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Background: Resection margins are an important prognostic factor for patients with head and neck cancer. In general, for head and neck surgery, a margin >5 mm is advised by the Royal College of Pathologists. However, this cannot always be achieved during laryngeal and hypopharyngeal surgery. The aim of this study is to identify the resection surfaces and measure the maximum feasible margins per subsite. The clinical relevance of these maximum feasible resection margins were analyzed in this descriptive anatomical study. Methods: head and neck surgeons and a pathologist from the Erasmus MC performed a total laryngectomy and laryngopharyngectomy on a head and neck specimen specifically available for research. Results: For a total laryngectomy, resection margins >5 mm were not feasible for the ventral and dorsal resection surface. For a total laryngopharyngectomy, resection margins >5 mm were not feasible for the ventral, dorsal and lateral resection surface. Conclusion: Clear resection margins, defined as a margin >5 mm, are not always feasible in laryngeal and hypopharyngeal surgery, due to the anatomy of the larynx and tumor location. However, striving for a maximum feasible margin is still the main goal. We propose a new guideline for maximum feasible but adequate resection margins in larynx and hypopharynx tumor surgery.

Radiotherapy in the head-and-neck area is one of the main curative treatment options. However, this comes at the cost of varying levels of normal tissue toxicity, affecting up to 80% of patients. Mucositis can cause pain, weight loss and treatment delays, leading to worse outcomes and a decreased quality of life. Therefore, there is an urgent need for an approach to predicting normal mucosal responses in patients prior to treatment. We here describe an assay to detect irradiation responses in healthy oral mucosa tissue. Mucosa specimens from the oral cavity were obtained after surgical resection, cut into thin slices, irradiated and cultured for three days. Seven samples were irradiated with X-ray, and three additional samples were irradiated with both X-ray and protons. Healthy oral mucosa tissue slices maintained normal morphology and viability for three days. We measured a dose-dependent response to X-ray irradiation and compared X-ray and proton irradiation in the same mucosa sample using standardized automated image analysis. Furthermore, increased levels of inflammation-inducing factors—major drivers of mucositis development—could be detected after irradiation. This model can be utilized for investigating mechanistic aspects of mucositis development and can be developed into an assay to predict radiation-induced toxicity in normal mucosa.

Background: Laryngeal and hypopharyngeal cancer is complex and resection margins are therefore constrained. The aim of this study was to investigate the clinical relevance of resection margins in laryngeal and hypopharyngeal surgery. Methods: A retrospective cohort study was performed for patients treated with a total laryngectomy (TL) or laryngopharyngectomy (TLP) for laryngeal or hypopharyngeal squamous cell carcinoma (LSCC and HSCC, respectively). Within the groups primary LSCC, recurrent LSCC, primary HSCC, and recurrent HSCC the relationship between the status of the resection margin according to the Royal Collage of Pathology and the recurrence and survival rates were investigated. Results: Positive resection margins were found in 54% for primary LSCC, 29% for recurrent LSCC, 62% for primary HSCC, and 44% for recurrent HSCC. For primary and recurrent LSCC, there was a linear association between total recurrence and narrowing margins (p = 0.007 resp. p = 0.008). Multivariate survival analysis for primary and recurrent LSCC showed a significantly worse disease free and disease-specific survival in case of positive margins compared to clear margins. Conclusion: Similar survival rates were recorded for close and clear margins for primary and recurrent LSCC. This may suggest that a margin > 5 mm is not clinically relevant in terms of survival. Therefore, a margin of 1–5 mm should be accepted in certain subsites. Margins < 1 mm are related to significantly worse outcomes and should be avoided.

Background: Various operative techniques exist to reconstruct partial hypopharyngeal defects following total laryngectomy. The current study aimed to investigate and compare complications and functional results following commonly used reconstructive techniques. Methods: A systematic review and meta-analysis were performed using studies that investigated outcomes after the reconstruction of a partial hypopharyngeal defect. The outcomes of interest were fistulas, strictures, flap failure, swallowing function and postoperative speech. Results: Of the 4035 studies identified, 23 were included in this review. Four common reconstructive techniques were reported, with a total of 794 patients: (1) pectoralis major myocutaneous and (2) myofascial flap, (3) anterolateral thigh free flap and (4) radial forearm free flap. Fistulas occurred significantly more often than pectoralis major myocutaneous flaps (34%, 95% CI 23–47%) compared with other flaps (p < 0.001). No significant differences in the rates of strictures or flap failure were observed. Pectoralis major myofascial flaps were non-inferior to free-flap reconstructions. Insufficient data were available to assess speech results between flap types. Conclusion: Pectoralis myocutaneous flaps should not be the preferred method of reconstruction for most patients, considering their significantly higher rate of fistulas. In contrast, pectoralis major myofascial flaps yield promising results compared to free-flap reconstructions, warranting further investigation.

BACKGROUND: Few studies have examined health-related quality of life (HRQOL) outcomes in long-term total laryngectomy survivors in relation to the type of hypopharyngeal defect.METHODS: A cross-sectional study was performed in long-term total laryngectomy survivors, treated between 2000 and 2020. The primary outcome was HRQOL, assessed using the FACE-Q Head and Neck Cancer Module, in relation to the type of hypopharyngeal closure (primary closure, partial or circumferential reconstruction).RESULTS: Seventy-nine survivors were included with a median follow-up of 92.1 months (IQR 75.6-140.2 months). Patients requiring partial hypopharyngeal reconstruction (n = 18) scored significantly worse than patients with primary closure (n = 51) on 4 of 13 FACE-Q domains: functional domains of eating (p = 0.03), speech (p = 0.05), and swallowing (p = 0.03), and the psychological domain of speaking-related distress (p = 0.02). No statistically significant differences were found between the circumferential hypopharyngeal defect reconstruction group (n = 10). Stricture occurrence was the only clinical factor associated with worse eating, speaking, swallowing, eating-related distress, and cancer worry in multivariable analyses.CONCLUSION: Several functional and psychological domains were significantly worse following partial hypopharyngeal reconstruction than in patients who received primary closure. Efforts to reduce stricture rates to enhance reconstructive outcomes following total laryngectomy merit further research.

Objective: Evidence suggests that distant metastasis in head and neck squamous cell carcinoma is a spectrum of disease. Previous studies show that oligometastasis has favorable survival compared with polymetastasis. The quality of life of patients with oligometastasis remains unknown. To further solidify the position of oligometastasis as a separate entity, we hypothesized that oligometastatic patients experience better quality of life than polymetastatic patients.Methods: Patients with distant metastasis were stratified into three groups: oligometastasis (≤3 metastatic foci in ≤2 anatomic sites), explosive metastasis (≥4 metastatic foci at one anatomic site), and explosive-disseminating metastasis (spread to ≥3 anatomic sites). Quality of life was assessed every 2 months post distant metastasis diagnosis. Results: Between January 1, 2016, and December 31, 2021, a total of 161 patients with distant metastasis were identified, with a total of 397 measurements. In this group, 57 (35.4%) patients had oligometastasis, 35 (21.7%) patients had explosive metastasis, and 69 (42.9%) patients had explosive-disseminating metastasis. Their median post-distant metastasis survivals were 8.5 months, 3.2 months, and 3.2 months respectively (p < 0.001). A significantly better overall quality of life was observed in the oligometastasis group compared with the polymetastatic groups (+0.75 out of 7, p < 0.05). Furthermore, oligometastatic patients performed better in the subdomains of “physical functioning,” “fatigue,” and “pain.”. Conclusion: Results from this study underscore that subgroups exist regarding quality of life and survival within distant metastasis, with polymetastatic patients performing worse than oligometastatic patients. This highlights the significance of tailored interventions that consider the unique challenges faced by each metastatic group of patients. Level of Evidence: 3, retr

Objective: Since the implementation of value-based healthcare, there has been a growing emphasis on utilizing patient-reported experience measures (PREMs) to enhance the quality of care. However, the current PREMs are primarily generic and static, whereas healthcare is constantly evolving and encompasses a wide variety of aspects that impact care quality. To continuously improve care requires a dynamic PREM. The aim of this study was to propose an item bank for the establishment of a dynamic and care-specific patient-reported evaluation. Methods: In co-creation with patients, a mixed methods study was conducted involving: (1) an explorative review of the literature, (2) a focus group analysis with (ex-)patients, (3) qualitative analyses to formulate themes, and (4) a quantitative selection of items by patients and experts through prioritization. Results: Eight existing PREMs were evaluated. After removing duplicates, 141 items were identified. Through qualitative analyses of the focus group in which the patient journey was discussed, eight themes were formulated: “Organization of healthcare,” “Competence of healthcare professionals,” “Communication,” “Information & services,” “Patient empowerment,” “Continuity & informal care,” “Environment,” and “Technology.” Seven patients and eleven professionals were asked to prioritize what they considered the most important items. From this, an item bank with 76 items was proposed. Conclusion: In collaboration with patients and healthcare professionals, we have proposed a PREM-item bank to evaluate the experiences of patients’ receiving cancer care in an outpatient clinic. This item bank is the first step to dynamically assess the quality of cancer care provided in an outpatient setting.

BACKGROUND: It remains unclear whether a tubed fasciocutaneous or jejunal free flap (FCFF and JFF) is preferable for reconstruction of circumferential pharyngolaryngoesophageal defects.METHODS: All consecutive patients with circumferential pharyngolaryngoesophageal defects reconstructed with an FCFF or JFF between 2000 and 2022 were included. Outcomes of interest were rates of fistulas, strictures, and donor-site complications.RESULTS: In total, 112 patients were included (35 FCFFs and 77 JFFs). Fistula and stricture rates were significantly lower following JFF compared to FCFF reconstructions, with 12% versus 34% (p = 0.008) and 29% versus 49% (p = 0.04), respectively. Severe donor-site complications leading to surgical intervention or ICU admittance only occurred after JFF reconstructions (18%, p = 0.007).CONCLUSIONS: The high fistula and stricture rates in FCFF reconstructions and the rate of severe abdominal complications in JFF reconstructions illustrate inherent procedure-specific advantages and disadvantages. Relative pros and cons should be carefully weighed when tailoring treatments to the individual needs of patients.

Objective: Early-stage glottic cancer (ESGC) is a malignancy of the head and neck. Besides disease control, preservation and improvement of voice quality are essential. To enable expectation management and well-informed decision-making, patients should be sufficiently counseled with individualized information on expected voice quality. This study aims to develop an individualized dynamic prediction model for patient-reported voice quality. This model should be able to provide individualized predictions at every time point from intake to the end of follow-up. Study Design: Longitudinal cohort study. Setting: Tertiary cancer center. Methods: Patients treated for ESGC were included in this study (N = 294). The Voice Handicap Index was obtained prospectively. The framework of mixed and joint models was used. The prognostic factors used are treatment, age, gender, comorbidity, performance score, smoking, T-stage, and involvement of the anterior commissure. The overall performance of these models was assessed during an internal cross-validation procedure and presentation of absolute errors using box plots. Results: The mean age in this cohort was 67 years and 81.3% are male. Patients were treated with transoral CO2 laser microsurgery (57.8%), single vocal cord irradiation up to (24.5), or local radiotherapy (17.5%). The mean follow-up was 43.4 months (SD 21.5). Including more measurements during prediction improves predictive performance. Including more clinical and demographic variables did not provide better predictions. Little differences in predictive performance between models were found. Conclusion: We developed a dynamic individualized prediction model for patient-reported voice quality. This model has the potential to empower patients and professionals in making well-informed decisions and enables tailor-made counseling.

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Background: Patients with head and neck squamous cell carcinoma (HNSCC) relatively frequent develop second primary tumors (SPTs) in the esophagus. Endoscopic screening could lead to timely detection of SPTs in early stages and therefore improves the survival. Methods: We performed a prospective endoscopic screening study in patients with HNSCC in a Western country. Patients with curably treated HNSCC diagnosed January 2017 to July 2021 were included. Routine imaging for HNSCC consisted of flexible transnasal endoscopy with PET/CT or MRI-scan, depending on primary HNSCC location. Screening was performed synchronously(<6 months) or metachronously (≥6 months) after HNSCC diagnosis. The primary outcome was prevalence of SPTs, defined as presence of esophageal high-grade dysplasia or squamous cell carcinoma. Results: We included 202 patients (81% male, mean age 65 years) and performed 250 screening endoscopies. HNSCC was located in the oropharynx(32%), hypopharynx(26%), larynx(22%), and oral cavity(19%). Endoscopic screening was performed within 6 months(34%), 6 months to 1 year(8%), 1 to 2 years(34%), and 2 to 5 years(24%) after HNSCC diagnosis. We detected 11 SPTs in 10 patients(5.0%, 95%CI: 2.4-8.9%) during synchronous(6/85) and metachronous screening(5/165). Most SPTs were detected in early stages(91%) and treated with curative intent with endoscopic resection(80%). No SPTs in screened patients were detected with routine imaging for HNSCC before endoscopic screening. Conclusion: In 5% of patients with HNSCC, an SPT was detected with endoscopic screening. Endoscopic screening should be considered in a selection of HNSCC patients to detect early-stage SPTs, based on highest SPT-risk and life expectancy depending on HNSCC and comorbidities.

BACKGROUND: To date, few comparative studies exist for partial hypopharyngeal defect reconstruction following total laryngectomy. In the absence of objective evidence from comparative studies, the ideal flap choice remains controversial, leading to heterogeneity in institutional treatment protocols. Comparative studies between different reconstructive techniques are required. Therefore, this study compared postoperative outcomes of pectoralis major myocutaneous (PMMC) and myofascial (PMMF) flaps.METHODS: A single-center retrospective cohort study was performed between 2000 and 2022, which included all consecutive patients who underwent a PMMC or PMMF flap reconstruction following total laryngectomy and partial hypopharyngectomy. Primary outcomes were suture line leakages (conservative management), fistulas (surgical management), and strictures. Secondary outcomes included flap failure, donor-site morbidity, and the start of oral intake.RESULTS: In total, 122 patients were included (109 PMMC and 13 PMMF flap reconstructions). The incidence of suture line leakage was significantly higher (p = 0.007) after PMMC flaps (57%) compared with PMMF flaps (15%). Between PMMC and PMMF flaps, fistula (19% vs. 0%) and stricture rates (22% vs. 15%) did not differ significantly. No differences in flap failure, donor-site morbidity, or start of oral intake were observed.CONCLUSIONS: PMMF flaps have inherent advantages (e.g., reduced bulk, increased pliability) over conventional PMMC flaps and have non-inferior results compared to the latter in terms of postoperative complications. Although the final choice for reconstruction should be patient-tailored, a PMMF flap can be considered a reliable primary choice that is feasible in most patients.

Purpose: Early stage lip squamous cell carcinoma (lip SCC) can be treated with conventional excision, Mohs micrographic surgery (MMS), or brachytherapy. The aim of this retrospective study was to describe the medical outcomes, patient-reported outcomes, and costs of these treatments. Methods: A retrospective cohort study of T1–T2 lip SSCs treated between 1996 and 2019. Medical outcomes, recurrences, and survival were retrieved from medical records. Facial appearance, facial function, and Quality of Life (QoL) were measured with the Face-Q H&N and EQ-5D-5L questionnaires. Costs were also calculated. Results: Of the 336 lip SCCs, 122 were treated with excision, 139 with MMS, and 75 with brachytherapy. Locally, the recurrence rate was 2.7% and regionally 4.8%. There were 2% disease-related deaths. T2-stage and poor tumor differentiation were associated with recurrences. Posttreatment QoL, facial function, and appearance were rated as good. Brachytherapy was the most expensive treatment modality. Conclusion: Early-stage lip SCC has a good prognosis, with a disease-specific survival of 98.2% after a median follow-up of 36 months, there was a high QoL and satisfaction at long-term follow-up. Based on the costs and the risk of locoregional recurrences, we believe that, for most noncomplex lip SCCs, MMS would be the most logical treatment option.

Objective: Patients with head and neck cancer (HNC) are characterized by a poor lifestyle and comorbidity. The Geriatric 8 (G8) is an established screening tool to identify frail older patients with cancer. However, studies evaluating frailty in younger HNC patients are lacking. The aim of this study is to evaluate if the G8 can identify frailty and if it is related to mortality in younger HNC patients. Study Design: Case-control study design. Setting: Tertiary cancer center. Methods: We studied patients <70 years with HNC. Patients with G8 ≤ 14 were considered frail. Patients were matched to nonfrail (G8 > 14) control patients. Patients were matched according to sex, age, smoking, tumor location, and period of first consultation. Baseline health characteristics were compared between frail patients and nonfrail controls. Second, the treatment plan and adverse outcomes were compared. Results: Forty-five patients with G8 ≤ 14 were included and matched to 90 nonfrail controls. The median follow-up time was 357 days. Frail patients had a significantly lower body mass index and level of education, a worse World Health Organization performance status, and reported lower experienced overall health. 28.9% of the frail patients died after 1 year versus 10% of the nonfrail control patients (hazard ratio: 3.87 [95% confidence interval: 1.32-11.36], p = 0.014). Conclusion: The G8 is a valid screening tool to identify frail patients in younger HNC patients.

Objective: Informal caregivers of head and neck cancer (HNC) patients have a high caregiver burden and often face complex practical caregiving tasks. This may result in unmet supportive care needs, which can impact their quality of life (QoL) and cause psychological distress. In this study, we identify caregivers’ unmet needs during long-term follow-up and identify caregivers prone to unmet supportive care needs. Methods: Data were used from the multicenter prospective cohort study NETherlands QUality of life and Biomedical cohort studies In Cancer (NET-QUBIC). The unmet supportive care needs, psychological distress, caregiver burden, and QoL were measured for 234 informal caregivers and their related patients at baseline, 3, 6, 12, and 24 months after. Mixed effect models for repeated measurements were used. Results: At baseline, most caregivers (70.3%) reported at least one unmet supportive care need, with most of the identified needs in the “healthcare & illness” domain. During the follow-up period, caregivers’ unmet needs decreased significantly in all domains. Nevertheless, 2 years after treatment, 28.3% were still reporting at least one unmet need. Financial problems were increasingly associated with unmet needs over time. Furthermore, caring for a patient who themselves had many unmet needs, an advanced tumor stage, or severe comorbidity was associated with significantly more unmet needs in caregivers. Conclusions: The current study shows the strong likelihood of caregivers of HNC patients facing unmet supportive care needs and the interaction between the needs of patients and caregivers. It is important to optimally support informal caregivers by involving them from the start when counseling patients, by providing them with relevant and understandable information, and by referring vulnerable caregivers for (psychosocial) support.

OBJECTIVE: Patient-reported voice quality is an important outcome during counseling in early-stage glottic cancer. However, there is a paucity of adequate longitudinal studies concerning voice outcomes. This study aimed to investigate longitudinal trajectories for patient-reported voice quality and associated risk factors for treatment modalities such as transoral CO2 laser microsurgery, single vocal cord irradiation, and local radiotherapy.STUDY DESIGN: A longitudinal observational cohort study.SETTING: Tertiary cancer center.METHODS: Patients treated for Tcis-T1b, N0M0 glottic cancer were included in this study (N = 294). The Voice Handicap Index was obtained at baseline and during follow-up (N = 1944). Mixed-effects models were used for investigating the different trajectories for patient-reported voice quality.RESULTS: The mean follow-up duration was 43.4 (SD 21.5) months. Patients received transoral CO2 laser microsurgery (57.8%), single vocal cord irradiation (24.5%), or local radiotherapy (17.5%). A steeper improvement during the first year after treatment for single vocal cord irradiation (-15.7) and local radiotherapy (-12.4) was seen, compared with a more stable trajectory for laser surgery (-6.1). All treatment modalities showed equivalent outcomes during long-term follow-up. Associated risk factors for different longitudinal trajectories were age, tumor stage, and comorbidity.CONCLUSION: Longitudinal patient-reported voice quality after treatment for early-stage glottic cancer is heterogeneous and nonlinear. Most improvement is seen during the first year of follow-up and differs between treatment modalities. No clinically significant differences in long-term trajectories were found. Insight into longitudinal trajectories can enhance individual patient counseling and provide the foundation for an individualized dynamic prediction model.

Background: Head and neck squamous cell carcinoma (HNSCC) displays a large heterogeneity in treatment response, and consequently in patient prognosis. Despite extensive efforts, no clinically validated model is available to predict tumor response. Here we describe a functional test for predicting tumor response to radiation and chemotherapy on the level of the individual patient. Methods: Resection material of 17 primary HNSCC patients was cultured ex vivo, irradiated or cisplatin-treated, after which the effect on tumor cell vitality was analyzed several days after treatment. Results: Ionizing radiation (IR) affected tumor cell growth and viability with a clear dose-response relationship, and marked heterogeneity between tumors was observed. After a single dose of 5Gy, proliferation in IR-sensitive tumors dropped below 30% of the untreated level, while IR-resistant tumors maintained at least 60% of proliferation. IR-sensitive tumors showed on average a twofold increase in apoptosis, as well as an increased number and size of DNA damage foci after treatment. No differences in the homologous recombination (HR) proficiency between IR-sensitive and –resistant tumors were detected. Cisplatin caused a decrease in proliferation, as well as induction of apoptosis, again with marked variation between the samples. Conclusions: Our functional ex vivo assay discriminated between IR-sensitive and IR-resistant HNSCC tumors, and may also be suitable for predicting response to cisplatin. Its predictive value is currently under investigation in a prospective clinical study.

Objective: Patients with palliative head and neck cancer experience many symptoms in a short period of time. Longitudinal data on patient-reported outcomes in this phase are lacking. The aim of this study is to use structurally obtained patient-reported outcome data combined with clinical patient data and obtain insight in patient-reported outcomes, survival, circumstances of death, and interventions and treatment during the palliative phase in order to improve the quality of end-of-life care and patient-centered counseling. Study Design: Longitudinal observational cohort study. Setting: Tertiary cancer center. Method: Quality of life was prospectively collected using the European Organization for Research and Treatment of Cancer QLQ-C15-PAL. Tumor- and patient-specific data were retrospectively collected. Descriptive statistics, linear mixed models, and regression analyses were performed. Results: A significant deterioration was found in global health status, physical functioning, fatigue, dyspnea, appetite loss, and constipation over time. However, emotional functioning improved. Median survival was 5.1 months, and only a low percentage of in-hospital death was observed (7.8%). Higher global health status at intake was associated with prolonged survival. Conclusion: Structural measurement of patient-reported outcome together with clinical outcomes provides unique insight, which enables improvement of patient-centered counseling and care.

Objective: In order to understand how informal caregivers of head and neck cancer (HNC) patients deal with the consequences of the disease, we investigated their self-efficacy and coping style in relation to symptoms of anxiety and depression (distress) and quality of life (QoL) over time. In addition, factors associated with self-efficacy and coping style were investigated. Methods: A total of 222 informal caregivers and their related HNC patients were prospectively followed as part from the multicenter cohort NETherlands QUality of life and Biomedical cohort studies In Cancer (NET-QUBIC). Self-efficacy and coping style were measured at baseline, and distress and QoL at baseline and 3, 6, 12, and 24 months after treatment. Results: Informal caregivers had a high level of self-efficacy comparable with patients. Caregivers used “seeking social support,” “passive reacting,” and “expression of emotions” more often than patients. Factors associated with self-efficacy and coping were higher age and lower education. Higher self-efficacy was related with better QoL and “active tackling” was associated with less depression symptoms. “Passive reacting” and “expression of emotions” were associated with higher psychological distress and reduced QoL. Conclusion: Among informal caregivers of HNC patients, higher self-efficacy and “active tackling” were associated with better functioning over time, while “passive reacting” and “expression of negative emotions” were associated with worse functioning. Awareness of the differences in self-efficacy skills and coping and their relationship with QoL and psychological distress will help clinicians to identify caregivers that may benefit from additional support that improve self-efficacy and “active tackling” and reduce negative coping styles.