Multidisciplinary Treatment, Including Locoregional Chemotherapy, for Merkel-Polyomavirus-Positive Merkel Cell Carcinomas: Perspectives for Patients Exhibiting Oncogenic Alternative Δ exon 6–7 TrkAIII Splicing of Neurotrophin Receptor Tropomyosin-Related Kinase A
Abstract
:1. Introduction
2. Results
2.1. Clinical Data
2.2. Molecular Data
3. Discussion
4. Patients and Methods
4.1. Patients
4.2. Clinical Methods
4.3. Molecular Methods
4.4. Statistical Analysis
5. Conclusions
Author Contributions
Funding
Conflicts of Interest
Abbreviations
bp | base pair |
CLND | complete lymph node dissection |
CD56 | neural cell adhesion molecule |
CT | computerised tomography |
EpCAM | epithelial cell adhesion molecule |
FDA | food and drug administration |
FFPE | formalin-fixed paraffin-embedded |
IF | indirect immunofluorescence |
IgG1 | immunoglobulin G1 |
INFγ | interferon gamma |
ILI | isolated limb infusion |
ILP | isolated limb perfusion |
IPLP | isolated pelvic and limb perfusion |
MCCs | Merkel cell carcinomas |
MCPyV | Merkel cell polyomavirus |
NB | neuroblastoma |
NCCN | National Comprehensive Cancer Network |
NIH3T3 | mouse embryonic fibroblast cells |
OS | overall survival |
PD-1 | programmed cell death protein 1 |
PD-L1 | programmed death-ligand 1 |
RNAs | ribonucleic acids |
RT | radiotherapy |
RT-PCR | real-time polymerase chain reaction |
SNB | sentinel lymph node biopsy |
SD | standard deviation |
SV40 | simian vacuolating 40 polyomavirus |
TNF | tumour necrosis factor |
TrkA | tropomyosin-related kinase A |
USA | United States of America |
UV | ultraviolet |
VEGFR | vascular endothelial growth factor receptor |
WSE | wide surgical excisions |
WGSE | wide gluteal surgical excision |
SDi | stable disease |
PFS | Progression-free survival |
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Clinical Characteristics | N (%) |
---|---|
Gender | |
Female | 7 (58.3) |
Male | 5 (41.7) |
Age (Years) | |
≤65 | 4 (33.3) |
>65 | 8 (66.7) |
Primary Location | |
Head and/or Neck | 2 (16.7) |
Trunk | 4 (33.3) |
Extremities | 6 (50.0) |
Stage (AJCC 2019) at Molecular Analysis | |
I | 2 (16.7) |
II A | 4 (33.3) |
II B | 1 (8.3) |
III B | 3 (25.0) |
IV | 2 (16.7) |
Multidisciplinary Treatment | |
Surgical excision | 12 (100.0) |
Radiation therapy | 2 (16.7) |
Melphalan IPLP | 3 (25.0) |
Systemic chemotherapy | 2 (16.7) |
Immune checkpoint inhibitors | 2 (16.7) |
Status | |
Dead | 10 (83.3) |
Alive | 2 (16.7) |
(A) Patient Id (B) Primary Site (C) Recurrence Location/Age (Years)/Stage | (A) Previous Therapy (B) Concomitant Disease (Therapy) | 1st Treatment Distant Disease Status | 2nd Treatment Distant Disease Status | 3rd Treatment Distant Disease Status | (A) Concomitant Therapy Before Progression (B) PFS from 1st Locoregional Treatment (C) Progression Site (D) Therapy at Progression | Censor (February 2020) OS from 1st Locoregional Treatment |
---|---|---|---|---|---|---|
(A) 1 (B) Calcaneal region (C) Groin and limb /73/IIIB (pathological) | (A) WSE; SNB; CLND Chronic Neutropenia (B) Hepatitis C (Sofosbuvir/ Daclastavir) | WSE (10 nodules >1 cm diameter) IPLP | WSE (3 nodules <1 cm diameter) IPLP | WSE (1 nodule <1 cm diameter) IPLP | (A) Sofosbuvir/ Daclastavir (24 months) (B) 56 months (C) Locoregional (D) Avelumab | Dead 59 months |
(A) 2 (B) Anterior abdomen (C) Pelvis and limb plus distant/58/IV (clinical) | (A) WSE and RT | WSE (7 nodules >2 cm diameter) IPLP SDi in bone metastases | WSE (5 nodules >2 cm diameter) IPLP SDi in bone metastases | WSE (4 nodules >2 cm diameter) IPLP SDi in bone metastases | (B) 7 months (C) Locoregional and distant (D) Platinum-based systemic chemotherapy until dead | Dead 12 months |
(A) 3 (B) Gluteal region (C) Pelvis and limb plus distant/75/IV (clinical) | (A) WSE (B) Heart arrhythmia (Coumadin); Glaucoma (Propanolol) | WGSE/CLND (5 metastatic lymph nodes) IPLP SDi in lung, liver and brain metastases | IPLP alone SDi in lung, liver and brain metastases | (A) Coumadin/ Propanolol (B) 3 months (C) Locoregional and distant (D) Platinum-based systemic chemotherapy for 23 months | Dead 30 months |
MCC Molecular Characteristics. | N (%) |
---|---|
MCPyV Gene Expression | |
Yes | 11 (91.7) |
No | 1 (8.3) |
MCPyV Large T-Antigen | |
Present | 11 (91.7) |
High | 10 (83.4) |
Moderate | 1 (8.3) |
Negative | 1 (8.3) |
TrkA Expression | |
High | 1 (8.3) |
Moderate | 4 (33.3) |
Low | 7 (58.4) |
TrkAIII Expression | |
High | 8 (66.7) |
Moderate | 3 (25.0) |
Low | 1 (8.3) |
Y490 Phosphorylated TrkA/TrkAIII IF | |
High. | 6 (50.0) |
Moderate | 2 (16.7) |
Low | 1 (8.3) |
Negative | 3 (25.0) |
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Guadagni, S.; Farina, A.R.; Cappabianca, L.A.; Sebastiano, M.; Maccarone, R.; Zelli, V.; Clementi, M.; Chiominto, A.; Bruera, G.; Ricevuto, E.; et al. Multidisciplinary Treatment, Including Locoregional Chemotherapy, for Merkel-Polyomavirus-Positive Merkel Cell Carcinomas: Perspectives for Patients Exhibiting Oncogenic Alternative Δ exon 6–7 TrkAIII Splicing of Neurotrophin Receptor Tropomyosin-Related Kinase A. Int. J. Mol. Sci. 2020, 21, 8222. https://doi.org/10.3390/ijms21218222
Guadagni S, Farina AR, Cappabianca LA, Sebastiano M, Maccarone R, Zelli V, Clementi M, Chiominto A, Bruera G, Ricevuto E, et al. Multidisciplinary Treatment, Including Locoregional Chemotherapy, for Merkel-Polyomavirus-Positive Merkel Cell Carcinomas: Perspectives for Patients Exhibiting Oncogenic Alternative Δ exon 6–7 TrkAIII Splicing of Neurotrophin Receptor Tropomyosin-Related Kinase A. International Journal of Molecular Sciences. 2020; 21(21):8222. https://doi.org/10.3390/ijms21218222
Chicago/Turabian StyleGuadagni, Stefano, Antonietta Rosella Farina, Lucia Annamaria Cappabianca, Michela Sebastiano, Rita Maccarone, Veronica Zelli, Marco Clementi, Alessandro Chiominto, Gemma Bruera, Enrico Ricevuto, and et al. 2020. "Multidisciplinary Treatment, Including Locoregional Chemotherapy, for Merkel-Polyomavirus-Positive Merkel Cell Carcinomas: Perspectives for Patients Exhibiting Oncogenic Alternative Δ exon 6–7 TrkAIII Splicing of Neurotrophin Receptor Tropomyosin-Related Kinase A" International Journal of Molecular Sciences 21, no. 21: 8222. https://doi.org/10.3390/ijms21218222