Use of a Dermal Regeneration Template in a two-stage reconstruction after extensive skin surgery for Bowen's disease of the anterior neck - Case report.

INTRODUCTION: Dermal Regeneration Templates may be used in the reconstruction of large skin defects after cutaneous malignancy excisions. Bowen's disease (BD; squamous cell carcinoma in situ) is a common and persistent condition that can be related to chronic sun damage, and consequently, is usually located on the head and neck area or on the lower limbs. Literature does not provide clear guidelines on the treatment of BD, limiting itself to describing a wide range of different methods that can be used, including surgery, laser therapy or topical options. However, large lesions tend to scar in the post-operative setting and hence are difficult to treat surgically. PRESENTATION OF CASE: In this paper the authors present a case of a male in his 60s, ASA III score, who presented with a history of histopathologically-confirmed squamocellular carcinoma in the neck and supraclavicular region. Due to recurrent carcinomas the patient was treated with an extensive skin excision and a successful reconstruction using a Dermal Regeneration Template. The work has been reported in line with the SCARE criteria. DISCUSSION: The main surgical problem caused by BD is reaching complete oncological resection and, consequently, the need for extensive skin excisions. CONCLUSION: The use of the skin substitute resulted in a satisfactory functional and aesthetic result, with total clearance and no recurrence observed after 16 months.

Neuro-Oncology and Positron Emission Tomography: "Just Can't Get Enough".

Imaging has a pivotal role in neuro-oncology for the management of primary and secondary brain tumors [...].

Add-on radioiodine during long-term BRAF/MEK inhibition in patients with RAI-refractory thyroid cancers: a reasonable option?

Dual modulation of the MAPK pathway with BRAF (e.g., dabrafenib) and MEK (e.g., trametinib) inhibitors has the potential to re-establish radioiodine (RAI) sensitivity in BRAF-mutated RAI-refractory (RAI-R)-differentiated thyroid carcinoma (DTC) cells. Here we showed that (1) double BRAF/MEK inhibition may still reach a significant redifferentiation in patients with a long-history RAI-R DTC and multiple previous treatments; (2) the addition of high RAI activities may obtain a significant structural response in such patients; and (3) a divergence between increasing thyroglobulin and structural response may be a reliable biomarker or redifferentiation. Accordingly, the add-on prescription of high activities of 131I should be considered in RAI-R patients under multikinase inhibitors with stable or responding structural disease and divergent increase of Tg levels.

Similar local recurrence and survival in patients with T1 radial growth phase melanoma on head and neck treated with 5 or 10 mm margins: A retrospective study.

BACKGROUND: Melanoma guidelines recommend surgical excision with 10 mm margins for T1 melanomas (invasive melanomas with Breslow thickness ≤1 mm), including those in radial growth phase, which are without metastatic potential; however, such margins may be problematic on head-and-neck. OBJECTIVE: We compared outcomes of wide (10 mm margins) versus narrow (5 mm margins) excisions in patients with radial growth phase T1 melanoma on head-and-neck including face. METHODS: We retrospectively examined 610 consecutive patients excised with wide versus narrow margins, from 2001 to 2018, at six European centres. In all cases, radial growth phase, and clear margins with 5 or 10 mm of clearance, were ascertained histologically. Multivariable models investigated associations of margins and other factors with overall survival and local recurrence. RESULTS: Three hundred and sixteen (51.8%) patients received wide excision, 219 (69.3%) with primary wound closure, 97 (30.7%) with reconstruction; 294 (48.2%) patients received narrow excision, 264 (89.8%) with primary wound closure, 30 (10.2%) with reconstruction (p < 0.001). Median follow-ups were 88 months (wide) and 187 months (narrow) (inter-quartile ranges 43-133 and 79-206, respectively). Ten-year overall survival (95% confidence interval) was 96.7% (94.2%-99.3%) in wide and 98.2% (96.4%-100%) in narrow patients. Ten-year local recurrence incidence was 6.4% (4.1%-10.1%) in wide and 7.8% (5.3%-11.6%) in narrow groups. Lentigo maligna melanoma subtype appeared associated with increased risk of local recurrence in narrow versus wide patients (15.0% vs. 7.5%; p = 0.190). CONCLUSIONS: Narrower excision margins for T1 radial growth phase melanoma are not associated with worse overall survival (hazard ratio 0.97, p = 0.996) or increased local recurrence (subdistribution hazard ratio: 0.87; p = 0.751) compared to wider margins, and may be safely applied to such lesions, although caution may be required in the presence of lentigo maligna melanoma.

Diagnostic Accuracy of PET/CT or PET/MRI Using PSMA-Targeting Radiopharmaceuticals in High-Grade Gliomas: A Systematic Review and a Bivariate Meta-Analysis.

BACKGROUND: Several studies proposed the use of positron emission tomography (PET) with Prostate Specific Membrane Antigen (PSMA)-targeting radiopharmaceuticals in brain tumors. Our aim is to calculate the diagnostic accuracy of these methods in high-grade gliomas (HGG) with a bivariate meta-analysis. METHODS: A comprehensive literature search of studies on the diagnostic accuracy of PET/CT or PET/MRI with PSMA-targeting radiopharmaceuticals in HGG was performed. Original articles evaluating these imaging methods both in the differential diagnosis between HGG and low-grade gliomas (LGG) and in the assessment of suspicious HGG recurrence were included. Pooled sensitivity, specificity, positive and negative likelihood ratios (LR+ and LR-), and diagnostic odds ratio (DOR) including 95% confidence intervals (95% CI) were calculated. Statistical heterogeneity was also assessed using the I2 test. RESULTS: The meta-analysis of six selected studies (157 patients) provided the following results about PET/CT or PET/MRI with PSMA-targeting radiopharmaceuticals in the diagnosis of HGG: sensitivity 98.2% (95% CI: 75.3-99.9%), specificity 91.2% (95% CI: 68.4-98.1%), LR+ 4.5 (95% CI: 2.2-9.3), LR- 0.07 (95% CI: 0.04-0.15), and DOR 70.1 (95% CI: 19.6-250.9). No significant statistical heterogeneity among the included studies was found (I2 = 0%). CONCLUSIONS: the quantitative data provided demonstrate the high diagnostic accuracy of PET/CT or PET/MRI with PSMA-targeting radiopharmaceuticals for HGG detection. However, more studies are needed to confirm the promising role of PSMA-targeted PET in this clinical setting.

The role of palliative care in relapsed and metastatic head and neck cancer patients in a single ESMO integrated oncology and palliative care centre.

BACKGROUND: Palliative care (PC) for patients with advanced cancer improves symptom management and quality of life and may promote home deaths. Limited data are available regarding PC in advanced head and neck cancer (HNC) patients. The aim of this study was to describe the type of care and modalities of integration of specialized PC in a population of relapsed and/or metastatic head and neck cancer patients, followed in a single institution over 4 years. METHODS: Between January 2016 and December 2019, data on patients with relapsed and/or metastatic head and neck cancer not suitable for curative treatment diagnosed at the Oncology Institute of Southern Switzerland were reviewed retrospectively. Site, type and lines of treatment, treatment response, referral to specialist palliative care (yes or no), type of symptoms, tracheostomy and/or feeding-tube presence, and site of death were documented. Comparisons were made between patients benefitting from PC integration vs standard care. RESULTS: Eighty-six patients with relapsed/metastatic HNC were identified, 63 (73.3%) of whom were referred to specialized PC. Patients were mainly men (66, 76.7%), with a median age of 69 years (range 44-95). The most common site of tumour was the oropharynx (31, 36%), followed by the larynx (21, 24.4%), oral cavity (19, 22.1%), hypopharynx (14, 16.3%), and unknown primary (1, 1.2%). Forty-four patients (51.2%) were treated with systemic treatment. The median time interval between the diagnosis and palliative care referral was 1.7 months. At the time of our analysis, 69 patients had died (58 in the PC group and 11 in the non-PC group). Fifteen patients (25.9%) in the PC group and 4 (36.4%) in the non-PC group had received aggressive treatment (chemotherapy, tracheostomy and/or feeding tube) in the last month of life, with no significant difference between groups (p = 0.44). There was no difference in the incidence of home death (19.1% PC group vs 9.1% non-PC group, p = 0.67) or presence of caregiver (69.8% PC group vs 78.2% non-PC group, p = 0.58) between groups, while palliative care was associated with more opioid use (90.5% vs 17.4%, p < 0.0001). Patients in the PC group had a shorter survival compared to the non-PC group (5.7 vs 19.9 months, p = 0.0063). CONCLUSIONS: This study shows that patients appear to be at risk of receiving inappropriate invasive treatments close to death and of dying in hospital settings. Further research is needed to investigate how early PC may affect decision-making around treatments and improve HNC patients' holistic wellbeing.

Covid-19 and beyond: Broadening horizons about social media use in oncology. A survey study with healthcare professionals caring for youth with cancer.

Objectives: The study aimed to explore the attitudes of Swiss healthcare professionals toward the use of social media in adolescent and young adult oncology, and to examine whether the ongoing social restrictions due to COVID-19 might have altered these attitudes. Methods: This research was a survey study. The subjects were healthcare providers working in pediatric or adult oncology settings in Switzerland. 62 providers completed the survey. We performed descriptive and inferential statistical analyses. Results: While considered useful for various professional aspects (professional life 62.1%, educational purposes 72.7%, networking 83.3%, patient engagement 57.6%, clinical trial recruitment 51.5%), only a small proportion of participants actually used social media for professional reasons weekly (32.8%). Just over half considered themselves skillful in using these platforms (56.1%). Regression analysis revealed that self-assessed skillfulness with social media, the Covid-19 impact on attitudes, and the oncology setting, significantly predicted assessment of the usefulness of social media. Although, in answers to open items, institutional guidelines were deemed crucial to improve social media use, many respondents seemed unaware of their existence (50.8%). Only a minority reported an impact of Covid-19 on their attitudes towards the professional implementation of social media (25.0%). Conclusion: The global health crisis creates important challenges for young patients with cancer and their healthcare providers. In times of social restrictions, social media may be a promising tools to facilitate health information provision, connectivity, and patient care. Virtual mentorship and targeted social media training interventions might be a good way to improve familiarity with using social media and to increase awareness about existing ethical guidelines for their use.

Do oncologists prefer subspecialty radiology reports? A quality care study.

BACKGROUND: The main objective was to assess whether CT reports of radiologists subspecialized in oncologic imaging respond better to oncological referrals than reports from general radiologists. The secondary objective was to assess differences in ratings between a senior and junior oncologist. Two hundred radiological reports pertaining to oncological patients were retrospectively selected of which 100 each were written by subspecialized radiologists and general radiologists, respectively. The senior and junior oncologists each rated all CT reports using a Likert scale from 1 to 5 (1 = very poor, 5 = excellent) for the following information: anatomical details; interpretation of findings; need for further explanations; appropriateness of conclusions; overall satisfaction. Comparisons between ratings assigned to reports from generalist radiologists and subspecialty radiologists were performed using the Mann-Whitney U test. Agreement between both oncologists was assessed through Gwet's coefficient. RESULTS: For all but two of the five items obtained from the senior oncologist, oncologists' ratings were significantly higher for subspecialty radiologists' reports (p < 0.01); mean values from both oncologists were generally higher for subspecialty reports (p < 0.001). Agreement between the senior and junior oncologist in the rating of reports from general and subspecialty radiologists was either moderate to substantial (0.5986-0.6788) or substantial to almost perfect (0.6958-0.8358). CONCLUSIONS: According to a senior and junior oncologist, CT reports performed by subspecialized radiologists in oncologic imaging are clearer, more accurate, and more appropriate in the interpretation and conclusions compared to reports written by general radiologists. Likewise, the overall satisfaction of the oncologist from a subspecialized radiologist report is higher.

Analysis of Sentinel Node Biopsy and Clinicopathologic Features as Prognostic Factors in Patients With Atypical Melanocytic Tumors.

BACKGROUND: Atypical melanocytic tumors (AMTs) include a wide spectrum of melanocytic neoplasms that represent a challenge for clinicians due to the lack of a definitive diagnosis and the related uncertainty about their management. This study analyzed clinicopathologic features and sentinel node status as potential prognostic factors in patients with AMTs. PATIENTS AND METHODS: Clinicopathologic and follow-up data of 238 children, adolescents, and adults with histologically proved AMTs consecutively treated at 12 European centers from 2000 through 2010 were retrieved from prospectively maintained databases. The binary association between all investigated covariates was studied by evaluating the Spearman correlation coefficients, and the association between progression-free survival and all investigated covariates was evaluated using univariable Cox models. The overall survival and progression-free survival curves were established using the Kaplan-Meier method. RESULTS: Median follow-up was 126 months (interquartile range, 104-157 months). All patients received an initial diagnostic biopsy followed by wide (1 cm) excision. Sentinel node biopsy was performed in 139 patients (58.4%), 37 (26.6%) of whom had sentinel node positivity. There were 4 local recurrences, 43 regional relapses, and 8 distant metastases as first events. Six patients (2.5%) died of disease progression. Five patients who were sentinel node-negative and 3 patients who were sentinel node-positive developed distant metastases. Ten-year overall and progression-free survival rates were 97% (95% CI, 94.9%-99.2%) and 82.2% (95% CI, 77.3%-87.3%), respectively. Age, mitotic rate/mm2, mitoses at the base of the lesion, lymphovascular invasion, and 9p21 loss were factors affecting prognosis in the whole series and the sentinel node biopsy subgroup. CONCLUSIONS: Age >20 years, mitotic rate >4/mm2, mitoses at the base of the lesion, lymphovascular invasion, and 9p21 loss proved to be worse prognostic factors in patients with ATMs. Sentinel node status was not a clear prognostic predictor.

Factors Affecting Sentinel Node Metastasis in Thin (T1) Cutaneous Melanomas: Development and External Validation of a Predictive Nomogram.

PURPOSE: Thin melanomas (T1; ≤ 1 mm) constitute 70% of newly diagnosed cutaneous melanomas. Regional node metastasis determined by sentinel node biopsy (SNB) is an important prognostic factor for T1 melanoma. However, current melanoma guidelines do not provide clear indications on when to perform SNB in T1 disease and stress an individualized approach to SNB that considers all clinicopathologic risk factors. We aimed to identify determinants of sentinel node (SN) status for incorporation into an externally validated nomogram to better select patients with T1 disease for SNB. PATIENTS AND METHODS: The development cohort comprised 3,666 patients with T1 disease consecutively treated at the Istituto Nazionale Tumori (Milan, Italy) between 2001 and 2018; 4,227 patients with T1 disease treated at 13 other European centers over the same period formed the validation cohort. A random forest procedure was applied to the development data set to select characteristics associated with SN status for inclusion in a multiple binary logistic model from which a nomogram was elaborated. Decision curve analyses assessed the clinical utility of the nomogram. RESULTS: Of patients in the development cohort, 1,635 underwent SNB; 108 patients (6.6%) were SN positive. By univariable analysis, age, growth phase, Breslow thickness, ulceration, mitotic rate, regression, and lymphovascular invasion were significantly associated with SN status. The random forest procedure selected 6 variables (not growth phase) for inclusion in the logistic model and nomogram. The nomogram proved well calibrated and had good discriminative ability in both cohorts. Decision curve analyses revealed the superior net benefit of the nomogram compared with each individual variable included in it as well as with variables suggested by current guidelines. CONCLUSION: We propose the nomogram as a decision aid in all patients with T1 melanoma being considered for SNB.

Stent screw-assisted internal fixation (SAIF): clinical report of a novel approach to stabilizing and internally fixating vertebrae destroyed by malignancy.

OBJECTIVE: Severe lytic cancerous lesions of the spine are associated with significant morbidity and treatment challenges. Stabilization and restoration of the axial load capability of the vertebral body (VB) are important to prevent or arrest vertebral collapse. Percutaneous stent screw-assisted internal fixation (SAIF), which anchors a VB stent/cement complex with pedicular screws to the posterior vertebral elements, is a minimally invasive, image-guided, 360° internal fixation technique that can be utilized in this patient cohort. The purpose of this study was to assess the feasibility, safety, and stabilization efficacy of VB reconstruction via the SAIF technique in a cohort of patients with extensive lytic vertebral lesions, who were considered to have an unstable or potentially unstable spine according to the Spinal Instability Neoplastic Score (SINS). METHODS: This study was a retrospective assessment of a prospectively maintained database of a consecutive series of patients with neoplastic extensive extracompartmental osteolysis (Tomita type 4-6) of the VB treated with the SAIF technique. VB reconstruction was assessed on postprocedure plain radiographs and CT by two independent raters. Technical and clinical complications were recorded. Clinical and imaging follow-ups were assessed. RESULTS: Thirty-five patients with extensive osteolytic metastatic lesions of the VB underwent 36 SAIF procedures. SAIF was performed as a stand-alone procedure in 31/36 cases and was associated with posterior surgical fixation in 5/36 (4/5 with decompressive laminectomy). In 1 case an epidural cement leak required surgical decompression. VB reconstruction was categorized as satisfactory (excellent or good rating) by the two raters in 34/36 cases (94.5%) with an interrater reliability of 94.4% (Cohen's kappa of 0.8). Follow-up, ranging from 1 to 30 months, was available for 30/36 levels. Long-term follow-up (6-30 months, mean 11.5 months) was available for 16/36 levels. Stability during follow-up was noted in 29/30 cases. CONCLUSIONS: SAIF provides 360° nonfusion internal fixation that stabilizes the VB in patients with extensive lytic lesions that would otherwise be challenging to treat.

Immunotherapies and Future Combination Strategies for Head and Neck Squamous Cell Carcinoma.

Head and neck squamous cell carcinoma (HNSCC) is often diagnosed at an advanced stage and has a dismal prognosis. Nearly 10 years after the approval of cetuximab, anti-PD1/PD-L1 checkpoint inhibitors are the first drugs that have shown any survival benefit for the treatment on platinum-refractory recurrent/metastatic (R/M) HNSCC. Furthermore, checkpoint inhibitors are better tolerated than chemotherapy. The state of the art in the treatment of R/M HNSCC is changing, thanks to improved results for checkpoint inhibitors. Results for these treatments are also awaited in curative settings and for locally advanced HNSCC. Unfortunately, the response rate of immunotherapy is low. Therefore, the identification of predictive biomarkers of response and resistance to anti-PD1/PD-L1 is a key point for better selecting patients that would benefit the most from immunotherapy. Furthermore, the combination of checkpoint inhibitors with various agents is being currently evaluated to improve the response rate, prolong response duration, and even increase the chances for a cure. In this review, we summarize the most important results regarding immune targeting agents for HNSCC, predictive biomarkers for resistance to immune therapies, and future perspectives.

Time to systemic treatment and prognosis in patients with recurrent and metastatic head and neck squamous cell cancer.

BACKGROUND: Delay of systemic treatment in recurrent/metastatic head and neck squamous cell cancer (r/mHNSCC) has never been assessed. Whether time span to start systemic treatment affects survival and whether referral to a medical oncologist is important has not been explored. METHODS: We analyzed our head and neck database to assess the prognostic impact of time between diagnosis of r/mHNSCC and start of systemic treatment (time to treatment [TTT]). Secondarily, we assessed the prognostic impact of time to referral to a medical oncologist (referral time). For this purpose, we used pairwise correlation analysis and multivariate Cox regression analysis as statistical tests. RESULTS: A total of 110 patients with r/mHNSCC were evaluable for analysis. TTT correlated significantly with OS from r/mHNSCC diagnosis ( R = 0.43, p < 0.0001). A nonsignificant, positive correlation was found between referral time and OS ( R = 0.17, p = 0.10). CONCLUSIONS: Results of this retrospective analysis suggest that longer TTT is not associated with worse prognosis. Referral time seems not to have an impact on prognosis.

Vertebral body stent augmentation to reconstruct the anterior column in neoplastic extreme osteolysis.

BACKGROUND: Extensive lytic lesions of the vertebral body (VB) increase risk of fracture and instability and require stabilization of the anterior column. Vertebral augmentation is an accepted treatment option, but when osteolysis has extensively destroyed the VB cortical boundaries (a condition herein defined as 'extreme osteolysis'), the risk of cement leakage and/or insufficient filling is high. Vertebral body stents (VBSs) might allow partial restoration of VB height, cement containment, and reinforcement, but their use in extreme osteolysis has not been investigated. OBJECTIVE: To assess retrospectively the feasibility and safety of VBS augmentation in patients with 'extreme osteolysis' of the VB. METHODS: We retrospectively analyzed 41 treated vertebrae (from T1 to L5). VB reconstruction was assessed on postprocedure CT images and rated on a qualitative 4-point scale (poor-fair-good-excellent). Clinical and radiological follow-up was performed at 1 month and thereafter at intervals in accordance with oncological protocols. RESULTS: VBS augmentation was performed at 12 lumbar and 29 thoracic levels, with bilateral VBS in 23/41. VB reconstruction was judged satisfactory (good or excellent) in 37/41 (90%) of levels. Bilateral VBS received higher scores than unilateral (p=0.057, Pearson's X2). We observed no periprocedural complications. Cement leaks (epidural or foraminal) occurred at 5/41 levels (12.2%) without clinical consequences. Follow-up data were available for 27/29 patients, extending beyond 6 months for 20 patients (7-28 months, mean 15.3 months). VBS implant stability was observed in 40/41 cases (97.5%). CONCLUSIONS: Our results support the use of VBS as a minimally invasive, safe and effective option for reconstructing the anterior column in prominent VB osteolysis.

Comparison of contemporary staging systems for oropharynx cancer in a surgically treated multi-institutional cohort.

BACKGROUND: Between the publication of the Union of International Cancer Control staging system (UICC) 7th and 8th editions, other staging algorithms for oropharyngeal squamous cell carcinoma (OPSCC) were proposed from Radiation Therapy Oncology Group (RTOG), MD Anderson Cancer Center (MDACC), and Yale University. METHODS: With C-statistics, the above-mentioned five staging algorithms were compared for overall and relapse-free survival endpoints in a multi-institutional cohort of OPSCC cases (n = 338) treated with primary surgery. RESULTS: Pathological UICC 8th ed yielded the highest C-indexes in the entire cohort and in the HPV- subset, whereas MDACC was superior for HPV+ OPSCC. RTOG was the simplest and holistic algorithm with a noninferior discriminatory power. CONCLUSION: UICC 8th ed, MDACC, and RTOG offer moderate and comparable efficacy for staging in this OPSCC patient cohort undergoing surgical treatment. Notable discrepancy between clinical and pathological UICC 8th ed algorithms poses potential concerns in diagnosis, treatment, research, and data management.

Prolonged Versus Short-Duration Use of Nasogastric Tubes in Patients with Head and Neck Cancer During Radiotherapy Alone or Combined Chemoradiotherapy.

To compare safety and effectiveness of prolonged (>28 days) versus short duration (≤28 days) use of nasogastric tube for enteral nutrition and weight loss prevention during curative radiotherapy with or without concurrent chemotherapy or cetuximab for head and neck cancer patients. We performed a retrospective study and database review of all patients at our center, treated with radiotherapy for head and neck cancer receiving enteral nutrition by nasogastric tube. Type of treatment, weight and body mass index changes, and related complications (gastroesophageal reflux, pneumonia, ulcer, feeding tube obstruction, or dislocation) were documented. Comparison between patients with prolonged (>28 days, group A) and short duration (≤28 days, group B) of EN through nasogastric tube was performed. Data expressed as mean ± SD or median (min; max) values as appropriate, and analyzed by ANOVA repeated measures and Kaplan-Meier estimates. We identified 114 patients who fulfilled the inclusion criteria. Among them, 10% were treated with radiotherapy alone, while 90% received concurrent chemotherapy or cetuximab. Ninety-four patients (82%, group A) had a nasogastric tube in place for a period >28 days and 20 (18%, group B) for ≤28 days during treatment. Patients were mainly men (86 patients, 75%), with a median age of 61 years (range 49-73) and advanced stage IV disease in most cases (87 patients, 76%) without differences between both groups (p = 0.53, 0.47, and 0.30, respectively). Treatment discontinuation did not occur within both groups. Fifty-six patients (49%) developed complications, without a significant difference between both groups (P = 0.23). Body weight and BMI changes did not differ during EN (-0.8 ± 4.5 and -0.3 ± 1.6), the oncological treatment (-5.3 ± 4.0 and -1.8 ± 1.4), or 6 months after the end of treatment (-0.6 ± 4.4 and -0.2 ± 1.5). Our findings suggest that prolonged enteral nutrition by nasogastric tube is safe and effective in preventing weight loss during curative radiotherapy or radio-chemotherapy for head and neck cancer.

Gene signatures and expression of miRNAs associated with efficacy of panitumumab in a head and neck cancer phase II trial.

OBJECTIVE: Platinum-based chemotherapy plus the anti-EGFR monoclonal antibody (mAb) cetuximab is used to treat recurrent/metastatic (RM) head-neck squamous cell carcinoma (HNSCC). Recently, we defined Cluster3 gene-expression signature as a potential predictor of favorable progression-free survival (PFS) in cetuximab-treated RM-HNSCC patients and predictor of partial metabolic FDG-PET response in an afatinib window-of-opportunity trial. Another anti-EGFR-mAb (panitumumab) was used as the treatment agent in RM-HNSCC patients in the phase II PANI01trial. PANI01 tumor samples were analyzed using functional genomics to explore response predictors to anti-EGFR therapy. MATERIALS AND METHODS: Whole-gene expression and real-time PCR analyses were applied to pre-treatment samples from 25 PANI01 patients. Three gene signatures (Cluster3 score, RAS onco-signature, microenvironment score) and seven selected miRNAs were separately analyzed for association with panitumumab efficacy. RESULTS: Cluster3 expression levels had a profile with a significant bimodal separation of samples (P =  3.08 E-13). Higher RAS activation, microenvironment score, and miRNA expression were associated with low-Cluster3 patients. The same biomarkers were separately associated with PFS. Patients with high-Cluster3 had significantly longer PFS than patients with low-Cluster3 (median PFS: 174 versus 51 days; log-rank P = 0.0021). ROC analysis demonstrated accuracy in predicting PFS (AUC = 0.877). CONCLUSIONS: Despite differences in clinical settings and anti-EGFR inhibitors used for treatment, response prediction by the Cluster3 signature and selected miRNAs was essentially the same. Translation into a useful clinical assay requires validation in a broader setting.

Percutaneous Endoscopic Gastrostomy Tube Is a Negative Prognostic Factor for Recurrent/Metastatic Head and Neck Cancer.

BACKGROUND/AIM: Recurrent/metastatic head and neck squamous cell cancer (r/mHNSCC) patients often need a percutaneous endoscopic gastrostomy feeding tube (PEG). Among known prognostic factors, PEG could be prognostic as well. PATIENTS AND METHODS: We retrospectively analyzed r/mHNSCC patients referred for systemic treatment. Kaplan-Meier and multivariate cox regression models were applied to assess prognostic impact of PEG. RESULTS: One hunderd and ten patients were identified, 42 had a PEG at treatment start. Median survival from start of 1st-line systemic treatment was 8 months (95%CI=6.5-12.0 months), 4.5 months (95%CI=2.5-7.0 months) for patients with PEG and 11.5 months (95%CI=7.5-14.5 months) without PEG (adjusted HR=1.98, p=0.011). Similarly, survival from first recurrence of distant metastases was lower in patients with PEG as compared to patients without (7.5 vs. 15.5 months, adjusted HR=2.60, p<0.001). CONCLUSION: Presence of PEG feeding tube has an unfavourable prognostic impact on survival in patients with r/mHNSCC. While any causality remains speculative, potential complications should be appreciated before PEG implantation.