| 1. |
- Högmo, Anders, et al.
(författare)
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Base of tongue squamous cell carcinomas, outcome depending on treatment strategy and p16 status. A population-based study from the Swedish Head and Neck Cancer Register
- 2022
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Ingår i: Acta Oncologica. - : Taylor & Francis. - 0284-186X .- 1651-226X. ; 61:4, s. 433-440
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Tidskriftsartikel (refereegranskat)abstract
- Background: The base of tongue squamous cell carcinoma (BOTSCC) is mainly an HPV-related tumor. Radiotherapy (EBRT) ± concomitant chemotherapy (CT) is the backbone of the curatively intended treatment, with brachytherapy (BT) boost as an option. With four different treatment strategies in Sweden, a retrospective study based on the population-based Swedish Head and Neck Cancer Register (SweHNCR) was initiated.Material and methods: Data on tumors, treatment and outcomes in patients with BOTSCC treated between 2008 and 2014 were validated through medical records and updated as needed. Data on p16 status were updated or completed with immunohistochemical analysis of archived tumor material. Tumors were reclassified according to the UICC 8th edition.Results: Treatment was EBRT, EBRT + CT, EBRT + BT or EBRT + CT + BT in 151, 145, 82 and 167 patients respectively (n = 545). A p16 analysis was available in 414 cases; 338 were p16+ and 76 p16−. 5-year overall survival (OS) was 68% (95% CI: 64–72%), with76% and 37% for p16+ patients and p16− patients, respectively. An increase in OS was found with the addition of CT to EBRT for patients with p16+ tumors, stages II–III, but for patients with tumor stage I, p16+ (UICC 8) none of the treatment strategies was superior to EBRT alone.Conclusion: In the present retrospective population-based study of BOTSCC brachytherapy was found to be of no beneficial value in curatively intended treatment. An increase in survival was found for EBRT + CT compared to EBRT alone in patients with advanced cases, stages II and III (UICC 8), but none of the regimes was significantly superior to EBRT as a single treatment modality for stage I (UICC 8), provided there was p16 positivity in the tumor. In the small group of patients with p16− tumors, a poorer prognosis was found, but the small sample size did not allow any comparisons between different treatment strategies.
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| 2. |
- Adnan, Ali, et al.
(författare)
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Health-related quality of life among tonsillar carcinoma patients in Sweden in relation to treatment and comparison with quality of life among the population
- 2020
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Ingår i: Head and Neck-Journal for the Sciences and Specialties of the Head and Neck. - : Wiley. - 1043-3074 .- 1097-0347. ; 42:5, s. 860-872
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Tidskriftsartikel (refereegranskat)abstract
- Background The health-related quality of life (HRQOL) of tonsillar carcinoma survivors was explored to investigate any HRQOL differences associated with tumor stage and treatment. The survivors' HRQOL was also compared to reference scores from the population. Methods In this exploratory cross-sectional study patients were invited 15 months after their diagnosis and asked to answer two quality of life questionnaires (EORTC QLQ- C30, EORTC QLQ- HN35), 405 participated. Results HRQOL was associated with gender, with males scoring better than females on a few scales. Patients' HRQOL was more associated with treatment than tumor stage. Patients' HRQOL was worse than that in an age- and sex-matched reference group from the normal population, the largest differences were found for problems with dry mouth followed by problems with sticky saliva, senses, swallowing and appetite loss. Conclusions The tonsillar carcinoma patients had a worse HRQOL compared to the general population one year after treatment.
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| 3. |
- Berg, Malin, 1976, et al.
(författare)
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A national study of health-related quality of life in patients with cancer of the base of the tongue compared to the general population and to patients with tonsillar carcinoma
- 2021
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Ingår i: Head and Neck-Journal for the Sciences and Specialties of the Head and Neck. - : Wiley. - 1043-3074 .- 1097-0347. ; 43:12, s. 3843-3856
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Tidskriftsartikel (refereegranskat)abstract
- Background This exploratory, registry-based, cross-sectional study aimed to evaluate patients' health-related quality of life (HRQOL) in a subsite of oropharyngeal cancer: cancer of the base of the tongue (CBT). Methods CBT patients, treated with curative intent, completed the EORTC QLQ-C30 and QLQ-H&N35 questionnaires 15 months after diagnosis. The HRQOL of CBT patients was compared to reference scores from the general population and to that of tonsillar carcinoma patients. Results The 190 CBT patients scored significantly worse than members of the general population on most scales. CBT patients with human papilloma virus (HPV)-positive tumors had significantly better HRQOL on 8 of 28 scales than HPV-negative patients. Compared to 405 tonsillar carcinoma patients, CBT patients had significantly worse HRQOL on 8 of the 28 scales, the majority local head and neck related problems. Conclusion One year after treatment, CBT patients' HRQOL was significantly worse in many areas compared to that of the general population and slightly worse than that of tonsillar carcinoma patients.
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| 4. |
- Matić, Nataša, 1977-
(författare)
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Biomarkers in the tumor microenvironment with impact on treatment response and survival in head and neck cancer
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Head and neck squamous cell cancer (HNSCC) is the sixth most common cancer type worldwide and disease detects at a locally advanced stage in approximately 60% of all patients with HNSCC. Despite the advances in both diagnosis and treatment of cancer, therapy failure with local recurrence and second primary tumors as consequences is still a huge problem. Furthermore, HNSCC is heterogeneous disease and treatment response differs largely within this patient’s group. Owing to such heterogeneity, the individually designed treatment approach, based on biomarkers predicting treatment response is needed. The personalized treatment strategy is a new and promising form of cancer therapy to improve effectiveness of anti-cancer treatment and reduce suffering in patients diagnosed with HNSCC.The main aim of this thesis was to search for new predictive biomarkers with potential to foresee treatment response in HNSCC patients by investigating components and properties of the tumor microenvironment, such as metabolism, hypoxia and cancer-associated fibroblasts (CAF).In paper I we developed an in vitro method for the measurement of intracellular glucose (18F FDG) uptake with gamma spectrometry (GS). Quantity of glucose uptake was associated with treatment (radiation or cetuximab) response, where the radiosensitive cell line and the most cetuximab-sensitive cell lines showed a significant decrease of glucose uptake after treatment. The results were compared with those of a clinical PET/CT scanner and the results in glucose uptake between radiated cells and controls were similar in both methods. Furthermore, we investigated GLUT1 mRNA expression in cell lines after cetuximab treatment and our analysis showed a significant increase of GLUT1 mRNA expression.In paper II, we found a negative impact of hypoxia on radiotherapy response in HNSCC cells and enhanced expression of epithelial–mesenchymal transition (EMT)- and cancer stem cells (CSC)-associated genes during culturing cells in hypoxic conditions. With cDNA microarrays analysis we identified a number of hypoxia regulated genes that were involved in multiple biological functions as well as support growth and proliferation of cancer cells. Furthermore, with use of siRNA silencing, we investigated a possible impact of a panel of hypoxia-responsive genes (HIF-1α, CDH2, CA9, SERPINE1, AREG and EREG) on radiotherapy treatment. Nevertheless, downregulation of these hypoxia regulated genes did not affect the sensitivity to radiotherapy of the investigated HNSCC cell lines.In the following study (paper III) we continued to investigate the most hypoxia-dysregulated genes from previous study (CA9, CASP14, LOX, GLUT3, SERPINE1, AREG, EREG, CCNB1 and KIF14), and their impact on the survival of HNSCC patients treated with radiotherapy. Patients with high KIF14 mRNA expression showed significantly longer overall survival (OS) compared with patients with low KIF14 mRNA expression. Moreover, HNSCC patients with high mRNA expression of KIF14 and low mRNA expression of CA9 (hypoxia marker) showed better OS compared with those with the opposite mRNA expression.In paper IV, we investigated the influence of cancer-associated fibroblasts (CAFs) on tumor cell gene expression profile. Cells were cultured in 2D and 3D models where HNSCC cells and CAFs derived from the same tumor were co-cultured. The microarray analysis revealed a higher number of CAF-regulated genes in tumor cells grown in spheroids compared to tumor cells grown in 2D. Next, the expression pattern of most changed CAF-regulated genes (MMP1, MMP9, POSTN, GREM1, FMOD, COL1A2, GREM1, IVL) was analyzed in normal oral tissue and in pretreatment biopsies from HNSCC patients treated with radiotherapy showing differences in gene expression between HNSCC tumor tissue and normal oral tissue. High mRNA expression of MMP9 and FMOD were found to be significantly associated with better overall survival (OS) in patients treated with radiotherapy.Taken together, we developed a reliable in vitro method for the measurement of intracellular glucose uptake with gamma spectrometry and glucose uptake was associated with treatment response. Furthermore, we found that hypoxia has a negative impact on radiotherapy in HNSCC cells and we identified a panel of hypoxia-dysregulated genes involved in the multiple biological functions in cancer cells, however downregulation of single hypoxia-regulated genes did not affect response to radiotherapy. Further analysis indicated KIF14 mRNA as potential predictor of radiotherapy response but more studies with a larger patient cohort are required. Beside hypoxia, CAFs have an important role in cancer progression. The gene expression profile in HNSCC cell lines was found to be dysregulated by CAF-derived signals in vitro. Additionally, CAF-regulated genes, MMP9 and FMOD are potential candidates as biomarkers of OS in HNSCC patients treated with radiotherapy, however more studies must be undertaken to investigate our hypothesis.
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| 5. |
- Wennerberg, Johan, et al.
(författare)
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Results from a prospective, randomised study on (accelerated) preoperative versus (conventional) postoperative radiotherapy in treatment of patients with resectable squamous cell carcinoma of the oral cavity : The ARTSCAN 2 study
- 2022
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Ingår i: Radiotherapy and Oncology. - : Elsevier. - 0167-8140 .- 1879-0887. ; 166, s. 26-32
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Tidskriftsartikel (refereegranskat)abstract
- Background and purposeAn earlier prospective randomised multicentre study (ARTSCAN) in head and neck cancer patients that compared conventionally fractionated radiotherapy (CF) with accelerated radiotherapy (AF) was inconclusive. In the subgroup of oral cavity squamous cell cancer (OCSCC) a large absolute, but not statistically significant, difference in local control was seen in favour of AF. This difference was more pronounced in resectable tumours. The finding raised the hypothesis that AF could be beneficial for OCSCC patients. In addition, the longstanding controversy on pre- or postoperative radiotherapy was addressed.Materials and methodsPatients with OCSCC, judged to withstand and likely benefit from combined therapy, were recruited. Subjects were randomised to either preoperative AF with 43 fractions given as a concomitant boost with two fractions/day to the tumour bearing volume to a total dose of 68 Gy in 4.5 weeks followed by surgery, or primary surgery with postoperative CF, total dose 60 or 66 Gy in 6–7 weeks. For patients whose tumours had high-risk features, 66 Gy and concomitant cisplatin was prescribed.Results250 patients were randomised. Median follow-up was 5 years for locoregional control (LRC) and 9 years for overall survival (OS). There were no statistically significant differences between the two treatment arms regarding LRC and OS. LRC at five years was 73% (95% CI, 65–82) in preoperative AF and 78% (95% CI, 70–85) in postoperative CF.Toxicity was more pronounced in preoperative AF.ConclusionThis study does not support that AF prior to surgery improves outcome in oral cavity cancer compared with postoperative CF.
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