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.

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.

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.

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.

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.

Multicenter Phase II Study of Panitumumab in Platinum Pretreated, Advanced Head and Neck Squamous Cell Cancer.

LESSONS LEARNED: Panitumumab shows activity in terms of disease control rate and preventing disease progression but not for tumor shrinkage in head and neck squamous cell cancer for second-line treatment. Epidermal growth factor receptor (EGFR) copy number gain, a property of tumor cells that theoretically could identify patients more likely to experience disease response, was common among patients having disease control.Our trial, given the lower toxicity with an every-2-week schedule, provides guidance for future trials, for example, in combinations of immune therapies and anti-EGFR-antibodies. BACKGROUND: The objective of this study was to investigate the efficacy and safety of panitumumab (anti-epidermal growth factor receptor [EGFR] antibody) given as a single agent in platinum-pretreated head and neck squamous cell cancer (HNSCC). METHODS: Patients with advanced HNSCC previously treated with platinum-containing therapy were included. Panitumumab was administered intravenously every 2 weeks at a dose of 6 mg/kg. Primary endpoint was overall response rate (ORR) according to Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1; secondary endpoints were progression-free survival (PFS) and safety. A Simon's two-step design was chosen; 4 partial remissions (PR) in the first 32 patients were required for continuing to step two. An exploratory biomarker analysis was performed. RESULTS: Thirty-three patients were enrolled. Two patients obtained a PR for an ORR of 6%, and 15 (45%) showed stable disease (SD) for at least 2 months, resulting in a 51% disease control rate. Median PFS was 2.6 months (95% confidence interval [CI]: 1.7-3.7), while median OS was 9.7 months (95% CI: 6.3-17.2). The most frequent adverse drug reactions were cutaneous rash (64%) and hypomagnesemia (55%). Overall, 30% of patients experienced grade 3/4 adverse events. No infusion-related reactions occurred. EGFR copy number gain (CNG) was more frequent in patients who benefitted from panitumumab. Two uncommon KRAS mutations (G48E, T50I) and 3 canonical PIK3CA mutations (all E545K) were detected. High-risk HPV16 was found in 10 patients and EGFR CNG in 13 treated patients. EGFR CNG seems to be more frequent in individuals with at least SD compared with patients with progressive disease (59% vs. 30%). PFS for patients with EGFR CNG was 4.6 months (95% CI: 1.0-9.2 months) and 1.9 months (95% CI: 1.0-3.2 months) for patients without CNG (p = .02). CONCLUSION: Panitumumab monotherapy in pretreated HNSCC patients was well tolerated but moderately active. We observed a considerable disease control rate. Future strategies with this agent comprise right patient selection through the identification of reliable biomarkers and gene signatures predicting response and, considering good tolerability and convenience, combination strategies with novel agents and immune therapeutic agents.

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.