Activity of platinum and cetuximab in cutaneous squamous cell cancer not amenable to curative treatment

Background: Unresectable or metastatic cutaneous squamous cell cancers (cSCCs) are rare but potentially life-threatening diseases. In this setting, systemic therapy has a palliative intent with limited benefit, but there is no established consensus regarding the proper management of this tumour. This retrospective study aimed to review outcomes in patients with non-curable cSCC treated with platinum-based chemotherapy and cetuximab. Methods: We considered 12 consecutive patients treated between June 2010 and March 2016. All patients had received previous treatment for the local disease. Results: The overall response rate was 50%, and the disease control rate was 67%. Median progression-free survival and overall survival were 6.6 (95% confidence interval [CI]: 1.9-8.4) and 14.6 (95% CI: 9.4-20.1) months, respectively. The median duration of response was 4.8 months (95% CI: 1.2-5.9). The most frequent toxicities were skin reactions (58%; grade 3: 25%) and anaemia (10%). No grade 4 toxicities were observed. Conclusions: Cetuximab and platinum-based chemotherapy were shown to be feasible and active in cSCC, with an acceptable toxicity profile, even if with a limited duration of response

Prognostic and predictive value of EGFR in head and neck squamous cell carcinoma

EGFR is an extensively studied biomarker in head and neck squamous cell carcinoma (HNSCC). In this review, we discuss the prognostic and predictive role of EGFR in HNSCC, focusing on the different molecular alterations in specific treatment modalities such as radiotherapy alone (RT), combination of surgery, RT and chemotherapy (CT), EGFR inhibitors. We considered EGFR at different molecular levels: protein expression, protein activation, gene copy number, polymorphisms, mutation, EGFRvIII expression and EGFR ligand expression. Considering RT alone, evidence supports the predictive and prognostic role of high EGFR expression only when evaluated by quantitative assays: this may help select the patients who can mostly benefit from accelerated treatment. Conversely, no predictive biomarkers are available when treatment is a combination of surgery, CT and RT. For this combined treatment, several studies indicate that EGFR expression represents a good prognostic parameter only when measured by a "quantitative" or at least semi-quantitative method. With respect to EGFR inhibitors, neither EGFR expression nor increased gene copy number represent prognostic/predictive factors. If validated, nuclear EGFR, TGF\u3b1 levels, EGFR phopshorylation and polymorphisms could represent additional prognostic factors in relation to combination of surgery, CT and RT, while EGFR polymorphisms and high amphiregulin levels could have prognostic value in patients treated with EGFR inhibitors

HER2 status in recurrent/metastatic androgen receptor overexpressing salivary gland carcinoma patients

Background: Overexpression of human epidermal growth factor receptor type 2 (HER2) occurs in almost 25-30% of androgen receptor (AR)-positive salivary gland carcinomas (SGCs), notably salivary duct carcinoma (SDC) and adenocarcinoma not otherwise specified (NOS). In the last years, several studies have reported the clinical benefit of HER2 directed therapies in this setting. This work aims at describing the natural history of AR-positive recurrent/metastatic (R/M) SGC patients, based on HER2 amplification status. Methods: Consecutive R/M AR-positive SGC patients accessing our Institution from 2010 to 2021 were analyzed. Descriptive statistics and survival analyses were performed to present the clinical characteristics of the selected patients and the outcomes, based on HER2 status. A specific focus was dedicated to patients developing metastases to the central nervous system (CNS). Results: Seventy-four R/M AR-positive SGC patients (72 men) were analyzed. Median follow-up was 36.18 months (95% CI 30.19-42.66). HER2 status was available in 62 cases (84%) and in 42% the protein was overexpressed (HER2+). Compared with patients with HER2- SGCs, in patients with HER2+ disease, HR for disease recurrence was 2.97 (95% CI 1.44-6.1, p=0.003), and HR for death from R/M disease was 3.22 (95% CI 1.39-7.49, p=0.007). Moreover, the HER2+ group showed a non-significant trend towards a higher prevalence of CNS metastases (40% vs. 24%, p=0.263). Patients developing CNS metastases had shorter survival than those who did not; at bivariate analysis (covariates: CNS disease and HER2 status), HER2 status demonstrated its independent prognostic significance. Discussion: In our patient population, HER2 amplification was a negative prognostic factor, and it was associated with a non-statistically significant higher risk of developing CNS metastasis. Further studies are needed to explore the potential clinical benefit of tackling the two biological pathways (AR and HER2) in patients affected by this rare and aggressive malignancy

Increasing capacity for the treatment of common musculoskeletal problems: A non-inferiority RCT and economic analysis of corticosteroid injection for shoulder pain comparing a physiotherapist and orthopaedic surgeon

Background Role substitution is a strategy employed to assist health services manage the growing demand for musculoskeletal care. Corticosteroid injection is a common treatment in this population but the efficacy of its prescription and delivery by physiotherapists has not been established against orthopaedic standards. This paper investigates whether corticosteroid injection given by a physiotherapist for shoulder pain is as clinically and cost effective as that from an orthopaedic surgeon. Methods A double blind non-inferiority randomized controlled trial was conducted in an Australian public hospital orthopaedic outpatient service, from January 2013 to June 2014. Adults with a General Practitioner referral to Orthopaedics for shoulder pain received subacromial corticosteroid and local anaesthetic injection prescribed and delivered independently by a physiotherapist or a consultant orthopaedic surgeon. The main outcome measure was total Shoulder Pain and Disability Index (SPADI) score at baseline, six and 12 weeks, applying a non-inferiority margin of 15 points. Secondary outcomes tested for superiority included pain, shoulder movement, perceived improvement, adverse events, satisfaction, quality of life and costs. Results 278 participants were independently assessed by the physiotherapist and the orthopaedic surgeon, with 64 randomised (physiotherapist 33, orthopaedic surgeon 31). There were no significant differences in baseline characteristics between groups. Non-inferiority of injection by the physiotherapist was declared from total SPADI scores at 6 and 12 weeks (upper limit of the 95% one-sided confidence interval 13.34 and 7.17 at 6 and 12 weeks, respectively). There were no statistically significant differences between groups on any outcome measures at 6 or 12 weeks. From the perspective of the health funder, the physiotherapist was less expensive. Conclusions Corticosteroid injection for shoulder pain, provided by a suitably qualified physiotherapist is at least as clinically effective, and less expensive, compared with similar care delivered by an orthopaedic surgeon. Policy makers and service providers should consider implementing this model of care

The Interplay between Age and Viral Status in EBV-Related Nasopharyngeal and HPV-Related Oropharyngeal Carcinoma Patients

Background. The aim of this work was to analyze the interplay between age and viral status on the outcomes in loco-regionally advanced oropharyngeal and nasopharyngeal cancer patients treated with radiotherapy and different chemotherapy combinations. Methods. A retrospective (2006–2017) analysis was performed on non-metastatic loco-regionally advanced oropharyngeal (both HPV+ and HPV−) and EBV+ nasopharyngeal cancer patients (young: <65 years vs. elderly: ≥65 years) treated with radiotherapy with or without chemotherapy. The impact of age and viral status on overall (OS) and disease-free survival (DFS) were studied with multivariable models, which were adjusted for smoking, stage, comorbidities, chemotherapy dose intensity and treatment strategy. Results. We analyzed 324 patients (146 HPV+ oropharynx, 63 HPV−, 115 nasopharynx). Elderly patients had more comorbidities, and received less intensive treatments when compared to younger subjects. Although OS and DFS were shorter in older patients, after adjustment for stage, smoking, comorbidities, treatment strategy and dose intensity, no significant differences in terms of survival were observed according to age (65 vs. 50 years of age: HR 1.89, 95% CI 0.45–7.84 for HPV+ OPC; HR 0.91, 95% CI 0.29–2.89 for HPV− OPC; HR 1.99, 95% CI 0.9–4.39 for NPC; p = 0.395). Conclusions. Several potential age-related (comorbidities, treatment intensity) and disease-related (stage) confounding factors play a prognostic role with differential impacts on both virus and non-virus-related tumors. In HPV+ oropharyngeal cancer and in EBV+ nasopharyngeal cancer patients, age should be considered as the expression of an array of host- and tumor-related features rather than an independent prognostic factor

RANK expression in EBV positive nasopharyngeal carcinoma metastasis: A ready-to-treat target?

Epstein Barr Virus (EBV) related Nasopharyngeal Carcinoma (NPC), is an highly chemo- and radiosensitive endemic malignancy in southeast Asia. More than one third of locally advanced cases relapse after curative treatment, especially because of bone, liver and lung metastases. Lymphocyte sub-populations favour EBV-associated carcinogenesis and tumour progression and several strategies aim to reverse this phenomenon. Receptor activator of NF-kB (RANK) and its Ligand (RANKL), key regulator of bone metabolisms, are expressed in several malignancies and tumorinfiltrating Tregs. We collected 17 paired FFPE specimen of primary and metachronous metastatic or regionally relapsed EBV related NPC and evaluated RANK expression by immunohistochemistry. All primary tumour specimens resulted not evaluable whereas all metastatic specimens, regardless of sites, showed high RANK IHC expression in the tumor with no staining in normal surrounding tissues. This observation deserves further clarifications and could open the way to trials testing the hypotesis that targeting the RANK/RANKL pathway with denosumab, an already available, clinically approved monoclonal antibody for metastatic bone lesions, might restore proper antitumor immune response in NPC metastatic patients

Classification of eddy current NDT data by Probabilistic Neural Networks

In this paper we discuss the use of the Probabilistic Neural Network (PNN) for the classification of the defects detected via the Remote Field Eddy Current (RFEC) inspection technique. The neural network is employed in order to associate each defect to one of the predefined classes. Each defect is represented by means of the phase response of the probe system. The reported results show that the proposed artificial neural network allows reliable classification results