Malnutrition risk and frailty in head and neck cancer patients: coexistent but distinct conditions.

PURPOSE: Both malnutrition and frailty are associated with adverse treatment outcomes. Malnutrition (risk) and frailty are each commonly present in patients with head and neck cancer (HNC). However, their coexistence and association is unknown. Main goal of this study is to determine the coexistence of, and the association between malnutrition risk and frailty in patients with HNC. METHODS: In this retrospective analysis on prospectively collected data, newly diagnosed patients with HNC, enrolled in the OncoLifeS databiobank were included. The Patient-Generated Subjective Global Assessment Short Form (PG-SGA SF) was used to assess malnutrition risk. The Groningen Frailty Indicator (GFI) was used to assess frailty status. Multivariate logistic regression analyses were performed, taking into account several patient- and tumor-related factors. RESULTS: In total, 197 patients were included. Seventy-six patients (39%) had a medium or high malnutrition risk and 71 patients (36%) were frail. In 38 patients (19%), malnutrition risk coexisted with frailty. Patients with medium and high malnutrition risk were, respectively, 4.0 (95% CI 1.5-11.2) and 13.4 (95% CI 4.0-48.7) times more likely to be frail, compared to patients with low malnutrition risk. In turn, frail patients were 6.4 times (95% CI 2.6-14.9) more likely to have malnutrition risk compared to non-frail patients. CONCLUSIONS: Malnutrition risk and frailty frequently coexist but not fully overlap in newly diagnosed patients with HNC. Therefore, screening for both conditions is recommended.

Cortactin expression assessment improves patient selection for a watchful waiting strategy in pT1cN0-staged oral squamous cell carcinomas with a tumor infiltration depth below 4 mm.

BACKGROUND: In this feasibility study we aimed to evaluate the value of previously reported molecular tumor biomarkers associated with lymph node metastasis in oral squamous cell carcinoma (OSCC) to optimize neck strategy selection criteria. METHODS: The association between expression of cortactin, cyclin D1, FADD, RAB25, and S100A9 and sentinel lymph node status was evaluated in a series of 87 (cT1-2N0) patients with OSCC treated with primary resection and SLNB procedure. RESULTS: Tumor infiltration depth and tumor pattern of invasion were independent prognostic markers for SLN status, while none of the tumor makers showed a better prognostic value to replace SLNB as neck staging technique in the total cohort. However, in the subgroup of patients with pT1N0 OSCC, cortactin expression (OR 16.0, 95%CI 2.0-127.9) was associated with SLN classification. CONCLUSIONS: Expression of cortactin is a promising immunohistochemical tumor marker to identify patients at low risk that may not benefit from SLNB or END.

Reorganizing the Multidisciplinary Team Meetings in a Tertiary Centre for Gastro-Intestinal Oncology Adds Value to the Internal and Regional Care Pathways. A Mixed Method Evaluation.

INTRODUCTION: The reorganisation of the structure of a Gastro-Intestinal Oncology Multidisciplinary Team Meeting (GIO-MDTM) in a tertiary centre with three care pathways is evaluated on added value. METHODS: In a mixed method investigation, process indicators such as throughput times were analysed and stakeholders were interviewed regarding benefits and drawbacks of the reorganisation and current MDTM functioning. RESULTS: For the hepatobiliary care pathway, the time to treatment plan increased, but the time to start treatment reduced significantly. The percentage of patients treated within the Dutch standard of 63 days increased for the three care pathways. From the interviews, three themes emerged: added value of MDTMs, focus on planning integrated care and awareness of possible improvements. DISCUSSION: The importance of evaluating interventions in oncology care pathways is shown, including detecting unexpected drawbacks. The evaluation provides insight into complex dynamics of the care pathways and contributes with recommendations on functioning of an MDTM. CONCLUSIONS: Throughput times are only partly determined by oncology care pathway management, but have influence on the functioning of MDTMs. Process indicator information can help to reflect on integration of care in the region, resulting in an increase of patients treated within the Dutch standard.

Perception and Performance of Physical Activity Behavior after Head and Neck Cancer Treatment: Exploration and Integration of Qualitative and Quantitative Findings.

Maintaining or increasing physical activity (PA) may prevent loss of muscle mass and strength after completion of head and neck cancer (HNC) treatment. However, the exercise level of HNC patients may not meet PA guidelines. We aimed to explore HNC survivors' views on PA, their report of PA, and to compare these with objectively measured PA. Combined qualitative and quantitative data of HNC survivors were explored post-treatment. Data from semi-structured interviews, questionnaires, and objective measurements of PA were collected, analyzed, and integrated. This resulted in the identification of five themes related to prioritizing, day-to-day life, intention, positive feelings, and social support, respectively, in nine HNC survivors (male: n = 5; age: 52-67 years). Objectively measured PA levels were sedentary to low. The lack of intention to increase PA may be related to HNC survivors' perception that their current activity level is sufficient, despite low levels of measured PA. While some participants feel they need no help with PA, others are insecure about possible harms. Healthcare professionals may be able to help improve PA in HNC survivors with a tailored approach that reduces fear of harm and helps to incorporate higher intensity PA in daily activities.

Prognostic factors associated with a restricted mouth opening (trismus) in patients with head and neck cancer: Systematic review.

BACKGROUND: To prescribe early trismus therapy, prognostic factors influencing the restricted mouth opening should be identified first. Our aim is to present an overview of these factors in patients with head and neck cancer. METHODS: PubMed, Cochrane, EMBASE, and CINAHL were searched using terms related to head and neck cancer and mouth opening. Risk of bias was assessed using the "Quality in Prognosis Studies" tool. A best evidence synthesis was performed. RESULTS: Of the identified 1418 studies, 53 were included. Three studies contained a prognostic multivariate model for a restricted mouth opening. CONCLUSIONS: Patients with head and neck cancer will most likely develop a restricted mouth opening when they have a large tumor near the masticatory muscles that requires extensive cancer treatment. A restricted mouth opening most likely occurs within 6 months after cancer treatment. Further research is necessary on factors related to healing tendency or pain intensity.

Targeted Photodynamic Therapy of Human Head and Neck Squamous Cell Carcinoma with Anti-epidermal Growth Factor Receptor Antibody Cetuximab and Photosensitizer IR700DX in the Mouse Skin-fold Window Chamber Model.

Targeted photodynamic therapy (PDT) in head/neck cancer patients with a conjugate of the anti-epidermal growth factor receptor (EGFR) antibody, Cetuximab and a phthalocyanine photosensitizer IR700DX is under way, but the exact mechanisms of action are still not fully understood. In this study, the EGFR-overexpressing human head/neck OSC-19-luc2-cGFP tumor with transfected GFP gene was used in a skin-fold window chamber model in BALB/c nude mice. The uptake and localization of the conjugate in the tumor and its surrounding normal tissues were studied by an intravital confocal laser scanning microscopy with image analyses. The tumor was also irradiated with 690 nm laser light 24 h after conjugate administration. The vascular and tumor responses were examined by morphological evaluation and immunohistochemistry (IHC). The amount of conjugate in the tumor peaked at 24-48 h after injection. Image analyses of colocalization correlation parameters demonstrated a high fraction of the conjugate IR700DX colocalized in the GFP-expressing tumor cells. PDT-treated tumors showed extensive necrotic/apoptotic destruction with little vascular damage, while IHC showed no HIF-1α expression and decreased EGFR and Ki67 expression with activated caspase-3 overexpression, indicating a direct killing of tumor cells through both necrotic and apoptotic cell death.

In-Vivo Optical Monitoring of the Efficacy of Epidermal Growth Factor Receptor Targeted Photodynamic Therapy: The Effect of Fluence Rate.

Targeted photodynamic therapy (PDT) has the potential to improve the therapeutic effect of PDT due to significantly better tumor responses and less normal tissue damage. Here we investigated if the efficacy of epidermal growth factor receptor (EGFR) targeted PDT using cetuximab-IRDye700DX is fluence rate dependent. Cell survival after treatment with different fluence rates was investigated in three cell lines. Singlet oxygen formation was investigated using the singlet oxygen quencher sodium azide and singlet oxygen sensor green (SOSG). The long-term response (to 90 days) of solid OSC-19-luc2-cGFP tumors in mice was determined after illumination with 20, 50, or 150 mW·cm-2. Reflectance and fluorescence spectroscopy were used to monitor therapy. Singlet oxygen was formed during illumination as shown by the increase in SOSG fluorescence and the decreased response in the presence of sodium azide. Significantly more cell death and more cures were observed after reducing the fluence rate from 150 mW·cm-2 to 20 mW·cm-2 both in-vitro and in-vivo. Photobleaching of IRDye700DX increased with lower fluence rates and correlated with efficacy. The response in EGFR targeted PDT is strongly dependent on fluence rate used. The effectiveness of targeted PDT is, like PDT, dependent on the generation of singlet oxygen and thus the availability of intracellular oxygen.

Low muscle mass is associated with early termination of chemotherapy related to toxicity in patients with head and neck cancer.

BACKGROUND & AIMS: We studied whether low pre-treatment muscle mass, measured with CT at thoracic (T4) or lumbar level (L3) associates with early termination of chemotherapy related to toxicity in head and neck cancer (HNC) patients. METHODS: This was a retrospective chart and image review. Adult HNC patients treated with (surgery and) platinum-based chemo-radiotherapy were included if a pre-treatment CT scan at T4 or L3 level was available. Muscle mass was evaluated by assessment of skeletal muscle index (SMI; cm2/m2). T4 and L3 SMI measurements were corrected for deviation from their respective means and were merged into one score for SMI difference (cm2/m2). All cases were assessed for presence of toxicity-related unplanned early termination of chemotherapy ('early termination'). Univariate and multivariate logistic regression models were used to investigate associations between pooled SMI and early termination. RESULTS: 213 patients (age: 57.9 ± 10.3 y, male: 77%, T4 image: 45%) were included. A significant association between SMI as a continuous variable and early termination was found, both in the univariate analysis (p = 0.007, OR = 0.96 [0.94-0.99]) and the multivariate analysis (p = 0.021, OR 0.96 [0.92-0.99]). The multivariate models identified potential associations with type of chemotherapy, presence of co-morbidity, a combination of (former) smoking and alcohol consumption, and sex. CONCLUSION: Lower muscle mass was robustly associated with higher odds of early termination of chemotherapy in HNC patients. Further prospective studies are required to tailor the care for patients with low muscle mass and to avoid early termination of chemotherapy.

Self-Completion of the Patient-Generated Subjective Global Assessment Short Form Is Feasible and Is Associated With Increased Awareness on Malnutrition Risk in Patients With Head and Neck Cancer.

BACKGROUND: We aimed to assess feasibility of self-completion of the Patient-Generated Subjective Global Assessment Short Form (PG-SGA SF) by head and neck cancer patients, and to assess self-reported increased awareness regarding malnutrition risk after self-completion. METHODS: Participants were randomized to complete the PG-SGA SF by paper or app. Feasibility was assessed by time needed to complete the PG-SGA SF, perceived difficulty, and help needed during completion. Participants were asked if they knew what malnutrition was (yes/no) and if they could define "malnutrition." They were also asked 9 questions on whether they perceived increased awareness of malnutrition risk after having completed the PG-SGA SF and 2 on their intention to change lifestyle habits. RESULTS: Of all participants (n = 59; 65.9 ± 12.6 years; 73% male), 55% completed the PG-SGA SF paper version and 46% the Pt-Global app. Median time needed for self-completion of the PG-SGA SF was 2 minutes 41 seconds (interquartile range: 1 minute 49 seconds-3 minutes 50 seconds). Forty-eight percent needed help with completion, indicating acceptable feasibility. Participants who completed the Pt-Global app needed help significantly more often (66%; 21/32) than those who completed the PG-SGA SF paper version (26%; 7/27) (P = 0.005). All difficulty scores were excellent. For 7/9 questions on malnutrition risk awareness, >50% of the participants answered positively. CONCLUSION: The results of this study show that self-completion of the PG-SGA SF by head and neck cancer patients is feasible and that awareness regarding malnutrition risk may increase after completing the PG-SGA SF.

The use of stretching devices for treatment of trismus in head and neck cancer patients: a randomized controlled trial.

PURPOSE: To compare the effects of two stretching devices, the TheraBite® Jaw Motion Rehabilitation System™ and the Dynasplint Trismus System®, on maximal mouth opening in head and neck cancer patients. METHODS: Patients were randomly assigned to one of two exercise groups: the TheraBite® Jaw Motion Rehabilitation System™ group or the Dynasplint Trismus System® group. Patients performed stretching exercises for 3 months. During the three study visits, maximal mouth opening was measured and the patients completed questionnaires on mandibular function and quality of life. RESULTS: In our study population (n = 27), five patients did not start the exercise protocol, eight patients discontinued exercises, and two patients were lost to follow-up. No significant differences regarding the change in mouth opening between the two devices were found. Patients had an increase in MMO of 3.0 mm (IQR - 2.0; 4.0) using the TheraBite® Jaw Motion Rehabilitation System™ and 1.5 mm (IQR 1.0; 3.0) using the Dynasplint Trismus System®. Exercising with either stretching device was challenging for the patients due to the intensive exercise protocol, pain during the exercises, fitting problems with the stretching device, and overall deterioration of their medical condition. CONCLUSIONS: The effects of the two stretching devices did not differ significantly in our study population. The factors described, influencing the progression of stretching exercises, need to be taken into account when prescribing a similar stretching regimen for trismus in head and neck cancer patients. TRIAL REGISTRATION: NTR - Dutch Trial Register number: 5589.

Addition of tumour infiltration depth and extranodal extension improves the prognostic value of the pathological TNM classification for early-stage oral squamous cell carcinoma.

AIMS: In the 8th edition of the American Joint Committee on Cancer TNM staging manual, tumour infiltration depth and extranodal extension are added to the pathological classification for oral squamous cell carcinoma. The currently available 8th TNM validation studies lack patients with conservative neck treatment, and changes in the classification especially affect patients with small tumours. The aim of this study was to determine the potential impact of the changes in the 8th edition pTNM classification on the prognosis and treatment strategy for oral squamous cell carcinoma in a well-defined series of pT1-T2 patients with long-term follow-up. METHODS AND RESULTS: Two hundred and eleven first primary pT1-T2 oral squamous cell carcinoma patients, with surgical resection as primary treatment, were analysed retrospectively. One hundred and seventy-three patients underwent a neck dissection, and 38 patients had frequent clinical neck assessments. Long-term follow-up (median 64 months) and reassessed tumour infiltration depth were available. Classification according to the 8th edition criteria resulted in 36% total upstaging with the T classification and 16% total upstaging with the N classification. T3-restaged patients (n = 30, 14%) had lower 5-year disease-specific survival rates than T2-staged patients (81% versus 67%, P = 0.042). Postoperative (chemo)radiotherapy could have been considered in another seven (3%) patients on the basis of the 8th edition criteria. CONCLUSIONS: Addition of tumour infiltration depth and extranodal extension in the 8th TNM classification leads to the identification of oral squamous cell carcinoma patients with a worse prognosis who might benefit from an improved postoperative treatment strategy.

Reasons for low uptake of a psychological intervention offered to cancer survivors with elevated depressive symptoms.

OBJECTIVE: In line with screening guidelines, cancer survivors were consecutively screened on depressive symptoms (as part of standard care), with those reporting elevated levels of symptoms offered psychological care as part of a trial. Because of the low uptake, no conclusions could be drawn about the interventions' efficacy. Given the trial set-up (following screening guidelines and strict methodological quality criteria), we believe that this observational study reporting the flow of participation, reasons for and characteristics associated with nonparticipation, adds to the debate about the feasibility and efficiency of screening guidelines. METHODS: Two thousand six hundred eight medium- to long-term cancer survivors were consecutively screened on depressive symptoms using the Patient Health Questionnaire-9 (PHQ-9). Those with moderate depressive symptoms (PHQ-9 ≥ 10) were contacted and informed about the trial. Patient flow and reasons for nonparticipation were carefully monitored. RESULTS: One thousand thirty seven survivors (74.3%) returned the questionnaire, with 147 (7.6%) reporting moderate depressive symptoms. Of this group, 49 survivors (33.3%) were ineligible, including 26 survivors (17.7%) already receiving treatment and another 44 survivors (30.0%) reporting no need for treatment. Only 25 survivors (1.0%) participated in the trial. CONCLUSION: Of the approached survivors for screening, only 1% was eligible and interested in receiving psychological care as part of our trial. Four reasons for nonparticipation were: nonresponse to screening, low levels of depressive symptoms, no need, or already receiving care. Our findings question whether to spend the limited resources in psycho-oncological care on following screening guidelines and the efficiency of using consecutive screening for trial recruitment in cancer survivors.

Criterion for trismus in head and neck cancer patients: a verification study.

PURPOSE: Several cut-off points for trismus in head and neck cancer patients have been used. A mouth opening of 35 mm or less is most frequently used as cut-off point. Due to the variation in cut-off points, prevalence, risk factors and treatment outcomes of trismus cannot be studied in a uniform manner. To provide uniformity, we aimed to verify the cut-off point of 35 mm or less. Additionally, we aimed to determine associated covariates with reported difficulties when opening the mouth. METHODS: In a cross-sectional design, we measured the mouth opening in 671 head and neck cancer patients at the Department of Oral and Maxillofacial Surgery, at the University Medical Center Groningen. The cut-off point was determined using the receiver operating characteristic curve and Youden index, with reported difficulties when opening the mouth as criterion for trismus. Cut-off points for significant covariates were also determined. RESULTS: The Youden index was highest at 35 mm, with a sensitivity of 0.71 and a specificity of 0.86. Of the covariates analysed, type of treatment modality was significantly associated with reported difficulties when opening the mouth. The highest Youden index for patients treated with surgery alone was 37 mm and for patients treated with radiotherapy alone 33 mm. CONCLUSIONS: The cut-off point of 35 mm or less for trismus was confirmed in a head and neck cancer population and is recommended to be used in future studies. Patients receiving different treatment modalities experience difficulty when opening the mouth differently.

Effect of adjuvant radiotherapy on the local recurrence of oral squamous cell carcinoma with perineural invasion: A systematic review.

OBJECTIVES OF THE REVIEW: The decision whether to include postoperative radiotherapy on patients with oral squamous cell carcinoma depends on the risk of local recurrence. The objectives of this study were to systematically review literature on whether perineural invasion in oral squamous cell carcinoma patients is associated with higher local recurrence rates and whether local recurrence is influenced by the administration of postoperative radiotherapy in patients presenting with perineural invasion. TYPE OF REVIEW: Systematic review. SEARCH STRATEGY: Embase, PubMed, Web Of Science. EVALUATION METHOD: The databases above were searched for studies that analysed: the treatment of oral squamous cell carcinoma patients with perineural invasion, local recurrence and postoperative radiotherapy. The data of seven studies were analysed qualitatively. RESULTS: The overall quality of the studies was moderate to low. There was no evidence of the effect of postoperative radiotherapy on local recurrence rates in patients presenting with perineural invasion. Some evidence suggests that local recurrence rates may increase in cases of multifocal perineural invasion, especially if nerves >1 mm are involved but these data should be interpreted with caution due to the low-quality evidence. CONCLUSIONS: High-quality evidence regarding the prognostic value of perineural invasion and the impact of postoperative radiotherapy in patients presenting with perineural invasion is lacking in the literature, making it difficult to select a postoperative strategy for early-stage tumours.

Prevalence and prediction of trismus in patients with head and neck cancer: A cross-sectional study.

BACKGROUND: Trismus occurs frequently in patients with head and neck cancer. Determining the prevalence and associated factors of trismus would enable prediction of the risk of trismus for future patients. METHODS: Based on maximal mouth opening measurements, we determined the prevalence of trismus in 730 patients with head and neck cancer. Associated factors for trismus were analyzed using univariate analyses and multivariate logistic regression analyses. Based on the regression model, a calculation tool to predict trismus was made. RESULTS: Prevalence of trismus was 23.6%. Factors associated with trismus were: advanced age; partial or full dentition; tumors located at the maxilla; mandible; cheek; major salivary glands; oropharynx; an unknown primary; a free soft tissue transfer after surgery; reirradiation; and chemotherapy. CONCLUSION: About one-fourth of patients with head and neck cancer develop trismus. Based on prevalence and associated factors of trismus, a simple calculation tool predicts the risk of trismus in these patients.

Multidisciplinary first-day consultation accelerates diagnostic procedures and throughput times of patients in a head-and-neck cancer care pathway, a mixed method study.

BACKGROUND: Head and neck cancers are fast growing tumours that are complex to diagnose and treat. Multidisciplinary input into organization and logistics is critical to start treatment without delay. A multidisciplinary first-day consultation (MFDC) was introduced to reduce throughput times for patients suffering from head and neck cancer in the care pathway. In this mixed method study we evaluated the effects of introducing the MFDC on throughput times, number of patient hospital visits and compliance to the Dutch standard to start treatment within 30 calendar-days. METHODS: Data regarding 'days needed for referral', 'days needed for diagnostic procedures', 'days to start first treatment', and 'number of hospital visits' (process indicators) were retrieved from the medical records and analysed before and after implementation of the MFDC (before implementation: 2007 (n = 21), and after 2008 (n = 20), 2010 (n = 24) and 2013 (n = 24)). We used semi-structured interviews with medical specialists to explore a sample of outliers. RESULTS: Comparing 2007 and 2008 data (before and after MFDC implementation), days needed for diagnostic procedures and to start first treatment reduced with 8 days, the number of hospital visits reduced with 1.5 visit on average. The percentage of new patients treated within the Dutch standard of 30 calendar-days after intake increased from 52 to 83%. The reduction in days needed for diagnostic procedures was sustainable. Days needed to start treatment increased in 2013. Semi-structured interviews revealed that this delay could be attributed to new treatment modalities, patients needed more time to carefully consider their treatment options or professionals needed extra preparation time for organisation of more complex treatment due to early communication on diagnostic procedures to be performed. CONCLUSIONS: A MFDC is efficient and benefits patients. We showed that the MFDC implementation in the care pathway had a positive effect on efficiency in the care pathway. As a consequence, the extra efforts of four specialist disciplines, a nurse practitioner, and a coordinating nurse seeing the patient together during intake, were justified. Start treatment times increased as a result of new treatment modalities that needed more time for preparation.

Epidermal growth factor receptor (EGFR) density may not be the only determinant for the efficacy of EGFR-targeted photoimmunotherapy in human head and neck cancer cell lines.

OBJECTIVE: The aim of this study was to investigate the effects of targeted photoimmunotherapy (PIT) in vitro on cell lines with various expression levels of epidermal growth factor receptor (EGFR) using an anti-EGFR targeted conjugate composed of Cetuximab and IR700DX, phthalocyanine dye. MATERIALS AND METHODS: Relative EGFR density and cell binding assay was conducted in three human head & neck cancer cell lines (scc-U2, scc-U8, and OSC19) and one reference cell line A431. After incubation with the conjugate for 1 or 24 hours, cellular uptake and localization were investigated by confocal laser scanning microscopy and quantified by image analysis. Cell survival was determined using the MTS assay and alamarBlue assay after PIT with a 690 nm laser to a dose of 7 J.cm-2 (at 5 mW.cm-2 ). The mode of cell death was examined with flow cytometry using apoptosis/necrosis staining by Annexin V/propidium iodide, together with immunoblots of anti-apoptotic Bcl-2 family proteins Bcl-2 and Bcl-xL. RESULTS: A431 cells had the highest EGFR density followed by OSC19, and then scc-U2 and scc-U8. The conjugates were localized both on the surface and in the cytosol of the cells after 1- and 24-hour incubation. After 24-hour incubation the granular pattern was more pronounced and in a similar pattern of a lysosomal probe, suggesting that the uptake of conjugates by cells was via receptor-mediated endocytosis. The results obtained from the quantitative imaging analysis correlate with the level of EGFR expression. Targeted PIT killed scc-U8 and A431 cells efficiently; while scc-U2 and OSC19 were less sensitive to this treatment, despite having similar EGFR density, uptake and localization pattern. Scc-U2 cells showed less apoptotic cell dealth than in A431 after 24-hour targeted PIT. Immunoblots showed significantly higher expression of anti-apoptotic Bcl-2 and Bcl-xL proteins in scc-U2 cell lines compared to scc-U8. CONCLUSION: Our study suggests that the effectiveness of EGFR targeted PIT is not only dependent upon EGFR density. Intrinsic biological properties of tumor cell lines also play a role in determining the efficacy of targeted PIT. We have shown that in scc-U2 cells this difference may be caused by differences in the apoptopic pathway. Lasers Surg. Med. 50:513-522, 2018. © 2018 Wiley Periodicals, Inc.

Data-Driven prioritisation of antibody-drug conjugate targets in head and neck squamous cell carcinoma.

BACKGROUND: For patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) palliative treatment options that improve overall survival are limited. The prognosis in this group remains poor and there is an unmet need for new therapeutic options. An emerging class of therapeutics, targeting tumor-specific antigens, are antibodies bound to a cytotoxic agent, known as antibody-drug conjugates (ADCs). The aim of this study was to prioritize ADC targets in HNSCC. METHODS: With a systematic search, we identified 55 different ADC targets currently targeted by registered ADCs and ADCs under clinical evaluation. For these 55 ADC targets, protein overexpression was predicted in a dataset containing 344 HNSCC mRNA expression profiles by using a method called functional genomic mRNA profiling. The ADC target with the highest predicted overexpression was validated by performing immunohistochemistry (IHC) on an independent tissue microarray containing 414 HNSCC tumors. RESULTS: The predicted top 5 overexpressed ADC targets in HNSCC were: glycoprotein nmb (GPNMB), SLIT and NTRK-like family member 6, epidermal growth factor receptor, CD74 and CD44. IHC validation showed combined cytoplasmic and membranous GPNMB protein expression in 92.0% of the cases. Strong expression was seen in 65.9% of the cases. In addition, 86.5% and 67.7% of cases showed ≥5% and >25% GPNMB positive tumor cells, respectively. CONCLUSIONS: This study provides a data-driven prioritization of ADCs targets that will facilitate clinicians and drug developers in deciding which ADC should be taken for further clinical evaluation in HNSCC. This might help to improve disease outcome of HNSCC patients.

Viable tumor in salvage neck dissections in head and neck cancer: Relation with initial treatment, change of lymph node size and human papillomavirus.

OBJECTIVES: To identify predictive factors for the presence of viable tumor and outcome in head and neck cancer patients who undergo therapeutic salvage neck dissections. MATERIALS AND METHODS: Retrospective analysis of 76 salvage neck dissections after radiotherapy alone (n = 22), radiotherapy in combination with carboplatin/5-fluorouracil (n = 42) or with cetuximab (n = 12). RESULTS: Viable tumor was detected in 41% of all neck dissections. Univariate analysis revealed initial treatment with radiotherapy without systemic therapy (OR 6.93, 95%CI: 2.28-21.07, p < .001), increased lymph node size after initial treatment compared to pretreatment CT scan (OR 20.48, 95%CI: 2.46-170.73, p = .005), more extensive neck dissections (OR 8.40, 95%CI: 2.94-23.98, p < .001), and human papillomavirus negative cancer (OR 4.22, 95%CI: 1.10-16.22, p = .036) as predictors of viable tumor. Patients with decreased or stable, but persistently enlarged lymph node size after chemoradiation had a significantly lower chance of viable tumor (OR 0.15, 95%CI: 0.05-0.41, p < .001). Disease-specific 5-year survival was 34% in case of viable tumor, and 78% when no viable tumor was found (p < .001). CONCLUSIONS: Viable tumor in salvage neck dissections is associated with reduced survival. Radiotherapy alone, human papillomavirus negative cancer and increase in lymph node size, are associated with viable tumor in salvage neck dissections. In case of decreased or stable lymph node size after chemoradiation, watchful waiting could be considered.

Translation and Cultural Adaptation of the Scored Patient-Generated Subjective Global Assessment: An Interdisciplinary Nutritional Instrument Appropriate for Dutch Cancer Patients.

BACKGROUND: Assessment of malnutrition is important in cancer patients. The Scored Patient-Generated Subjective Global Assessment (PG-SGA), an instrument that enables interdisciplinary assessment of malnutrition and its risk factors, was not available in Dutch. OBJECTIVE: Translation and cultural adaption of the original English PG-SGA to the Dutch setting. METHODS: The PG-SGA was translated and culturally adapted, following the International Society for Pharmacoeconomics and Outcomes Research principles. Perceived content validity, comprehensibility, and difficulty were explored among a multidisciplinary sample of healthcare professionals and their cancer patients. Content validity, comprehensibility, and difficulty were operationalized by calculating item and scale indices. On scale level, indices of 0.80 to 0.90 were considered acceptable, and indices of 0.90 or greater were considered excellent. RESULTS: Consensus was reached on 91 and 8 differences in the forward and back translations, respectively. Scale Content Validity Index was 0.89. Scale Comprehensibility Index and Scale Difficulty Index of the patient-generated component of the PG-SGA were 0.99 and 0.96, respectively. Scale Comprehensibility Index and Scale Difficulty Index of the professional component were 0.81 and 0.55, respectively. CONCLUSIONS: Translation and cultural adaptation of the PG-SGA according to the International Society for Pharmacoeconomics and Outcomes Research principles resulted in a Dutch version that maintained the purpose, meaning, and format and have acceptable content validity. Now a Dutch version of the PG-SGA is available that is considered comprehensible and easy by patients, and comprehensible and relevant by professionals. However, the professional component was considered difficult by the PG-SGA-naive professionals, which indicates a need for training. IMPLICATIONS FOR PRACTICE: A similar systematic approach for future translations of the PG-SGA is recommended, to safeguard cultural equivalence.