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1.
Oral Oncol ; 153: 106830, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38718459

ABSTRACT

BACKGROUND: Conventional clinicopathological characteristics insufficiently predict prognosis in oral squamous cell carcinoma (OSCC). We aimed to assess the added predictive value of tumor microenvironment immune cell composition (TMICC) in addition to conventional clinicopathological characteristics. METHODS: Primary tumor samples of 290 OSCC patients were immunohistochemically stained for CD4, CD8, CD20, CD68, CD163, CD57, FoxP3 and Programmed cell Death Ligand 1. Additionally, clinicopathological characteristics were obtained from patients' medical files. Predictive models were trained and validated by conducting Least Absolute Shrinkage and Selection Operator (LASSO) regression analyses with cross-validation. To quantify the added predictive power of TMICC within models, receiver operating characteristic (ROC) analyses were used. RESULTS: Recurrence occurred in 74 patients (25.5%). Conventional clinicopathological characteristics (tumor localization, pathological T-stage, pathological N-stage, extracapsular spread, resection margin, differentiation grade, perineural invasion, lymphovascular invasion) and treatment modality, were used to build a LASSO logistic regression-based predictive model. Addition of TMICC to the model resulted in a comparable AUC of respectively 0.79 (±0.01) and 0.76 (±0.1) in the training and test sets. The model indicated that high numbers of CD4+ T cells protected against recurrence. Lymph node metastasis, extracapsular spread, perineural invasion, positive surgical margins and reception of adjuvant treatment were associated with increased risk for recurrence. CONCLUSIONS: The TMICC, specifically the number of CD4+ T cells, is an independent predictor , however, addition to conventional clinicopathological characteristics does not improve the performance of a predictive model for recurrence in OSCC.


Subject(s)
Carcinoma, Squamous Cell , Mouth Neoplasms , Tumor Microenvironment , Humans , Tumor Microenvironment/immunology , Mouth Neoplasms/immunology , Mouth Neoplasms/pathology , Male , Female , Middle Aged , Carcinoma, Squamous Cell/immunology , Carcinoma, Squamous Cell/pathology , Aged , Adult , Prognosis , Neoplasm Recurrence, Local/pathology , Aged, 80 and over
2.
Expert Rev Pharmacoecon Outcomes Res ; 21(3): 413-414, 2021 Jun.
Article in English | MEDLINE | ID: mdl-33852815

ABSTRACT

Purpose: Predictive diagnostics play an increasingly important role in personalized medicine for cancer treatment. Whole-genome sequencing (WGS)-based treatment selection is expected to rapidly increase worldwide. This study aimed to calculate and compare the total cost of currently used diagnostic techniques and of WGS in treatment of non-small cell lung carcinoma (NSCLC), melanoma, colorectal cancer (CRC), and gastrointestinal stromal tumor (GIST) in the Netherlands.Methods: The activity-based costing (ABC) method was conducted to calculate total cost of included diagnostic techniques based on data provided by Dutch pathology laboratories and the Dutch-centralized cancer WGS facility. Costs were allocated to four categories: capital costs, maintenance costs, software costs, and operational costs.Results: The total cost per cancer patient per technique varied from € 58 (Sanger sequencing, three amplicons) to € 2925 (paired tumor-normal WGS). The operational costs accounted for the vast majority (over 90%) of the total per cancer patient technique costs.Conclusion: This study outlined in detail all costing aspects and cost prices of current and new diagnostic modalities used in treatment of NSCLC, melanoma, CRC, and GIST in the Netherlands. Detailed cost differences and value comparisons between these diagnostic techniques enable future economic evaluations to support decision-making.


Subject(s)
Genetic Testing/methods , Neoplasms/diagnosis , Whole Genome Sequencing/methods , Costs and Cost Analysis , Genetic Testing/economics , Humans , Neoplasms/genetics , Netherlands , Precision Medicine , Whole Genome Sequencing/economics
3.
Oral Oncol ; 77: 131-136, 2018 02.
Article in English | MEDLINE | ID: mdl-29362119

ABSTRACT

OBJECTIVES: To identify predictive factors for the presence of viable tumor and outcome in head and neck cancer patients who undergo therapeutic salvage neck dissections. MATERIALS AND METHODS: Retrospective analysis of 76 salvage neck dissections after radiotherapy alone (n = 22), radiotherapy in combination with carboplatin/5-fluorouracil (n = 42) or with cetuximab (n = 12). RESULTS: Viable tumor was detected in 41% of all neck dissections. Univariate analysis revealed initial treatment with radiotherapy without systemic therapy (OR 6.93, 95%CI: 2.28-21.07, p < .001), increased lymph node size after initial treatment compared to pretreatment CT scan (OR 20.48, 95%CI: 2.46-170.73, p = .005), more extensive neck dissections (OR 8.40, 95%CI: 2.94-23.98, p < .001), and human papillomavirus negative cancer (OR 4.22, 95%CI: 1.10-16.22, p = .036) as predictors of viable tumor. Patients with decreased or stable, but persistently enlarged lymph node size after chemoradiation had a significantly lower chance of viable tumor (OR 0.15, 95%CI: 0.05-0.41, p < .001). Disease-specific 5-year survival was 34% in case of viable tumor, and 78% when no viable tumor was found (p < .001). CONCLUSIONS: Viable tumor in salvage neck dissections is associated with reduced survival. Radiotherapy alone, human papillomavirus negative cancer and increase in lymph node size, are associated with viable tumor in salvage neck dissections. In case of decreased or stable lymph node size after chemoradiation, watchful waiting could be considered.


Subject(s)
Head and Neck Neoplasms/pathology , Head and Neck Neoplasms/surgery , Lymph Nodes/pathology , Neck Dissection , Salvage Therapy , Squamous Cell Carcinoma of Head and Neck/pathology , Squamous Cell Carcinoma of Head and Neck/surgery , Aged , Alphapapillomavirus/isolation & purification , Female , Head and Neck Neoplasms/virology , Humans , Male , Middle Aged , Retrospective Studies , Squamous Cell Carcinoma of Head and Neck/virology
4.
Eur Arch Otorhinolaryngol ; 273(10): 3231-6, 2016 Oct.
Article in English | MEDLINE | ID: mdl-27188508

ABSTRACT

Aim of this study was to explore influence of the quadrivalent HPV vaccine (Gardasil(®)) on the immune status of recurrent respiratory papillomatosis (RRP) patients. In retrospective observational study, six RRP patients who received the quadrivalent HPV vaccine and whose HPV seroreactivity was measured were included. Multiplex HPV Serology was used to determine HPV-specific antibodies pre- and post-vaccination. Surgical interventions and patient records were analyzed. Five HPV6 and 1 HPV11 infected patient were included. Mean antibody reactivity against the associated HPV type rose from 1125 median fluorescence intensity (MFI) pre-vaccination to 4690 MFI post-vaccination (p < 0.001). Median post-vaccination follow-up was 4 years. Poisson regression analysis showed that the quadrivalent HPV vaccine decreased the incidence rate of surgeries. The immune system of RRP patients is able to increase antibody reactivity against the associated HPV type. A double blind randomized controlled trial is needed to determine whether this immunological increase can cause decrease in number of surgeries.


Subject(s)
Human Papillomavirus Recombinant Vaccine Quadrivalent, Types 6, 11, 16, 18/therapeutic use , Papillomavirus Infections/prevention & control , Respiratory Tract Infections/prevention & control , Adult , Antibodies, Viral/blood , Female , Humans , Male , Papillomaviridae/immunology , Papillomavirus Infections/surgery , Regression Analysis , Respiratory Tract Infections/surgery , Retrospective Studies
5.
Head Neck ; 37(11): 1625-32, 2015 Nov.
Article in English | MEDLINE | ID: mdl-24955561

ABSTRACT

BACKGROUND: Recurrent respiratory papillomatosis (RRP) is mainly associated with human papillomavirus (HPV)6 or HPV11. The purpose of this study was to compare clinical outcome, aggressiveness, and treatment response between HPV6- and HPV11-associated RRP. METHODS: A retrospective cohort of 55 patients with RRP (1974-2012) was used. Surgical interventions (n = 814) were analyzed, and complications scored. HPV6/11-specific polymerase chain reaction (PCR) was performed on RRP biopsies. RESULTS: Seventy-six percent of patients (42 of 55) were infected with HPV6 and 24% (13 of 55) with HPV11. The HPV11 group had anatomically more widespread disease. The expected number of surgical interventions was higher in the younger age (<22.4 years) HPV11 group, and the older age (<22.4 years) HPV6 group. Regardless of HPV type, earlier age of onset of RRP resulted in a higher number of surgical interventions. CONCLUSION: Anatomically, HPV11-associated RRP behaves more aggressively. Younger patients with HPV11 and older patients with HPV6 experience a worse clinical course of RRP.


Subject(s)
Human papillomavirus 11/isolation & purification , Human papillomavirus 6/isolation & purification , Papillomavirus Infections/pathology , Papillomavirus Infections/virology , Respiratory Tract Infections/pathology , Respiratory Tract Infections/virology , Adult , Age Distribution , Biopsy, Needle , Cohort Studies , Female , Hospitals, University , Humans , Immunohistochemistry , Incidence , Male , Netherlands , Papillomavirus Infections/epidemiology , Papillomavirus Infections/surgery , Polymerase Chain Reaction/methods , Prognosis , Respiratory Tract Infections/epidemiology , Respiratory Tract Infections/surgery , Retrospective Studies , Risk Assessment , Severity of Illness Index , Sex Distribution , Young Adult
6.
Am J Pathol ; 181(1): 303-12, 2012 Jul.
Article in English | MEDLINE | ID: mdl-22658485

ABSTRACT

New treatment targets need to be identified in gastrointestinal stromal tumors (GISTs) to extend the treatment options for patients experiencing failure with small-molecule tyrosine kinase inhibitors, such as imatinib. Insulin-like growth factor (IGF)-II acts as an autocrine factor in several tumor types by binding to IGF receptor type 1 (IGF-1R) and/or the insulin receptor (IR) isoform A. The aim of the present study was to investigate the putative role of unprocessed pro-IGF-II, called 'big'-IGF-II, in GISTs. The imatinib-sensitive GIST882 and imatinib-resistant GIST48 cell lines secrete high levels of big-IGF-II as demonstrated by ELISA and Western blotting analyses. IR isoform A mRNA and protein expression, but not that of IGF-1R, was found in these KIT mutant cell lines and in KIT and platelet-derived growth factor receptor α-mutant GIST specimens. Down-regulation of either big-IGF-II or IR affected AKT and MAPK signaling and reduced survival in both cell lines. Disruption of big-IGF-II signaling in combination with imatinib had additive cytotoxic effects on GIST882 cells. IGF-II mRNA as determined by in situ hybridization was present in 91% of 60 primary GISTs. Immunohistochemical analysis of big-IGF-II protein expression was associated with moderate- to high-risk tumors compared with tumors with a lower risk classification (P < 0.028). Our data put forth the big-IGF-II/IR isoform A axis as an autocrine survival pathway and potential therapeutic target in GISTs.


Subject(s)
Gastrointestinal Stromal Tumors/physiopathology , Insulin-Like Growth Factor II/physiology , Protein Precursors/physiology , Adult , Aged , Aged, 80 and over , Antineoplastic Agents/pharmacology , Autocrine Communication/drug effects , Autocrine Communication/physiology , Benzamides , Cell Death/drug effects , Cell Death/physiology , Cell Survival/physiology , Down-Regulation/physiology , Female , Gastrointestinal Stromal Tumors/metabolism , Gastrointestinal Stromal Tumors/pathology , Humans , Imatinib Mesylate , Insulin-Like Growth Factor II/metabolism , Male , Middle Aged , Neoplasm Proteins/metabolism , Piperazines/pharmacology , Protein Precursors/metabolism , Pyrimidines/pharmacology , Receptor, IGF Type 1/metabolism , Receptor, Insulin/metabolism , Tumor Cells, Cultured , Young Adult
7.
J Pathol ; 206(3): 328-36, 2005 Jul.
Article in English | MEDLINE | ID: mdl-15887291

ABSTRACT

Loss of both HLA class I and class II expression in B cell lymphomas is a mechanism of escape from a cytotoxic T lymphocyte (CTL) immune response and will therefore give a strong selective survival advantage in tumours expressing strong immunogenic antigens. We investigated loss of HLA expression using specific antibodies on tissue sections from 254 B cell lymphomas originating from nodal and different extranodal sites in relation to numbers of tumour-infiltrating T cells. Complete loss of HLA class I and II was observed in a minority of the nodal, stomach, and skin lymphomas but in the majority of the lymphomas originating from the testis and the CNS. Interestingly, relatively high percentages of activated CTLs were detected in both primary testicular and CNS lymphomas compared to lymphomas at other sites, with highest percentages in the testis (p < 0.0001). We conclude that loss of both HLA class I and II expression occurs very frequently in lymphomas originating from the testis and the CNS as compared to nodal and some other extranodal sites. The presence of high percentages of activated CTLs in the testicular and CNS lymphomas suggests that loss of HLA expression provides a strong growth advantage for lymphoma cells in these immune-privileged sites.


Subject(s)
Brain Neoplasms/genetics , HLA Antigens/genetics , Lymphoma, B-Cell/genetics , Lymphoma, Large B-Cell, Diffuse/genetics , T-Lymphocytes, Cytotoxic/immunology , Testicular Neoplasms/genetics , Brain Neoplasms/immunology , CD3 Complex/genetics , CD3 Complex/immunology , CD4 Antigens/analysis , CD4 Antigens/genetics , CD8 Antigens/analysis , CD8 Antigens/genetics , Gene Expression Regulation, Neoplastic/genetics , Gene Expression Regulation, Neoplastic/immunology , HLA Antigens/immunology , Histocompatibility Antigens Class I/genetics , Histocompatibility Antigens Class I/immunology , Histocompatibility Antigens Class II/genetics , Histocompatibility Antigens Class II/immunology , Humans , Lymphocyte Count/methods , Lymphocytes, Tumor-Infiltrating/immunology , Lymphoma, B-Cell/immunology , Lymphoma, Large B-Cell, Diffuse/immunology , Male , Phenotype , Skin Neoplasms/genetics , Skin Neoplasms/immunology , Stomach Neoplasms/genetics , Stomach Neoplasms/immunology , T-Lymphocyte Subsets/immunology , Testicular Neoplasms/immunology
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