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1.
Ann Diagn Pathol ; 54: 151800, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1321982

ABSTRACT

BACKGROUND: Challenging emerging entities with distinctive molecular signatures may benefit from algorithms for diagnostic work-up. METHODS: Fusion sarcomas (2020-2021, during pandemic) were diagnosed by clinicoradiology, morphology, phenotype, and next-generation sequencing (NGS). RESULTS: Six fusion sarcomas in two males and four females involved the chest-wall, neck, or extremities; ages ranged 2-73, median 18 years. Sizes ranged 5.3-25.0, median 9.1 cm. These include high grade 1) TPR-NTRK1 of proximal femur with a larger rounded soft tissue mass, previously considered osteosarcoma yet without convincing tumor matrix. A pathologic fracture necessitated emergency hemipelvectomy (NED) and 2) novel KANK1-NTRK2 sarcoma of bone and soft tissue with spindled pleomorphic to epithelioid features (AWD metastases). 3) Novel ERC1-ALK unaligned fusion, a low grade infiltrative deep soft tissue hand sarcoma with prominent-vascularity, myopericytoid/lipofibromatosis-like ovoid cells, and collagenized stroma, was successfully treated with ALK-inhibitor (Crizotinib), avoiding amputation. These NTRK and ALK tumors variably express S100 and CD34 and were negative for SOX10. 4) and 5) CIC-DUX4 round cell tumors (rapid metastases/demise), one with COVID superinfection, were previously treated as Ewing sarcoma. These demonstrated mild pleomorphism and necrosis, variable myxoid change and CD99 reactivity, and a distinctive dot-like-Golgi WT1 immunostaining pattern. 6) A chest wall/thoracic round cell sarcoma, focal CD34/ keratins/CK7, revealed nuclear-STAT6, STAT6-NAB2 by NGS, confirming malignant solitary fibrous tumor, intermediate-risk-stratification (AWD metastases). CONCLUSIONS: Recent fusion sarcomas include new KANK1-NTRK2 and ERC1-ALK, the latter successfully treated by targeted-therapy. ALK/NTRK fusion partners TPR and KANK1 suggest unusual high-grade morphology/behavior. Clinicoradiologic, morphologic, and phenotypic algorithms can prompt molecular-targeted immunostains or NGS for final classification and promising inhibitor therapy.


Subject(s)
Biomarkers, Tumor/genetics , Femoral Neoplasms/genetics , Gene Fusion , Head and Neck Neoplasms/genetics , Sarcoma/genetics , Soft Tissue Neoplasms/genetics , Thoracic Neoplasms/genetics , Adolescent , Adult , Aged , Algorithms , Antineoplastic Agents/therapeutic use , Child , Child, Preschool , Extremities/pathology , Female , Femoral Neoplasms/diagnosis , Femoral Neoplasms/drug therapy , Femoral Neoplasms/pathology , Head and Neck Neoplasms/diagnosis , Head and Neck Neoplasms/drug therapy , Head and Neck Neoplasms/pathology , High-Throughput Nucleotide Sequencing , Humans , Male , Middle Aged , Neoplasm Grading , Phenotype , Prognosis , Sarcoma/diagnosis , Sarcoma/drug therapy , Sarcoma/pathology , Soft Tissue Neoplasms/diagnosis , Soft Tissue Neoplasms/drug therapy , Soft Tissue Neoplasms/pathology , Thoracic Neoplasms/diagnosis , Thoracic Neoplasms/drug therapy , Thoracic Neoplasms/pathology , Thoracic Wall/pathology , Young Adult
2.
Anal Chem ; 93(5): 2767-2775, 2021 02 09.
Article in English | MEDLINE | ID: covidwho-1039622

ABSTRACT

Clinical tissue specimens are often unscreened, and preparation of tissue sections for analysis by mass spectrometry imaging (MSI) can cause aerosolization of particles potentially carrying an infectious load. We here present a decontamination approach based on ultraviolet-C (UV-C) light to inactivate clinically relevant pathogens such as herpesviridae, papovaviridae human immunodeficiency virus, or SARS-CoV-2, which may be present in human tissue samples while preserving the biodistributions of analytes within the tissue. High doses of UV-C required for high-level disinfection were found to cause oxidation and photodegradation of endogenous species. Lower UV-C doses maintaining inactivation of clinically relevant pathogens to a level of increased operator safety were found to be less destructive to the tissue metabolome and xenobiotics. These doses caused less alterations of the tissue metabolome and allowed elucidation of the biodistribution of the endogenous metabolites. Additionally, we were able to determine the spatially integrated abundances of the ATR inhibitor ceralasertib from decontaminated human biopsies using desorption electrospray ionization-MSI (DESI-MSI).


Subject(s)
Decontamination/methods , Ultraviolet Rays , Animals , Azetidines/analysis , Azetidines/therapeutic use , COVID-19/pathology , COVID-19/virology , Head and Neck Neoplasms/chemistry , Head and Neck Neoplasms/drug therapy , Head and Neck Neoplasms/pathology , Humans , Male , Metabolome , Naphthalenes/analysis , Naphthalenes/therapeutic use , Photolysis/radiation effects , Rats , Rats, Wistar , SARS-CoV-2/isolation & purification , SARS-CoV-2/radiation effects , Spectrometry, Mass, Electrospray Ionization/methods , Terfenadine/chemistry , Virus Inactivation/radiation effects
3.
Radiol Med ; 126(2): 343-347, 2021 Feb.
Article in English | MEDLINE | ID: covidwho-834039

ABSTRACT

OBJECTIVES: The objective of the paper was to assess real-life experience in the management of head and neck cancer (HNC) patients during the COVID-19 pandemic in radiotherapy departments and to evaluate the variability in terms of adherence to American Society of Radiation Oncology (ASTRO) and European Society for Radiotherapy and Oncology (ESTRO) recommendations. MATERIALS AND METHODS: In May 2020, an anonymous 30-question online survey, comparing acute phase of outbreak and pre-COVID-19 period, was conducted. Two sections exploited changes in general management of HNC patients and different HNC primary tumors, addressing specific statements from ASTRO ESTRO consensus statement as well. RESULTS: Eighty-eight questionnaires were included in the demographic/clinical workflow analysis, and 64 were analyzed for treatment management. Forty-eight percent of radiotherapy departments became part of oncologic hubs. First consultations reduced, and patients were addressed to other centers in 33.8 and 18.3% of cases, respectively. Telematic consultations were used in 50% of follow-up visits and 73.9% of multidisciplinary tumor board discussions. There were no practical changes in the management of patients affected by different primitive HNCs. Hypofractionation was not favored over conventional schedules. CONCLUSIONS: Compared to pre-COVID era, the clinical workflow was highly re-organized, whereas there were no consistent changes in RT indications and schedules.


Subject(s)
COVID-19/epidemiology , Head and Neck Neoplasms/radiotherapy , Pandemics , Radiation Oncology/statistics & numerical data , SARS-CoV-2 , Europe/epidemiology , Guideline Adherence/statistics & numerical data , Head and Neck Neoplasms/drug therapy , Health Care Surveys/statistics & numerical data , Humans , Induction Chemotherapy , Italy/epidemiology , Radiotherapy/methods , Radiotherapy/statistics & numerical data , Radiotherapy Dosage , Referral and Consultation/statistics & numerical data , Societies, Medical , Telemedicine/statistics & numerical data , Workflow
4.
Cancer ; 126(15): 3426-3437, 2020 08 01.
Article in English | MEDLINE | ID: covidwho-457377

ABSTRACT

BACKGROUND: The objective of this study was to identify a subgroup of patients with head and neck squamous cell carcinoma (HNSCC) who might be suitable for hypofractionated radiotherapy (RT-hypo) during the COVID-19 pandemic. METHODS: HNSCC cases (oropharynx/larynx/hypopharynx) treated with definitive RT-hypo (60 Gy in 25 fractions over 5 weeks), moderately accelerated radiotherapy (RT-acc) alone (70 Gy in 35 fractions over 6 weeks), or concurrent chemoradiotherapy (CCRT) during 2005-2017 were included. Locoregional control (LRC) and distant control (DC) after RT-hypo, RT-acc, and CCRT were compared for various subgroups. RESULTS: The study identified 994 human papillomavirus-positive (HPV+) oropharyngeal squamous cell carcinoma cases (with 61, 254, and 679 receiving RT-hypo, RT-acc, and CCRT, respectively) and 1045 HPV- HNSCC cases (with 263, 451, and 331 receiving RT-hypo, RT-acc, and CCRT, respectively). The CCRT cohort had higher T/N categories, whereas the radiotherapy-alone patients were older. The median follow-up was 4.6 years. RT-hypo, RT-acc, and CCRT produced comparable 3-year LRC and DC for HPV+ T1-2N0-N2a disease (seventh edition of the TNM system [TNM-7]; LRC, 94%, 100%, and 94%; P = .769; DC, 94%, 100%, and 94%; P = .272), T1-T2N2b disease (LRC, 90%, 94%, and 97%; P = .445; DC, 100%, 96%, and 95%; P = .697), and T1-2N2c/T3N0-N2c disease (LRC, 89%, 93%, and 95%; P = .494; DC, 89%, 90%, and 87%; P = .838). Although LRC was also similar for T4/N3 disease (78%, 84%, and 88%; P = .677), DC was significantly lower with RT-hypo or RT-acc versus CCRT (67%, 65%, and 87%; P = .005). For HPV- HNSCC, 3-year LRC and DC were similar with RT-hypo, RT-acc, and CCRT in stages I and II (LRC, 85%, 89%, and 100%; P = .320; DC, 99%, 98%, and 100%; P = .446); however, RT-hypo and RT-acc had significantly lower LRC in stage III (76%, 69%, and 91%; P = .006), whereas DC rates were similar (92%, 85%, and 90%; P = .410). Lower LRC in stage III predominated in patients with laryngeal squamous cell carcinoma receiving RT-acc (62%) but not RT-hypo (80%) or CCRT (92%; RT-hypo vs CCRT: P = .270; RT-acc vs CCRT: P = .004). CCRT had numerically higher LRC in comparison with RT-hypo or RT-acc in stage IV (73%, 65%, and 66%; P = .336). CONCLUSIONS: It is proposed that RT-hypo be considered in place of CCRT for HPV+ T1-T3N0-N2c (TNM-7) HNSCCs, HPV- T1-T2N0 HNSCCs, and select stage III HNSCCs during the COVID-19 outbreak.


Subject(s)
Head and Neck Neoplasms/radiotherapy , Radiation Dose Hypofractionation , Squamous Cell Carcinoma of Head and Neck/radiotherapy , Adult , Aged , Aged, 80 and over , COVID-19 , Coronavirus Infections/epidemiology , Female , Follow-Up Studies , Head and Neck Neoplasms/drug therapy , Head and Neck Neoplasms/mortality , Head and Neck Neoplasms/virology , Humans , Male , Middle Aged , Neoplasm Recurrence, Local , Oropharyngeal Neoplasms/drug therapy , Oropharyngeal Neoplasms/radiotherapy , Oropharyngeal Neoplasms/virology , Pandemics , Papillomavirus Infections/complications , Pneumonia, Viral/epidemiology , Radiotherapy, Intensity-Modulated , Risk Factors , Squamous Cell Carcinoma of Head and Neck/drug therapy , Squamous Cell Carcinoma of Head and Neck/mortality , Squamous Cell Carcinoma of Head and Neck/virology , Treatment Outcome
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