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OBJECTIVES: Robotic transoral mucosectomy of the base of tongue was introduced as a diagnostic procedure in patients treated for head and neck cancer with unknown primary (CUP), increasing the identification rate of the primary tumour. For the treatment of CUP, a considerable percentage of patients require adjuvant (chemo)radiation. The aim of this study was to investigate swallowing outcomes among CUP patients after TORS and adjuvant treatment. SUBJECTS AND METHODS: A systematic review was carried out on studies investigating the impact of TORS and adjuvant treatment on swallowing-related outcomes among CUP patients In addition, a cross-sectional study was carried out on swallowing problems (measured using the SWAL-QOL questionnaire) among CUP patients in routine care who visited the outpatient clinic 1-5 years after TORS and adjuvant treatment. RESULTS: The systematic review (6 studies; n = 98) showed that most patients returned to a full oral diet. The cross-sectional study (n = 12) showed that all patients were able to return to a full oral diet, nevertheless, 50% reported swallowing problems in daily life (SWAL-QOL total score ≥14). CONCLUSION: Although after TORS and adjuvant treatment for CUP a full oral diet can be resumed, patients still experience problems with eating and drinking in daily life.
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PURPOSE: To evaluate the effect of implant-based dental rehabilitation (IDR) on health-related quality of life (HRQoL) in head and neck cancer (HNC) patients after reconstruction with a free vascularized fibula flap (FFF). METHODS: Eligible patients were identified by retrospectively reviewing the medical records of patients treated in Amsterdam UMC-VUmc. HRQoL data were used from OncoQuest, a hospital-based system to collect patient-reported outcome measures in routine care. Data were used of the EORTC QLQ-C30 and QLQ-H&N 35 before FFF reconstruction (T0) and after completing IDR (T1). Data were statistically analysed with the chi-square test, independent samples t test and linear mixed models. RESULTS: Out of 96 patients with maxillofacial FFF reconstruction between January 2006 and October 2017, 57 patients (19 with and 38 without IDR) had HRQoL data at T0 and T1. In the cross-sectional analysis, patients with IDR scored significantly better at T0 and T1 on several EORTC domains compared to the patients without IDR. Weight loss was significantly different in the within-subject analysis between T0 and T1 for patients with IDR (p = 0.011). However, there were no significant differences in the mean changes of all the EORTC QLQ-C30 and EORTC QLQ-H&N35 scores between the defined timepoints for patients with IDR compared to those without. CONCLUSIONS: In this study, no differences were found in the course of HRQoL in HNC patients who had undergone IDR after maxillofacial FFF reconstruction, compared to those who had not. Patients should be preoperatively informed to have realistic expectations regarding the outcome of IDR.
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Neoplasias de Cabeça e Pescoço , Qualidade de Vida , Estudos Transversais , Fíbula , Neoplasias de Cabeça e Pescoço/cirurgia , Humanos , Estudos RetrospectivosRESUMO
OBJECTIVES: To assess (I) correlations between diffusion-weighted (DWI), intravoxel incoherent motion (IVIM), dynamic contrast-enhanced (DCE) MRI, and 18F-FDG-PET/CT imaging parameters capturing tumor characteristics and (II) their predictive value of locoregional recurrence-free survival (LRFS) and overall survival (OS) in patients with head and neck squamous cell carcinoma (HNSCC) treated with (chemo)radiotherapy. METHODS: Between 2014 and 2018, patients with histopathologically proven HNSCC, planned for curative (chemo) radiotherapy, were prospectively included. Pretreatment clinical, anatomical, and functional imaging parameters (obtained by DWI/IVIM, DCE-MRI, and 18F-FDG-PET/CT) were extracted for primary tumors (PT) and lymph node metastases. Correlations and differences between parameters were assessed. The predictive value of LRFS and OS was assessed, performing univariable, multivariable Cox and CoxBoost regression analyses. RESULTS: In total, 70 patients were included. Significant correlations between 18F-FDG-PET parameters and DWI-/DCE volume parameters were found (r > 0.442, p < 0.002). The combination of HPV (HR = 0.903), intoxications (HR = 1.065), PT ADCGTV (HR = 1.252), Ktrans (HR = 1.223), and Ve (HR = 1.215) was predictive for LRFS (C-index = 0.546; p = 0.023). N-stage (HR = 1.058), HPV positivity (HR = 0.886), hypopharyngeal tumor location (HR = 1.111), ADCGTV (HR = 1.102), ADCmean (HR = 1.137), D* (HR = 0.862), Ktrans (HR = 1.106), Ve (HR = 1.195), SUVmax (HR = 1.094), and TLG (HR = 1.433) were predictive for OS (C-index = 0.664; p = 0.046). CONCLUSIONS: Functional imaging parameters, performing DWI/IVIM, DCE-MRI, and 18F-FDG-PET/CT, yielded complementary value in capturing tumor characteristics. More specific, intoxications, HPV-negative status, large tumor volume-related parameters, high permeability (Ktrans), and high extravascular extracellular space (Ve) parameters were predictive for adverse locoregional recurrence-free survival and adverse overall survival. Low cellularity (high ADC) and high metabolism (high SUV) were additionally predictive for decreased overall survival. These different predictive factors added to estimated locoregional and overall survival. KEY POINTS: ⢠Parameters of DWI/IVIM, DCE-MRI, and 18F-FDG-PET/CT were able to capture complementary tumor characteristics. ⢠Multivariable analysis revealed that intoxications, HPV negativity, large tumor volume and high vascular permeability (Ktrans), and extravascular extracellular space (Ve) were complementary predictive for locoregional recurrence. ⢠In addition to predictive parameters for locoregional recurrence, also high cellularity (low ADC) and high metabolism (high SUV) were complementary predictive for overall survival.
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Fluordesoxiglucose F18 , Neoplasias de Cabeça e Pescoço , Imagem de Difusão por Ressonância Magnética , Neoplasias de Cabeça e Pescoço/diagnóstico por imagem , Neoplasias de Cabeça e Pescoço/terapia , Humanos , Imageamento por Ressonância Magnética , Recidiva Local de Neoplasia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos , Carcinoma de Células Escamosas de Cabeça e PescoçoRESUMO
OBJECTIVE: The web-based application Oncokompas was developed to support cancer patients to self-manage their symptoms. This qualitative study was conducted to obtain insight in patients' self-management strategies to cope with cancer and their experiences with Oncokompas as a fully automated behavioural intervention technology. METHODS: Data were collected from semi-structured interviews with 22 participants (10 head and neck cancer survivors and 12 incurably ill patients). Interview questions were about self-management strategies and experiences with Oncokompas. Interviews were audio-recorded, transcribed verbatim and analysed using thematic analysis. RESULTS: Participants applied several self-management strategies, among which trying to stay in control and make the best of their situation. They described Oncokompas' added value: being able to monitor symptoms and having access to a personal online library. Main reasons for not using Oncokompas were concentration problems, lack of time or having technical issues. Recommendations were made for further development of Oncokompas, relating to its content, technical and functional aspects. CONCLUSIONS: Survivors and incurably ill patients use various self-management strategies to cope with cancer. The objectives of self-management interventions as Oncokompas correspond well with these strategies: taking a certain responsibility for your well-being and being in charge of your life as long as possible by obtaining automated information (24/7) on symptoms and tailored supportive care options.
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Neoplasias de Cabeça e Pescoço , Autogestão , Telemedicina , Humanos , Pesquisa Qualitativa , Qualidade de Vida , SobreviventesRESUMO
BACKGROUND: Transoral robotic surgery (TORS) is increasingly used in head and neck surgery and in carcinoma of unknown primary (CUP) origin specifically. Due to the rising incidence of human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OPSCC), there is a rationale for finding ways to de-escalate treatment strategies. This review aims to test the hypothesis that TORS is a meaningful adjunct in the diagnostic (and therapeutic) pathway in CUP in head and neck. METHODS: A structured search of the literature was performed with the search terms 'TORS' and 'Carcinoma of Unknown Primary'. RESULTS: Two hundred and seventy four cases of CUP in which TORS was used were identified for further analysis. Workup for CUP was comparable in all series with regard to physical examination, fine and/or gross needle examination of cervical nodes, fibre optic endoscopy, imaging and robot assisted mucosectomy of the base of tongue (BOT). Identification rate of the primary tumour was 72% on average (range 17%- 90%), and 55%- 96% were HPV positive. Clear margins were achieved in 60% (range 0%-85%) of resected occult tumours. Complication rate of TORS BOT mucosectomy was low with mainly grade I-III sequelae according to Clavien-Dindo. CONCLUSIONS: Transoral robotic surgery seems to be a useful and safe adjunct in the diagnostic and therapeutic pathway in case of CUP in an era of increasing incidence of HPV-positive OPSCC.
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Neoplasias de Cabeça e Pescoço/cirurgia , Mucosa Bucal/cirurgia , Cirurgia Endoscópica por Orifício Natural/métodos , Neoplasias Primárias Desconhecidas/cirurgia , Procedimentos Cirúrgicos Robóticos/métodos , Língua/cirurgia , Neoplasias de Cabeça e Pescoço/secundário , Humanos , Boca , Neoplasias Primárias Desconhecidas/diagnóstico , Língua/patologiaRESUMO
BACKGROUND: Three-weekly high-dose cisplatin (100 mg/m2) is considered the standard systemic regimen given concurrently with postoperative or definitive radiotherapy in locally advanced squamous cell carcinoma of the head and neck (LA-SCCHN). Concurrent chemoradiation (CRT) with high-dose cisplatin is associated with significant acute and late toxicities, including acute kidney injury (AKI). The aims of this study were to investigate the incidence of AKI in patients with LA-SCCHN during and after treatment with high-dose cisplatin-based CRT, to identify risk factors for cisplatin-induced AKI, and to describe the impact of AKI on long-term renal function and treatment outcomes. METHODS: This is a retrospective cohort study with measurements of renal function before CRT, weekly during CRT, every 1 or 2 days during hospitalizations, and 3 and 12 months after CRT in patients with LA-SCCHN. AKI was defined as increase in serum creatinine (sCr) of ≥1.5 times baseline or by ≥0.3 mg/dL (≥26.5 µmol/L) using the Kidney Disease Improving Global Outcomes (KDIGO) classification. Logistic regression models were estimated to analyze renal function over time and to identify predictors for AKI. RESULTS: One hundred twenty-four patients completed all measurements. AKI was reported in 85 patients (69%) with 112 episodes of AKI. Sixty of 85 patients experienced 1 AKI episode; 20 patients experienced ≥2 AKI episodes. Ninety-three (83%) AKI episodes were stage 1, 13 (12%) were stage 2, and 6 (5%) AKI episodes were stage 3. Median follow-up time was 29 months (Interquartile Range, IQR 22-33). Hypertension (Odds Ratio, OR 2.7, 95% Confidence Interval, CI 1.1-6.6; p = 0.03), and chemotherapy-induced nausea and vomiting (CINV; OR 4.3, 95% CI 1.6-11.3; p = 0.003) were associated with AKI. In patients with AKI, renal function was significantly more impaired at 3 and 12 months post-treatment compared to patients without AKI. AKI did not have a negative impact on treatment outcomes. CONCLUSION: AKI occurred in 69% of patients with LA-SCCHN undergoing CRT with high-dose cisplatin. Long-term renal function was significantly more impaired in patients with AKI. Hypertension and CINV are significant risk factors. Optimizing prevention strategies for CINV are urgently needed.
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Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/epidemiologia , Antineoplásicos/uso terapêutico , Quimiorradioterapia/efeitos adversos , Cisplatino/uso terapêutico , Neoplasias de Cabeça e Pescoço/terapia , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia , Adulto , Idoso , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Creatinina/sangue , Feminino , Seguimentos , Humanos , Hipertensão , Incidência , Masculino , Pessoa de Meia-Idade , Náusea/induzido quimicamente , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento , Vômito/induzido quimicamenteRESUMO
BACKGROUND: In definitive radiation therapy for head and neck cancer, clinically uninvolved cervical lymph nodes are irradiated with a so-called 'elective dose' in order to achieve control of clinically occult metastases. As a consequence of high-resolution diagnostic imaging, occult tumor volume has significantly decreased in the last decades. Since the elective dose is dependent on occult tumor volume, the currently used elective dose may be higher than necessary. Because bilateral irradiation of the neck contributes to dysphagia, xerostomia and hypothyroidism in a dose dependent way, dose de-escalation to these regions can open a window of opportunity to reduce toxicity and improve quality of life after treatment. METHODS: UPGRADE-RT is a multicenter, phase III, single-blinded, randomized controlled trial. Patients to be treated with definitive radiation therapy for a newly diagnosed stage T2-4 N0-2 M0 squamous cell carcinoma of the oropharynx, hypopharynx or larynx are eligible. Exclusion criteria are recurrent disease, oncologic surgery to the head and neck area, concomitant chemotherapy or epidermal growth factor receptor inhibitors. In total, 300 patients will be randomized in a 2:1 ratio to a treatment arm with or without de-escalation of the elective radiation dose and introduction of an intermediate dose-level for selected lymph nodes. Radiation therapy planning FDG-PET/CT-scans will be acquired to guide risk assessment of borderline-sized cervical nodes that can be treated with the intermediate dose level. Treatment will be given with intensity-modulated radiation therapy or volumetric arc therapy with simultaneous-integrated boost using an accelerated fractionation schedule, 33 fractions in 5 weeks. The primary endpoint is 'normalcy of diet' at 1 year after treatment (toxicity). The secondary endpoint is the actuarial rate of recurrence in electively irradiated lymph nodes at 2 years after treatment (safety). DISCUSSION: The objective of the UPGRADE-RT trial is to investigate whether de-escalation of elective radiation dose and the introduction of an intermediate dose-level for borderline sized lymph nodes in the treatment of head and neck cancer will result in less radiation sequelae and improved quality of life after treatment without compromising the recurrence rate in the electively treated neck. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02442375 .
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Carcinoma de Células Escamosas/radioterapia , Fluordesoxiglucose F18 , Neoplasias de Cabeça e Pescoço/radioterapia , Tomografia por Emissão de Pósitrons/métodos , Dosagem Radioterapêutica , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/diagnóstico por imagem , Feminino , Neoplasias de Cabeça e Pescoço/diagnóstico por imagem , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Lesões por Radiação/prevenção & controle , Planejamento da Radioterapia Assistida por Computador/métodos , Método Simples-CegoRESUMO
Purpose: Selecting patients who will benefit from proton therapy is laborious and subjective. We demonstrate a novel automated solution for creating high-quality knowledge-based plans (KBPs) using proton and photon beams to identify patients for proton treatment based on their normal tissue complication probabilities (NTCP). Methods and Materials: Two previously validated RapidPlan PT models for locally advanced head and neck cancer were used in combination with scripting to automatically create proton and photon KBPs for 72 patients with recent oropharynx cancer. NTCPs were calculated for each patient based on the KBPs, and patient selection was simulated according to the current Dutch national protocol. Results: The photon/proton KBP exhibited good correlation between predicted and achieved organ-at-risk mean doses, with a ≤5 Gy difference in 208/196 out of 215 structures relevant for the head and neck cancer NTCP model. The proton KBPs yielded on average 7.1/6.1/7.6 Gy lower dose to salivary/swallowing structures/oral cavity than the photon KBPs. This reduced average grade 2/3 dysphagia and xerostomia by 7.1/3.3 and 5.5/2.0 percentage points, resulting in 16 of 72 patients (22%) being indicated for proton treatment. The entire automated process took <30 minutes per patient. Conclusions: Automated support for decision making using KBP is feasible and fast. The planning solution has potential to speed up the planning and patient-selection process significantly without major compromises to the plan quality.
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BACKGROUND: Patients with locally-advanced head and neck squamous cell carcinoma (HNSCC) have variable responses to (chemo)radiotherapy. A reliable prediction of outcomes allows for enhancing treatment efficacy and follow-up monitoring. METHODS: Fifty-seven histopathologically-proven HNSCC patients with curative (chemo)radiotherapy were prospectively included. All patients had an MRI (DW,-IVIM, DCE-MRI) and 18F-FDG-PET/CT before and 10 days after start-treatment (intratreatment). Primary tumor functional imaging parameters were extracted. Univariate and multivariate analysis were performed to construct prognostic models and risk stratification for 2 year locoregional recurrence-free survival (LRFFS), distant metastasis-free survival (DMFS) and overall survival (OS). Model performance was measured by the cross-validated area under the receiver operating characteristic curve (AUC). RESULTS: The best LRFFS model contained the pretreatment imaging parameters ADC_kurtosis, Kep and SUV_peak, and intratreatment imaging parameters change (Δ) Δ-ADC_skewness, Δ-f, Δ-SUV_peak and Δ-total lesion glycolysis (TLG) (AUC = 0.81). Clinical parameters did not enhance LRFFS prediction. The best DMFS model contained pretreatment ADC_kurtosis and SUV_peak (AUC = 0.88). The best OS model contained gender, HPV-status, N-stage, pretreatment ADC_skewness, D, f, metabolic-active tumor volume (MATV), SUV_mean and SUV_peak (AUC = 0.82). Risk stratification in high/medium/low risk was significantly prognostic for LRFFS (p = 0.002), DMFS (p < 0.001) and OS (p = 0.003). CONCLUSIONS: Intratreatment functional imaging parameters capture early tumoral changes that only provide prognostic information regarding LRFFS. The best LRFFS model consisted of pretreatment, intratreatment and Δ functional imaging parameters; the DMFS model consisted of only pretreatment functional imaging parameters, and the OS model consisted ofHPV-status, gender and only pretreatment functional imaging parameters. Accurate clinically applicable risk stratification calculators can enable personalized treatment (adaptation) management, early on during treatment, improve counseling and enhance patient-specific post-therapy monitoring.
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Depending on the clinical situation, different combinations of lymph node (LN) levels define the elective LN target volume in head-and-neck cancer (HNC) radiotherapy. The accurate auto-contouring of individual LN levels could reduce the burden and variability of manual segmentation and be used regardless of the primary tumor location. We evaluated three deep learning approaches for the segmenting individual LN levels I−V, which were manually contoured on CT scans from 70 HNC patients. The networks were trained and evaluated using five-fold cross-validation and ensemble learning for 60 patients with (1) 3D patch-based UNets, (2) multi-view (MV) voxel classification networks and (3) sequential UNet+MV. The performances were evaluated using Dice similarity coefficients (DSC) for automated and manual segmentations for individual levels, and the planning target volumes were extrapolated from the combined levels I−V and II−IV, both for the cross-validation and for an independent test set of 10 patients. The median DSC were 0.80, 0.66 and 0.82 for UNet, MV and UNet+MV, respectively. Overall, UNet+MV significantly (p < 0.0001) outperformed other arrangements and yielded DSC = 0.87, 0.85, 0.86, 0.82, 0.77, 0.77 for the combined and individual level I−V structures, respectively. Both PTVs were also significantly (p < 0.0001) more accurate with UNet+MV, with DSC = 0.91 and 0.90, respectively. The accurate segmentation of individual LN levels I−V can be achieved using an ensemble of UNets. UNet+MV can further refine this result.
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BACKGROUND: Definitive concomitant cisplatin-based chemoradiotherapy (CRT) is the current gold standard for most patients with advanced stage head and neck squamous cell carcinoma (HNSCC) of the pharynx and larynx. Since previous meta-analysis on CRT outcomes in HNSCC have been reported, advances have been made in radiotherapy techniques and clinical management, while HPV-status has been identified as a strong confounding prognostic factor in oropharyngeal cancer. Here, we present real-world outcome data from a large multicenter cohort of HPV-negative advanced stage HNSCC treated with CRT using contemporary IMRT-based techniques. METHOD: Retrospective data were collected from a multicenter cohort of 513 patients treated with definitive concurrent platinum-based CRT with curative intent between January 2009 and August 2017. Only patients with HPV-negative advanced stage (III-IV) HNSCC were included. A prognostic model for outcome was developed based on clinical parameters and compared to TNM. RESULTS: Nearly half of the 513 patients (49%) had an oropharyngeal tumor, often locally advanced (73.3% T3-T4b) and with involvement of the regional lymph nodes (84%). Most patients (84%) received cisplatin as single agent. In total 66% received the planned number of cycles and 75% reached a cumulative cisplatin dose of ≥200 mg/m2. Locoregional control was achieved in 324 (63%) patients during follow-up, and no association with tumor sites was observed (p = 0.48). Overall survival at 5 year follow-up was 47%, with a better survival for laryngeal cancer (p = 0.02) compared to other sites. A model with clinical variables (gender, high pre-treatment weight loss, N2c/N3-stage and <200 mg/m2 dose of cisplatin) provided a noticeably stronger association with overall survival than TNM-staging (C- index 0.68 vs 0.55). Simultaneous Integrated Boosting (SIB) significantly outperformed Sequential Boosting (SEQ) to reduce the development of distant metastasis (SEQ vs SIB: OR 1.91 (1.11-3.26; p = 0.02). CONCLUSION: Despite advances in clinical management, more than a third of patients with HPV-negative HNSCC do not complete CRT treatment protocols due to cisplatin toxicity. A model that consists of clinical variables and treatment parameters including cisplatin dose provided the strongest association with overall survival. Since cisplatin toxicity is a major obstacle in completing definitive CRT, the development of alternative and less toxic radiosensitizers is therefore warranted to improve treatment results. The association of RT-boost technique with distant metastasis is an important finding and requires further study.
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Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Orofaríngeas , Infecções por Papillomavirus , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Cisplatino/efeitos adversos , Infecções por Papillomavirus/complicações , Estudos Retrospectivos , Platina/uso terapêutico , Carcinoma de Células Escamosas/patologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Quimiorradioterapia/efeitos adversos , Quimiorradioterapia/métodos , Neoplasias Orofaríngeas/tratamento farmacológicoRESUMO
BACKGROUND AND PURPOSE: Primary radiotherapy is often preferred for early-stage cancer of the nasal vestibule (CNV), combining high disease control with preservation of nasal anatomy. However, due to practice variation and an absence of comparative trials, no consensus exists on preference for brachytherapy (BT) or external beam radiotherapy (EBRT). We compared these modalities in terms of disease control, nose preservation rates and toxicity. MATERIALS AND METHODS: Medical records of 225 patients with T1-T2 squamous cell carcinoma of the nasal vestibule treated with 3D image-guided primary radiotherapy between Jan 2010 and Dec 2016 in 6 Dutch institutions were reviewed retrospectively. RESULTS: 153 of 225 patients were treated with BT, 65 with EBRT and 7 with other modalities. Median follow-up was 46 months. Overall 3-year local control (LC) and regional control (RC) were 87% and 89%. Five-year disease-specific survival (DSS) and overall survival (OS) were 94% and 82%. Three-year survival with preserved nose (SPN) was 76%. BT provided higher 3-year LC (95% vs 71%, p < 0.01) and SPN compared with EBRT (82% vs 61%, p < 0.01). Multivariable and propensity-score-matched cohort analyses confirmed better outcomes after BT. No difference was seen in DSS or OS. Five-year incidence of CTCAE 5.0 grade ≥2 toxicity was higher after BT (20% vs 3%, p = 0.03) and consisted mostly of radiation ulcers. 50% of all late toxicity recovered. CONCLUSION: In this largest-to-date multicenter analysis of T1-T2 CNV, BT achieved superior LC and SPN compared with EBRT. Grade 1-2 radiation ulcers occurred more frequently after brachytherapy, but were transient in half the cases. Considering these results, BT can be recommended as first-line treatment for T1-T2 CNV.
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Braquiterapia , Neoplasias da Próstata , Radioterapia Guiada por Imagem , Braquiterapia/efeitos adversos , Humanos , Masculino , Pontuação de Propensão , Estudos RetrospectivosRESUMO
INTRODUCTION: A recent randomized controlled trial (RCT) in patients with head and neck cancer (HNC) with psychological distress showed that a stepped care (SC) program targeting psychological distress compared with care as usual (CAU), is (cost)effective in reducing psychological distress. AIM: The aim of the present study was to investigate whether SC can coalleviate problems with sexual interest and enjoyment. A secondary aim was to investigate whether the presence of an unmet sexual health need and having a psychiatric disorder (depression or anxiety) at baseline moderated any effect of SC on these sexual variables until 1-year follow-up. METHODS: HNC survivors (N = 134), randomized to SC or CAU, were assessed regarding their sexual interest and enjoyment before and after the intervention and at 3, 6, 9, and 12 months follow-up. Linear mixed models were used to evaluate differences in the course of sexual interest and enjoyment between SC and CAU. MAIN OUTCOME MEASURE: The "sexuality" symptom subscale, part of the European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire, Head and Neck Cancer-specific module. RESULTS: Of all patients, 76.1% had an unmet sexual need at baseline, 24.6% had a psychiatric disorder (anxiety or depression). SC did not reduce problems with sexual interest and enjoyment at any of the follow-up measurements compared with CAU (P = .85). This was neither moderated by an unmet sexual health need at baseline (P = .64) nor by the presence of a psychiatric disorder at baseline (P = .59). CONCLUSION: A substantial number of patients with HNC have unmet sexual health needs. SC targeting psychological distress does not reduce problems with sexuality in these patients. Interventions specifically targeting sexuality are recommended. Schutte LER, Melissant HC, Jansen F, et al. Effect of Stepped Care on Sexual Interest and Enjoyment in Distressed Patients with Head and Neck Cancer: A Randomized Controlled Trial. Sex Med 2021;9:100304.
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PURPOSE: The emerge of improved personalized treatment adaptations and outcome prediction is accompanied with increasing non-invasive assessments in early treatment phase, leading to increased patient burden. This study assessed the adherence of patients with head and neck squamous cell carcinoma (HNSCC) to undergo pretreatment and research-related intratreatment imaging, and assessed which factors caused drop-out. METHOD: Between 2013 and 2019, advanced-staged HNSCC patients were prospectively included, underwent (chemo) radiotherapy with curative intent and planned for both pre-treatment and intratreatment sequential 18F-FDG-PET/CT, 18F-FDG-PET/MRI and thereafter MRI (including DWI/DCE). Drop-out-factors were described as healthcare-related (logistics and imaging-system defects) and patient-related (psychological, physical, not-specified). Common Toxicity Criteria (CTC) were routinely scored by radiation/medical oncologists throughout the first 3 weeks, and compared between patient drop-outs and who complete imaging. RESULTS: Ninety-seven patients (mean age 61 ± 6.8 years) were included; 95 patients (97.9%) underwent pretreatment imaging and 63 (64.9%) intratreatment imaging. For 18F-FDG-PET/CT, 18F-FDG-PET/MRI and MRI pretreatment drop-outs were 2, 10 and 3 patients and for intratreatment drop-outs were 34, 39 and 35 patients, respectively. Patient-related drop-out-factors were physical (n = 16, e.g. dysphagia), psychological (n = 6, e.g. claustrophobia) and non-specified (n = 12). Healthcare-related drop-out-factors were logistics (n = 6) and 18F-FDG-PET/CT-/MRI-system defects (n = 2). The CTC mucosal toxicity was significantly higher (p = 0.023) at week 2 of (chemo)radiotherapy in patient drop-outs than with complete imaging. CONCLUSIONS: The drop-out frequency of advanced-staged HNSCC patients for imaging during (chemo)radiotherapy in a research-setting was high and mainly patient-related. Treatment of patient-related inconveniences, communication of rationale and healthcare-related imaging protocol efficiency improvements may contribute to improved adherence.
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Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Idoso , Quimiorradioterapia/efeitos adversos , Fluordesoxiglucose F18 , Neoplasias de Cabeça e Pescoço/diagnóstico por imagem , Neoplasias de Cabeça e Pescoço/radioterapia , Humanos , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos , Carcinoma de Células Escamosas de Cabeça e PescoçoRESUMO
BACKGROUND: Locoregionally advanced head and neck squamous cell carcinoma (HNSCC) patients have high relapse and mortality rates. Imaging-based decision support may improve outcomes by optimising personalised treatment, and support patient risk stratification. We propose a multifactorial prognostic model including radiomics features to improve risk stratification for advanced HNSCC, compared to TNM eighth edition, the gold standard. PATIENT AND METHODS: Data of 666 retrospective- and 143 prospective-stage III-IVA/B HNSCC patients were collected. A multivariable Cox proportional-hazards model was trained to predict overall survival (OS) using diagnostic CT-based radiomics features extracted from the primary tumour. Separate analyses were performed using TNM8, tumour volume, clinical and biological variables, and combinations thereof with radiomics features. Patient risk stratification in three groups was assessed through Kaplan-Meier (KM) curves. A log-rank test was performed for significance (p-value < 0.05). The prognostic accuracy was reported through the concordance index (CI). RESULTS: A model combining an 11-feature radiomics signature, clinical and biological variables, TNM8, and volume could significantly stratify the validation cohort into three risk groups (p < 0â01, CI of 0.79 as validation). CONCLUSION: A combination of radiomics features with other predictors can predict OS very accurately for advanced HNSCC patients and improves on the current gold standard of TNM8.
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Technical improvements in head and neck cancer radiotherapy over the last decade have resulted in substantial reductions in dose to organs-at-risk. For a mix of tumors, we saw less xerostomia moving from 3D-conformal to more advanced techniques. For oropharynx-only there were additional improvements, including in global quality-of-life and sticky saliva.
Assuntos
Neoplasias de Cabeça e Pescoço , Radioterapia Conformacional , Xerostomia , Neoplasias de Cabeça e Pescoço/radioterapia , Humanos , Qualidade de Vida , Saliva , Xerostomia/etiologia , Xerostomia/prevenção & controleRESUMO
To evaluate diagnostic accuracy of qualitative analysis and interobserver agreement of single ultrafast-DCE, DWI or 18F-FDG-PET and the combination of modalities for the detection of unknown primary tumor (UPT) in patients presenting with cervical lymph node metastasis from squamous cell carcinoma (SCC). Between 2014-2019, patients with histologically proven cervical lymph node metastasis of UPT SCC were prospectively included and underwent DWI, ultrafast-DCE, and 18F-FDG-PET/CT. Qualitative assessment was performed by two observers per modality. Interobserver agreement was calculated using the proportion specific agreement. Diagnostic accuracy of combined use of DWI, ultrafast-DCE and 18F-FDG-PET/CT was assessed. Twenty-nine patients were included (20 males. [68%], median age 60 years). Nine (31%) primary tumors remained occult. Ultrafast-DCE added reader confidence for suspicious locations (one additional true positive (5%), 2 decisive true malignant (10%). The per-location analysis showed highest specific positive agreement for ultrafast-DCE (77.6%). The per-location rating showed highest sensitivity (95%, 95%CI = 75.1-99.9, YI = 0.814) when either one of all modalities was scored positive, and 97.4% (95%CI = 93.5-99.3, YI = 0.774) specificity when co-detected on all. The per-patient analysis showed highest sensitivity (100%) for 18F-FDG-PET/CT (YI = 0.222) and either DWI or PET (YI = 0.111). Despite highest trends, no significant differences were found. The per-patient analysis showed highest specific positive agreement when co-detected on all modalities (55.6%, 95%CI = 21.2-86.3, YI = 0.456). Ultrafast-DCE showed potential to improve detection of unknown primary tumors in addition to DWI and 18F-FDG-PET/CT in patients with cervical squamous cell carcinoma lymph node metastasis. The combined use of ultrafast-DCE, DWI and 18F-FDG-PET/CT yielded highest sensitivity.
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Background: Chemoradiotherapy (CRT) including three cycles of cisplatin is considered the standard of care for locally advanced head and neck squamous cell carcinoma (LA-HNSCC). However, around one-third of the patients cannot complete cisplatin because of toxicity. Carboplatin plus 5-fluorouracil (carbo-5FU) is another accepted treatment option with a different toxicity profile. We compared tolerability and efficacy of concomitant carbo-5FU and cisplatin. Patients and Methods: We conducted a retrospective analysis of LA-HNSCC patients treated with CRT in two Dutch cancer centers between 2007 and 2016. All patients received intensity-modulated radiotherapy. One center routinely administered carboplatin 300-350 mg/m2 at day 1, 22, and 43 followed by 5FU 600 mg/m2/day for 96 h. The other center used cisplatin 100 mg/m2 at day 1, 22, and 43. The primary endpoint of this study was chemotherapy completion rate. Secondary endpoints included overall survival (OS), disease-free survival (DFS), locoregional control (LRC) and distant metastasis-free interval (DMFS), toxicity, and unplanned admissions. Results: In the carbo-5FU cohort (n = 211), 60.2% of the patients completed chemotherapy vs. 76.7% (p < 0.001) of the patients in the cisplatin cohort (n = 223). Univariate analysis showed a higher risk of death in the carbo-5FU cohort [hazard ratio (HR) 1.53, 95% CI, 1.09-2.14, p = 0.01] with a 3-year OS of 65.4 vs. 76.5% for cisplatin. OS was independently associated with T and N stage and p16 status, but not with chemotherapy regimen (HR 1.08, 95% CI, 0.76-1.55, p = 0.65). Three-year DFS was 70.0% for carbo-5FU vs. 78.6% for cisplatin (HR 1.37, 95% CI, 0.93-2.01, p = 0.05). A similar outcome was observed for both LRC (HR 1.27, 95% CI, 0.74-2.09, p = 0.4) and DMFS (HR 1.08, 95% CI 0.62-1.90, p = 0.77). The risk of discontinuation for chemotherapy-associated toxicity was higher in the carbo-5FU cohort than in the cisplatin cohort (relative risk = 1.69). Conclusion: LA-HNSCC patients treated with concomitant carbo-5FU completed chemotherapy less frequently than patients treated with cisplatin. Treatment regimen was not an independent prognostic factor for OS.
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OBJECTIVES: The majority of patients with locally advanced larynx or hypopharynx squamous cell carcinoma are treated with organ-preserving chemoradiotherapy (CRT). Clinical outcome following CRT varies greatly. We hypothesized that tumor microRNA (miRNA) expression is predictive for outcome following CRT. METHODS: Next-generation sequencing (NGS) miRNA profiling was performed on 37 formalin-fixed paraffin-embedded (FFPE) tumor samples. Patients with a recurrence-free survival (RFS) of less than 2 years and patients with late/no recurrence within 2 years were compared by differential expression analysis. Tumor-specific miRNAs were selected based on normal mucosa miRNA expression data from The Cancer Genome Atlas database. A model was constructed to predict outcome using group-regularized penalized logistic ridge regression. Candidate miRNAs were validated by RT-qPCR in the initial sample set as well as in 46 additional samples. RESULTS: Thirteen miRNAs were differentially expressed (p < 0.05, FDR < 0.1) according to outcome group. Initial class prediction in the NGS cohort (n = 37) resulted in a model combining five miRNAs and disease stage, able to predict CRT outcome with an area under the curve (AUC) of 0.82. In the RT-qPCR cohort (n = 83), 25 patients (30%) experienced early recurrence (median RFS 8 months; median follow-up 42 months). Class prediction resulted in a model combining let-7i-5p, miR-192-5p and disease stage, able to discriminate patients with good versus poor clinical outcome (AUC:0.80). CONCLUSION: The combined miRNA expression and disease stage prediction model for CRT outcome is superior to using either factor alone. This study indicates NGS miRNA profiling using FFPE specimens is feasible, resulting in clinically relevant biomarkers.
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BACKGROUND: Radiomics is aimed at image-based tumor phenotyping, enabling application within clinical-decision-support-systems to improve diagnostic accuracy and allow for personalized treatment. The purpose was to identify predictive 18-fluor-fluoro-2-deoxyglucose (18F-FDG) positron-emission tomography (PET) radiomic features to predict recurrence, distant metastasis, and overall survival in patients with head and neck squamous cell carcinoma treated with chemoradiotherapy. METHODS: Between 2012 and 2018, 103 retrospectively (training cohort) and 71 consecutively included patients (validation cohort) underwent 18F-FDG-PET/CT imaging. The 434 extracted radiomic features were subjected, after redundancy filtering, to a projection resulting in outcome-independent meta-features (factors). Correlations between clinical, first-order 18F-FDG-PET parameters (e.g., SUVmean), and factors were assessed. Factors were combined with 18F-FDG-PET and clinical parameters in a multivariable survival regression and validated. A clinically applicable risk-stratification was constructed for patients' outcome. RESULTS: Based on 124 retained radiomic features from 103 patients, 8 factors were constructed. Recurrence prediction was significantly most accurate by combining HPV-status, SUVmean, SUVpeak, factor 3 (histogram gradient and long-run-low-grey-level-emphasis), factor 4 (volume-difference, coarseness, and grey-level-non-uniformity), and factor 6 (histogram variation coefficient) (CI = 0.645). Distant metastasis prediction was most accurate assessing metabolic-active tumor volume (MATV)(CI = 0.627). Overall survival prediction was most accurate using HPV-status, SUVmean, SUVmax, factor 1 (least-axis-length, non-uniformity, high-dependence-of-high grey-levels), and factor 5 (aspherity, major-axis-length, inversed-compactness and, inversed-flatness) (CI = 0.764). CONCLUSIONS: Combining HPV-status, first-order 18F-FDG-PET parameters, and complementary radiomic factors was most accurate for time-to-event prediction. Predictive phenotype-specific tumor characteristics and interactions might be captured and retained using radiomic factors, which allows for personalized risk stratification and optimizing personalized cancer care. TRIAL REGISTRATION: Trial NL3946 (NTR4111), local ethics commission reference: Prediction 2013.191 and 2016.498. Registered 7 August 2013, https://www.trialregister.nl/trial/3946.