Browsing by Subject "LONG-TERM SURVIVORS"

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  • Laury, Anna Ray; Blom, Sami; Ropponen, Tuomas; Virtanen, Anni; Carpen, Olli Mikael (2021)
    High-grade extrauterine serous carcinoma (HGSC) is an aggressive tumor with high rates of recurrence, frequent chemotherapy resistance, and overall 5-year survival of less than 50%. Beyond determining and confirming the diagnosis itself, pathologist review of histologic slides provides no prognostic or predictive information, which is in sharp contrast to almost all other carcinoma types. Deep-learning based image analysis has recently been able to predict outcome and/or identify morphology-based representations of underlying molecular alterations in other tumor types, such as colorectal carcinoma, lung carcinoma, breast carcinoma, and melanoma. Using a carefully stratified HGSC patient cohort consisting of women (n = 30) with similar presentations who experienced very different treatment responses (platinum free intervals of either = 18 months), we used whole slide images (WSI, n = 205) to train a convolutional neural network. The neural network was trained, in three steps, to identify morphologic regions (digital biomarkers) that are highly associating with one or the other treatment response group. We tested the classifier using a separate 22 slide test set, and 18/22 slides were correctly classified. We show that a neural network based approach can discriminate extremes in patient response to primary platinum-based chemotherapy with high sensitivity (73%) and specificity (91%). These proof-of-concept results are novel, because for the first time, prospective prognostic information is identified specifically within HGSC tumor morphology.
  • Broch, Kaspar; Gude, Einar; Karason, Kristjan; Dellgren, GÖran; Radegran, Goran; Gjesdal, Grunde; Gustafsson, Finn; Eiskjaer, Hans; Lommi, Jyri; Pentikäinen, Markku; Lemström, Karl B.; Andreassen, Arne K.; Gullestad, Lars (2020)
    Background Cardiac allograft vasculopathy (CAV) is characterized by diffuse thickening of the arterial intima. Statins reduce the incidence of CAV, but despite the use of statins, CAV remains one of the leading causes of long-term death after heart transplant. Inhibitors of proprotein convertase subtilisin-kexin type 9 (PCSK9) substantially reduce cholesterol levels but have not been tested in heart transplant recipients. Methods The Cholesterol lowering with EVOLocumab to prevent cardiac allograft Vasculopathy in De-novo heart transplant recipients (EVOLVD) trial ( Identifier: NCT03734211) is a randomized, double-blind trial designed to test the effect of the PCSK9 inhibitor evolocumab on coronary intima thickness in heart transplant recipients. Adults who have received a cardiac transplant within the past 4-8 weeks are eligible. Exclusion criteria include an estimated glomerular filtration rate <20 mL/min/1.73 m(2), renal replacement therapy, or contraindications to coronary angiography with intravascular ultrasound. 130 patients will be randomized (1:1) to 12-month treatment with evolocumab or matching placebo. The primary endpoint is the coronary artery intima thickness as measured by intravascular ultrasound. Conclusion The EVOLVD trial is a randomized clinical trial designed to show whether treatment with the PCSK9 inhibitor evolocumab can ameliorate CAV over the first year after heart transplant.
  • Munier, Francis L.; Beck-Popovic, Maja; Chantada, Guillermo L.; Cobrinik, David; Kivelä, Tero T.; Lohmann, Dietmar; Maeder, Philippe; Moll, Annette C.; Carcaboso, Angel Montero; Moulin, Alexandre; Schaiquevich, Paula; Bergin, Ciara; Dyson, Paul J.; Houghton, Susan; Puccinelli, Francesco; Vial, Yvan; Gaillard, Marie-Claire; Stathopoulos, Christina (2019)
    Retinoblastoma is lethal by metastasis if left untreated, so the primary goal of therapy is to preserve life, with ocular survival, visual preservation and quality of life as secondary aims. Historically, enucleation was the first successful therapeutic approach to decrease mortality, followed over 100 years ago by the first eye salvage attempts with radiotherapy. This led to the empiric delineation of a window for conservative management subject to a "state of metastatic grace" never to be violated. Over the last two decades, conservative management of retinoblastoma witnessed an impressive acceleration of improvements, culminating in two major paradigm shifts in therapeutic strategy. Firstly, the introduction of systemic chemotherapy and focal treatments in the late 1990s enabled radiotherapy to be progressively abandoned. Around 10 years later, the advent of chemotherapy in situ, with the capitalization of new routes of targeted drug delivery, namely intra-arterial, intravitreal and now intracameral injections, allowed significant increase in eye preservation rate, definitive eradication of radiotherapy and reduction of systemic chemotherapy. Here we intend to review the relevant knowledge susceptible to improve the conservative management of retinoblastoma in compliance with the "state of metastatic grace", with particular attention to (i) reviewing how new imaging modalities impact the frontiers of conservative management, (ii) dissecting retinoblastoma genesis, growth patterns, and intraocular routes of tumor propagation, (iii) assessing major therapeutic changes and trends, (iv) proposing a classification of relapsing retinoblastoma, (v) examining treatable/preventable disease-related or treatment-induced complications, and (vi) appraising new therapeutic targets and concepts, as well as liquid biopsy potentiality.
  • Mauramo, Matti; Rohde, Luzius; Ramseier, Adrian M.; Rovo, Alicia; Waltimo, Tuomas (2017)
    The aetiology of hyposalivation in haematopoietic stem cell transplantation (HSCT) recipients is not fully understood. This study examined the effects of treatment-related aetiological factors, particularly medications, on stimulated salivary flow in HSCT recipients. Adult HSCT recipients (N = 118, 66 males, 27 autologous and 91 allogeneic transplants) were examined. Stimulated whole salivary flow rates (SWSFR) were measured before HSCT and at 6 and 12 months post-HSCT. Linear regression models were used to analyse the associations of medications and transplant-related factors with salivary flow rates, which were compared to salivary flow rates of generally healthy controls (N = 247). The SWSFR of recipients were lower pre-HSCT (mean +/- standard deviation, 0.88 +/- 0.56 ml/min; P <0.001), 6 months post-HSCT (0.84 +/- 0.61; P <0.001) and 12 months post-HSCT (1.08 +/- 0.67; P = 0.005) than the SWSFR of controls (1.31 +/- 0.65). In addition, hyposalivation (<0.7 ml/min) was more frequent among HSCT recipients pre-HSCT (P <0.001), 6 months post-HSCT (P <0.001) and 12 months post-HSCT (P = 0.01) than among controls. The SWSFR was observed to improve over time being significantly higher 12 months post-HSCT compared to pre-HSCT (P <0.001). The observed decrease of salivary flow could not be explained by the examined transplant-related factors and medications. Decreased stimulated salivary flow rates could not be explained by the examined factors alone; these findings indicate that hyposalivation in HSCT recipients exhibits a multifactorial aetiology. All HSCT recipients should be considered to be at high risk of hyposalivation and consequent oral diseases, and they should be treated accordingly.
  • Kero, A. E.; Madanat-Harjuoja, L. M.; Jarvela, L. S.; Malila, N.; Matomaki, J.; Lahteenmaki, P. M. (2016)
    Purpose: Childhood cancer survivors are at risk for developing metabolic syndrome (MetS), which subsequently leads to cardiovascular morbidity and excess mortality. Our aim was to investigate the purchases of medications associated with MetS among 7551 early onset cancer patients compared to siblings. Methods: Our nationwide Finnish population-based registry study analyzed the drug purchase of medication among early onset cancer patients diagnosed with cancer below the age of 35 years between 1994 and 2004 compared to siblings by linkage to the drug purchase registry, allowing for a maximal follow-up of 18 years. Results: The hazard ratios (HRs) for purchasing antihypertensives and diabetes drugs were higher after both childhood (HR 4.6, 95% CI 3.1-7.0; HR 3.0, 95% 1.5-6.1) and young adulthood (YA) cancer (HR 1.5, 95% CI 1.3-1.8; HR 1.6, 95% CI 1.1-2.2) compared to siblings. The HRs for purchasing lipid-lowering drugs were elevated both after childhood (HR 4.3,95% CI 0.9-19.5) and YA cancer (HR 1.6, 95% CI 1.04-2.5), but only reached significance in YA cancer patients. Among specific cancer diagnosis groups, highest HR values for antihypertensives were found in childhood acute lymphoblastic leukemia (ALL) (HR 6.1, 95% CI 3.7-10.3) and bone tumor (HR 4.3, 95% CI 1.9-9.4), and YA ALL (HR 4.8, 95% CI 3.1-7.0) and acute myeloid leukemia (AML) (HR 3.4, 95% CI 2.5-5.1) patients. Moreover, childhood ALL (HR 6.3, 95% CI 2.7-14.8), AML (HR 7.6, 95% CI 1.9-24.5) and central nervous system (CNS)-tumor (HR 3.5, 95% CI 1.3-9.2) and YA ALL (HR 3.7, 95% CI 1.2-9.5) patients showed the strongest likelihood of purchasing diabetes drugs compared to siblings. Conclusion: The purchase of medications associated with MetS was increased after early onset cancer and highly dependent on the age at cancer diagnosis and the cancer diagnosis. Prevention strategies are imperative for reducing potentially life-threatening cardiovascular complications after early onset cancer. (C) 2016 Elsevier Ltd. All rights reserved.
  • Lehtomäki, Kaisa; Stedt, Hanna P.; Osterlund, Emerik; Muhonen, Timo; Soveri, Leena-Maija; Halonen, Päivi; Salminen, Tapio K.; Kononen, Juha; Kallio, Raija; Algars, Annika; Heerva, Eetu; Lamminmaki, Annamarja; Uutela, Aki; Nordin, Arno; Lehto, Juho; Saarto, Tiina; Sintonen, Harri; Kellokumpu-Lehtinen, Pirkko-Liisa; Ristamäki, Raija; Glimelius, Bengt; Isoniemi, Helena; Osterlund, Pia (2022)
    Simple Summary Metastatic colorectal cancer is the second most common cause of cancer death. Long-term survival and cure can be achieved after intensive treatments, including metastasectomy, i.e., the removal of all metastases. We wanted to clarify whether a patient health-related quality of life (HRQoL) was reduced by treatments that aimed to maximise metastasectomy rates, and whether HRQoL of treated patients is comparable to the general population. In a cross-sectional study of 444 patients (1751 questionnaires) in the RAXO-study population, we show that HRQoL of intensively treated patients, sometimes with multiple and multisite metastasectomies-usually combined with systemic therapy-remains at a high level during and after curative treatment and when compared with the general population. Good HRQoL was also seen during non-curative treatment from first- to later-lines, with an impaired HRQoL only at end-of-life. Thus, we should aim at maximising metastasectomies since they give long-term survival and sometimes cure with a high HRQoL. Metastasectomy and/or local ablative therapy in metastatic colorectal cancer (mCRC) patients often provide long-term survival. Health-related quality of life (HRQoL) data in curatively treated mCRC are limited. In the RAXO-study that evaluated repeated resectability, a multi-cross-sectional HRQoL substudy with 15D, EQ-5D-3L, QLQ-C30, and QLQ-CR29 questionnaires was conducted. Mean values of patients in different treatment groups were compared with age- and gender-standardized general Finnish populations. The questionnaire completion rate was 444/477 patients (93%, 1751 questionnaires). Mean HRQoL was 0.89-0.91 with the 15D, 0.85-0.87 with the EQ-5D, 68-80 with the EQ-5D-VAS, and 68-79 for global health status during curative treatment phases, with improvements in the remission phase (disease-free >18 months). In the remission phase, mean EQ-5D and 15D scores were similar to the general population. HRQoL remained stable during first- to later-line treatments, when the aim was no longer cure, and declined notably when tumour-controlling therapy was no longer meaningful. The symptom burden affecting mCRC survivors' well-being included insomnia, impotence, urinary frequency, and fatigue. Symptom burden was lower after treatment and slightly higher, though stable, through all phases of systemic therapy. HRQoL was high in curative treatment phases, further emphasizing the strategy of metastasectomy in mCRC when clinically meaningful.
  • Salooja, Nina; Greinix, Hildegaard; Ruutu, Tapani; van der Werf, Steffie; van Biezen, Anja; Lawitschka, Anita; Basak, Grzegorz; Duarte, Rafael (2020)
    Reduced bone mineral density (BMD) is a well-recognized complication of hematopoietic cell transplantation (HCT), with significant drops in BMD occurring within the first 12 months after HCT. Guidance on identifying and managing this complication is available in several published guidelines. In this study, we investigated current practices in the investigation and management of low BMD in centers registered with the European Society for Blood and Marrow Transplantation (EBMT). A questionnaire about bone health was sent to all registered centers, and responses were received from 99 centers in 25 countries (52%) currently registered with the EBMT. Our data highlight considerable heterogeneity in practices across European centers in relation to investigations, management, and use of guidelines. Our data demonstrate the need for better dissemination and implementation of existing guidelines and also for the development of multidisciplinary guidelines with input from all relevant stakeholders. (c) 2020 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc.
  • Salakari, Minna; Suominen, Sakari; Nurminen, Raija; Sillanmaki, Lauri; Pylkkanen, Liisa; Rautava, Paivi; Koskenvuo, Markku (Springer-Verlag, 2016)
    Communications in Computer and Information Science
    The purpose of the study was to compare the life satisfaction (LS) and sense of coherence (SOC) of women recovering from breast cancer (BC) to LS and SOC of women with depression or hypertension and of healthy controls. Finnish Health and Social Support (HeSSup) follow-up survey data in 2003 was linked with national health registries. BC patients were followed up for mortality until the end of 2012. The statistical computations were carried out with SAS (R). There were no significant differences in LS and SOC between the groups with BC, arterial hypertension or healthy controls. Women recovering from BC are as satisfied with their life as healthy controls, and their perceived LS is better and SOC is stronger compared to women with depression. SOC correlated positively (r(2) = 0.36, p <0.001) with LS. However, more studies on determinants of the LS are needed for designing and organizing health care services for BC survivors.
  • Haavisto, Anu; Mathiesen, Sidsel; Suominen, Anu; Lähteenmäki, Päivi; Sorensen, Kaspar; Ifversen, Marianne; Juul, Anders; Nielsen, Malene Mejdahl; Müller, Klaus; Jahnukainen, Kirsi (2020)
    There are many known endocrine complications after allogeneic hematopoietic stem cell transplantation (HSCT) in childhood including increased risk of biochemical hypogonadism. However, little is known about sexuality in adulthood following childhood HSCT. In this multicenter study, sexual functions and possible risk factors were assessed comprehensively in two national cohorts (Finland and Denmark) of male adult survivors of childhood HSCT. Compared to a healthy control group (n= 56), HSCT survivors (n= 97) reported less sexual fantasies, poorer orgasms, lower sexual activity with a partner and reduced satisfaction with their sex life, even in the presence of normal erectile functions and a similar frequency of autoerotic acts. Of the HSCT survivors, 35% were cohabitating/married and 66% were sexually active. Risk factors for poorer self-reported sexual functions were partner status (not cohabitating with a partner), depressive symptoms, CNS and testicular irradiation. Sexual dysfunction increased by age in the HSCT group with a pace comparable to that of the control group. However, because of the lower baseline level of sexual functions in the HSCT group, they will reach the level of clinically significant dysfunction at a younger age. Hence, male survivors of childhood HSCT should be interviewed in detail about their sexual health beyond erectile functions.
  • Sallinen, Hanne; Sairanen, Tiina; Strbian, Daniel (2019)
    Objectives: Quality of life (QoL) after intracerebral hemorrhage (ICH) is poorly known. This study investigated factors affecting QoL and depression after spontaneous ICH. Materials and Methods: This prospective study included patients admitted to Helsinki University Hospital between May 2014 and December 2016. Health-related QoL (HRQoL) at 3 months after ICH was measured using the European Quality of Life Scale (EQ-5D-5L), and the 15D scale. Logistic regression analyses were used to test factors affecting HRQoL. EQ-5D-5L anxiety/depression dimension was used to analyze factors associated with anxiety/depression. Results: Of 277 patients, 220 were alive, and sent QoL questionnaire. The questionnaire was returned by 124 patients. Nonreturners had more severe strokes with admission National Institutes of Health Stroke Scale (NIHSS) 7.8 (IQR 3.0-14.8) versus 5.0 (IQR 2.3-11.0); p = 0.018, and worse outcome assessed as modified Rankin Scale 3-5 at 3 months 59.4% versus 44.4% (p = 0.030). Predictors for lower HRQoL by both scales were higher NIHSS with OR 1.28 (95% CI 1.13-1.46) for EQ-5D-5L, and OR 1.28 (1.15-1.44) for 15D, older age (OR 1.10 [1.03-1.16], and OR 1.09 [1.03-1.15]), and chronic heart failure (OR 18.12 [1.73-189.27], and OR 12.84 [1.31126.32]), respectively. Feeling sad/depressed for more than 2 weeks during the year prior to ICH was predictor for lower EQ-5D-5L (OR 10.64 [2.39-47.28]), and history of ICH for lower 15D utility indexes (OR 11.85 [1.01-138.90]). Prior feelings of sadness/ depression were associated with depression/anxiety at 3 months after ICH with OR 3.62 (1.14-11.45). Conclusions: In this cohort of ICH patients with milder deficits, HRQoL was affected by stroke severity, comorbidities and age. Feelings of depression before ICH had stronger influence on reporting depression/anxiety after ICH than stroke severity-related and outcome parameters. Thus, simple questions on patient's premorbid feelings of sadness/depression could be used to identify patients at risk of depression after ICH for focusing follow-up and treatment.
  • Skinner, Roderick; Mulder, Renee L.; Kremer, Leontien C.; Hudson, Melissa M.; Constine, Louis S.; Bardi, Edit; Boekhout, Annelies; Borgmann-Staudt, Anja; Brown, Morven C.; Cohn, Richard; Dirksen, Uta; Giwercman, Alexsander; Ishiguro, Hiroyuki; Jahnukainen, Kirsi; Kenney, Lisa B.; Loonen, Jacqueline J.; Meacham, Lilian; Neggers, Sebastian; Nussey, Stephen; Petersen, Cecilia; Shnorhavorian, Margarett; van den Heuvel-Eibrink, Marry M.; van Santen, Hanneke M.; Wallace, William H. B.; Green, Daniel M. (2017)
    Treatment with chemotherapy, radiotherapy, or surgery that involves reproductive organs can cause impaired spermatogenesis, testosterone deficiency, and physical sexual dysfunction in male pubertal, adolescent, and young adult cancer survivors. Guidelines for surveillance and management of potential adverse effects could improve cancer survivors' health and quality of life. Surveillance recommendations vary considerably, causing uncertainty about optimum screening practices. This clinical practice guideline recommended by the International Late Effects of Childhood Cancer Guideline Harmonization Group in collaboration with the PanCareSurFup Consortium, developed using evidence-based methodology, critically synthesises surveillance recommendations for gonadotoxicity in male childhood, adolescent, and young adult (CAYA) cancer survivors. The recommendations were developed by an international multidisciplinary panel including 25 experts in relevant medical specialties, using a consistent and transparent process. Recommendations were graded according to the strength of underlying evidence and potential benefit gained by early detection and appropriate management. The aim of the recommendations is to enhance evidence-based care for male CAYA cancer survivors. The guidelines reveal the paucity of high-quality evidence, highlighting the need for further targeted research.
  • ALiCCS study group; Oskarsson, Trausti; Duun-Henriksen, Anne Katrine; Bautz, Andrea; Madanat-Harjuoja, Laura; Falck Winther, Jeanette (2021)
    The dynamic growth of the skeleton during childhood and adolescence renders it vulnerable to adverse effects of cancer treatment. The lifetime risk and patterns of skeletal morbidity have not been described in a population-based cohort of childhood cancer survivors. A cohort of 26 334 1-year cancer survivors diagnosed before 20 years of age was identified from the national cancer registries of Denmark, Finland, Iceland and Sweden as well as a cohort of 127 531 age- and sex-matched comparison subjects randomly selected from the national population registries in each country. The two cohorts were linked with data from the national hospital registries and the observed numbers of first-time hospital admissions for adverse skeletal outcomes among childhood cancer survivors were compared to the expected numbers derived from the comparison cohort. In total, 1987 childhood cancer survivors had at least one hospital admission with a skeletal adverse event as discharge diagnosis, yielding a rate ratio (RR) of 1.35 (95% confidence interval, 1.29-1.42). Among the survivors, we observed an increased risk for osteonecrosis with a RR of 25.9 (15.0-44.5), osteoporosis, RR 4.53 (3.28-6.27), fractures, RR 1.27 (1.20-1.34), osteochondropathies, RR 1.57 (1.28-1.92) and osteoarthrosis, RR 1.48 (1.28-1.72). The hospitalization risk for any skeletal adverse event was higher among survivors up to the age of 60 years, but the lifetime pattern was different for each type of skeletal adverse event. Understanding the different lifetime patterns and identification of high-risk groups is crucial for developing strategies to optimize skeletal health in childhood cancer survivors.
  • Ylanen, Kaisa; Eerola, Anneli; Vettenranta, Kim; Poutanen, Tuija (2016)
    Longitudinal motion significantly contributes to the contraction of the ventricles. We studied the left (LV) and right ventricular (RV) longitudinal functions in 75 anthracycline-exposed, long-term childhood cancer survivors and 75 healthy controls with conventional echocardiography, tissue Doppler imaging (TDI), speckle tracking echocardiography (STE) of the mitral and tricuspid annular motion, and real-time three-dimensional echocardiography (RT-3DE). Cardiac magnetic resonance (CMR) imaging was performed on 61 of the survivors. The survivors had lower systolic myocardial velocities in the LV and lower diastolic velocities in both ventricles by TDI than did their healthy peers. The STE-based tissue motion annular displacement (TMAD) values describing the LV and RV systolic longitudinal function (MAD and TAD mid%, respectively) were also lower among the survivors (15.4 +/- 2.4 vs. 16.1 +/- 2.2 %, p = 0.049 and 22.5 +/- 3.0 vs. 23.5 +/- 3.0 %, p = 0.035). MAD and TAD mid in millimeters correlated with the respective ventricular volumes measured with RT-3DE or CMR. Conclusion: Childhood cancer survivors exposed to low to moderate anthracycline doses had decreased longitudinal systolic and diastolic functions (TDI or STE) compared with healthy controls. The STE-based TMAD is a fast and reproducible method to assess cardiac longitudinal function.
  • Frederiksen, Line Elmerdahl; Mader, Luzius; Feychting, Maria; Mogensen, Hanna; Madanat-Harjuoja, Laura; Malila, Nea; Tolkkinen, Anniina; Hasle, Henrik; Winther, Jeanette Falck; Erdmann, Friederike (2019)
    Substantial improvements in childhood cancer survival have resulted in a steadily increasing population of childhood cancer survivors. Whereas somatic late effects have been assessed in many studies, less is known about the impact of childhood cancer on socioeconomic outcomes in survivors. The aim of this article was to evaluate and summarise the evidence on the socioeconomic conditions of childhood cancer survivors and to identify survivors at particular risk of adverse socioeconomic outcomes. An extensive literature search of three electronic databases was conducted. Of 419 articles identified, 52 met the inclusion criteria. All the selected articles were appraised for quality, and findings were summarised in a narrative synthesis. Childhood cancer survivors were at higher risk of adverse socioeconomic outcomes with regard to educational achievement, income and social security benefits than the general population or a sibling comparison group. The risks for unemployment and a lower occupational position were significantly increased only for survivors of a central nervous system tumour. Notably, survivors of central nervous system tumours, survivors treated with cranial radiotherapy and those diagnosed at younger age independent of cancer type were determinants of particular adverse socioeconomic outcomes. Given the increasing population of childhood cancer survivors, targeted follow-up interventions and support strategies addressing not only the somatic and psychiatric late effects but also the socioeconomic difficulties that some childhood cancer survivors face is of high importance to reduce social inequity, and ensure a high quality of life after childhood cancer.