was performed. RESULTS: 101 patients were analyzed, with 18.8% pathologic complete response, 18.8% with 1-10% viable tumor and 60.4% with > 10% viable tumor. 61 (60.4%) had unifocal disease while 19 (18.8%) had multifocal disease. Tumor focality was significantly associated with LRC but not OS, where the 3-year LRC was 82%, 69% and 52% (p = 0.015) for no viable tumor, unifocal disease and multifocal disease respectively. On multivariate analysis, multifocal disease (HR 10.43; 95 %CI 1.24-87.5) and extranodal extension (HR 4.4; 95 %CI 1.60-12.07) continued to be significant independent predictors of LRC. MPR group displayed significantly better 3-year OS (75% vs 51%, p = 0.041) and 3-year LRC (80% vs 62%, p = 0.011) than those with > 10% viable tumor. CONCLUSION: Multifocal regression and less than MPR after NAC in HNSCC predicts for locoregional recurrence and should be routinely reported.

The impact of COVID-19 on head and neck cancer diagnosis and disease extent.

BACKGROUND: Due to COVID-19, diagnostic delays and a surge of advanced head and neck cancer (HNC) is anticipated. We hereby evaluate patient and tumor characteristics before and during the early COVID-19 period. METHODS: Retrospective review of patients with HNC presented at a multidisciplinary tumor conference from May 14, 2020 to June 18, 2020 was performed and compared to a similar 6-week period a year before. Demographics, time to diagnosis, and tumor characteristics were analyzed. RESULTS: There was a 25% reduction in newly diagnosed malignancies. Groups were similar in baseline characteristics, duration of symptoms, and time to diagnosis. However, median primary tumor size was significantly larger (p = 0.042) and T stage more advanced for mucosal subsites (p = 0.025) in the COVID-19 group. CONCLUSION: Our findings suggest increased tumor burden in patients with HNC presenting during the pandemic, despite a similar time to diagnosis. This may become more pronounced as the pandemic duration is extended.

Overview of COVID-19 testing and implications for otolaryngologists.

BACKGROUND: Testing for SARS-CoV-2 is important for decision making prior to surgery in otolaryngology. An understanding of current and developing testing methods is important for interpreting test results. METHODS: We performed a literature review of current evidence surrounding SARS-CoV-2 diagnostic testing highlighting its utility, limitations, and implications for otolaryngologists. RESULTS: The currently accepted RT-PCR test for SARS-CoV-2 has varying sensitivity according to which subsite of the aerodigestive tract is sampled. Nasal swab sensitivities appear to be about 70%. Chest CT imaging for screening purposes is not currently recommended. CONCLUSION: Due to the current sensitivity of RT-PCR based testing for SARS-CoV-2, a negative test cannot rule out COVID-19. Full PPE should be worn during high-risk procedures such as aerosol generating procedures even if testing is negative. Patients who test positive during screening should have their surgeries postponed if possible until asymptomatic and have tested negative for SARS-CoV-2.

Respiratory droplet generation and dispersal during nasoendoscopy and upper respiratory swab testing.

Respiratory particle generation and dispersal during nasoendoscopy and swab testing is studied with high-speed video and laser light illumination. Video analysis reveals droplet formation in three manoeuvres during nasoendoscopy - sneezing, vocalization, and nasal decongestion spray. A capillary bridge of mucus can be seen when a nasoendoscope exits wet nares. No droplet formation is seen during oral and nasopharyngeal swab testing. We outline the following recommendations: pull the face mask down partially and keep the mouth covered, only allowing nasal access during nasoendoscopy; avoid nasal sprays if possible; if nasal sprays are used, procedurists should be in full personal protective equipment prior to using the spray; withdrawal of swabs and scopes should be performed in a slow and controlled fashion to reduce potential dispersion of droplets when the capillary bridge of mucus breaks up.

Changing practice patterns in head and neck oncologic surgery in the early COVID-19 era.

BACKGROUND: The novel coronavirus 2019 (COVID-19) pandemic has changed health care, challenged by resource constraints and fears of transmission. We report the surgical practice pattern changes in a Head and Neck Surgery department of a tertiary cancer care center and discuss the issues surrounding multidisciplinary care during the pandemic. METHODS: We report data regarding outpatient visits, multidisciplinary treatment planning conference, surgical caseload, and modifications of oncologic therapy during this pandemic and compared this data to the same interval last year. RESULTS: We found a 46.7% decrease in outpatient visits and a 46.8% decrease in surgical caseload, compared to 2019. We discuss the factors involved in the decision-making process and perioperative considerations. CONCLUSIONS: Surgical practice patterns in head and neck oncologic surgery will continue to change with the evolving pandemic. Despite constraints, we strive to prioritize and balance the oncologic and safety needs of patients with head and neck cancer in the face of COVID-19.

Impact of the COVID-19 pandemic on Otolaryngology trainee education.

BACKGROUND: The COVID-19 pandemic has reduced clinical volume with a negative impact on trainee education. METHODS: Survey study of Otolaryngology trainees in North America, during the COVID-19 pandemic in April 2020. RESULTS: Of 216 respondents who accessed the survey, 175 (83%) completed the survey. Respondents reported a universal decrease in clinical activities (98.3%). Among participants who felt their program utilized technology well, there were significantly decreased concerns to receiving adequate educational knowledge (29.6% vs 65.2%, P = .003). However, 68% of trainees still expressed concern in ability to receive adequate surgical training. In addition, 54.7% of senior trainees felt that the pandemic had a negative impact on their ability to secure a job or fellowship after training. CONCLUSIONS: Trainees universally felt a negative impact due to the COVID-19 pandemic. Use of technology was able to alleviate some concerns in gaining adequate educational knowledge, but decreased surgical training remained the most prevalent concern.

Head and neck surgical oncology in the time of a pandemic: Subsite-specific triage guidelines during the COVID-19 pandemic.

BACKGROUND: COVID-19 pandemic has strained human and material resources around the world. Practices in surgical oncology had to change in response to these resource limitations, triaging based on acuity, expected oncologic outcomes, availability of supportive resources, and safety of health care personnel. METHODS: The MD Anderson Head and Neck Surgery Treatment Guidelines Consortium devised the following to provide guidance on triaging head and neck cancer (HNC) surgeries based on multidisciplinary consensus. HNC subsites considered included aerodigestive tract mucosa, sinonasal, salivary, endocrine, cutaneous, and ocular. RECOMMENDATIONS: Each subsite is presented separately with disease-specific recommendations. Options for alternative treatment modalities are provided if surgical treatment needs to be deferred. CONCLUSION: These guidelines are intended to help clinicians caring for patients with HNC appropriately allocate resources during a health care crisis, such as the COVID-19 pandemic. We continue to advocate for individual consideration of cases in a multidisciplinary fashion based on individual patient circumstances and resource availability.

Meta-analysis of induction chemotherapy as a selection marker for chemoradiation in the head and neck.

OBJECTIVE: Many trials incorporate induction chemotherapy (IC) in selecting for organ preservation in head and neck squamous cell carcinomas (HNSCC). However, few studies examine IC response in predicting for chemoradiation therapy (CRT) response. This meta-analysis aims to determine the predictive accuracy of IC for subsequent response to CRT and overall survival (OS). DATA SOURCES: Medline, EMBASE, Cochrane register. METHODS: A systematic search identified studies from database inception to October 2016 that used IC prior to CRT as definitive treatment for advanced HNSCC. The sensitivities and specificities of IC response predicting for complete CRT response were calculated, and the results were pooled in a summary receiver operating curve. One-, 2- and 5-year OS data were extracted. RESULTS: Seven studies (n = 423 patients) were analyzed for response and six (n = 439) for OS. Pooled median sensitivity and specificity of IC response predicting CRT response were 0.95 (95% confidence interval [CI]: 0.72-0.98) and 0.43 (95% CI: 0.00-0.61), respectively. Patients were more likely to respond to CRT given previous response to IC (positive likelihood ratio = 1.6; 95% CI: 1.21-2.11) and less likely to respond to CRT if they failed to respond to IC (negative likelihood ratio = 0.16; 95% CI: 0.07-0.38). At 2 years, good response to IC was a statistically significant prognostic marker with a risk ratio of 1.35 (95% CI: 1.12-1.64). CONCLUSION: Our data suggests that patients with poor IC response will have poorer response to CRT and should be directed to other modalities. In contrast, good IC response does not guarantee a favorable outcome to CRT; however, because these patients are likely to have better prognoses, they should be offered salvage therapies of curative intent despite treatment failure. LEVEL OF EVIDENCE: NA. Laryngoscope, 128:1594-1601, 2018.

Salivary fistula: Blue dye testing as part of an algorithm for early diagnosis.

Objective: Orocutaneous and pharyngocutaneous fistula (OPCF) is a debilitating complication of head and neck surgery for squamous cell carcinoma (SCC), resulting in delayed adjuvant treatment and prolonged hospitalization. As yet, there is no established test that can help in prompt and accurate diagnosis of OPCF. This study aims to determine the accuracy of bedside blue dye testing and its role as part of an algorithm for early diagnosis. We also analyze the risk factors predisposing to OPCF. Study Design: Retrospective cohort study from 2012 to 2014. Methods: Patients with head and neck SCC who underwent major resection and reconstruction, at risk of OPCF, were included. Results of blue-dye and video-fluoroscopic swallow-studies (VFSS) testing for OPCF were recorded. For the patients that were noted to develop OPCF, the length of time to diagnosis of fistula and subsequent mode of management were examined. Results: Of the 93 patients in this study, 25 (26.9%) developed OPCF. Advanced T-classification (T3/T4) was the only significant predisposing risk factor (p = 0.013). The sensitivity and specificity of the bedside blue dye testing was found to be 36.4% and 100%, respectively. The test positive patients were diagnosed with OPCF at a median of postoperative day (POD) 9.5 as compared to POD 13 for the test negative patients (p = 0.001). Early diagnosis was associated with faster fistula resolution with treatment. Conclusion: Blue dye testing is a simple bedside test that can assist in the early diagnosis of OPCF in patients, allowing treatment to be instituted earlier with improved outcomes. Level of Evidence: 3.