Sunday, March 13, 2022

Long-term control of melanoma adrenal metastasis treated with radiotherapy

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Introduction Melanoma remains a large global burden with a significant proportion of patients succumbing to metastatic disease. The adrenal gland is a common area for metastasis with surgical treatment as the main modality. Radiotherapy is less utilised in this setting with uncertainty over deliverability and efficacy. Here, we present the details and outcomes of 20 patients treated with radiotherapy, with or without systemic therapy, for melanoma adrenal metastasis in a single institute. Methods Twenty patients were identified from radiation treatment and medical records from between 2015 and 2019 at our institution. Three patients had bilateral radiotherapy treatments and therefore 23 adrenal lesions were analysed. Demographics, indications for treatment, radiotherapy methodology and outcomes were recorded. Outcomes were based on serial 18F FDG PET/computerized tomography scans reporting using the PERCIST criteria. Results The most common indication for radiotherapy was oligo-progressive disease (70%) followed by symptom palliation. Eight (35%) of the treatments were delivered by stereotactic ablative body radiotherapy. Twelve (60%) patients had concurrent immunotherapy. Twenty of twenty-three (87%) adrenal lesions had an initial response to treatment with 12 (60%) maintaining local control until death or end of follow-up. Median adrenal-specific progression-free survival was 13 months. Four patients (17%) required salvage adrenalectomy. Symptom palliation was achieved in the majority of patients for which it was indicated and there were no grade three toxicities. The median time from radiotherapy to change of immunotherapy treatment was 4 months. Conclusions Radiotherapy for melanoma adrenal metastasis is effective and deliverable. With the majority of patients achieving a palliative and clinically relevant durable response, adrenalectomy can be reserved as a salvage option. Received 2 August 2021 Accepted 13 February 2022 Correspondence to Brendan McCann, MbChB, Department of Radiation Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia, Tel: +44 7505398515; e-mail: brendanmccann85@gmail.comBrendan.mccann@ggc.scot.nhs.uk Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.
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Real-world data on melanoma brain metastases and survival outcome

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Introduction Novel medical therapies have revolutionized outcome for patients with melanoma. However, patients with melanoma brain metastases (MBM) still have poor survival. Data are limited as these patients are generally excluded from clinical trials, wherefore real-world data on clinical outcome may support evidence-based treatment choices for patients with MBM. Methods Patients diagnosed with MBM between 2008 and 2020 were included retrospectively. Patient characteristics, treatment, and outcome data were recorded from The Danish Metastatic Melanoma Database, pathology registries, electronic patient files, and radiation plans. Anti-programmed cell death protein 1 antibodies and the combination of BRAF/MEK-inhibitors were introduced in Denmark in 2015, and the cohort was split accordingly for comparison. Results A total of 527 patients were identified; 148 underwent surgical excision of MBM, 167 had stereotactic radiosurgery (SRS), 270 received whole-brain radiation therapy (WBRT), and 343 received systemic therapies. Median overall survival (mOS) for patients diagnosed with MBM before and after 2015 was 4.4 and 7.6 months, respectively. Patients receiving surgical excision as first choice of treatment had the best mOS of 10.9 months, whereas patients receiving WBRT had the worst outcome (mOS, 3.4 months). Postoperative SRS did not improve survival or local control after surgical excision of brain metastases. Of the 40 patients alive >3 years after diagnosis of MBM, 80% received immunotherapy at some point after diagnosis. Patients with meningeal carcinosis did not benefit from treatment with CPI. Conclusion Outcome for patients with MBM has significantly improved after 2015, but long-term survivors are rare. Most patients alive >3 years after diagnosis of MBM received immunotherapy. Supplemental Digital Content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website, www.melanomaresearch.com. Received 2 November 2021 Accepted 13 February 2022 Correspondence to Eva Ellebaek, MD, PhD, Center for Cancer Immune Therapy, Department of Oncology, Copenhagen University Hospital, Herlev and Gentofte, Borgmester Ib Juuls Vej 1, 2730 Herlev, Denmark, Tel: +45 38689517; e-mail: eva.ellebaek.steensgaard@regionh.dk Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.
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Management of lateral neck nodes in common and aggressive variants of thyroid cancer

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imagePurpose of review Although nodal metastasis in thyroid cancer does not have a major impact on outcome, it does have some prognostic implication in adverse metastasis and aggressive histology. The purpose of this review is to discuss evaluation and management of lateral neck nodes in thyroid cancer. Recent findings There is a high incidence of central and lateral neck node metastasis in thyroid cancer. Appropriate preoperative evaluation is key prior to first surgical procedure. The distribution of nodal metastasis is well recognized and so generally a modified neck dissection is recommended from levels II through V. The risk of nodal metastasis at level IIb is rare. The complications of lateral neck dissection, though rare, are of significant importance to the quality of life. Summary Appropriate preoperative evaluation, including good ultrasound and CT scan with contrast, is recommended. Preoperative FNA of the lateral neck node will be helpful, along with thyroglobulin management if indicated. The neck dissection should include significant levels of neck, avoiding neural injury. Nonsurgical therapies may be recommended in selected patients.
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Radiomics and deep learning approach to the differential diagnosis of parotid gland tumors

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imagePurpose of review Advances in computer technology and growing expectations from computer-aided systems have led to the evolution of artificial intelligence into subsets, such as deep learning and radiomics, and the use of these systems is revolutionizing modern radiological diagnosis. In this review, artificial intelligence applications developed with radiomics and deep learning methods in the differential diagnosis of parotid gland tumors (PGTs) will be overviewed. Recent findings The development of artificial intelligence models has opened new scenarios owing to the possibility of assessing features of medical images that usually are not evaluated by physicians. Radiomics and deep learning models come to the forefront in computer-aided diagnosis of medical images, even though their applications in the differential diagnosis of PGTs have been limited because of the scarcity of data sets related to these rare neoplasms. Nevertheless, recent studies have shown that artificial intelligence tools can classify common PGTs with reasonable accuracy. Summary All studies aimed at the differential diagnosis of benign vs. malignant PGTs or the identification of the commonest PGT subtypes were identified, and five studies were found that focused on deep learning-based differential diagnosis of PGTs. Data sets were created in three of these studies with MRI and in two with computed tomography (CT). Additional seven studies were related to radiomics. Of these, four were on MRI-based radiomics, two on CT-based radiomics, and one compared MRI and CT-based radiomics in the same patients.
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Parotid lymph nodes in primary malignant salivary neoplasms

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imagePurpose of review To review the literature on parotid lymph nodes and their involvement in primary malignant epithelial salivary gland neoplasms (PMESGN). The parotid gland has two identifiable lymphatic systems – extraglandular and intraglandular both topographically separate but functioning as a single unit. Recent findings The publications available have concentrated on intraparotid lymph nodal metastatic (IPLN) disease only. Summary The data reported was retrospective and observational. The limitations encountered was the variability of extent of the parotid surgery, unclear evaluation of IPLN limited or inconsistent follow-up periods, small subgroups limiting the explanatory power and the multivariate analysis. One multicentric publication reported on 289 patients with parotid PMESGN treated by surgery between 1995 and 2018 at four centres: three Italian and one in the United Kingdom. IPLN+ was proven in 22.1%, preoperative imaging failed to identify occult IPLN+ in 20.1%, IPLN+ and cervical nodal metastasis (cpN+) was 47.4% and cpN+ was 100% in patients bearing greater than 4 IPLN+ nodes. A multicentric prospective study is required detailing preoperative imaging, using a standardized surgical management, pathological specimen search, histopathological grading and patient outcome analysis specifically designed to resolve the role of IPLN in patients diagnosed with PMESGN.
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Sarcopenia and its impact in head and neck cancer treatment

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imagePurpose of review The aim of this review is to discuss recent studies on the assessment of sarcopenia and its predictive and prognostic value in head and neck cancer (HNC) patients. Recent findings There is increasing evidence that low skeletal muscle mass (SMM), often named sarcopenia, can easily be assessed on cross-sectional imaging of the head and neck and is associated with chemotherapy (dose limiting) and radiotherapy toxicity and survival. Summary SMM measurement at the level of the third cervical vertebra (C3) on routine computed tomography and magnetic resonance imaging is easy and robust to perform. Several studies have shown a significantly higher incidence of cisplatin dose limiting toxicity in HNC patients with a low SMM. In HNC patients pretreatment low SMM is associated with acute and late toxicity and adverse events of radiotherapy, complications of major head and neck surgery and decreased disease-specific and overall survival. This information can be used for individualized treatment planning in HNC patients with low SMM.
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Indications of external beams radiation for thyroid cancer

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imagePurpose of review The use of external beam radiation therapy (EBRT) for the treatment of the different histologic subtypes of thyroid cancer is a matter of debate. This article provides an up-to-date review on the current evidence concerning the benefits of EBRT in thyroid cancer in specific indications. Recent findings Based on retrospective studies, adjuvant EBRT lessens the risk of locoregional recurrence in locally advanced differentiated thyroid cancer (DTC) and medullary thyroid cancer (MTC) with high-risk features. The effect of EBRT on overall survival remains uncertain. EBRT should also be part of the multimodality treatment in anaplastic thyroid cancer (ATC), as it improves survival rates in incompletely resected ATC. Summary The role of EBRT in thyroid cancer remains unclear. To date, no randomized control studies are available. Retrospective data showed improved outcomes in patients with high-risk features for locoregional recurrence.
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Subjective Fatigue in Children With Unaided and Aided Unilateral Hearing Loss

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Objectives

Fatigue is frequently observed in children with chronic diseases and can affect the quality of life (QoL). However, research in children with unilateral hearing loss (UHL) is scarce. Subsequently, no studies investigated the effects of hearing aids on fatigue in children. This study investigates subjective fatigue and hearing-related QoL in children with UHL. Furthermore, it evaluates the influence of hearing aids, subject-specific factors, and respondent-type on subjective fatigue.

Study Design

A cross-sectional study was conducted from June 2020 until September 2020 at the department of otorhinolaryngology in a tertiary referral center.

Methods

The primary outcome was the difference in subjective fatigue and hearing-related QoL between children with unaided UHL, aided UHL, and normal hearing. Subjective fatigue and hearing-related QoL were measured using the Pediatric Quality of Life Inventory™ Multidimensional Fatigue Scale (PedsQL™-MFS) and Hearing Environments and Reflection on Quality of Life (HEAR-QL™) questionnaires.

Results

Along with 36 aided children with UHL, 34 unaided and 36 normal-hearing children were included. Child reports revealed significantly more cognitive fatigue in children with aided UHL than children with normal hearing (median difference 12.5, P = .013). Parents reported more fatigue in children with UHL compared to normal-hearing siblings. Especially children with aided UHL seemed at increased risk for fatigue. Children with UHL scored lower on hearing-related QoL than children with normal hearing. No apparent differences were found in fatigue and QoL between children with unaided and aided UHL.

Conclusion

Children with unaided and even aided UHL seem to experience more subjective fatigue and lower hearing-related QoL than children with normal hearing. Prospective longitudinal studies are required to investigate the influence of hearing aids on fatigue and QoL in individual patients.

Level of Evidence

Level 3 Laryngoscope, 2021 Laryngoscope, 2022

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Ultrasound Guided Biopsy in Patients With HPV‐Associated Oropharyngeal Squamous Cell Carcinoma

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Objectives

To identify the differences in sensitivity and accuracy between ultrasound-guided and palpation-guided fine needle aspirations (FNA) of suspicious lymph nodes in patients with human papillomavirus (HPV) (+) oropharyngeal squamous cell carcinoma (OPSCC). Additional objectives included identifying patient specific factors affecting biopsy accuracy and evaluating potential differences in accuracy between fine and core needle biopsies.

Study Design

Retrospective chart review.

Materials and Methods

A retrospective study of diagnostic sensitivity was completed at a single tertiary care center between 1/1/2006–12/31/2016. Participants included patients who underwent pretreatment FNA biopsy with HPV(+)OPSCC confirmed pathologically following neck dissection or excisional lymph node biopsy. A true positive (TP) on FNA biopsy was defined as an FNA biopsy concerning for squamous cell carcinoma (SCC) that was confirmed on excisional biopsy or neck dissection. A false negative (FN) was defined as a negative FNA but metastatic disease identified on excisional biopsy or neck dissection. Sensitivity was calculated as TPs/(TPs + FNs). Sensitivity was compared among techniques using chi-square and Fisher exact tests.

Results

A total of 209 FNA biopsies among 198 patients were included in the study, including 31 (15%) palpation-guided FNAs, 160 (77%) ultrasound-guided FNAs, and 18 (9%) ultrasound-guided FNA + core biopsies. Sensitivity was significantly different among palpation-guided FNA, ultrasound-guided FNA, and ultrasound-guided FNA + core biopsies (48% vs. 83% vs. 94%, respectively; P < .001) but there was no significant difference in sensitivity between ultrasound-guided FNA versus ultrasound-guided FNA + core biopsies (P = .31).

Conclusion

The use of ultrasound guidance in FNA biopsies of nodal metastases in HPV(+)OPSCC improves sensitivity compared to palpation guidance alone. Ultrasound guided biopsies are preferred in patients with suspected nodal metastasis from HPV(+)OPSCC.

Level of Evidence

3 Laryngoscope, 2022

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Pathogenic DST sequence variants result in either epidermolysis bullosa simplex (EBS) or hereditary sensory and autonomic neuropathy type 6 (HSAN‐VI)

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Abstract

DST encodes bullous pemphigoid antigen-1 (BPAG1), a protein with eight tissue-specific isoforms expressed in the skin, muscle, brain, and nerves. Accordingly, mutations in this gene are associated with epidermolysis bullosa simplex (EBS) and hereditary sensory and autonomic neuropathy type 6 (HSAN-VI). The genotypic spectrum is attested to by 19 distinct mutations but genotype-phenotype correlation for both disorders is not well established. In this study, we performed next-generation sequencing (NGS) on two families with different phenotypic presentations, one fetus (P1) with musculoskeletal and neurological malformations established by prenatal ultrasound and family history, and a 15-year-old female (P2) with skin blistering. P1 had a novel homozygous nonsense mutation, DST: NM_001144769, c.3805C>T, p.R1269* within a region of homozygosity (ROH). This mutation resides within the plakin domain of BPAG1 and ablates all isoforms of this protein, leading to novel ex tracutaneous phenotypes consistent with HSAN-VI in P1. P2 had a recurrent homozygous mutation DST: NM_001723.7, c.3370C>T, p.Gln1124* that presented with giant, trauma-induced skin blisters without extracutaneous involvement. This mutation is located within the coiled-coil domain present on the skin isoform of DST, BPGA1-e, associated with EBS. In summary, we report two families with pathogenic DST variants and expand the spectrum of DST genotype and phenotypes.

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Autologous lipoaspirate as a new treatment of vulvar lichen sclerosus: a review on literature

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Abstract

Lichen sclerosus (LS) is a chronic inflammatory dermatosis that mostly affects the genital and anal skin areas. Symptoms may vary from pruritis and pain to sexual dysfunction, however, LS can also be asymptomatic. LS occurs at all ages and in both sexes. Approximately 5% of all women affected by vulvar LS will develop vulvar squamous cell carcinoma. Topical treatment is safe but less effective resulting in chronic course in most patients, who suffer from persistent itching and pain. In severe cases of therapy-resistant LS, there is no adequate treatment. Fat grafting is a novel regenerative therapy to reduce dermal fibrosis. The therapeutic effect of adipose tissue grafts for LS is already investigated in various pioneering studies. This review provides an overview of these studies and the putative mechanisms-of-action of fat grafting to treat LS.

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