Browsing by Subject "radiotherapy"

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  • Tuohinen, Suvi Sirkku; Skyttä, Tanja; Huhtala, Heini; Poutanen, Tuija; Virtanen, Vesa; Kellokumpu-Lehtinen, Pirkko-Liisa; Raatikainen, Pekka (2021)
    BACKGROUND Radiation therapy (RT) results in myocardial changes consisting of diffuse fibrosis, which may result in changes in diastolic function. OBJECTIVES The aim of this study was to explore RT-associated changes in left ventricular (LV) diastolic function. METHODS Sixty chemotherapy-naive patients with left-sided, early-stage breast cancer were studied with speckle tracking echocardiography at 3 time points: prior to, immediately after, and 3 years after RT. Global and regional early diastolic strain rate (SRe) were quantified, as were parameters of systolic function. RESULTS Regional changes in SRe, particularly the apical and anteroseptat segments, were observed over time and were more evident than global changes. The apical SRe declined from a median of 1.24 (interquartile range: 1.01 to 1.39) s(-1) at baseline to 1.02 (interquartile range: 0.79 to 1.15) s(-1) at 3 years of follow-up (p < 0.001). This decline was associated with the left ventricular maximal radiation dose (beta = 0.36, p = 0.007). The global SRe was CONCLUSIONS RT resulted in changes in the SRe in the apical and anteroseptat segments over 3 years of follow-up. Changes in SRe apical segments were present even in patients with preserved systolic function and were independently associated with RT dose and cardiovascular comorbidities. (C) 2021 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation.
  • Keskin, Mutlu; Lähteenmäki, Hanna; Rathnayake, Nilminie; Räisänen, Ismo T.; Tervahartiala, Taina; Pärnänen, Pirjo; Senisik, Ahmet Murat; Karacetin, Didem; Balkanay, Ayben Yentek; Heikkilä, Pia; Hagström, Jaana; Rautava, Jaana; Haglund, Caj; Gursoy, Ulvi Kahraman; Silbereisen, Angelika; Bostanci, Nagihan; Sorsa, Timo (2021)
    Background: This cohort study investigated the role of the active matrix metalloproteinase-8 (aMMP-8) and interleukin-6 (IL-6) as oral fluid biomarkers for monitoring the periodontal degeneration occurring in head and neck cancer (HNC) patients treated by radiotherapy. Research design and methods: Eleven patients, aged 28-74, diagnosed with HNC were included in the study. Complete periodontal and oral examinations were performed pre-radiotherapy and 1 month after radiotherapy. Mouthrinse samples (pre-radiotherapy, after 6 weeks of radiotherapy and 1 month after radiotherapy) were assayed by aMMP-8 point-of-care-kit (PerioSafe (R)/ORALyzer (R)) for aMMP-8 and ELISA for IL-6. Results: HNC radiotherapy had a deteriorating impact on the periodontium and a significant impact on periodontal biomarkers aMMP-8 and IL-6 and increased their levels in mouthrinse. Clinical-attachment-loss (CAL) (site of greatest loss: mean = 1.7 mm, range = 1-3 mm) corresponding to rapid progression of periodontitis. There was a positive repeated measures correlation (rmcorr = 0.667) between the aMMP-8 and IL-6 levels. Conclusions: Elevated aMMP-8 levels were observed 1 month after radiotherapy among some HNC patients suggesting a prolonged increased susceptibility to further periodontal tissue destruction. Currently available aMMP-8 point-of-care testing could be useful to monitor and assess quantitatively online and real-time the risk of deterioration of periodontal health during HNC radiotherapy.
  • Kallio, Pauliina; Jokinen, Elina; Das, Suvendu; Högström, Jenny; Heino, Sarika; Lähde, Marianne; Alitalo, Kari (Helsingin yliopisto, 2018)
    Radiation induced tumor cell death is strongly dependent on oxygen. As abnormal tumor vasculature promotes tumor hypoxia, drugs that induce vascular normalization, such as the anti-vascular endothelial growth factor (VEGF) antibody, have been tested as radiation sensitizers in preclinical and clinical settings. The insufficient benefit obtained with anti-VEGF therapy prompted us to test if antibodies blocking the endothelial growth factor angiopoietin-2 (Ang2) could improve the effect of radiation in mouse tumor allografts and human tumor xenografts. Mouse or human tumor cells were injected subcutaneously in isogenic immunocompetent or immunodeficient (NSG) mice, respectively, and tumors were allowed to form. The mice were injected with anti-Ang2 or control antibodies every three or four days starting three days before 3x2 Gy or 4x0.5 Gy whole-body radiation, followed by analysis of tumor growth, histology, vasculature, hypoxia and necrosis. Combination treatment with anti-Ang2 and radiation improved tumor growth inhibition and extended the survival of mice with melanoma or colorectal carcinoma allografts. A similar anti-Ang2 plus radiation response was also obtained in immunodeficient mice implanted with a human colorectal carcinoma xenograft, indicating that the adaptive immune response was not essential for the effect. Histological and immunohistochemical analysis of the tumors showed that the combination treatment decreased tumor vasculature, and increased tumor hypoxia and tumor necrosis in comparison with control tumors and tumors treated with the monotherapies. Our results suggest that a combination of Ang2 blocking antibodies and radiation increases tumor growth inhibition and extends the survival of tumor-bearing mice. Significance: These findings offer a preclinical rationale for further testing of the use of Ang2 blocking antibodies in combination with radiation to improve the overall outcome of cancer treatment.
  • Vento, Seija Inkeri; Vähämurto, Pauli; Silventoinen, Kaija; Karjalainen-Lindsberg, Marja-Liisa; Mannisto, Susanna; Leppa, Sirpa; Makitie, Antti Aarni (2017)
    Objectives: Extramedullary plasmacytoma in the sinonasal tract or nasopharynx is rare. The aim of the study was to review data on symptoms, clinical findings, treatment and follow-up of plasmacytomas in the sinonasal and nasopharyngeal regions in order to delineate the main clinical characteristics and the optimal management. Method: Twenty-five patients with sinonasal or nasopharyngeal plasmacytoma, diagnosed and treated at the Helsinki University Hospital during a 39-year period from 1975 to 2013 were retrospectively reviewed. Results: There were 18 males and 7 females with a median age of 66 years (range, 36-80). Sixty-eight percent received only radiotherapy or (chemo)radiotherapy. Forty-seven percent of them had a complete response to primary radiotherapy and one patient had a complete response after receiving additional brachytherapy. Four patients were treated primarily with surgery only. Two of them had a local recurrence, but were then successfully treated with radiotherapy. Altogether, four patients received a combination of surgery and (chemo)radiotherapy. Forty-four percent were alive with no evidence of disease after a median follow-up time of 78 months. Forty percent died of their disease and 16% died of other causes. Conclusions: Our study supports radiotherapy as a treatment of choice, but for small tumours surgery alone or in combination with radiotherapy may also be considered. Chinese abstract
  • Nicoli, Taija K.; Atula, Timo; Sinkkonen, Saku T.; Korpi, Jarkko; Vnencak, Matej; Tarkkanen, Jussi; Mäkitie, Antti A.; Jero, Jussi (2022)
    Background Ear canal and middle ear tumors are rare and exhibit variability in histology and clinical manifestation. Surgical resection remains the treatment of choice, but individualized approach is needed to preserve function when possible. Aims/objectives To review the management and outcome of ear canal and middle ear tumors at an academic referral center. Materials and methods Helsinki University Hospital (HUS) patient files were searched for clinically and histologically confirmed ear canal and middle ear tumors over a 14-year period. The minimum follow-up time was 2 years. Results Eighty-seven patients with 88 tumors were identified. There were 20 (23%) benign external auditory canal (EAC), 36 (41%) benign middle ear space (MES), 29 (33%) malignant EAC, and 3 (3%) malignant MES tumors. Most (92%) tumors were managed with primary resection. Thirty-five percent of the operatively managed patients had a residual or a recurrent tumor. Conclusions and significance EAC and MES tumors show great diagnostic and histologic heterogeneity with need for individualized investigative and treatment approaches. In benign tumors, we advocate aggressive local surgical control without sacrificing vital structures. In malignant tumors, we recommend local surgical control with or without adjunct RT.
  • Sundholm, Johnny K. M.; Suominen, Anu; Sarkola, Taisto; Jahnukainen, Kirsi (2020)
    The long-term vascular effects following childhood hematopoietic stem cell transplantation (HSCT) are not well characterized. We compared arterial wall morphology and function using very-high resolution ultrasound (25-55 MHz) in 62 patients following autologous (n= 19) or allogenic (n= 43) HSCT for childhood malignancies and hematological disease (median age 25.9 years, IQR 21.1-30.1; median follow-up time 17.5 years IQR 14.1-23.0) with an age matched healthy control group (n= 44). Intima-media thickness of carotid (CIMT 0.49 +/- 0.11 vs. 0.42 +/- 0.06 mm,p<0.001), brachial, femoral, radial arteries, and local carotid stiffness, but not adventitial thickness, were increased (p<0.001). Diffuse intimal thickening (>0.06 mm) of femoral or radial arteries (n= 17) and subclinical carotid or femoral plaques (n= 18) were more common (p<0.001). Radiation predicted plaques (p<0.001) and local carotid stiffness (p<0.001), but not intimal thickening. CIMT was predicted by age, BMI >30 kg/m(2), hsCRP >2.5 mg/L, hypertension, HbA1c > 42 mmol/L, and cumulative anthracycline >150 mg/m(2). Cumulative metabolic syndrome criteria and cardiovascular disease (CVD) risk factors were more common among HSCT and related with CIMT (p<0.001), but CIMT was similar among controls and HSCT without CVD risk factors. Long-term childhood HSCT survivors show early arterial aging related with radiation, metabolic, and CVD risk factors. Prevention of risk factors could potentially decelerate early arterial wall thickening.
  • Kiiski, Johanna; Fagerholm, Rainer; Tervasmaki, Anna; Pelttari, Liisa M.; Khan, Sofia; Jamshidi, Maral; Mantere, Tuomo; Pylkas, Katri; Bartek, Jiri; Bartkova, Jirina; Mannermaa, Arto; Tengstrom, Maria; Kosma, Veli-Matti; Winqvist, Robert; Kallioniemi, Anne; Aittomäki, Kristiina; Blomqvist, Carl; Nevanlinna, Heli (2016)
    Breast cancer (BC) is a heterogeneous disease, and different tumor characteristics and genetic variation may affect the clinical outcome. The FANCM c.5101C> T nonsense mutation in the Finnish population associates with increased risk of breast cancer, especially for triple-negative breast cancer patients. To investigate the association of the mutation with disease prognosis, we studied tumor phenotype, treatment outcome, and patient survival in 3,933 invasive breast cancer patients, including 101 FANCM c.5101C> T mutation carriers and 3,832 non-carriers. We also examined association of the mutation with nuclear immunohistochemical staining of DNA repair markers in 1,240 breast tumors. The FANCM c.5101C>T mutation associated with poor 10-year breast cancer-specific survival (hazard ratio (HR) 51.66, 95% confidence interval (CI) 1.09-2.52, p=0.018), with a more pronounced survival effect among familial cases (HR=2.93, 95% CI 1.5-5.76, p=1.80 x 10 23). Poor disease outcome of the carriers was also found among the estrogen receptor (ER) positive subgroup of patients (HR=1.8, 95% CI 1.09-2.98, p=0.021). Reduced survival was seen especially among patients who had not received radiotherapy (HR=3.43, 95% CI 1.6-7.34, p=1.50x10(-3)) but not among radiotherapy treated patients (HR=1.35, 95% CI 0.82-2.23, p=0.237). Significant interaction was found between the mutation and radiotherapy (p=0.040). Immunohistochemical analyses show that c.5101C> T carriers have reduced PAR-activity. Our results suggest that FANCM c.5101C>T nonsense mutation carriers have a reduced breast cancer survival but postoperative radiotherapy may diminish this survival disadvantage.
  • Salminen, Samuli H.; Sampo, Mika M.; Böhling, Tom O.; Tuomikoski, Laura; Tarkkanen, Maija; Blomqvist, Carl P. (2018)
    Radiation-associated sarcoma (RAS) is a rare complication of radiation therapy (RT) to breast cancer (BC). This study explored RAS after RT to BC in a nationwide population-based material. The Finnish Cancer Registry was queried for patients with BC treated during 1953-2014 who were later diagnosed with a secondary sarcoma in 1953-2014. Registry data, patient files, and sarcoma specimens were analyzed to confirm diagnosis and location of RAS at or close to the RT target volume. A total of 132 512 patients were diagnosed with invasive BC during the study period. A subsequent sarcoma was diagnosed in 355 patients. After exclusion, 96 RAS were identified. Angiosarcoma (AS) was the most prevalent histology in 50 (52%) of 96 patients. However, the first radiation-associated AS was diagnosed in a patient treated for BC with breast-conserving surgery in 1984, and thereafter, the proportion of AS continuously increased. The 5-year sarcoma-specific survival was 75.1% for RAS treated with a curative intent. The distribution of histologic subtypes of RAS has changed during the 60 years of this registry study. The first radiation-associated AS was diagnosed in 1989, and presently, AS is the most common histologic subtype of RAS. It is possible that changes in BC treatment strategies are influencing the characteristics of RAS.
  • Remes, Tiina Maria; Suo-Palosaari, Maria Helena; Koskenkorva, Päivi K. T.; Sutela, Anna K.; Toiviainen-Salo, Sanna-Maria; Arikoski, Pekka M.; Arola, Mikko O.; Heikkilä, Vesa-Pekka; Kapanen, Mika; Lähteenmäki, Päivi Maria; Lönnqvist, Tuula R. I.; Niiniviita, Hannele; Pokka, Tytti M-L; Porra, Liisa; Riikonen, V. Pekka; Seppälä, Jan; Sirkiä, Kirsti H.; Vanhanen, Antti; Rantala, Heikki M. J.; Harila-Saari, Arja H.; Ojaniemi, Marja K. (2020)
    Background. Cranial radiotherapy may damage the cerebral vasculature. The aim of this study was to understand the prevalence and risk factors of cerebrovascular disease (CVD) and white matter hyperintensities (WMHs) in childhood brain tumors (CBT) survivors treated with radiotherapy. Methods. Seventy CBT survivors who received radiotherapy were enrolled in a cross-sectional study at a median 20 years after radiotherapy cessation. The prevalence of and risk factors for CVD were investigated using MRI, MRA, and laboratory testing. Tumors, their treatment, and stroke-related data were retrieved from patients' files. Results. Forty-four individuals (63%) had CVD at a median age of 27 years (range, 16-43 years). The prevalence rates at 20 years for CVD, small-vessel disease, and large-vessel disease were 52%, 38%, and 16%, respectively. Ischemic infarcts were diagnosed in 6 survivors, and cerebral hemorrhage in 2. Lacunar infarcts were present in 7, periventricular or deep WMHs in 34 (49%), and mineralizing microangiopathy in 21 (30%) survivors. Multiple pathologies were detected in 44% of the participants, and most lesions were located in a high-dose radiation area. Higher blood pressure was associated with CVD and a presence of WMHs. Higher cholesterol levels increased the risk of ischemic infarcts and WMHs, and lower levels of high-density lipoprotein and higher waist circumference increased the risk of lacunar infarcts. Conclusions. Treating CBTs with radiotherapy increases the risk of early CVD and WMHs in young adult survivors. These results suggest an urgent need for investigating CVD prevention in CBT patients.
  • Kavaluus, Henna; Seppälä, Tiina; Koivula, Lauri; Salli, Eero; Collan, Juhani; Saarilahti, Kauko; Tenhunen, Mikko (2020)
    Purpose of our research was to develop a four-dimensional (4D) magnetic resonance imaging (MRI) method of liver. Requirements of the method were to create a clinical procedure with acceptable imaging time and sufficient temporal and spatial accuracy. The method should produce useful planning image sets for stereotactic body radiation therapy delivery both during breath-hold and in free breathing. The purpose of the method was to improve the localization of liver metastasis. The method was validated with phantom tests. Imaging parameters were optimized to create a 4D dataset compressed to one respiratory cycle of the whole liver with clinically reasonable level of image contrast and artifacts. Five healthy volunteers were imaged with T2-weighted SSFSE research sequence. The respiratory surrogate signal was observed by the linear navigator interleaved with the anatomical liver images. The navigator was set on head-feet - direction on the superior surface of the liver to detect the edge of diaphragm. The navigator signal and 2D liver image data were retrospectively processed with a self-developed MATLAB algorithm. A deformable phantom for 4D imaging tests was constructed by combining deformable tissue-equivalent material and a commercial programmable motor unit of the 4D phantom with a clinically relevant range of deformation patterns. 4D Computed Tomography images were used as reference to validate the MRI protocol. The best compromise of reasonable accuracy and imaging time was found with 2D T2-weighted SSFSE imaging sequence using parameters: TR = 500-550 ms, images/slices = 20, slice thickness = 3 mm. Then, image processing with number of respiratory phases = 8 constructed accurate 4D images of liver. We have developed the 4D-MRI method visualizing liver motions three-dimensionally in one representative respiratory cycle. From phantom tests it was found that the spatial agreement to 4D-CT is within 2 mm that is considered sufficient for clinical applications.
  • Aro, Katri; Ho, Allen S.; Luu, Michael; Kim, Sungjin; Tighiouart, Mourad; Yoshida, Emi J.; Mallen-St Clair, Jon; Shiao, Stephen L.; Leivo, Ilmo; Zumsteg, Zachary S. (2019)
    Objective To evaluate the impact of postoperative radiotherapy (PORT) and chemotherapy on survival in salivary gland cancer (SGC) treated with curative-intent local resection and neck dissection. Study Design Retrospective population-based cohort study. Setting National Cancer Database. Subjects and Methods Patients with SGC who were undergoing surgery were identified from the National Cancer Database between 2004 and 2013. Neck dissection removing a minimum of 10 lymph nodes was required. Because PORT violated the proportional hazards assumption, this variable was treated as a time-dependent covariate. Results Overall, 4145 cases met inclusion criteria (median follow-up, 54 months). PORT was associated with improved overall survival in multivariable analysis, both 9 months (HR, 0.75; 95% CI, 0.66-0.86; P <.001). In propensity score-matched cohorts, 5-year overall survival was 67.1% and 60.6% with PORT and observation, respectively (P <.001). Similar results were observed in landmark analysis of patients surviving at least 6 months following diagnosis. Adjuvant chemotherapy was not associated with improved survival (HR, 1.15; 95% CI, 0.99-1.34; P = .06). Conclusion PORT, but not chemotherapy, is associated with improved survival among patients with SGC for whom neck dissection was deemed necessary. These results are not applicable to low-risk SGCs not requiring neck dissection.