1. Expression of DNA-damage response and repair genes after exposure to DNA-damaging agents in isogenic head and neck cells with altered radiosensitivityVesna Todorović, Blaž Grošelj, Maja Čemažar, Ajda Prevc, Martina Nikšić Žakelj, Primož Strojan, Gregor Serša, 2022, original scientific article Abstract: Background: Increased radioresistance due to previous irradiation or radiosensitivity due to human papilloma virus (HPV) infection can be observed in head and neck squamous cell carcinoma (HNSCC). The DNA-damage response of cells after exposure to DNA-damaging agents plays a crucial role in determining the fate of exposed cells. Tightly regulated and interconnected signaling networks are activated to detect, signal the presence of and repair the DNA damage. Novel therapies targeting the DNA-damage response are emerging; however, an improved understanding of the complex signaling networks involved in tumor radioresistance and radiosensitivity is needed. Materials and methods: In this study, we exposed isogenic human HNSCC cell lines with altered radiosensitivity to DNA-damaging agents: radiation, cisplatin and bleomycin. We investigated transcriptional alterations in the DNA-damage response by using a pathway-focused panel and reverse-transcription quantitative PCR. Results: In general, the isogenic cell lines with altered radiosensitivity significantly differed from one another in the expression of genes involved in the DNA-damage response. The radiosensitive (HPV-positive) cells showed overall decreases in the expression levels of the studied genes. In parental cells, upregulation of DNA-damage signaling and repair genes was observed following exposure to DNA-damaging agents, especially radiation. In contrast, radioresistant cells exhibited a distinct pattern of gene downregulation after exposure to cisplatin, whereas the levels in parental cells were unchanged. Exposure of radioresistant cells to bleomycin did not significantly affect the expression of DNA-damage signaling and repair genes. Conclusions: Our analysis identified several possible targets: NBN, XRCC3, ATR, GADD45A and XPA. These putative targets should be studied and potentially exploited for sensibilization to ionizing radiation and/or cisplatin in HNSCC. The use of predesigned panels of DNA-damage signaling and repair genes proved to offer a convenient and quick approach to identify possible therapeutic targets.
Keywords: DNA-damaging agents, gene expression, head and neck cancer, squamous cell carcinoma
Published in DiRROS: 24.07.2024; Views: 133; Downloads: 94
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2. Assessment of hyperbaric oxygenation treatment response in parotid glands by T2 mapping following radiotherapy for head and neck tumoursJernej Vidmar, Ksenija Cankar, Maja Grošelj, Žarko Finderle, Igor Serša, 2022, original scientific article Abstract: Background: The study was designed to evaluate the influence of hyperbaric oxygenation therapy (HBOT) on the parotid gland in patients following radiotherapy for head and neck tumours. Patients and methods: HBOT response was monitored by 3T magnetic resonance imaging (MRI) using T 2 mapping and subsequent measurement of mean T 2 and T 2 variability as well as by salivary tests (salivary flow, buffer capacity, and pH). Eighteen patients previously treated with irradiation doses between 50 and 80 Gy as well as 18 healthy gender and age matched controls were enrolled. MRI was performed prior to HBOT (40.2 ± 20 months after radiotherapy) and after 20 daily HBOT at 2.5 ATA (absolute atmosphere). Each HBOT consisted of breathing 100% oxygen for 90 minutes. Results: Significant differences in mean T 2 prior to HBOT were observed between the ipsilateral irradiated (121 ± 20 ms), contralateral parotids (107 ± 21) and control group (96 ± 12 ms). A positive correlation in patients between T 2 variability and irradiation dose was detected in contralateral parotids before HBOT (R = 0.489, p = 0.0287). In addition, negative correlations were observed between mean T 2 in the ipsilateral as well as the contralateral gland and salivary flow before and after HBOT. Negative correlations between mean T 2, T 2 variability and pH of unstimulated saliva were also observed in the sides of parotid before and after HBOT. Conclusions: The study confirmed that T 2 mapping had a potential for monitoring the differences between irradiated and normal parotid glands. It could also be useful in the assessment of the glandular tissue response to HBOT.
Keywords: MRI, T2 mapping, hyperbaric oxygenation therapy, head and neck tumours
Published in DiRROS: 24.07.2024; Views: 128; Downloads: 61
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4. Combining radiotherapy and immunotherapy in definitive treatment of head and neck squamous cell carcinoma : review of current clinical trialsGaber Plavc, Primož Strojan, 2020, review article Abstract: Head and neck squamous cell carcinoma (HNSCC) presents as locally advanced disease in a majority of patients and is prone to relapse despite aggressive treatment. Since immune checkpoint inhibitors (ICI) have shown clinically significant efficacy in patients with recurrent/metastatic HNSCC (R/M HNSCC), a plethora of trials are investigating their role in earlier stages of disease. At the same time, preclinical data showed the synergistic role of concurrently administered radiotherapy and ICIs (immunoradiotherapy) and explained several mechanisms behind it. Therefore, this approach is prospectively tested in a neoadjuvant, definitive, or adjuvant setting in non-R/M HNSCC patients. Due to the intricate relationship between host, immunotherapy, chemotherapy, and radiotherapy, each of these approaches has its advantages and disadvantages. In this narrative review we present the biological background of immunoradiotherapy, as well as a rationale for, and possible flaws of, each treatment approach, and provide readers with a critical summary of completed and ongoing trials. Conclusions. While immunotherapy with ICIs has already become a standard part of treatment in patients with R/M HNSCC, its efficacy in a non-R/M HNSCC setting is still the subject of extensive clinical testing. Irradiation can overcome some of the cancer%s immune evasive manoeuvres and can lead to a synergistic effect with ICIs, with possible additional benefits of concurrent platinum-based chemotherapy. However, the efficacy of this combination is not robust and details in trial design and treatment delivery seem to be of unprecedented importance.
Keywords: head and neck neoplasms, immunoradiotherapy, radiotherapy, immunotherapy
Published in DiRROS: 16.07.2024; Views: 118; Downloads: 29
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8. Implant-prosthetic rehabilitation after radiation treatment in head and neck cancer patients : a case-series report of outcomeJasna Cotič, Jure Jamšek, Milan Kuhar, Nataša Ihan Hren, Andrej Kansky, Mutlu Özcan, Peter Jevnikar, 2017, original scientific article Abstract: Background. Slovenia has a high burden of head and neck cancer. Patients are mostly treated with surgery followed by radiation therapy. Advanced surgical and prosthodontic techniques have expanded the rehabilitation options. The aim of the study was to review the outcome of implant-prosthetic treatment after radiation therapy. Patients and methods. Twenty irradiated head and neck cancer patients who received a removable implantsupported denture at the University Medical Centre Ljubljana were included in the study. Kaplan-Meier survival analysis, Cox proportional hazard models and logistic regression were used to assess the implant survival and success rate. Results. Twenty patients had 100 implants inserted. The estimated implant survival rate was 96% after 1 year and 87% after 5 years. Failures were mostly observed before loading (91.2%). Implants inserted in the transplanted bone were significantly more likely to fail. Out of 89 implants supporting the dentures, 79 implants (88.7%) were successful, meaning that they were functionally loaded and exhibited no pain, radiolucency or progressive bone loss. Prosthetic treatment was significantly less successful in older patients. The attachment system and the number of implants did not have a statistically significant influence on the success rate. Conclusions. Implant-supported dentures have been shown to be a reliable treatment modality after head and neck cancer surgery and radiation therapy. Possible early failures should be communicated with the patients.
Keywords: head and neck cancer, radiation therapy, dental implants
Published in DiRROS: 03.06.2024; Views: 187; Downloads: 85
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9. Electrochemotherapy in mucosal cancer of the head and neck : a systematic reviewPrimož Strojan, Aleš Grošelj, Gregor Serša, Christina Caroline Plaschke, Jan B. Vermorken, Sandra Nuyts, Remco De Bree, Avraham Eisbruch, William M. Mendenhall, Robert Smee, Alfio Ferlito, 2021, review article Abstract: Electrochemotherapy (ECT) is a local ablative treatment that is based on the reversible electroporation and intracellular accumulation of hydrophilic drug molecules, which greatly increases their cytotoxicity. In mucosal head and neck cancer (HNC), experience with ECT is limited due to the poor accessibility of tumors. In order to review the experience with ECT in mucosal HNC, we undertook a systematic review of the literature. In 22 articles, published between 1998 and 2020, 16 studies with 164 patients were described. Curative and palliative intent treatment were given to 36 (22%) and 128 patients (78%), respectively. The majority of tumors were squamous cell carcinomas (79.3%) and located in the oral cavity (62.8%). In the curative intent group, complete response after one ECT treatment was achieved in 80.5% of the patients, and in the palliative intent group, the objective (complete and partial) response rate was 73.1% (31.2% and 41.9%). No serious adverse events were reported during or soon after ECT and late effects were rare (19 events in 17 patients). The quality-of-life assessments did not show a significant deterioration at 12 months post-ECT. Provided these preliminary data are confirmed in randomized controlled trials, ECT may be an interesting treatment option in selected patients with HNC not amenable to standard local treatment.
Keywords: electrochemotherapy, head and neck cancer, mucosal cancer
Published in DiRROS: 23.09.2022; Views: 707; Downloads: 355
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10. Neuroendocrine carcinoma of the larynx and pharynx : a clinical and histopathological studyPrimož Strojan, Robert Šifrer, Alfio Ferlito, Cvetka Grašič-Kuhar, Boštjan Lanišnik, Gaber Plavc, Nina Zidar, 2021, original scientific article Abstract: Neuroendocrine carcinomas (NECs) of the head and neck are rare and the experience scanty. The Cancer Registry of Slovenia database was used to identify cases of laryngeal and pharyngeal NECs diagnosed between 1995%2020. Biopsies were analyzed for the expression of standard neuroendocrine markers (synaptophysin, chromogranin, CD56), INSM1, Ki-67, p16, and PD-L1 (using the combined positive score, CPS). In situ hybridization for human papillomavirus (HPV) and Epstein%Barr virus (EBV) was performed. Twenty patients (larynx, 12; pharynx, 8) were identified. One tumor was well differentiated (WD), five were moderately differentiated (MD), and 14 were poorly differentiated (PD). Disease control was achieved solely by surgery in 4/4 MD/PD T1-2N0-1 tumors. Eight patients died of the disease, seven of which were due to distant metastases. All three traditional markers were positive in 11/17 NECs and the INSM1 marker in all 20 tumors. Two of fourteen p16-positive tumors were HPV-positive, but all three nasopharyngeal NECs were EBV-negative. Three tumors had CPSs % 1. In conclusion, INSM1 was confirmed to be a reliable marker of neuroendocrine differentiation. Except in WD and early-stage MD/PD tumors, aggressive multimodal therapy is needed; the optimal systemic therapy remains to be determined. p16, HPV, and EBV seem to bear no prognostic information.
Keywords: electrochemotherapy, head and neck cancer, neuroendocrinic carcinoma
Published in DiRROS: 07.09.2022; Views: 693; Downloads: 307
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