Browsing by Subject "RADIATION-THERAPY"

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  • Sundquist, Fredrik; Georgantzi, Kleopatra; Jarvis, Kirsten Brunsvig; Brok, Jesper; Koskenvuo, Minna; Rascon, Jelena; van Noesel, Max; Grybaeck, Per; Nilsson, Joachim; Braat, Arthur; Sundin, Mikael; Wessman, Sandra; Herold, Nikolas; Hjorth, Lars; Kogner, Per; Granberg, Dan; Gaze, Mark; Stenman, Jakob (2022)
    Background:& nbsp;Half the children with high-risk neuroblastoma die with widespread metastases. Molecular radiotherapy is an attractive systemic treatment for this relatively radiosensitive tumor. I-131-mIBG is the most widely used form in current use, but is not universally effective. Clinical trials of (177)Lutetium DOTATATE have so far had disappointing results, possibly because the administered activity was too low, and the courses were spread over too long a period of time, for a rapidly proliferating tumor. We have devised an alternative administration schedule to overcome these limitations. This involves two high-activity administrations of single agent Lu-177-DOTATATE given 2 weeks apart, prescribed as a personalized whole body radiation absorbed dose, rather than a fixed administered activity. "A phase II trial of (177)Lutetium-DOTATATE in children with primary refractory or relapsed high-risk neuroblastoma - LuDO-N " (EudraCT No: 2020-004445-36, Identifier: NCT04903899) evaluates this new dosing schedule.& nbsp;Methods:& nbsp;The LuDO-N trial is a phase II, open label, multi-center, single arm, two stage design clinical trial. Children aged 18 months to 18 years are eligible. The trial is conducted by the Nordic Society for Pediatric Hematology and Oncology (NOPHO) and it has been endorsed by SIOPEN (). The Karolinska University Hospital, is the sponsor of the LuDO-N trial, which is conducted in collaboration with Advanced Accelerator Applications, a Novartis company. All Scandinavian countries, Lithuania and the Netherlands participate in the trial and the UK has voiced an interest in joining in 2022.& nbsp;Results:& nbsp;The pediatric use of the Investigational Medicinal Product (IMP) Lu-177-DOTATATE, as well as non-IMPs SomaKit TOC (R) (Ga-68-DOTATOC) and LysaKare (R) amino acid solution for renal protection, have been approved for pediatric use, within the LuDO-N Trial by the European Medicines Agency (EMA). The trial is currently recruiting. Recruitment is estimated to be finalized within 3-5 years.& nbsp;Discussion:& nbsp;In this paper we present the protocol of the LuDO-N Trial. The rationale and design of the trial are discussed in relation to other ongoing, or planned trials with similar objectives. Further, we discuss the rapid development of targeted radiopharmaceutical therapy and the future perspectives for developing novel therapies for high-risk neuroblastoma and other pediatric solid tumors.
  • Hyytiäinen, Aini; Wahbi, Wafa; Väyrynen, Otto; Saarilahti, Kauko; Karihtala, Peeter; Salo, Tuula; Al-Samadi, Ahmed (2021)
    Background Head and neck squamous cell carcinoma (HNSCC) carries poor survival outcomes despite recent progress in cancer treatment in general. Angiogenesis is crucial for tumour survival and progression. Therefore, several agents targeting the pathways that mediate angiogenesis have been developed. We conducted a systematic review to summarise the current clinical trial data examining angiogenesis inhibitors in HNSCC. Methods We carried out a literature search on three angiogenesis inhibitor categories-bevacizumab, tyrosine kinase inhibitors and endostatin-from Ovid MEDLINE, Cochrane Library, Scopus and database. Results Here, we analysed 38 clinical trials, total of 1670 patients, investigating 12 angiogenesis inhibitors. All trials were in phase I or II, except one study in phase III on bevacizumab. Angiogenesis inhibitors were used as mono- and combination therapies together with radio-, chemo-, targeted- or immunotherapy. Among 12 angiogenesis inhibitors, bevacizumab was the most studied drug, included in 13 trials. Although bevacizumab appeared effective in various combinations, it associated with high toxicity levels. Endostatin and lenvatinib were well-tolerated and their anticancer effects appeared promising. Conclusions Most studies did not show benefit of angiogenesis inhibitors in HNSCC treatment. Additionally, angiogenesis inhibitors were associated with considerable toxicity. However, some results appear encouraging, suggesting that further investigations of angiogenesis inhibitors, particularly in combination therapies, for HNSCC patients are warranted. Systematic Review Registration PROSPERO (, identifier CRD42020157144.
  • Atallah, Sarah; Marc, Morgane; Schernberg, Antoine; Huguet, Florence; Wagner, Isabelle; Mäkitie, Antti; Baujat, Bertrand (2022)
    Introduction: Adenoid cystic carcinoma (AdCC) is a rare tumour as it accounts for about 10% of all salivary gland neoplasms. It occurs in all age groups with a predominance of women, but no risk factors have been identified to date. Although AdCC behaves as a slow-growing tumour, it is characterized by multiple and late recurrences. Therefore, we aim to update the knowledge of the treatment options in advanced and recurrent cases. Materials and Methods: We performed a systematic literature review to provide a synthesis of the practical knowledge required for AdCC non-surgical management. Altogether, 99 out of the 1208 available publications were selected for analysis. Results: AdCC is described as a basaloid tumour consisting of epithelial and myoepithelial cells. Immunohistochemistry is useful for diagnosis (PS100, Vimentin, CD117, CKit, muscle actin, p63) and for prognosis (Ki67). Identified mutations could lead to therapeutic opportunities (MYB-NFIB, Notch 1). The work-up is mainly based on neck and chest CT scan and MRI, and PET-CT with 18-FDG or PSMA can be considered. Surgical treatment remains the gold standard in resectable cases. Post-operative intensity modulated radiotherapy is the standard of care, but hadron therapy may be used in specific situations. Based on the available literature, no standard chemotherapy regimen can be recommended. Conclusion: There is currently no consensus on the use of chemotherapy in AdCC, either concomitantly to RT in a postoperative setting or at a metastatic stage. Further, the available targeted therapies do not yet provide significant tumour response.
  • Mäkinen, Anna; Mäkitie, Antti; Meurman, Jukka H. (2021)
    Background: Previous studies have shown an increased prevalence of candidiasis in patients receiving radiotherapy for head and neck cancer. However, little is known of the effect the different cancer treatment modalities have on the oral Candida status. Objective and hypothesis: The objective of this study was to investigate the change in salivary Candida status of oral squamous cell carcinoma (OSCC) patients undergoing cancer treatment. The hypothesis was that cancer treatments change the oral microbial environment favouring an increase in the prevalence of more pathogenic non-albicans Candida (NAC). Methods: We collected paraffin-stimulated saliva from 44 OSCC patients before surgery and after a minimum of 19 months of follow-up. Chromagar, Bichro-Dupli-test and API ID 32 C were used for identification of different Candida species and results were analysed statistically. Results: At both timepoints, 75% of samples were Candida positive with C. albicans being the most common yeast. NAC strains were present in 16% of the pre-operative samples and 14% of the follow-up samples. The NAC species found were C. dubliniensis, C. krusei, C. guilliermondii (preoperatively only) and C. glabrata (at follow-up only). In 73% of the cases, the salivary Candida status remained unchanged. There was an 18% increase in the prevalence of candidiasis. However, the different treatment modalities did not statistically significantly affect the Candida status of the patients. Conclusion: The intraindividual prevalence of salivary Candida among OSCC patients seems to be stable and different treatment modalities have little to no effect on the salivary Candida status. (c) 2021 The Authors. Published by Elsevier Ltd on behalf of Royal College of Surgeons of Edinburgh (Scottish charity number SC005317) and Royal College of Surgeons in Ireland. This is an open access article under the CC BY-NC-ND license (http://creativecommons. org/licenses/by-nc-nd/4.0/).
  • Lopez, Fernando; Suarez, Carlos; Poorten, Vincent Vander; Makitie, Antti; Nixon, Iain J.; Strojan, Primoz; Hanna, Ehab Y.; Pablo Rodrigo, Juan; de Bree, Remco; Quer, Miquel; Takes, Robert P.; Bradford, Carol R.; Shaha, Ashok R.; Sanabria, Alvaro; Rinaldo, Alessandra; Ferlito, Alfio (2019)
    The parapharyngeal space is a complex anatomical area. Primary parapharyngeal tumors are rare tumors and 80% of them are benign. A variety of tumor types can develop in this location; most common are salivary gland neoplasm and neurogenic tumors. The management of these tumors has improved greatly owing to the developments in imaging techniques, surgery, and radiotherapy. Most tumors can be removed with a low rate of complications and recurrence. The transcervical approach is the most frequently used. In some cases, minimally invasive approaches may be used alone or in combination with a limited transcervical route, allowing large tumors to be removed by reducing morbidity of expanded approaches. An adequate knowledge of the anatomy and a careful surgical plan is essential to tailor management according to the patient and the tumor. The purpose of the present review was to update current aspects of knowledge related to this more challenging area of tumor occurrence.
  • Golusinski, Pawel; Corry, June; Vander Poorten, Vincent; Simo, Ricard; Sjogren, Elisabeth; Mäkitie, Antti; Kowalski, Luis Paulo; Langendijk, Johannes; Braakhuis, Boudewijn J. M.; Takes, Robert P.; Coca-Pelaz, Andres; Rodrigo, Juan P.; Willems, Stefan M.; Forastiere, Arlene A.; De Bree, Remco; Saba, Nabil F.; Teng, Yong; Sanabria, Alvaro; Di Maio, Pasquale; Szewczyk, Mateusz; Ferlito, Alfio (2021)
    Human papilloma virus (HPV) is a well-established causative factor in a subset of squamous cell carcinomas of the head and neck (HNSCC). Although HPV can be detected in various anatomical subsites, HPV-positive oropharyngeal squamous cell carcinoma (OPSCC) is the most common HPV-related malignancy of the head and neck, and its worldwide incidence is constantly rising. Patients with OPSCC are generally younger, have less co-morbidities and generally have better prognosis due to different biological mechanisms of carcinogenesis. These facts have generated hypotheses on potential treatment modifications, aiming to minimize treatmentrelated toxicities without compromising therapy efficacy. Numerous randomized clinical trials have been designed to verify this strategy and increasingly realworld evidence data from retrospective, observational studies is becoming available. Until now, the data do not support any modification in contemporary treatment protocols. In this narrative review, we outline recent data provided by both randomized controlled trials and real-world evidence of HPV-positive OPSCC in terms of clinical value. We critically analyze the potential value and drawbacks of the available data and highlight future research directions. This article was written by members and invitees of the International Head and Neck Scientific Group. (
  • Gregoire, Vincent; Evans, Mererid; Quynh-Thu Le; Bourhis, Jean; Budach, Volker; Chen, Amy; Eisbruch, Abraham; Feng, Mei; Giralt, Jordi; Gupta, Tejpal; Hamoir, Marc; Helito, Juliana K.; Hu, Chaosu; Hunter, Keith; Johansen, Jorgen; Kaanders, Johannes; Laskar, Sarbani Ghosh; Lee, Anne; Maingon, Philippe; Mäkitie, Antti; Micciche, Francesco; Nicolai, Piero; O'Sullivan, Brian; Poitevin, Adela; Porceddu, Sandro; Skiadowski, Krzysztof; Tribius, Silke; Waldron, John; Wee, Joseph; Yao, Min; Yom, Sue S.; Zimmermann, Frank; Grau, Cai (2018)
    Purpose: Few studies have reported large inter-observer variations in target volume selection and delineation in patients treated with radiotherapy for head and neck squamous cell carcinoma. Consensus guidelines have been published for the neck nodes (see Gregoire et al., 2003, 2014), but such recommendations are lacking for primary tumour delineation. For the latter, two main schools of thoughts are prevailing, one based on geometric expansion of the Gross Tumour Volume (GTV) as promoted by DAHANCA, and the other one based on anatomical expansion of the GTV using compartmentalization of head and neck anatomy. Method: For each anatomic location within the larynx, hypopharynx, oropharynx and oral cavity, and for each T-stage, the DAHANCA proposal has been comprehensively reviewed and edited to include anatomic knowledge into the geometric Clinical Target Volume (CTV) delineation concept. A first proposal was put forward by the leading authors of this publication (VG and CG) and discussed with opinion leaders in head and neck radiation oncology from Europe, Asia, Australia/New Zealand, North America and South America to reach a worldwide consensus. Results: This consensus proposes two CTVs for the primary tumour, the so called CTV-P1 and CVT-P2, corresponding to a high and lower tumour burden, and which should be associated with a high and a lower dose prescription, respectively. Conclusion: Implementation of these guidelines in the daily practice of radiation oncology should contribute to reduce treatment variations from clinicians to clinicians, facilitate the conduct of multi institutional clinical trials, and contribute to improved care of patients with head and neck carcinoma. (C) 2017 Elsevier B.V. All rights reserved.
  • Cooperative Weichteilsarkom; Scheer, Monika; Vokuhl, Christian; Blank, Bernd; Jahnukainen, Kirsi; Koscielniak, Ewa (2019)
    Background To evaluate optimal therapy and potential risk factors. Methods Data of DSRCT patients Results Median age of 60 patients was 14.5 years. Male:female ratio was 4:1. Tumors were abdominal/retroperitoneal in 56/60 (93%). 6/60 (10%) presented with a localized mass, 16/60 (27%) regionally disseminated nodes, and 38/60 (63%) with extraperitoneal metastases. At diagnosis, 23/60 (38%) patients had effusions, 4/60 (7%) a thrombosis, and 37/54 (69%) elevated CRP. 40/60 (67%) patients underwent tumor resection, 21/60 (35%) macroscopically complete. 37/60 (62%) received chemotherapy according to CEVAIE (ifosfamide, vincristine, actinomycin D, carboplatin, epirubicin, etoposide), 15/60 (25%) VAIA (ifosfamide, vincristine, adriamycin, actinomycin D) and, 5/60 (8%) P6 (cyclophosphamide, doxorubicin, vincristine, ifosfamide, etoposide). Nine received high-dose chemotherapy, 6 received regional hyperthermia, and 20 received radiotherapy. Among 25 patients achieving complete remission, 18 (72%) received metronomic therapies. Three-year event-free (EFS) and overall survival (OS) were 11% (+/- 8 confidence interval [CI] 95%) and 30% (+/- 12 CI 95%), respectively, for all patients and 26.7% (+/- 18.0 CI 95%) and 56.9% (+/- 20.4 CI 95%) for 25 patients achieving remission. Extra-abdominal site, localized disease, no effusion or ascites only, absence of thrombosis, normal CRP, complete tumor resection, and chemotherapy with VAIA correlated with EFS in univariate analysis. In multivariate analysis, significant factors were no thrombosis and chemotherapy with VAIA. In patients achieving complete remission, metronomic therapy with cyclophosphamide/vinblastine correlated with prolonged time to relapse. Conclusion Pleural effusions, venous thrombosis, and CRP elevation were identified as potential risk factors. The VAIA scheme showed best outcome. Maintenance therapy should be investigated further.
  • Kavaluus, Henna; Nousiainen, Katri; Kaijaluoto, Sampsa; Seppälä, Tiina; Saarilahti, Kauko; Tenhunen, Mikko (2021)
    Background and Purpose: Magnetic resonance imaging is increasingly used in radiotherapy planning; yet, the performance of the utilized scanners is rarely regulated by any authority. The aim of this study was to determine the geometric accuracy of several magnetic resonance imaging scanners used for radiotherapy planning, and to establish acceptance criteria for such scanners. Materials and Methods: The geometric accuracy of five different scanners was measured with three sequences using a commercial large-field-of-view phantom. The distortion magnitudes were determined in spherical volumes around the scanner isocenter and in cylindrical volumes along scanner z-axis. The repeatability of the measurements was determined on a single scanner with two quality assurance sequences with three single-setup and seven repeated-setup measurements. Results: For all scanners and sequences except one, the mean and median distortion magnitude was Conclusions: All tested scanners were geometrically accurate for their current use in radiotherapy planning. The acceptance criteria of geometric accuracy for regulatory inspections of a supervising authority could be set according to these results.
  • Tuohinen, Suvi Sirkku; Skytta, Tanja; Huhtala, Heini; Virtanen, Vesa; Kellokumpu-Lehtinen, Pirkko-Liisa; Raatikainen, Pekka (2022)
    Background/Aim: Radiotherapy (RT) related myocardial changes were analyzed by deformation imaging echocardiography in this study. Patients and Methods: Ninety-nine breast cancer patients were studied at baseline, after chemotherapy, after RT, and three years after RT (3Y). Eighty patients received RT only, and twenty patients had right-sided breast cancer. Echocardiography included cyclic variation of the integrated backscatter in the septum (sCV) and posterior wall (pCV), global longitudinal strain (GLS), and left ventricular ejection fraction (LVEF). Results: In patients with left-sided breast cancer, sCV declined from 11.3??3.3 dB at baseline to 10.3??2.9 dB after RT (p=0.001). No changes were observed after chemotherapy (p=0.211) or in patients with right-sided breast cancer after RT (p=0.977). No other parameters declined after RT. The decline in sCV was independently associated with the left anterior descending coronary artery radiation dose (??=???0.290, p=0.020). Conclusion: In contrast to other parameters, sCV correlated with heart radiation dose.
  • Pietila, Sari; Lenko, Hanna L.; Oja, Sakari; Koivisto, Anna-Maija; Pietila, Timo; Mäkipernaa, Anne Marja-Terttu (2016)
    This population-based cross-sectional study evaluates the clinical value of electroretinography and visual evoked potentials in childhood brain tumor survivors. A flash electroretinography and a checkerboard reversal pattern visual evoked potential (or alternatively a flash visual evoked potential) were done for 51 survivors (age 3.8-28.7 years) after a mean follow-up time of 7.6 (1.5-15.1) years. Abnormal electroretinography was obtained in 1 case, bilaterally delayed abnormal visual evoked potentials in 22/51 (43%) cases. Nine of 25 patients with infratentorial tumor location, and altogether 12 out of 31 (39%) patients who did not have tumors involving the visual pathways, had abnormal visual evoked potentials. Abnormal electroretinographies are rarely observed, but abnormal visual evoked potentials are common even without evident anatomic lesions in the visual pathway. Bilateral changes suggest a general and possibly multifactorial toxic/adverse effect on the visual pathway. Electroretinography and visual evoked potential may have clinical and scientific value while evaluating long-term effects of childhood brain tumors and tumor treatment.
  • Jouhi, Lauri; Halme, Elina; Irjala, Heikki; Saarilahti, Kauko; Koivunen, Petri; Pukkila, Matti; Hagström, Jaana; Haglund, Caj; Lindholm, Paula; Hirvikoski, Pasi; Vaittinen, Samuli; Ellonen, Anna; Tikanto, Jukka; Blomster, Henry; Laranne, Jussi; Grenman, Reidar; Mäkitie, Antti; Atula, Timo (2018)
    Background: Treatment for oropharyngeal squamous cell carcinoma (OPSCC) has changed, as the proportion of human papilloma virus (HPV)-related disease has increased. We evaluated nationwide information on its management and outcome during the treatment paradigm change period.Methods: We included all patients diagnosed and treated for OPSCC at the five Finnish university hospitals from 2000 to 2009. Patient records and pathology registries provided the clinicopathological data. p16 staining was performed on primary tumor samples of patients who had received treatment with curative intent.Results: A total of 674 patients were diagnosed and treated for OPSCC and the incidence increased along the study period. Of the evaluable tumors 58.5% were p16-positive and the number of p16-positive tumors increased along the years. The treatment was given with curative intent for 600 patients and it was completed in 564. Of them, 47.9% underwent primary surgery and 52.1% received definitive oncological treatment. Also, the treatment protocol changed towards a more oncological approach. Among patients treated with curative intent the five-year overall, disease-specific and disease-free survival rates were 60.1, 71.5 and 57.0%. In multivariate analysis, p16-positivity seemed to relate to reduced disease mortality in lateral and anterior-wall disease. Depending on primary tumor localization, also sex, classes T3-4, presence of regional metastasis and radiotherapy modality had an association with disease mortality.Conclusion: The incidence of p16-positive OPSCC and delivery of definitive oncological treatment increased in Finland during the study period. An improved survival outcome compared with the previous nationwide investigation was observed in this subset of patients.
  • Jussila, Miro-Pekka; Remes, Tiina; Anttonen, Julia; Harila-Saari, Arja; Niinimäki, Jaakko; Pokka, Tytti; Koskenkorva, Päivi; Sutela, Anna; Toiviainen-Salo, Sanna; Arikoski, Pekka; Riikonen, Pekka; Arola, Mikko; Lähteenmäki, Päivi; Sirkiä, Kirsti; Rantala, Heikki; Suo-Palosaari, Maria; Ojaniemi, Marja (2018)
    Purpose Long-term side effects of the treatments are common in survivors of irradiated pediatric brain tumors. Ionizing radiation in combination with surgery and chemotherapy during childhood may reduce vertebral height and bone mineral density (BMD), and cause growth failure. The aim of this study was to evaluate the late consequences of tumor treatments on vertebrae in survivors of childhood brain tumors. Methods 72 adult survivors (mean age 27.8 years, standard deviation 6.7) of irradiated childhood brain tumor were studied by spinal magnetic resonance imaging (MRI) for vertebral abnormalities from the national cohort of Finland. Patients were treated in five university hospitals in Finland between the years 1970 and 2008. Subject height and weight were measured and body mass index (BMI) was calculated. The morphology and height/ depth ratio of the vertebrae in the middle of the kyphotic thoracic curvature (Th8) and lumbar lordosis (L3) were examined. Vertebrae were analyzed by Genant's semiquantative (SQ) method and spinal deformity index (SDI) was calculated. BMD was measured by using dual X-ray absorptiometry. Results 4.2% (3/72) of the patients had undiagnosed asymptomatic vertebral fracture and 5.6% (4/72) of patients had radiation- induced decreased vertebral body height. Male patients had flatter vertebrae compared with females. Patient age at the time of irradiation, BMI and irradiation area correlated to vertebral morphology differentially in males and females. BMD had no association with the vertebral shape. Patients who had received craniospinal irradiation were shorter than the general population. Conclusion Childhood brain tumor survivors had a high number of vertebral abnormalities in young adulthood. Irradiation was associated with abnormal vertebral morphology and compromised final height. Male gender may predispose vertebrae to the side effects of irradiation.
  • Leea, Anne W. M.; Ng, Wai Tong; Chan, Jimmy Y. W.; Corry, June; Mäkitie, Antti; Mendenhall, William M.; Rinaldo, Alessandra; Rodrigo, Juan P.; Saba, Nabil F.; Strojan, Primoz; Suarez, Carlos; Vermorken, Jan B.; Yom, Sue S.; Ferlito, Alfio (2019)
    As a consequence of the current excellent loco-regional control rates attained using the generally accepted treatment paradigms involving intensity-modulated radiotherapy for nasopharyngeal carcinoma (NPC), only 10-20% of patients will suffer from local and/or nodal recurrence after primary treatment. Early detection of recurrence is important as localized recurrent disease is still potentially salvageable, but this treatment often incurs a high risk of major toxicities. Due to the possibility of radio-resistance of tumors which persist or recur despite adequate prior irradiation and the limited tolerance of adjacent normal tissues to sustain further additional treatment, the management of local failures remains one of the greatest challenges in this disease. Both surgical approaches for radical resection and specialized re-irradiation modalities have been explored. Unfortunately, available data are based on retrospective studies, and the majority of them are based on a small number of patients or relatively short follow-up. In this article, we will review the different salvage treatment options and associated prognostic factors for each of them. We will also propose a treatment algorithm based on the latest available evidence and discuss the future directions of treatment for locally recurrent NPC.
  • Sahi, Helka; Their, Jenny; Gissler, Mika; Koljonen, Virve (2020)
    Merkel cell carcinoma (MCC) is a rare cutaneous carcinoma that has gained enormous interest since the discovery of Merkel cell polyoma virus, which is a causative oncogenic agent in the majority of MCC tumours. Increased research has focused on effective treatment options with immuno-oncology. In this study, we reviewed the real-world data on different treatments given to MCC patients in Finland in 1986-2016. We used the Finnish Cancer Registry database to find MCC patients and the Hospital Discharge Register and the Cause-of-Death Register to obtain treatment data. We identified 376 MCC patients and 33 different treatment entities and/or combinations of treatment. An increase was noted in the incidence of MCC since 2005. Therefore, the cohort was divided into two groups: the "early" group with time of diagnosis between years 1986 and 2004 and the "late" group with time of diagnosis between 2005 and 2016. The multitude of different treatment combinations is a relatively new phenomenon; before the year 2005, only 11 treatments or treatment combinations were used for MCC patients. Our data show that combining radiation therapy with simple excision provided a survival advantage, which was, however, lost after adjustment for stage or age. Our registry study serves as a baseline treatment efficacy comparison as we move into the age of immunotherapy in MCC. Standardizing the treatment of MCC patients in Finland requires more work on awareness and multidisciplinary co-operation.
  • Kavaluus, Henna; Koivula, Lauri; Salli, Eero; Seppälä, Tiina; Saarilahti, Kauko; Tenhunen, Mikko (2022)
    Background and purpose A novel method of retrospective liver modeling was developed based on four-dimensional magnetic resonance (4D-MR) images. The 4D-MR images will be utilized in generation of the subject-specific deformable liver model to be used in radiotherapy planning (RTP). The purpose of this study was to test and validate the developed 4D-magnetic resonance imaging (MRI) method with extensive phantom tests. We also aimed to build a motion model with image registration methods from liver simulating phantom images. Materials and methods A deformable phantom was constructed by combining deformable tissue-equivalent material and a programmable 4D CIRS-platform. The phantom was imaged in 1.5 T MRI scanner with T2-weighted 4D SSFSE and T1-weighted Ax dual-echo Dixon SPGR sequences, and in computed tomography (CT). In addition, geometric distortion of the 4D sequence was measured with a GRADE phantom. The motion model was developed; the phases of the 4D-MRI were used as surrogate data, and displacement vector fields (DVF's) were used as a motion measurement. The motion model and the developed 4D-MRI method were evaluated and validated with extensive tests. Result The 4D-MRI method enabled an accuracy of 2 mm using our deformable phantom compared to the 4D-CT. Results showed a mean accuracy of
  • Remes, Tiina M.; Hoven, Emma; Ritari, Niina; Pohjasniemi, Heli; Puosi, Riina; Arikoski, Pekka M.; Arola, Mikko O.; Lähteenmäki, Päivi M.; Lönnqvist, Tuula R. I.; Ojaniemi, Marja K.; Riikonen, V. Pekka; Sirkiä, Kirsti H.; Winqvist, Satu; Rantala, Heikki M. J.; Harila, Marika; Harila-Saari, Arja H. (2021)
    Background. Little is known of the cognitive functions, employment, and social status in adult survivors of childhood brain tumor (BT). We aimed to determine the long-term neurocognitive profile of radiotherapy-treated adult survivors of childhood BT and the relationship between cognitive functions and employment and social status. Methods. Neurocognitive profiles of survivors were assessed in a Finnish national cohort of 71 radiotherapy-treated survivors of childhood BT (median follow-up time: 21 years [range: 5-33 years]) using a cross-sectional design. Neurocognitive outcomes were compared to control (n = 45) and normative values. Tumor- and treatment-related data were collected from the patient files. Information on employment and social status was gathered. Results. Survivors' (median age: 27 years [range: 16-43 years]) median verbal and performance intelligence quotient (IQ) was 90 (range: 49-121) and 87 (range: 43-119), respectively. The cognitive domains with the greatest impairment were executive functions (median z score, 3.5 SD [range: -25.0 to 1.3 SD]), and processing speed and attention (median z score, -2.5 SD [range: -24.9 to 0.5 SD]). Executive functions were associated with employment, educational level, living independently, having an intimate relationship, and having a driving license. Processing speed and attention were related to educational level, living independently, having an intimate relationship, and having a driving license. Performance IQ was associated with educational level and employment status. Working memory was associated with educational level and living independently. Conclusions. Radiotherapy-treated adult survivors of childhood BT experience significant neurocognitive impairment, which is associated with difficulties related to employment and social status.
  • Bossi, Paolo; Alfieri, Salvatore; Strojan, Primoz; Takes, Robert P.; Lopez, Fernando; Mäkitie, Antti; Saba, Nabil F.; Pablo Rodrigo, Juan; Bradford, Carol; Suarez, Carlos; Zafereo, Mark; Forastiere, Arlene A.; Vermorken, Jan B.; Quer, Miquel; Sanabria, Alvaro; Simo, Ricard; de Bree, Remco; Rinaldo, Alessandra; Ferlito, Alfio (2019)
    The pattern of clinical behaviour and response to treatment of recurrent and/or metastatic head and neck squamous cell carcinoma is heterogeneous. Treatment strategies that can be employed vary from potentially curative salvage surgery and re-irradiation to palliative systemic therapies and best supportive care. The advent of new therapeutic options, in terms of more sophisticated surgical approaches and techniques, highly conformal and precise radiation techniques and immunotherapy may offer improved control of disease and longer survival. Moreover, the epidemiological changes during the last decades, including the increase of human papilloma virus-related oropharyngeal primary tumors, are also reflected in the recurrent and metastatic setting. In this complex context the identification of predictive and prognostic factors is urgently needed to tailor treatment, to increase its efficacy, and to avoid unnecessary toxicities. A better knowledge of prognosis may also help the patients and caregivers in decision making on the optimal choice of care. The purpose of our review is to highlight the current evidence and shortcomings in this field.
  • Joensuu, Heikki; Eriksson, Mikael; Collan, Juhani; Balk, Marja H.; Leyvraz, Serge; Montemurro, Michael (2015)
    Purpose: Gastrointestinal stromal tumor (GIST) has been considered radiation-resistant, and radiotherapy is recommended only for palliation of bone metastases in current treatment guidelines. No registered prospective trial has evaluated GIST responsiveness to radiotherapy. Patients and methods: Patients with GIST progressing at intra-abdominal sites or the liver were entered to this prospective Phase II multicenter study (identifier NCT00515931). Metastases were treated with external beam radiotherapy using either conformal 3D planning or intensity modulated radiotherapy and conventional fractionation to a cumulative planning target volume dose of approximately 40 Gy. Systemic therapy was maintained unaltered during the study. Results: Of the 25 patients entered, 19 were on concomitant tyrosine kinase inhibitor therapy, most often imatinib. Two (8%) patients achieved partial remission, 20 (80%) had stable target lesion size for >= 3 months after radiotherapy with a median duration of stabilization of 16 months, and 3 (12%) progressed. The median time to radiotherapy target lesion progression was 4-fold longer than the median time to GIST progression at any site (16 versus 4 months). Radiotherapy was generally well tolerated. Conclusions: Responses to radiotherapy were infrequent, but most patients had durable stabilization of the target lesions. GIST patients with soft tissue metastases benefit frequently from radiotherapy. (C) 2015 The Authors. Published by Elsevier Ireland Ltd.
  • Santti, Kirsi; Beule, Annette; Tuomikoski, Laura; Rönty, Mikko; Jääskeläinen, Anna-Stiina; Saarilahti, Kauko; Ihalainen, Hanna R.; Tarkkanen, Maija; Blomqvist, Carl (2017)
    Background Desmoid tumors (aggressive fibromatosis) are rare soft tissue tumors which frequently recur after surgery. Desmoid tumors arise from musculoaponeurotic tissue in the extremities, head and neck, abdominal wall, or intraabdominally. Our aim was to examine the outcome of radiotherapy of desmoid tumors in a single institution series. Patients and methods We evaluated 41 patients with desmoid tumors treated with 49 radiotherapies between 1987 and 2012. Radiologic images for response evaluation were reassessed and responses to treatment registered according to RECIST criteria 1.1. For patients with local failures radiation dose distribution was determined in each local failure volume using image co-registration. Recurrences were classified as in-target, marginal, or out-oftarget. Prognostic factors for radiotherapy treatment failure were evaluated. Results Radiotherapy doses varied from 20-63Gy (median 50 Gy) with a median fraction size of 2 Gy. The objective response rate to definitive radiotherapy was 55% (12/22 patients). Median time to response was 14 months. A statistically significant dose-response relation for definitive and postoperative radiotherapy was observed both in univariate (p-value 0.002) and in multivariate analysis (p-value 0.02) adjusted for potential confounding factors. Surgery before radiotherapy or surgical margin had no significant effect on time to progression. Nine of 11 (82%) local failures were classified as marginal and two of 11 (18%) in-target. None of the recurrences occurred totally out-of-target. Conclusions Radiotherapy is a valuable option for treating desmoid tumors. Radiotherapy dose appears to be significantly associated to local control.