Management of the neck in T1 and T2 buccal squamous cell carcinoma.

Buccal squamous cell carcinoma (SCC) appears to behave more aggressively than other oral subsites, in particular with regards to regional disease at presentation and regional recurrence. Adequate management of the neck is of the utmost importance but is still the subject of debate. An international multicentre retrospective review of 101 patients treated for T1-T2 buccal SCC was performed. Twenty-four were staged clinical node positive (cN+) and underwent therapeutic neck dissection, while 77 were node negative (cN0), with 32 undergoing elective neck dissection (END), with an occult nodal metastasis rate of 28.1%. Depth of invasion (DOI) < 4 mm was associated with a significantly lower rate of cervical nodal metastasis (87.5% versus 12.5%; P = 0.033). END demonstrated a non-significantly lower regional recurrence rate compared to observation (6.3% versus 8.9%, P = 0.670). Regional recurrence was more common in pN+ (24%) and undissected cases (8.9%) than in pN0 patients (0%) (P = 0.011) and was associated with DOI > 5 mm (P = 0.002). Regional recurrence resulted in a reduction in survival (24 versus 93 months, P < 0.001). In the pT2cN0 group, END improved survival (123 versus 26 months, P = 0.009). It is suggested that END be performed in cT2N0 buccal SCC, particularly for tumours with DOI > 4 mm.

Personalized neck irradiation guided by sentinel lymph node biopsy in patients with squamous cell carcinoma of the oropharynx, larynx or hypopharynx with a clinically negative neck: (Chemo)radiotherapy to the PRIMary tumor only. Protocol of the PRIMO study.

Background: Elective neck irradiation (ENI) is performed in head and neck cancer patients treated with definitive (chemo)radiotherapy. The aim is to eradicate nodal metastases that are not detectable by pretreatment imaging techniques. It is conceivable that personalized neck irradiation can be performed guided by the results of sentinel lymph node biopsy (SLNB). It is expected that ENI can be omitted to one or both sides of the neck in 9 out of 10 patients, resulting in less radiation side effects with better quality of life. Methods/design: This is a multicenter randomized controlled trial aiming to compare safety and efficacy of treatment with SLNB guided neck irradiation versus standard bilateral ENI in 242 patients with cN0 squamous cell carcinoma of the oropharynx, larynx or hypopharynx for whom bilateral ENI is indicated. Patients randomized to the experimental-arm will undergo SLNB. Based on the histopathologic status of the SLNs, patients will receive no ENI (if all SLNs are negative), unilateral neck irradiation only (if a SLN is positive at one side of the neck) or bilateral neck irradiation (if SLNs are positive at both sides of the neck). Patients randomized to the control arm will not undergo SLNB but will receive standard bilateral ENI. The primary safety endpoint is the number of patients with recurrence in regional lymph nodes within 2 years after treatment. The primary efficacy endpoint is patient reported xerostomia-related quality of life at 6 months after treatment. Discussion: If this trial demonstrates that the experimental treatment is non-inferior to the standard treatment in terms of regional recurrence and is superior in terms of xerostomia-related quality of life, this will become the new standard of care.

The complementary value of intraoperative fluorescence imaging and Raman spectroscopy for cancer surgery: combining the incompatibles.

A clear margin is an important prognostic factor for most solid tumours treated by surgery. Intraoperative fluorescence imaging using exogenous tumour-specific fluorescent agents has shown particular benefit in improving complete resection of tumour tissue. However, signal processing for fluorescence imaging is complex, and fluorescence signal intensity does not always perfectly correlate with tumour location. Raman spectroscopy has the capacity to accurately differentiate between malignant and healthy tissue based on their molecular composition. In Raman spectroscopy, specificity is uniquely high, but signal intensity is weak and Raman measurements are mainly performed in a point-wise manner on microscopic tissue volumes, making whole-field assessment temporally unfeasible. In this review, we describe the state-of-the-art of both optical techniques, paying special attention to the combined intraoperative application of fluorescence imaging and Raman spectroscopy in current clinical research. We demonstrate how these techniques are complementary and address the technical challenges that have traditionally led them to be considered mutually exclusive for clinical implementation. Finally, we present a novel strategy that exploits the optimal characteristics of both modalities to facilitate resection with clear surgical margins.

Reasons for not reaching or using web-based self-management applications, and the use and evaluation of Oncokompas among cancer survivors, in the context of a randomised controlled trial.

INTRODUCTION: The web-based self-management application Oncokompas was developed to support cancer survivors to monitor health-related quality of life and symptoms (Measure) and to provide tailored information (Learn) and supportive care options (Act). In a previously reported randomised controlled trial (RCT), 68% of 655 recruited survivors were eligible, and of those 45% participated in the RCT. Among participants of the RCT that were randomised to the intervention group, 52% used Oncokompas as intended. The aim of this study was to explore reasons for not participating in the RCT, and reasons for not using Oncokompas among non-users, and the use and evaluation of Oncokompas among users. METHODS: Reasons for not participating were assessed with a study-specific questionnaire among 243 survivors who declined participation. Usage was investigated among 320 participants randomised to the intervention group of the RCT via system data and a study-specific questionnaire that was assessed during the 1 week follow-up (T1) assessment. RESULTS: Main reasons for not participating were not interested in participation in scientific research (40%) and not interested in scientific research and Oncokompas (28%). Main reasons for not being interested in Oncokompas were wanting to leave the period of being ill behind (29%), no symptom burden (23%), or lacking internet skills (18%). Out of the 320 participants in the intervention group 167 (52%) used Oncokompas as intended. Among 72 non-users, main reasons for not using Oncokompas were no symptom burden (32%) or lack of time (26%). Among 248 survivors that activated their account, satisfaction and user-friendliness were rated with a 7 (scale 0-10). Within 3 (IQR 1-4) sessions, users selected 32 (IQR 6-37) topics. Main reasons for not using healthcare options in Act were that the information in Learn was already sufficient (44%) or no supportive care needs (32%). DISCUSSION: Main reasons for not reaching or using Oncokompas were no symptom burden, no supportive care needs, or lack of time. Users selected many cancer-generic and tumour-specific topics to address, indicating added value of the wide range of available topics.

Cost-utility of an eHealth application 'Oncokompas' that supports cancer survivors in self-management: results of a randomised controlled trial.

PURPOSE: The eHealth self-management application 'Oncokompas' was developed to support cancer survivors in monitoring health-related quality of life (HRQOL) and symptoms, and obtaining personalized feedback and options for supportive care. The aim of this study was to assess the cost-utility of Oncokompas compared with care as usual (CAU) among cancer survivors. METHODS: Survivors were randomly allocated to the intervention or control group. Direct (non-)medical, indirect non-medical costs, and HRQOL were measured at 3- and 6-month follow-up, using iMTA Medical Consumption and Productivity Costs and the EuroQol-5D questionnaires. Mean cumulative costs and quality-adjusted life-years (QALYs) were compared between both groups. RESULTS: In total, 625 survivors were randomized into intervention (n = 320) or control group (n = 305). Base case analysis showed that incremental costs from a societal perspective were - €163 (95% CI, - 665 to 326), and incremental QALYs were 0.0017 (95% CI, - 0.0121 to 0.0155) in the intervention group compared with those in the control group. The probability that, compared with CAU, Oncokompas is more effective was 60%, less costly 73%, and both more effective and less costly 47%. Sensitivity analyses showed that incremental costs vary between - €40 and €69, and incremental QALYs vary between - 0.0023 and - 0.0057. CONCLUSION: Oncokompas is likely to be equally effective on utilities, and not more expensive than CAU, and will therefore contribute to sustainable cancer survivorship care in a (cost-)effective manner. IMPLICATIONS FOR CANCER SURVIVORS: Oncokompas seems to improve HRQOL and reduces the burden of several tumour-specific symptoms, while costs from a societal perspective are similar to CAU.

The eHealth self-management application 'Oncokompas' that supports cancer survivors to improve health-related quality of life and reduce symptoms: which groups benefit most?

BACKGROUND: Oncokompas is a web-based self-management application that supports cancer survivors to monitor their health-related quality of life (HRQOL) and symptoms, and to obtain personalised feedback and tailored options for supportive care. In a large randomised controlled trial among survivors of head and neck cancer, colorectal cancer, and breast cancer and (non-)Hodgkin lymphoma, Oncokompas proved to improve HRQOL, and to reduce several tumour-specific symptoms. Effect sizes were however small, and no effect was observed on the primary outcome patient activation. Therefore, this study aims to explore which subgroups of cancer survivors may especially benefit from Oncokompas. MATERIALS AND METHODS: Cancer survivors (n = 625) were randomly assigned to the intervention group (access to Oncokompas, n = 320) or control group (6 months waiting list, n = 305). Outcome measures were HRQOL, tumour-specific symptoms, and patient activation. Potential moderators included socio-demographic (sex, age, marital status, education, employment), clinical (tumour type, stage, time since diagnosis, treatment modality, comorbidities), and personal factors (self-efficacy, personal control, health literacy, Internet use), and patient activation, mental adjustment to cancer, HRQOL, symptoms, and need for supportive care, measured at baseline. Linear mixed models were performed to investigate potential moderators. RESULTS: The intervention effect on HRQOL was the largest among cancer survivors with low to moderate self-efficacy, and among those with high personal control and those with high health literacy scores. Cancer survivors with higher baseline symptom scores benefitted more on head and neck (pain in the mouth, social eating, swallowing, coughing, trismus), and colorectal cancer (weight) specific symptoms. DISCUSSION: Oncokompas seems most effective in reducing symptoms in head and neck cancer and colorectal cancer survivors who report a higher burden of tumour-specific symptoms. Oncokompas seems most effective in improving HRQOL in cancer survivors with lower self-efficacy, and in cancer survivors with higher personal control, and higher health literacy.

Screening for head and neck second primary tumors in patients with esophageal squamous cell cancer: A systematic review and meta-analysis.

Background: Esophageal squamous cell carcinomas (ESCCs) are often accompanied by head and neck second primary tumors (HNSPTs). The prognosis of patients with an additional HNSPT is worse compared with patients with only ESCC. Therefore, early detection of HNSPTs may improve the overall outcome of patients with ESCC. The purpose of this study was to investigate the yield of endoscopic screening for HNSPTs in patients with primary ESCC. Methods: We conducted a systematic literature search of all available databases. Studies were included if ESCC patients were endoscopically screened for HNSPT. The primary outcome was the pooled prevalence of HNSPTs. Results: Twelve studies, all performed in Japan, were included in this systematic review with a total of 6483 patients. The pooled prevalence of HNSPTs was 6.7% (95% confidence interval: 4.9-8.4). The overall heterogeneity was high across the studies (I2 = 89.0%, p < 0.001). Most HNSPTs were low stage (85.3%) and located in the hypopharynx (60.3%). The proportion of synchronous (48.2%) and metachronous (51.8%) HNSPTs was comparable. Conclusion: Based on our results, HNSPT screening could be considered in patients with primary ESCC. All studies were performed in Japan; it is therefore not clear whether this consideration applies to the Western world.

Deep hyperthermia with the HYPERcollar system combined with irradiation for advanced head and neck carcinoma - a feasibility study.

PURPOSE: Radiotherapy (RT) treatment of locally-advanced and recurrent head and neck carcinoma (HNC) results in disappointing outcomes. Combination of RT with cisplatin or cetuximab improves survival but the increased toxicity and patient's comorbidity warrant the need for a less-toxic radiosensitizer. Stimulated by several randomized studies demonstrating the radio-sensitizing effect of hyperthermia, we developed the HYPERcollar. Here, we report early experience and toxicity in patients with advanced HNC. METHODS AND MATERIALS: 119 hyperthermia treatments given to 27 patients were analyzed. Hyperthermia was applied once a week by the HYPERcollar aimed at achieving 39-43 °C in the target area, up to patients' tolerance. Pre-treatment planning was used to optimize treatment settings. When possible, invasive thermometry catheters were placed. RESULTS: Mean power applied during the 119 hyperthermia treatments ranged from 120 to 1007 W (median 543 W). 15 (13%) hyperthermia treatments were not fully completed due to: pain allocated to hyperthermia (6/15), dyspnea from sticky saliva associated with irradiation (2/15) and unknown reasons (7/15). No severe complications or enhanced thermal or mucosal toxicities were observed. Excluding post-operative treatment, response rates after 3 months were 46% (complete) and 7% (partial). CONCLUSION: Hyperthermia with the HYPERcollar proved to be safe and feasible with good compliance and promising outcome.

Influence of anemia and BMI on prognosis of laryngeal squamous cell carcinoma: Development of an updated prognostic model.

OBJECTIVE: evaluating the impact of anemia and body mass index (BMI) on survival, and development of a prognostic model for overall survival for patients with laryngeal squamous cell carcinoma (LSCC). MATERIALS AND METHODS: A retrospective cohort study was performed including all consecutive patients with LSCC diagnosed and treated at the Erasmus Medical Center between January 2006 and December 2013. Patient- and tumor-specific data were collected using data from the Netherlands Comprehensive Cancer Organization and supplemented with data from patient records available in the Erasmus MC. All comorbidities were scored at the time of diagnosis. RESULTS: in total 788 patients were included. Mean follow-up time was 50 months (SD: ±30), during which 298 patients (37.8%) died. In both univariate and multivariate analysis BMI and anemia were significant predictors for overall survival. Multivariate analysis was performed using known predictors such as age, TNM-stage and comorbidity (ACE-27). The hazard ratio of anemia was 1.41 (95% CI: 1.05-1.90) and of BMI was 0.97 (95% CI: 0.94-0.99). BMI had an inverse association with overall survival in both univariate and multivariate survival analysis. Updating and validating an existing prognostic model with addition of anemia and BMI enhanced the performance of the prognostic model (C-statistic) from 0.77 (95% CI: 0.74-0.79) to 0.79 (95% CI: 0.77-0.82). CONCLUSION: anemia and BMI are predictors of overall survival for LSCC, independent of other known predictors of overall survival. Adding anemia and BMI to an existing prognostic model provides better prediction of overall survival.

Adjuvant radiotherapy in sinonasal mucosal melanoma: A retrospective analysis.

OBJECTIVES: Evaluation of outcome after curative treatment for sinonasal mucosal melanoma focused on the effect of adjuvant radiotherapy on recurrence and survival. DESIGN: Retrospective chart analysis. SETTING: Tertiary referral hospital. PARTICIPANTS: Fifty-one patients with primary sinonasal mucosal melanoma who underwent surgical resection with curative intention between 1980 and 2016 at Erasmus Medical Center, Rotterdam. MAIN OUTCOME MEASURES: Patients were categorised into 2 groups: surgery alone and surgery with adjuvant radiotherapy. Log-rank test was used to compare rates of recurrence and survival between treatment groups. Predictors for treatment modality, recurrence and survival were assessed with multivariate statistical analysis. RESULTS: Of all patients, 23.5% developed local recurrence and 47.1% developed distant metastasis. Estimated 5-year disease-free survival was 25.2%, and 5-year overall survival (OS) was 38.1%. Forty-three patients (84.3%) were treated with post-operative radiotherapy. Patients who underwent surgery with adjuvant radiotherapy presented more often with high tumour stage, tumour involving multiple sites and positive margins. Post-operative radiotherapy seemed to be associated with better local control (P = .549). No effect was found on occurrence of distant metastasis and OS. Positive margin status was an independent negative predictor for distant metastasis-free survival and overall survival. CONCLUSIONS: Our treatment outcomes are consistent with literature. Post-operative radiotherapy seems to be associated with improved local control despite advanced disease and positive margin status in this treatment group.

Postoperative value of serum squamous cell carcinoma antigen as a predictor of recurrence in sinonasal inverted papilloma.

OBJECTIVES: Sinonasal inverted papilloma (IP) has several unfavourable characteristics and therefore requires careful monitoring. The goal of this study was to identify whether serum squamous cell carcinoma antigen (SCCa) could predict IP recurrence. DESIGN: A retrospective cohort study. SETTING: Department of otolaryngology/head and neck surgery, Erasmus Medical Centre, Rotterdam, the Netherlands. PARTICIPANTS: One hundred and thirty patients with IP treated at our centre with SCCa measurements available were included. MAIN OUTCOME MEASUREMENTS: Follow-up of patients with IP since 2005, recurrence was defined as new disease within primary localisation at least 3 months after adequate surgical removal. We analysed the association between IP recurrence and serum SCCa values measured preoperatively, postoperatively and during follow-up. RESULTS: Preoperative SCCa values or values measured during follow-up were not associated with risk of recurrence. Postoperative SCCa was positively associated with the risk of recurrence (P < 0.001). Postoperative SCCa had a good discriminative ability for the identification of recurrence with an area under the curve of 80.9%. CONCLUSION: Postoperative SCCa is strongly associated with risk of recurrence. This might help the surgeon in the postoperative setting by identifying high-risk patients and planning follow-up strategy tailored to the individual patient.

Zenker's diverticulum: Rotterdam experience.

Different surgical techniques exist for the treatment of Zenker's diverticulum (ZD), of which minimally invasive techniques have become the standard. We reviewed our experience with management and treatment of ZD and sought to determine what type of treatment is most effective and efficient. We selected patients who underwent treatment for ZD between January 2004 and January 2014 at our tertiary referral center. All procedures were performed by ENT surgeons. The medical records were reviewed for pre- and intraoperative characteristics and follow-up. Of our 94 patients (58 male, 36 female), 75 underwent endoscopic cricopharyngeal myotomy (42 stapler, 33 laser) and 6 received treatment via transcervical approach. 13 interventions were aborted. Mean operating time was 49.0 min for stapler, 68.3 for laser and 124.0 for the transcervical approach. Its respective median post-operative admission durations were 2.0, 3.0 and 3.0 days. After the first treatment, of the 75 endoscopic procedures, 45 patients (23 stapler, 22 laser) had complete symptom resolution. In the transcervical group 4 (67 %) patients were symptom free and one patient died of complications. In the endoscopically treated patients, ten complications occurred, of which 8 G1 and 2 G2 (Clavien Dindo classification). In the transcervical group 2 complications occurred, 1 G3b and 1 G5. Both endoscopic techniques provide efficient management of Zenker's diverticulum with the stapler-assisted modality providing a shorter surgery duration and hospital admission. Although there is no significant difference in terms of complications or recurrence rates for both endoscopic techniques, it seems that stapler patients are at higher risk of having a re-intervention and of having more severe complications.

Discrimination between oral cancer and healthy tissue based on water content determined by Raman spectroscopy.

Tumor-positive resection margins are a major problem in oral cancer surgery. High-wavenumber Raman spectroscopy is a reliable technique to determine the water content of tissues, which may contribute to differentiate between tumor and healthy tissue. The aim of this study was to examine the use of Raman spectroscopy to differentiate tumor from surrounding healthy tissue in oral squamous cell carcinoma. From 14 patients undergoing tongue resection for squamous cell carcinoma, the water content was determined at 170 locations on freshly excised tongue specimens using the Raman bands of the OH-stretching vibrations (3350-3550 cm(-1)) and of the CH-stretching vibrations (2910-2965 cm(-1)). The results were correlated with histopathological assessment of hematoxylin and eosin stained thin tissue sections obtained from the Raman measurement locations. The water content values from squamous cell carcinoma measurements were significantly higher than from surrounding healthy tissue (p-value < 0.0001). Tumor tissue could be detected with a sensitivity of 99% and a specificity of 92% using a cutoff water content value of 69%. Because the Raman measurements are fast and can be carried out on freshly excised tissue without any tissue preparation, this finding signifies an important step toward the development of an intraoperative tool for tumor resection guidance with the aim of enabling oncological radical surgery and improvement of patient outcome.

Chronic serous otitis media as a manifestation of temporal meningioma.

Chronic serous otitis media is a common problem in the daily routine of the otorhinolaryngologist. In the majority of cases, the cause is related to dysfunction of the eustachian tube due to viral or bacterial rhinitis and occasionally to nasopharyngeal tumors. We report a case of a patient presenting with chronic serous otitis media that was resistant to conventional therapy. MRI with gadolinium finally revealed that the middle ear fluid was caused by leakage of cerebrospinal fluid (CSF) due to bone destruction by a temporal meningioma. The CSF leakage was closed by surgery. Histopathology confirmed meningioma in the temporal bone.

Transplantation of tracheal autografts: is a two-stage procedure necessary?

BACKGROUND: Tracheal autotransplantation has been shown to be a reliable technique for repairing the hemilaryngectomy defect that includes the hemicricoid cartilage and results from resection of unilateral laryngeal cancer with significant subglottic extension. The technique involves a two-stage procedure of cervical tracheal revascularization by wrapping the trachea in a vascularized radial forearm flap and subsequent tracheal transplantation on a newly created vascular pedicle consisting of the radial artery and vein (1, 2). OBJECTIVES: To experimentally (rabbits) investigate if a one-stage tracheal revascularization and transplantation procedure could be a viable option. METHODS: Tracheal patch autografts (1.5 cm x 1 cm) were excised and reimplanted at the anterior cervical trachea with four different patterns of vascular supply: group I: tracheal patch wrapped with vascularized fascia 14 days before excision of the patch (two-stage procedure); group II: tracheal patch wrapped with vascularized fascia at the time of patch excision; group III: tracheal patch without tissue wrapping; and group IV: tracheal patch wrapped with a sheet of Gore-Tex after reimplantation. After orthotopical reimplantation, the patches showed decreasing vascular contacts from group I to group IV. The patches were evaluated morphologically at the moment the animal became dyspnoeic or two weeks after reimplantation in asymptomatic animals. RESULTS: Group I patches fully preserved their viability (median percentage mucosal viability of 100%). Autografts in group II and III showed varying degrees of necrosis and graft take with a median percentage graft viability of 59 and 69% respectively. All group IV tracheal patches showed full thickness necrosis over the majority of their surface area (median percentage graft viability of 10%). CONCLUSION: Fascia enwrapped tracheal autografts show reliable revascularization through the intercartilaginous ligaments only when a 2 stage revascularization technique is used.

Squamous cell carcinoma of maxillary sinus.

BACKGROUND: Medical records of 43 patients with histologically proved diagnosis of squamous cell carcinoma who were treated between the years 1975 and 1994 at the department of Otolaryngology Head Neck Surgery, VU Amsterdam were examined. METHODS: Tumors were restaged according to UICC classification 1997. Thirty-eight patients were treated for cure, nine were treated with chemotherapy followed by external beam radiotherapy, and 28 patients were treated with surgery followed by postoperative radiotherapy. No patient was lost to follow-up. Data with respect to survival were analyzed. RESULTS: Eighty-three percent of the tumours were in stage III or stage IV at the time of first presentation. Five-year survival after surgery and postoperative radiotherapy for all patients was 64%. For stages II, III, and IV it was 83%, 49%, and 37%, respectively. Cervical nodal metastases were present in 4.1% at the time of presentation. Thirty-seven percent of the patients survived 2 years after chemotherapy followed by radiotherapy. CONCLUSIONS: Squamous cell carcinoma continues to be diagnosed late. Surgery followed by radiotherapy remains the treatment of choice. Mandibulotomy should be considered for better clearance of retromaxillary space in T3 -T4 tumors. The eye should be preserved whenever it is oncologically safe to do so.

Carcinoma of the ethmoid: results of treatment with conventional surgery and post-operative radiotherapy.

AIMS: A retrospective study was carried out of 50 patients with carcinoma of the ethmoid, treated over a period of 20 years. METHODS: The treatment used was surgery, followed by post-operative external beam radiotherapy and when possible supplemented by brachytherapy. RESULTS: Although the nature of surgery in the majority of cases was conventional, the 63% 5-year overall survival, except in adenocarcinomas, was slightly better than that achieved by more aggressive surgery. There was no mortality and morbidity was minimal. CONCLUSIONS: Conventional surgery in combination with radiotherapy and brachytherapy gives satisfactory and comparable results.