| 1. |
- Högmo, Anders, et al.
(författare)
-
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
-
Ingår i: Acta Oncologica. - : Taylor & Francis. - 0284-186X .- 1651-226X. ; 61:4, s. 433-440
-
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.
|
|
| 2. |
- Astradsson, Thorsteinn, et al.
(författare)
-
Serum Proteomics in Patients with Head and Neck Cancer : Peripheral Blood Immune Response to Treatment
- 2022
-
Ingår i: International Journal of Molecular Sciences. - : MDPI. - 1661-6596 .- 1422-0067. ; 23:11
-
Tidskriftsartikel (refereegranskat)abstract
- In this real-world study, the aims were to prospectively evaluate the expression of inflammatory proteins in serum collected from head and neck cancer patients before and after treatment, and to assess whether there were differences in expression associated with treatment modalities. The mixed study cohort consisted of 180 patients with head and neck cancer. The most common tumor sites were the oropharynx (n = 81), the oral cavity (n = 53), and the larynx (n = 22). Blood tests for proteomics analysis were carried out before treatment, 7 weeks after the start of treatment, and 3 and 12 months after the termination of treatment. Sera were analyzed for 83 proteins using an immuno-oncology biomarker panel (Olink, Uppsala, Sweden). Patients were divided into four treatment groups: surgery alone (Surg group, n = 24), radiotherapy with or without surgery (RT group, n = 94), radiotherapy with concomitant cisplatin (CRT group, n = 47), and radiotherapy with concomitant targeted therapy (RT Cetux group, n = 15). For the overall cohort, the expression levels of 15 of the 83 proteins changed significantly between the pretreatment sample and the sample taken 7 weeks after the start of treatment. At 7 weeks after the start of treatment, 13 proteins showed lower expression in the CRT group compared to the RT group. The majority of the inflammatory proteins had returned to their pretreatment levels after 12 months. It was clearly demonstrated that cisplatin-based chemoradiation has immunological effects in patients with head and neck cancer. This analysis draws attention to several inflammatory proteins that are of interest for further studies.
|
|
| 3. |
- Astradsson, Thorsteinn
(författare)
-
Systemic inflammation and prognostic markers in patients with head and neck cancer
- 2024
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Patients with head and neck cancer (HNC) often present with weight loss and malnutrition caused by systemic inflammation and dysphagia. This thesis explores the effects of systemic and local inflammation in the context of head and neck cancer treatment. The main aim of Paper I was to investigate whether trismus after radiotherapy affects the 5-year overall survival rate in a cohort of 244 patients with HNC. The maximum interincisal opening (MIO) of the patients was measured before treatment, 2, 6, and 12 months after the termination of radiotherapy, and trismus was defined as MIO ≤ 35 mm. All patients received instructions on jaw-opening exercises. The highest prevalence of trismus at 12 months was seen in patients with oral cancer (44%) and oropharyngeal cancer (37%) and it can be concluded that these patients should primarily be offered jaw-opening exercises. Patients with trismus at 12 months after termination of treatment had a tendency towards a worse overall 5-year survival rate than patients without trismus (p=0.64).Paper II explored the expression levels of cytokines and growth factors in serum before and up to one year after treatment. The cohort consisted of 30 patients with HNC and blood was drawn on four occasions and analyzed for 10 cytokines and 4 growth factors. Patients who received chemoradiotherapy had higher expression levels of IL-1β, IL-6, and IL-10 than other treatment groups at 7 weeks after the start of treatment. Patients with recurrence within 12 months after termination of treatment had higher expression levels of IL-1β, IL-6, IL-8, and IL-10 than the remaining patients at 7 weeks.In Paper III the expression levels of 83 immuno-oncologically significant proteins were determined at the same four time points as in Paper II in a cohort of 180 patients with HNC using a proteomics technique. Fifteen proteins had either decreased or increased expression levels at 7 weeks compared to pre-treatment expression levels. Treatment with radiotherapy with concomitant cisplatin was shown to be connected to significantly decreased expression of 13 proteins at 7 weeks after the start of treatment compared to radiotherapy which demonstrates an immunomodulatory effect of cisplatin also apparent in Paper II.The aim of Paper IV was to investigate how pre-treatment body mass index and fat free mass index correlate with early death in a cohort of 404 patients with head and neck squamous cell carcinoma (HNSCC). Body mass composition was measured at diagnosis using bioelectrical impedance analysis. Patients who died within 6 months of the start of treatment had significantly lower FFMI at diagnosis compared with patients who survived beyond 6 months (17.6 kg/m2 and 19.5 kg/m2, respectively, p=0.035). It can be recommended that assessment of fat free mass index should be included in the management of patients with HNSCC prior to treatment.
|
|
| 4. |
|
|
| 5. |
- Holm, Anna, et al.
(författare)
-
Mapping of Human Papilloma Virus, p16, and Epstein-Barr Virusin Non-Malignant Tonsillar Disease
- 2019
-
Ingår i: Laryngoscope Investigative Otolaryngology (LIO). - : Wiley-Blackwell. - 2378-8038. ; 4:3, s. 285-291
-
Tidskriftsartikel (refereegranskat)abstract
- Objectives: Due to their location in the entrance of the aero‐digestive tract, tonsils are steadily exposed to viruses. Human papilloma virus (HPV) and Epstein‐Barr virus (EBV) are two potentially oncogenic viruses that tonsils encounter. The incidence of HPV positive tonsillar cancer is on the rise and it is unknown when infection with HPV occurs.Aim: To investigate if tonsils are infected with HPV and EBV, to study the co‐expression of HPV and its surrogate marker p16, and to evaluate the number of EBV positive cells in benign tonsillar disease.Materials and Methods: Tonsils from 40 patients in a university hospital were removed due to hypertrophy, chronic or recurrent infection. These were analyzed for presence of HPV, its surrogate marker p16, and EBV. HPV was studied using PapilloCheck (a PCR method), while p16 was identified in epithelial and lymphoid tissue with immunohistochemistry and EBV using EBER‐ISH (Epstein‐Barr encoding region–in situ hybridization).Results: HPV was not detected, and p16 was present at low numbers in all epithelial samples as well as in 92.5% of the lymphoid tonsillar samples. At least one EBER‐positive cell was seen in 65% of cases. Larger numbers of EBER‐expressing cells were only seen in two cases.Conclusion: These findings demonstrate that EBV and HPV infect tonsils independently, but further studies are warranted to confirm their infectious relationship.Level of Evidence: Cross‐sectional study
|
|
| 6. |
- Jonasson, Kristina, et al.
(författare)
-
Squamous cell carcinoma of the mobile tongue in young adults: A Swedish head & neck cancer register (SweHNCR) population-based analysis of prognosis in relation to age and stage
- 2023
-
Ingår i: Oral Oncology. - : Elsevier BV. - 1368-8375 .- 1879-0593. ; 144
-
Tidskriftsartikel (refereegranskat)abstract
- Increased incidence of squamous cell carcinoma (SCC) of the tongue has been reported in young adults (YA) in several countries since the 1980s and confirmed in later studies. The etiology is unclear, the prognosis has been debated, and conflicting results have been published. Some studies show better survival in young adults than in older patients, some worse, and others no difference. Most studies are based on selected series or include other sites in the oral cavity. The definition of "YA" is arbitrary and varies between studies. It is thus difficult to use in general conclusions.This work uses data from the population-based Swedish Head and Neck Cancer register (SweHNCR), which has > 98% coverage. SweHNCR data includes age, gender, TNM, treatment intention, treatment given, lead times, performance status, and to a lesser degree, smoking habits. The current Swedish population is around 10 million.We analyzed outcomes for 1416 patients diagnosed with SCC of the oral tongue from 2008 to 2017 using 18-39 years to define YA age because it is the range most commonly used.We found no significant difference in relative survival (a proxy for diagnosis-specific survival) between age groups of patients treated with curative intent for SCC of the oral tongue. The stage at time of diagnosis was equally distributed among the age groups. Excess mortality rate correlated mainly with stage, subsite of the tongue, performance status, and lead time to treatment.
|
|
| 7. |
- Kareem, Heewa, et al.
(författare)
-
Blocking EGFR in the liver improves the tumor-to-liver uptake ratio of radiolabeled EGF
- 2010
-
Ingår i: Tumor Biology. - : Springer. - 1010-4283 .- 1423-0380. ; 31:2, s. 79-87
-
Tidskriftsartikel (refereegranskat)abstract
- Overexpression of epidermal growth factor receptor (EGFR) in several types of malignant tumors correlates with disease progression. EGFR could, therefore, be an excellent candidate for targeted radionuclide diagnostics. However, the high natural expression of EGFR in the liver may be problematic. The aim of this study was to improve the tumor-to-liver ratio of radiolabeled epidermal growth factor (EGF) by blocking its uptake by the liver with a nonradiolabeled EGFR-targeting molecule in tumorbearing mice. Intraperitoneally injected nonradiolabeled EGF was first evaluated as a blocking agent, preadministered at various time intervals before intravenous injection of 125I-labeled EGF. The anti-EGFR Affibody molecule (ZEGFR:955)2 was then assessed as a blocking agent of 111In-labeled EGF in a dual isotope study (50, 100, and 200μg, preadministered 30 or 60 min before 111In-EGF). The 30-min preadministration of nonradiolabeled EGF significantly decreased 125I-EGF uptake in the liver, whereas uptake in the tumor remained unchanged. Furthermore, preadministration of only 50μg (ZEGFR:955)2 as a blocking agent 30 min before the 111In-EGF decreased the uptake of 111In-EGF by the liver and increased its uptake by the tumor, thereby increasing the tumor-to-liver ratio sixfold. We conclude that the Affibody molecule (ZEGFR:955)2 shows promise as a blocking agent that could enhance the outcome of radionuclide-based EGFRexpressing tumor diagnostics and imaging.
|
|
| 8. |
- Mäkitie, Antti A., et al.
(författare)
-
Transoral Robotic Surgery in the Nordic Countries : Current Status and Perspectives
- 2018
-
Ingår i: Frontiers in Oncology. - : Frontiers Media S.A.. - 2234-943X. ; 8
-
Tidskriftsartikel (refereegranskat)abstract
- Background: The five Nordic countries with a population of 27 M people form a rather homogenous region in terms of health care. The management of head and neck cancer is centralized to the 21 university hospitals in these countries. Our aim was to gain an overview of the volume and role of transoral robotic surgery (TORS) and to evaluate the need to centralize it in this area as the field is rapidly developing.Materials and Methods: A structured questionnaire was sent to all 10 Departments of Otorhinolaryngology-Head and Neck Surgery in the Nordic countries having an active programme for TORS in December 2017.Results: The total cumulative number of performed robotic surgeries at these 10 Nordic centers was 528 and varied between 5 and 240 per center. The median annual number of robotic surgeries was 38 (range, 5-60). The observed number of annually operated cases remained fairly low (<25) at most of the centers.Conclusions: The present results showing a limited volume of performed surgeries call for considerations to further centralize TORS in the Nordic countries.
|
|
| 9. |
|
|
| 10. |
- Sandström, Karl, 1973-, et al.
(författare)
-
Improved Tumor-to-Organ Ratios of a Novel 67Ga-Human Epidermal Growth Factor Radionuclide Conjugate with Preadministered Antiepidermal Growth Factor Receptor Affibody Molecules
- 2011
-
Ingår i: Cancer Biotherapy and Radiopharmaceuticals. - : Mary Ann Liebert Inc. - 1084-9785 .- 1557-8852. ; 26:5, s. 593-601
-
Tidskriftsartikel (refereegranskat)abstract
- The over-expression of the epidermal growth factor receptor (EGFR) in head and neck squamous cell carcinoma (HNSCC) is associated with poor prognosis. Targeted nuclear imaging of the EGFR expression could improve the diagnostics in patients with HNSCC. However, the high expression of EGFR in normal organs may conceal the tumor uptake and therefore limit the use.In this study, we have assessed the biodistribution of a novel hEGF radionuclide conjugate after pre-injection with anti-EGFR Affibody molecules. hEGF was conjugated with p-SCN-Bn-NOTA and labeled with 67Ga. The biodistribution of [67Ga]Ga-NOTA-Bn-NCS-hEGF in nude mice with EGFR-expressing xenografts was evaluated either alone or 45 minutes after pre-injection with one of the anti-EGFR Affibody molecules ZEGFR:1907, (ZEGFR:1907)2 or (ZEGFR:955)2.The novel radioimmunoconjugate, [67Ga]Ga-NOTA-Bn-NCS-hEGF demonstrated high stability in vitro and specific binding to hEGF in vitro and in vivo. Pre-injection with anti-EGFR Affibody molecules improved the tumor-to-organ ratio in the liver, salivary glands and colon. Overall, the dimeric high affinity Affibody molecule (ZEGFR:1907)2 exhibited the best results.These findings show that pre-blocking with an anti-EGFR Affibody molecule is a promising tool that could improve the outcome of radionuclide-based imaging of EGFR-expressing tumors.
|
|
