Sarcopenia predicts short-term treatment-related toxicity in patients undergoing curative-intent therapy for head and neck cancer: A systematic review and meta-analysis.

Sarcopenia is an increasingly recognized biomarker associated with poorer outcomes. The objective of this study was to ascertain the effect of sarcopenia on treatment tolerance and short-term toxicity in head and neck cancer (HNC). A systematic review was performed using multiple databases. An inverse-variation, random-effects model was used to perform the meta-analysis to evaluate the effect of sarcopenia on severe treatment toxicity and poor treatment tolerance. Sixteen observational studies, including 3187 patients with HNC, were analyzed. The combined odds ratio (OR) for severe treatment toxicity and tolerance was 2.22 (95%CI 1.50-3.29) and 1.40 (95%CI 0.84-2.32), respectively. The effect of sarcopenia on short-term severe treatment toxicity was similar with upfront surgery (OR 2.03, 95%CI 1.22-3.37) and definitive radiotherapy (OR 2.24, 95%CI 1.18-4.27) Patients with sarcopenia are more than twice as likely to suffer a short-term treatment-related toxicity when undergoing curative-intent HNC treatment.

Quality of Life After Neoadjuvant Chemotherapy and Transoral Robotic Surgery for Oropharynx Cancer.

Importance: Efforts are underway to deintensified treatment protocols for patients with human papillomavirus virus-associated oropharyngeal squamous cell carcinoma (HPV-OPSCC) to achieve similar excellent oncologic outcomes while reducing treatment-related adverse effects. Transoral robotic surgery (TORS) as primary treatment often requires adjuvant therapy due to the high incidence of nodal metastasis. Treatment with neoadjuvant chemotherapy followed by TORS and neck dissection (NECTORS), reserving radiation therapy for salvage, yields excellent oncologic outcomes. Objective: To assess patient-reported quality of life (QOL) and functional outcomes among patients with HPV-OPSCC who undergo NECTORS. Design, Settings, and Participants: This was a multicenter prospective cohort study of patients with HPV-OPSCC treated with the NECTORS protocol in 2017 to 2022. Consecutive patients with stage III or IVa HPV-OPSCC treated with NECTORS in 2017 to 2022 who had completed the primary QOL questionnaire at baseline and at least once during the 24-month follow-up period were included. Ninety-four patients were eligible, and 67 were included in the analyses. Outcome Measures: QOL questionnaires at baseline, and at month 1, 3, 6, 12, 18, and 24 posttreatment. Global score on the 30-item European Organization for Research and Treatment of Cancer Core quality of life questionnaire (EORTC QLQ-C30) was the primary outcome; the head and neck extension module (EORTC QLQ-HN35); the MD Anderson Dysphagia Inventory for dysphagia-related QOL; and the Decision Regret Scale were also used. Paired t tests assessed change between the baseline and 12- or 24-month patient-reported outcomes. Results: Among the study population of 67 patients (median [range] age, 63 [58-67] years; 54 [80.6%] male) with HPV-OPSCC, the most frequent cancer subsites were palatine tonsil (41 [61%]) and base of tongue (26 [39%]); none required adjuvant RT. Global QOL at 24 months improved compared with baseline (mean difference, 9.49; 95% CI, 2.45 to 16.53). All EORTC QLQ-C30 functional scores returned to baseline or improved within 3 to 6 months posttreatment and remained stable at 24 months. EORTC QLQ-HN35 symptom scale scores improved or were stable at 24 months. The MD Anderson Dysphagia Inventory scores demonstrated no significant difference between baseline and month 12 for global scores (mean difference, 6.15; 95% CI, -4.18 to 16.49) and composite scores (mean difference, 2.73; 95% CI, -1.62 to 7.09). Median (range) score on the Decision Regret Scale was 5 of 100 (0-30), representing mild overall regret. Conclusion and Relevance: The findings of this multicenter cohort study indicate that use of the NECTORS protocol is associated with excellent QOL outcomes. QOL measures returned to baseline levels or were better than baseline, which represents positive outcomes for patients with HPV-OPSCC who undergo this treatment regimen.

Prioritization of head and neck cancer patient care during the COVID-19 pandemic: a retrospective cohort study.

BACKGROUND: The COVID-19 pandemic placed considerable strain on the healthcare system, leading to the re-allocation of resources and implementation of new practice guidelines. The objective of this study is to assess the impact of COVID-19 guideline modifications on head and neck cancer (HNC) care at two tertiary care centers in Canada. METHODS: A retrospective cohort study was conducted. HNC patients seen at two tertiary care centers before and after the onset of the COVID-19 pandemic (pre-pandemic: July 1st, 2019, to February 29th, 2020; pandemic: March 1st, 2020, to October 31st, 2020) were included. The pre-pandemic and pandemic cohorts were compared according to patient and tumor characteristics, duration of HNC workup, and treatment type and duration. Mean differences in cancer care wait times, including time to diagnosis, tumor board, and treatment as well as total treatment package time and postoperative hospital stay were compared between cohorts. Univariate and multivariate analyses were used to compare characteristics and outcomes between cohorts. RESULTS: Pre-pandemic (n = 132) and pandemic (n = 133) patients did not differ significantly in sex, age, habits, or tumor characteristics. The percentage of patients who received surgery only, chemo/radiotherapy (CXRT) only, and surgery plus adjuvant CXRT did not differ significantly between cohorts. Pandemic patients experienced a significant time reduction compared to pre-pandemic patients with regards to the date first seen by a HNC service until start of treatment ([Formula: see text] = 48.7 and 76.6 days respectively; p = .0001), the date first seen by a HNC service until first presentation at tumor board ([Formula: see text] = 25.1 and 38 days respectively; p = .001), mean total package time for patients who received surgery only ([Formula: see text] = 3.7 and 9.0 days respectively; p = .017), and mean total package time for patients who received surgery plus adjuvant CXRT ([Formula: see text] = 80.2 and 112.7 days respectively; p = .035). CONCLUSION: The time to treatment was significantly reduced during the COVID-19 pandemic as compared to pre-pandemic. This transparent model of patient-centered operative-room prioritization can serve as a model for improving resource allocation and efficiency of HNC care during emergency and non-emergency scenarios.

Response to Neoadjuvant Targeted Therapy in Operable Head and Neck Cancer Confers Survival Benefit.

PURPOSE: Neoadjuvant targeted therapy provides a brief, preoperative window of opportunity that can be exploited to individualize cancer care based on treatment response. We investigated whether response to neoadjuvant therapy during the preoperative window confers survival benefit in patients with operable head and neck squamous cell carcinoma (HNSCC). PATIENTS AND METHODS: A pooled analysis of treatment-naïve patients with operable HNSCC enrolled in one of three clinical trials from 2009 to 2020 (NCT00779389, NCT01218048, NCT02473731). Neoadjuvant regimens consisted of EGFR inhibitors (n = 83) or anti-ErbB3 antibody therapy (n = 9) within 28 days of surgery. Clinical to pathologic stage migration was compared with disease-free survival (DFS) and overall survival (OS) while adjusting for confounding factors using multivariable Cox regression. Circulating tumor markers validated in other solid tumor models were analyzed. RESULTS: 92 of 118 patients were analyzed; all patients underwent surgery following neoadjuvant therapy. Clinical to pathologic downstaging was more frequent in patients undergoing neoadjuvant targeted therapy compared with control cohort (P = 0.048). Patients with pathologic downstage migration had the highest OS [89.5%; 95% confidence interval (CI), 75.7-100] compared with those with no stage change (58%; 95% CI, 46.2-69.8) or upstage (40%; 95% CI, 9.6-70.4; P = 0.003). Downstage migration remained a positive prognostic factor for OS (HR, 0.22; 95% CI, 0.05-0.90) while adjusting for measured confounders. Downstage migration correlated with decreased circulating tumor markers, SOX17 and TAC1 (P = 0.0078). CONCLUSIONS: Brief neoadjuvant therapy achieved pathologic downstaging in a subset of patients and was associated with significantly better DFS and OS as well as decreased circulating methylated SOX17 and TAC1.

Development and validation of the modified index of fragility in head and neck cancer surgery.

BACKGROUND: This study aims to develop and validate, a clinically useful modified index of fragility (mIFG) to identify patients at risk of fragility and to predict postoperative adverse events. METHOD: An observational study was performed using the American College of Surgeons National Surgical Quality Improvement Program database, from 2006 to 2018. All patients undergoing nonemergency head and neck cancer surgery were included. A seven-item index (mIFG) was developed using variables associated with frailty, cachexia, and sarcopenia, drawn from the literature (weight loss, low body mass index, dyspnea, diabetes, serum albumin, hematocrit, and creatinine). Multivariable logistic regression was used to model the association between mIFG, postoperative adverse events and death. A validation cohort was then used to ascertain the diagnostic accuracy of the mIFG. RESULTS: A total of 23,438 cases were included (16,407 in the derivation group and 7031 in the validation group). There was a total of 4273 postoperative major adverse events (AE) and deaths, 1023 postoperative pulmonary complications and 1721 wound complications. Using the derivation cohort, the 7-item mIFG was independently associated with death, major AEs, pulmonary and wound complications, when controlling for significant covariates. The mIFG predicted death and major adverse events using the validation cohort with an accuracy of 0.70 (95% CI: 0.63-0.76) and 0.64 (95% CI: 0.63-0.66), respectively. The mIFG outperformed the modified Frailty index. CONCLUSION: The modified index of fragility is a reliable and easily accessible tool to predict risk of postoperative adverse events and death in patients undergoing head and neck cancer surgery.

Dealing with the Vicissitudes and Abject Consequences of Head and Neck Cancer: A Vital Role for Psycho-Oncology.

Patients with head and neck cancer face important life-altering effects in appearance and function, affecting distress and quality of life and requiring the involvement of a multidisciplinary team. Psycho-oncology makes an important contribution to the field, as head and neck cancers carry a huge adaptational toll. To illustrate the value of this discipline, we report two cases of patients with advanced head and neck cancer for which the treatment-related body changes were of major significance. A commentary by the treating surgeons and psycho-oncologists precedes a general discussion about the clinical management of such patients. The article outlines strategies to address health literacy, doctor-patient communication, treatment decision-making, and emotional distress; placing the person at the center of oncological care. It calls for the broad application of principles of psychological first aid by healthcare professionals in oncology.

Application of the Milan system for reporting salivary gland cytopathology using cell blocks.

The Milan system for reporting salivary gland cytopathology (MSRSGC) is a novel standardized classification tool for salivary gland cytology specimens based on the use of direct smears. Formalin-fixed paraffin-embedded (FFPE) cell blocks facilitate the use of ancillary studies, leading to improved diagnostic accuracy. However, the application of the MSRSGC with only cell blocks has not been well established. Consecutive cohort of all parotid gland cytology specimens between 01/01/2018 and 30/06/2021 was performed. All cytology specimens were processed into cell blocks only. Cytologic diagnoses were classified prospectively according to the MSRSGC categories. The risk of malignancy (ROM) for each diagnostic category and the diagnostic performance were calculated. A total of 230 FNA samples from 221 patients were identified, including 47% and 78.4% with surgical or clinical follow-up, respectively. The ROMs based on surgical follow-up for the non-diagnostic, non-neoplastic, AUS, neoplasm: benign, SUMP, SFM and malignant categories were 21.4%,0%,50%,0%,30%,100% and 100%, respectively. The ROMs based on the clinical follow-up for these categories were 7.3%,0%,37.3%,0%,27.3%,100% and 100%, respectively. Following surgical excision, all Milan IVa category samples were confirmed as benign, and all Milan V and VI category samples were confirmed as malignant. This study validates the application of the MSRSGC with the sole use of FFPE cell blocks. The diagnostic accuracy of MSRSGC is high and compares favorably to other institutions using traditional cytology assessment methods. Furthermore, FNA results using this technique enabled to provide optimal patient management based on the ROM of the different Milan system categories.

Historical Perspective: How the Discovery of HPV Virus Led to the Utilization of a Robot.

The treatment of oropharyngeal cancer has undergone many paradigms shifts in recent decades. First considered a surgical disease, improvements in radiotherapy led to its popularization in the 1990s. Subsequently, the discovery of the human papillomavirus (HPV) in the pathogenesis of oropharyngeal cancer, as well as the increase in HPV-associated oropharynx cancer incidence, have prompted a reevaluation of its management. Its sensitivity to standard treatment with a favorable prognosis compared to non HPV-associated oropharyngeal cancer led to a focus on minimizing treatment toxicity. Advances in radiation and surgical techniques, including the use of transoral robotic surgery, gave the rationale to ongoing de-escalation clinical trials in HPV-associated oropharynx cancer.

Poor treatment tolerance in head and neck cancer patients with low muscle mass.

BACKGROUND: We ascertain the role of a low cervical paraspinal skeletal muscle index (CPSMI) as a biomarker for poor treatment tolerance in patients with operable mucosal head and neck squamous cell carcinoma (HNSCC). METHODS: A prospective cohort of patients with operable HNSCC requiring microvascular reconstruction was evaluated. Low CPSMI was calculated using preoperative CT neck imaging. Poor treatment tolerance, a composite measure of incomplete therapy or severe morbidity/mortality during treatment, was the primary outcome. RESULTS: One hundred and twenty-seven patients underwent extirpative surgery with a mean age was 60.5. Poor treatment tolerance occurred in 71 (56%) patients with 21 not completing recommended adjuvant therapy and 66 having severe treatment-related morbidity. A low CPSMI was independently associated with poor treatment tolerance (OR 2.49, 95%CI 1.10-5.93) and delay to adjuvant therapy (OR 4.48, 95%CI 1.07-27.6) after adjusting for multiple confounders. CONCLUSION: Low CPSMI was independently associated with poor treatment tolerance in patients with operable HNSCC.

Above and Beyond Age: Prediction of Major Postoperative Adverse Events in Head and Neck Surgery.

OBJECTIVE: Major postoperative adverse events (MPAEs) following head and neck surgery are not infrequent and lead to significant morbidity. The objective of this study was to ascertain which factors are most predictive of MPAEs in patients undergoing head and neck surgery. METHODS: A cohort study was carried out based on data from patients registered in the National Surgical Quality Improvement Program (NSQIP) from 2006 to 2018. All patients undergoing non-ambulatory head and neck surgery based on Current Procedural Terminology codes were included. Perioperative factors were evaluated to predict MPAEs within 30-days of surgery. Age was classified as both a continuous and categorical variable. Retained factors were classified by attributable fraction and C-statistic. Multivariate regression and supervised machine learning models were used to quantify the contribution of age as a predictor of MPAEs. RESULTS: A total of 43 701 operations were analyzed with 5106 (11.7%) MPAEs. The results of supervised machine learning indicated that prolonged surgeries, anemia, free tissue transfer, weight loss, wound classification, hypoalbuminemia, wound infection, tracheotomy (concurrent with index head and neck surgery), American Society of Anesthesia (ASA) class, and sex as most predictive of MPAEs. On multivariate regression, ASA class (21.3%), hypertension on medication (15.8%), prolonged operative time (15.3%), sex (13.1%), preoperative anemia (12.8%), and free tissue transfer (9%) had the largest attributable fractions associated with MPAEs. Age was independently associated with MPAEs with an attributable fraction ranging from 0.6% to 4.3% with poor predictive ability (C-statistic 0.60). CONCLUSION: Surgical, comorbid, and frailty-related factors were most predictive of short-term MPAEs following head and neck surgery. Age alone contributed a small attributable fraction and poor prediction of MPAEs. LEVEL OF EVIDENCE: 3.

Thyroidectomy for Graves' Disease Predicts Postoperative Neck Hematoma and Hypocalcemia: A North American cohort study.

OBJECTIVE: Examine the association of Graves' disease with the development of postoperative neck hematoma. DESIGN: A cohort of patients participating in the Thyroid Procedure-Targeted Database of the National Surgical Quality Improvement Program from January 1, 2016 to December 31, 2018. SETTING: A North American surgical cohort study. METHODS: 17 906 patients who underwent thyroidectomy were included. Propensity score matching was performed to adjust for differences in baseline covariates. Multivariate logistic regression was used to ascertain the association between thyroidectomy for Graves' disease and risk of postoperative adverse events within 30 days of surgery. The primary outcome was postoperative hematoma. Secondary outcomes were postoperative hypocalcemia and recurrent laryngeal nerve injury. RESULTS: One-to-three propensity score matching yielded 1207 patients with mean age (SD) of 42.6 (14.9) years and 1017 (84.3%) female in the group with Graves' disease and 3621 patients with mean age (SD) of 46.7 (15.0%) years and 2998 (82.8%) female in the group with indications other than Graves' disease for thyroidectomy. The cumulative 30-day incidence of postoperative hematoma was 3.1% (38/1207) in the Graves' disease group and 1.9% (70/3621) in other patients. The matched cohort showed that Graves' disease was associated with higher odds of postoperative hematoma (OR 1.65, 95% CI 1.10-2.46) and hypocalcemia (OR 2.04, 95% CI 1.66-2.50) compared with other indications for thyroid surgery. There was no difference in recurrent laryngeal nerve injury among the 2 groups. CONCLUSIONS: Patients with Graves' disease undergoing thyroidectomy are more likely to suffer from postoperative hematoma and hypocalcemia compared to patients undergoing surgery for other indications.

Cervical paraspinal skeletal muscle index outperforms frailty indices to predict postoperative adverse events in operable head and neck cancer with microvascular reconstruction.

OBJECTIVE: Sarcopenia is increasingly being recognized as a negative prognostic factor in patients with head and neck cancer (HNC). We associate a sarcopenia biomarker measured radiographically from computed tomography (CT) of the neck to postoperative adverse events in patients with operable HNC. PATIENTS AND METHODS: A prospective cohort of treatment-naïve HNC patients undergoing surgery with microvascular reconstruction was performed. Cervical paraspinal skeletal muscle index (CPSMI) was calculated using preoperative CT neck imaging and adjusted for height and sex. Postoperative adverse events, including Clavien-Dindo Grade 3+ complications and fistula, were recorded within 30-days of the index surgery. Multivariate logistic regression was used to evaluate the association between CPSMI and postoperative complications. The modified frailty index (mFI) and Risk Assessment Index (RAI) were compared with CPSMI outcomes. RESULTS: A total of 127 patients with mucosal HNC were included in the study. The mean age was 60.5 years, and 87 (68.5%) patients were male. Sixty Clavien-Dindo grade 3+ events occurred; 17 patients developed an oro/pharyngocutaneous fistula. Low CPSMI was independently associated with Clavien-Dindo Grade 3+ events (OR 2.80, 95% CI of 1.18-6.99) and fistula (OR of 6.10, 95% CI of 1.53-24.3) when adjusted for multiple factors. CPSMI outperformed the mFI and RAI frailty indices to predict postoperative adverse events (p < .05). CONCLUSION: Low CPSMI is independently associated with postoperative adverse events and outperforms current frailty indices inoperable HNC with microvascular reconstruction.

Neoadjuvant chemotherapy followed by surgery for HPV-associated locoregionally advanced oropharynx cancer.

BACKGROUND: Neoadjuvant chemotherapy followed by surgery (NAC + S), a paradigm based on systemic escalation coupled with surgery-based de-escalation, is under investigation for treatment of HPV-associated oropharynx cancer (OPC). METHODS: Prospective cohort of patients with non-metastatic, p16 positive OPC enrolled in a clinical trial of NAC + S was compared to a historic cohort of patients undergoing concurrent chemoradiation (CCRT) to compare disease-free survival (DFS). RESULTS: Fifty-five patients were treated with NAC + S and 142 with CCRT. Stage-matched patients undergoing CCRT had higher frequency of smoking and alcohol consumption. 5-year DFS in the NAC + S group was 96.1% (95% CI 90.8-100) compared to 67.6% (95% CI 50.7-84.5) for CCRT (P = .01). At 12 months from treatment, 24.5% of patients undergoing CCRT and none of the patients in the NAC + S were feeding tube dependent (P < .0001). CONCLUSION: NAC + S may be a novel approach for HPV-associated OPC as it provides lower feeding tube dependence and improved survival compared to stage-matched patients undergoing CCRT.

Pathologic response to neoadjuvant chemotherapy in HPV-associated oropharynx cancer.

BACKGROUND: A paradigm shift has led to de-escalation trials for the treatment of HPV-positive oropharynx cancer (OPC). The objective of this study was to assess the ability of tumor volume reduction on imaging to predict pathological response to neoadjuvant chemotherapy in patients with HPV-positive OPC. METHODS: A prospective observational study of 54 patients with HPV-positive OPC enrolled in a clinical trial of neoadjuvant chemotherapy followed by surgery was performed. Patients underwent three cycles of induction chemotherapy (cisplatin/docetaxel); prechemotherapy and postchemotherapy imaging were obtained. Receiver operating characteristic curves and logistic regression analyses were used. RESULTS: The complete pathologic response (pCR) rate at primary and nodal sites were 72% and 57%, respectively. Tumor volume reduction of ≥90% following induction chemotherapy predicted pCR of the primary tumor. CONCLUSIONS: Neoadjuvant chemotherapy followed by definitive transoral surgery is a new paradigm worthy of further investigation and MRI is a reliable modality to assess preoperative response.

The infectious thyroid nodule: a case report of mucormycosis associated with ibrutinib therapy.

BACKGROUND: Acute invasive fungal infections of the head and neck secondary to tyrosine kinase inhibitors are rare and potentially life-threatening events. CASE PRESENTATION: We report a case of mucormycosis of the thyroid gland in a patient known for chronic lymphocytic leukemia receiving ibrutinib who presented with a rapidly growing thyroid nodule and dysphonia. An acute invasive fungal infection was identified on a core needle biopsy; mucormycosis was confirmed on culture. The patient was successfully treated with surgical debridement and long-term antifungal therapy. CONCLUSION: Patients on ibrutinib may be at risk of acute invasive fungal infections of the head and neck.

Magnetic Resonance Imaging Texture Analysis Predicts Recurrence in Patients With Nasopharyngeal Carcinoma.

BACKGROUND: The personalization of oncologic treatment using radiomic signatures is mounting in nasopharyngeal carcinoma (NPC). We ascertain the predictive ability of 3D volumetric magnetic resonance imaging (MRI) texture features on NPC disease recurrence. METHODS: A retrospective study of 58 patients with NPC undergoing primary curative-intent treatment was performed. Forty-two image texture features were extracted from pre-treatment MRI in addition to clinical factors. A multivariate logistic regression was used to model the texture features. A receiver operating characteristic curve on 100 bootstrap samples was used to maximize generalizability to out-of-sample data. A Cox proportional model was used to predict disease recurrence in the final model. RESULTS: A total of 58 patients were included in the study. MRI texture features predicted disease recurrence with an area under the curve (AUC), sensitivity, and specificity of 0.79, 0.73, and 0.71, respectively. Loco-regional recurrence was predicted with AUC, sensitivity, and specificity of 0.82, 0.73 and 0.74 respectively while prediction for distant metastasis had an AUC, sensitivity, and specificity of 0.92, 0.79 and 0.84, respectively. Texture features on MRI had a hazard ratio of 4.37 (95% confidence interval 1.72-20.2) for disease recurrence when adjusting for age, sex, smoking, and TNM staging. CONCLUSION: Texture features on MRI are independent predictors of NPC recurrence in patients undergoing curative-intent treatment.

Postoperative infection predicts poor survival in locoregionally advanced oral cancer.

BACKGROUND: We ascertain the association of postoperative infection on survival in patients with locoregionally advanced oral cavity squamous cell carcinoma (OCSCC). METHODS: A retrospective study of patients with stage III/IVA OCSCC undergoing curative-intent surgery was performed. Postoperative infection was considered within 30 days after surgery. Kaplan-Meier survival curves were used to compare overall survival (OS) in patients with postoperative infection. Cox regression and propensity-score matching were used to adjust for confounders. RESULTS: Fifty-four of 114 patients had a postoperative infection. The 5-year OS in patients with a postoperative infection (24.1%) was lower than those without (65.2%; P < .0001). Postoperative infection was a negative predictor of OS after adjusting for patient, antibiotic, pathologic, and operative factors; the adjusted hazard ratio for OS was 2.54 (95% confidence interval, 1.27-5.09). CONCLUSION: Postoperative infection is a strong negative predictor of OS in patients with OCSCC undergoing ablative surgery.