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1.
Mol Ther ; 32(6): 2021-2029, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38582964

RESUMO

We previously demonstrated the antitumor effectiveness of transiently T cell receptor (TCR)-redirected T cells recognizing a frameshift mutation in transforming growth factor beta receptor 2. We here describe a clinical protocol using mRNA TCR-modified T cells to treat a patient with progressive, treatment-resistant metastatic microsatellite instability-high (MSI-H) colorectal cancer. Following 12 escalating doses of autologous T cells electroporated with in-vitro-transcribed Radium-1 TCR mRNA, we assessed T cell cytotoxicity, phenotype, and cytokine production. Tumor markers and growth on computed tomography scans were evaluated and immune cell tumor infiltrate at diagnosis assessed. At diagnosis, tumor-infiltrating CD8+ T cells had minimal expression of exhaustion markers, except for PD-1. Injected Radium-1 T cells were mainly naive and effector memory T cells with low expression of exhaustion markers, except for TIGIT. We confirmed cytotoxicity of transfected Radium-1 T cells against target cells and found key cytokines involved in tumor metastasis, growth, and angiogenesis to fluctuate during treatment. The treatment was well tolerated, and despite his advanced cancer, the patient obtained a stable disease with 6 months survival post-treatment. We conclude that treatment of metastatic MSI-H colorectal cancer with autologous T cells electroporated with Radium-1 TCR mRNA is feasible, safe, and well tolerated and that it warrants further investigation in a phase 1/2 study.


Assuntos
Neoplasias Colorretais , Instabilidade de Microssatélites , Receptores de Antígenos de Linfócitos T , Humanos , Neoplasias Colorretais/terapia , Neoplasias Colorretais/patologia , Neoplasias Colorretais/genética , Receptores de Antígenos de Linfócitos T/genética , Receptores de Antígenos de Linfócitos T/metabolismo , Masculino , Imunoterapia Adotiva/métodos , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , Citocinas/metabolismo , Linfócitos do Interstício Tumoral/imunologia , Linfócitos do Interstício Tumoral/metabolismo , Resultado do Tratamento , Linfócitos T/imunologia , Linfócitos T/metabolismo , Pessoa de Meia-Idade , Citotoxicidade Imunológica
2.
Br J Cancer ; 130(12): 1921-1928, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38664577

RESUMO

BACKGROUND: We evaluated first-line treatment of metastatic microsatellite-stable colorectal cancer with short-course oxaliplatin-based chemotherapy alternating with immune checkpoint blockade. METHODS: Patients were randomly assigned to chemotherapy (the FLOX regimen; control group) or alternating two cycles each of FLOX and nivolumab (experimental group). Radiographic response assessment was done every eight weeks with progression-free survival (PFS) as the primary endpoint. Cox proportional-hazards regression models estimated associations between PFS and relevant variables. A post hoc analysis explored C-reactive protein as signal of responsiveness to immune checkpoint blockade. RESULTS: Eighty patients were randomised and 38 in each group received treatment. PFS was comparable-control group: median 9.2 months (95% confidence interval (CI), 6.3-12.7); experimental group: median 9.2 months (95% CI, 4.5-15.0). The adjusted Cox model revealed that experimental-group subjects aged ≥60 had significantly lowered progression risk (p = 0.021) with hazard ratio 0.17 (95% CI, 0.04-0.76). Experimental-group patients with C-reactive protein <5.0 mg/L when starting nivolumab (n = 17) reached median PFS 15.8 months (95% CI, 7.8-23.7). One-sixth of experimental-group cases (all KRAS/BRAF-mutant) achieved complete response. CONCLUSIONS: The investigational regimen did not improve the primary outcome for the intention-to-treat population but might benefit small subgroups of patients with previously untreated, metastatic microsatellite-stable colorectal cancer. TRIAL REGISTRATION: ClinicalTrials.gov number, NCT03388190 (02/01/2018).


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Colorretais , Nivolumabe , Oxaliplatina , Humanos , Nivolumabe/uso terapêutico , Nivolumabe/administração & dosagem , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Oxaliplatina/administração & dosagem , Oxaliplatina/uso terapêutico , Masculino , Feminino , Pessoa de Meia-Idade , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Idoso , Instabilidade de Microssatélites , Intervalo Livre de Progressão , Adulto , Metástase Neoplásica , Inibidores de Checkpoint Imunológico/uso terapêutico , Proteínas Proto-Oncogênicas p21(ras)/genética
3.
Colorectal Dis ; 26(1): 22-33, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38036898

RESUMO

AIM: Stage III colon cancer is routinely treated with adjuvant chemotherapy, which causes significant short-term morbidity. Its effect on long-term quality of life (QoL) is poorly investigated. The aim of this study was to investigate long-term QoL after curative treatment for colon cancer and explore the impact of chemotherapy on general and disease-specific QoL. METHOD: All patients aged under 75 years operated on for colon cancer between 30 September 2007 and 1 October 2019 were identified by the Cancer Registry of Norway. Exclusion criteria were distant metastasis, recurrence, dementia and rectal/rectosigmoid cancer operation. The primary outcome measure was Gastrointestinal Quality of Life Index (GIQLI). Secondary outcome measures included the Short Form Health Survey (SF-36). To achieve balanced groups when assessing differences in outcome measures the analyses were weighted by inverse probability weights based on a multiple logistic regression model with prechosen confounders. RESULTS: A total of 8627 patients were invited and 3109 responded (36% response rate). After exclusions 3025 patients were included, of whom 1148 (38%) had received adjuvant chemotherapy and 1877 (62%) had surgery alone, with mean follow-up of 75.5 versus 74.5 months, respectively. The GIQLI differed significantly between the groups [mean 111.0 (SD 18.4) vs. 115.6 (SD 17.8), respectively; mean difference: -4.6 (95% CI -5.9; -3.2); p < 0.001]. Those with the highest neurotoxicity exhibited the lowest GIQLI. The adjuvant chemotherapy group scored significantly lower in six of eight SF-36 domains compared with the surgery alone group. The main differences were found in social, physical and emotional function. CONCLUSION: Long-term QoL was significantly lower in patients who received adjuvant chemotherapy than in patients who did not. Neurotoxicity was closely related to reduced QoL in these patients. The low response rate limits the generalizability of the results.


Assuntos
Sobreviventes de Câncer , Neoplasias do Colo , Humanos , Idoso , Qualidade de Vida , Estudos de Coortes , Recidiva Local de Neoplasia , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/cirurgia , Quimioterapia Adjuvante/métodos , Sistema de Registros
4.
Palliat Med ; 38(2): 229-239, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38193250

RESUMO

BACKGROUND: Effects on anticancer therapy following the integration of palliative care and oncology are rarely investigated. Thus, its potential effect is unknown. AIM: To investigate the effects of the complex intervention PALLiON versus usual care on end-of-life anticancer therapy. DESIGN: Cluster-randomised controlled trial (RCT), registered at ClinicalTrials.gov (No. NCT03088202). The complex intervention consisted of a physician education program enhancing theoretical, clinical and communication skills, a patient-centred care pathway and patient symptom reporting prior to all consultations. Primary outcome was overall use, start and cessation of anticancer therapy in the last 3 months before death. Secondary outcomes were patient-reported outcomes. Mixed effects logistic regression models and Cox proportional hazard were used. SETTING: A total of 12 Norwegian hospitals (03/2017-02/2021). PARTICIPANTS: Patients ⩾18 years, advanced stage solid tumour, starting last line of anticancer therapy, estimated life expectancy ⩽12 months. RESULTS: A total of 616 (93%) patients were included (intervention: 309/control:307); 63% males, median age 69, 77% had gastrointestinal cancers. Median survival time from inclusion was 8 (IQR 3-14) and 7 months (IQR 3-12), and days between anticancer therapy start and death were 204 (90-378) and 168 (69-351) (intervention/control). Overall, 78 patients (13%) received anticancer therapy in the last month (intervention: 33 [11%]/control: 45 [15%]). No differences were found in patient-reported outcomes. CONCLUSION: We found no significant differences in the probability of receiving end-of-life anticancer therapy. The intervention did not have the desired effect. It was probably too general and too focussed on communication skills to exert a substantial influence on conventional clinical practice.


Assuntos
Neoplasias , Cuidados Paliativos , Masculino , Humanos , Idoso , Feminino , Qualidade de Vida , Neoplasias/patologia , Hospitais , Morte
5.
Br J Cancer ; 127(12): 2227-2233, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36229579

RESUMO

BACKGROUND: Immune checkpoint blockade (ICB) results in radiologic tumour response dynamics that differ from chemotherapy efficacy measures and require an early signal of clinical utility. METHODS: Previously untreated, unresectable microsatellite-stable (MSS)/mismatch repair-proficient (pMMR) colorectal cancer (CRC) patients were randomly assigned to the oxaliplatin-based Nordic FLOX regimen (control arm) or repeat sequential two FLOX cycles and two ICB cycles (experimental arm). The radiologic response was assessed every 8 weeks. In this post hoc analysis, we explored early target lesion (TL) dynamics as indicator of ICB responsiveness. Progression-free survival (PFS) was the primary endpoint. RESULTS: Using a landmark analysis approach, we categorised experimental-arm patients into ≥10% (N = 19) or <10% (N = 16) TL reduction at the first post-baseline response assessment. Median PFS for the groups was 16.0 (95% confidence interval (CI), 12.3-19.7) and 3.9 months (95% CI, 2.3-5.5), respectively, superior and inferior (both P < 0.01) to the median PFS of 9.8 months (95% CI, 4.9-14.7) for control arm patients (N = 31). CONCLUSIONS: Radiologic TL reduction of ≥10% at the first post-baseline response assessment identified patients with ICB-responsive metastatic MSS/pMMR-CRC. This pragmatic measure may be used to monitor patients in investigational ICB schedules, enabling early treatment adaptation for unresponsive cases. TRIAL REGISTRATION: ClinicalTrials.gov number, NCT03388190 (02/01/2018).


Assuntos
Neoplasias Colorretais , Inibidores de Checkpoint Imunológico , Humanos , Neoplasias Colorretais/diagnóstico por imagem , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Reparo de Erro de Pareamento de DNA
6.
J Transl Med ; 20(1): 225, 2022 05 14.
Artigo em Inglês | MEDLINE | ID: mdl-35568909

RESUMO

BACKGROUND: Matching treatment based on tumour molecular characteristics has revolutionized the treatment of some cancers and has given hope to many patients. Although personalized cancer care is an old concept, renewed attention has arisen due to recent advancements in cancer diagnostics including access to high-throughput sequencing of tumour tissue. Targeted therapies interfering with cancer specific pathways have been developed and approved for subgroups of patients. These drugs might just as well be efficient in other diagnostic subgroups, not investigated in pharma-led clinical studies, but their potential use on new indications is never explored due to limited number of patients. METHODS: In this national, investigator-initiated, prospective, open-label, non-randomized combined basket- and umbrella-trial, patients are enrolled in multiple parallel cohorts. Each cohort is defined by the patient's tumour type, molecular profile of the tumour, and study drug. Treatment outcome in each cohort is monitored by using a Simon two-stage-like 'admissible' monitoring plan to identify evidence of clinical activity. All drugs available in IMPRESS-Norway have regulatory approval and are funded by pharmaceutical companies. Molecular diagnostics are funded by the public health care system. DISCUSSION: Precision oncology means to stratify treatment based on specific patient characteristics and the molecular profile of the tumor. Use of targeted drugs is currently restricted to specific biomarker-defined subgroups of patients according to their market authorization. However, other cancer patients might also benefit of treatment with these drugs if the same biomarker is present. The emerging technologies in molecular diagnostics are now being implemented in Norway and it is publicly reimbursed, thus more cancer patients will have a more comprehensive genomic profiling of their tumour. Patients with actionable genomic alterations in their tumour may have the possibility to try precision cancer drugs through IMPRESS-Norway, if standard treatment is no longer an option, and the drugs are available in the study. This might benefit some patients. In addition, it is a good example of a public-private collaboration to establish a national infrastructure for precision oncology. Trial registrations EudraCT: 2020-004414-35, registered 02/19/2021; ClinicalTrial.gov: NCT04817956, registered 03/26/2021.


Assuntos
Antineoplásicos , Neoplasias , Antineoplásicos/uso terapêutico , Humanos , Oncologia , Neoplasias/diagnóstico , Neoplasias/genética , Neoplasias/terapia , Medicina de Precisão , Estudos Prospectivos
9.
Psychosomatics ; 55(6): 621-9, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24656688

RESUMO

BACKGROUND: Chronic fatigue (CF) is a common late effect after childhood cancer. OBJECTIVE: Based on findings among patients with the chronic fatigue syndrome (CFS), this study explored symptoms, neuroendocrine markers, and autonomic cardiovascular responses associated with CFS in childhood cancer survivors. METHODS: Long-term survivors of childhood lymphoma and acute lymphoblastic leukemia reporting CF were compared with survivors without CF. Data included patient-reported outcomes, clinical examination, head-up tilt test, and neuroendocrine markers in the blood and the urine. RESULTS: Of 102 included survivors, 15 were excluded from comparative analyses because of significant co-morbidity or pregnancy. Of the remaining 87 participants (median age 33.0 years, follow-up time 25.2 years), 35 had CF and 52 did not have CF. Compared with non-CF controls, CF cases reported a significantly (P < 0.01) higher frequency of symptoms typical of the CFS (muscle or joint pain or both and feeling confused/disoriented) and symptoms of autonomic dysfunction (palpitations, feeling intermittently heat and cold, and watery diarrhea). CF cases and controls did not differ regarding autonomic cardiovascular responses to orthostatic stress, but the CF group had lower levels of plasma adrenocorticotrophic hormone (P = 0.002) and higher levels of urine norepinephrine (P = 0.017). CONCLUSIONS: Survivors with CF reported a high symptom-burden compared with controls. There were few differences between both the groups regarding biomarkers, but slight alterations of the hypothalamus-pituitary-adrenal axis and sympathetic nervous activity were detected. CF in cancer survivors has features in common with the CFS, but further efforts are required to clarify the pathophysiology.


Assuntos
Adultos Sobreviventes de Eventos Adversos na Infância/psicologia , Fadiga/etiologia , Linfoma/complicações , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicações , Hormônio Adrenocorticotrópico/sangue , Hormônio Adrenocorticotrópico/urina , Adulto , Adultos Sobreviventes de Eventos Adversos na Infância/estatística & dados numéricos , Doenças do Sistema Nervoso Autônomo/epidemiologia , Doenças do Sistema Nervoso Autônomo/etiologia , Biomarcadores/sangue , Biomarcadores/urina , Sistema Cardiovascular/fisiopatologia , Estudos de Casos e Controles , Doença Crônica , Confusão/epidemiologia , Confusão/etiologia , Fadiga/epidemiologia , Fadiga/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Norepinefrina/urina , Teste da Mesa Inclinada , Adulto Jovem
10.
J Pediatr Hematol Oncol ; 36(6): 438-44, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24276036

RESUMO

BACKGROUND: Chronic fatigue (CF) is an important late effect after childhood malignancies. Our aim was to assess CF persistence over time, concurrent comorbidities, and associations with clinical symptoms. PROCEDURE: A total of 102 long-term survivors of childhood lymphomas and acute lymphoblastic leukemia, 53 and 49 reporting CF and no CF, respectively, at time point (TP)1, were evaluated for CF at a second TP after a median interval of 2.7 years. At TP2 a survey, including self-reported and objectively measured variables, assessed depressive symptoms, pain, and physical activity. RESULTS: A total of 32 of the 53 reported CF cases at both TPs and 40/49 survivors had no CF at both TPs, whereas 30 had changed their fatigue status between first and second assessment (converters). Major somatic comorbidities were equally distributed among the groups. After exclusion of converters and survivors with major comorbidity/pregnancy, 27 persistent CF (PCF) cases and 35 controls were compared. PCF cases reported significantly more depression, sleeping problems, anxiety, pain, and reduced physical function. Further, they were less physically active than controls (steps/d; P=0.009). In a multiple regression analysis, depressive symptoms remained the only significant predictor of PCF. CONCLUSIONS: Long-term survivors of childhood cancer with PCF are characterized by more depressive symptoms, anxiety, pain, insomnia, and less physical activity.


Assuntos
Síndrome de Fadiga Crônica/epidemiologia , Linfoma/epidemiologia , Linfoma/terapia , Leucemia-Linfoma Linfoblástico de Células Precursoras/epidemiologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Sobreviventes , Adulto , Transtornos de Ansiedade/epidemiologia , Criança , Dor Crônica/epidemiologia , Comorbidade , Transtorno Depressivo Maior/epidemiologia , Feminino , Inquéritos Epidemiológicos , Humanos , Modelos Logísticos , Masculino , Gravidez , Qualidade de Vida , Transtornos do Sono-Vigília/epidemiologia , Tempo
11.
BJS Open ; 8(5)2024 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-39240223

RESUMO

BACKGROUND: Radiotherapy reduces local recurrence in locally advanced rectal cancer, but may cause harm in patients who do not experience recurrence. The aim was to investigate the impact of radiotherapy on long-term quality of life after curative treatment for rectal cancer, i.e. in patients without a recurrence during the follow-up. METHODS: All patients operated on for rectal cancer in Norway under 75 years of age between 30 September 2007 and 1 October 2020 were identified using the Cancer Registry of Norway. Exclusion criteria were distant metastasis, recurrence and dementia. The primary outcome measure was the Gastrointestinal Quality of Life Index. Secondary outcome measures included the 36-item Short Form Survey. Inverse probability weights based on a multiple logistic regression model were used to balance prechosen covariates between the radiotherapy and no radiotherapy groups when assessing differences in outcomes. RESULTS: Of 5014 invited patients, 2142 (43%) eligible patients answered the questionnaires. Of these 762 (36%) were treated with neoadjuvant radiotherapy plus surgery and 1380 (64%) with surgery alone. The mean follow-up time was 6.4 and 7.4 years respectively. After propensity score matching, the Gastrointestinal Quality of Life Index differed significantly between irradiated and non-irradiated patients ((mean(s.d.), mean score 103.8(19.4) versus 110.8(19.6) respectively, mean difference: -6.96 (95% c.i. -8.72 to -5.19); P < 0.001). Among patients without a stoma the mean difference was -8.1 points, whereas it was -5.7 for patients with a stoma. The radiotherapy group also scored significantly lower in 7 of 8 36-item Short Form Survey domains compared with the surgery alone group. CONCLUSION: Long-term quality of life was significantly lower in patients without a recurrence during the follow-up who received radiotherapy compared with patients who did not. These findings warrant a critical re-evaluation of the use of radiotherapy both in traditional neoadjuvant treatment and in modern organ-preserving treatment regimens.


Assuntos
Qualidade de Vida , Neoplasias Retais , Sistema de Registros , Humanos , Neoplasias Retais/radioterapia , Neoplasias Retais/cirurgia , Neoplasias Retais/patologia , Masculino , Feminino , Pessoa de Meia-Idade , Noruega , Idoso , Sobreviventes de Câncer/psicologia , Sobreviventes de Câncer/estatística & dados numéricos , Recidiva Local de Neoplasia , Inquéritos e Questionários , Estudos de Coortes , Terapia Neoadjuvante , Adulto , Pontuação de Propensão
12.
Oncoimmunology ; 13(1): 2372886, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38952672

RESUMO

The randomized METIMMOX trial (NCT03388190) examined if patients with previously untreated, unresectable abdominal metastases from microsatellite-stable (MSS) colorectal cancer (CRC) might benefit from potentially immunogenic, short-course oxaliplatin-based chemotherapy alternating with immune checkpoint blockade (ICB). Three of 38 patients assigned to this experimental treatment had metastases from BRAF-mutant MSS-CRC, in general a poor-prognostic subgroup explored here. The ≥70-year-old females presented with ascending colon adenocarcinomas with intermediate tumor mutational burden (6.2-11.8 mutations per megabase). All experienced early disappearance of the primary tumor followed by complete response of all overt metastatic disease, resulting in progression-free survival as long as 20-35 months. However, they encountered recurrence at previously unaffected sites and ultimately sanctuary organs, or as intrahepatic tumor evolution reflected in the terminal loss of initially induced T-cell clonality in liver metastases. Yet, the remarkable first-line responses to short-course oxaliplatin-based chemotherapy alternating with ICB may offer a novel therapeutic option to a particularly hard-to-treat MSS-CRC subgroup.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Colorretais , Inibidores de Checkpoint Imunológico , Oxaliplatina , Proteínas Proto-Oncogênicas B-raf , Humanos , Oxaliplatina/uso terapêutico , Oxaliplatina/administração & dosagem , Feminino , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas B-raf/antagonistas & inibidores , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Inibidores de Checkpoint Imunológico/farmacologia , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Mutação , Instabilidade de Microssatélites/efeitos dos fármacos , Resultado do Tratamento , Idoso de 80 Anos ou mais
13.
Brain Behav Immun ; 30: 80-7, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23333795

RESUMO

INTRODUCTION: Fatigue is a common and distressing symptom in all phases of the cancer trajectory. Chronic fatigue (CF) is defined as fatigue with duration ⩾6months. The etiology of CF in cancer survivors is poorly understood, but a link to inflammatory activity has been suggested. In the present study we explored the relation between CF and the levels of 17 cytokines among a national representative sample of 232 adult survivors after childhood lymphoma and acute lymphoblastic leukemia (ALL). METHODS: Chalder's fatigue questionnaire assessed CF. The sera of the survivors were analyzed for 27 cytokines, where of 17 were detectable. RESULTS: Median age at survey and diagnosis was 29.7years (range 18.6-54.5years) and 9.6years (range 0.3-18.0years), respectively. Median follow-up time was 21.5years (range 7.1-40.0years). CF was not associated with increased levels of any of the 17 detectable cytokines when all three diagnostic groups were included in the analyses. In sub-analyses of the non-Hodgkin lymphoma survivors only, those with CF had significant higher levels of IL-9, FGF, PDGF and eotaxin compared to those without CF (p<0.05). Gender, age, diagnosis, obesity, or reduced heart function did not impact upon the results. Differences in cytokine levels between the diagnostic groups were observed irrespective of the presence/absence of CF. CONCLUSION: This study could not confirm a relation between levels of cytokines and CF in adults who survived childhood lymphoma and ALL, except for among NHL survivors. Despite the broad spectrum of cytokines and relatively large sample, small aberrances may not have been traced.


Assuntos
Citocinas/sangue , Fadiga/etiologia , Leucemia/complicações , Linfoma/complicações , Sobreviventes , Adolescente , Adulto , Estudos Transversais , Fadiga/sangue , Feminino , Seguimentos , Humanos , Leucemia/sangue , Linfoma/sangue , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Sistema de Registros , Inquéritos e Questionários
14.
Pediatr Blood Cancer ; 60(5): 849-55, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23335116

RESUMO

BACKGROUND: Previous studies of health-related quality of life (QoL) in childhood cancer survivors have hardly focused on factors associated with poor QoL. THE AIMS OF OUR STUDY WERE: (1) to assess QoL in long-term survivors (LTSs) of childhood acute lymphoblastic leukemia (ALL) and lymphomas compared to age-matched controls from the general population (NORMs). (2) To investigate factors associated with poor QoL in LTSs. PROCEDURE: This population-based cross-sectional study enrolled 285 LTSs of ALL and lymphomas diagnosed between 1970 and 2002 at age <18 years. The LTSs completed an extensive mailed questionnaire including the Short Form 36 (SF-36) as QoL-measure. NORMs consisted of five age-matched controls for each LTS (N = 1,425). Poor QoL was defined as SF-36 physical or mental component summary score <40. RESULTS: The median age of LTSs' at survey was 30 years (range: 18-54), median follow-up time 21 years (range: 7-39). Compared to NORMs, LTSs scored significantly lower on 7 of 8 SF-36 subscales. Among LTSs 32% reported poor QoL versus 19% among NORMs (P < 0.001). Among LTSs, psychosocial, lifestyle- and health-related variables, but not type of malignancy, treatment factors or socio-demographic factors were clinically significantly associated with poor QoL in bivariate regression analyses. In multivariate analysis, levels of fatigue, anxiety and depression, as well as obesity and insomnia remained significantly associated with poor QoL. CONCLUSION: Significantly more LTSs than age-matched NORMs experienced poor QoL. Clinically significant associations with fatigue, anxiety, depression, obesity and insomnia were observed, which may be amenable for interventions, and thereby improvement of QoL in LTSs.


Assuntos
Linfoma , Leucemia-Linfoma Linfoblástico de Células Precursoras , Qualidade de Vida , Sobreviventes/psicologia , Adolescente , Adulto , Ansiedade/epidemiologia , Estudos Transversais , Depressão/epidemiologia , Fadiga/epidemiologia , Feminino , Humanos , Linfoma/epidemiologia , Masculino , Pessoa de Meia-Idade , Obesidade/epidemiologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/epidemiologia , Distúrbios do Início e da Manutenção do Sono/epidemiologia , Inquéritos e Questionários , Adulto Jovem
15.
Pediatr Blood Cancer ; 59(2): 271-7, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22021108

RESUMO

BACKGROUND: Gonadal function decades after treatment for childhood lymphoma (CL) is not well described. This cross-sectional study had two aims: (1) describe long-term gonadal function and fertility in childhood lymphoma survivors (CLSs), and (2) explore anti-Mullerian hormone (AMH) as a measure of ovarian function in CLSs. PROCEDURE: Seventy-four male and 62 female CLSs participated in a survey consisting of a questionnaire, clinical examination, and blood/semen analysis. Prior treatment was categorized according to gonadotoxicity. Hypogonadism was determined by levels of gonadal hormones based on luteinizing hormone, follicle-stimulating hormone, testosterone (males), AMH (females <40 years), and menstrual status. Fertility was explored according to pregnancies achieved, semen analysis, and AMH. RESULTS: Hypogonadism was observed in 7 of 66 males (11%). Seven of 64 males (11%) were categorized as infertile. Nine of 45 females <40 years (20%) were at risk to develop premature ovarian failure (POF). Twenty of 45 females (44%) showed low-AMH levels indicating decreased fertility. Four "critically low" females reported pregnancies within the preceding 2 years. Sixty-four percent of the males and 93% of the females attempting parenthood had been successful (P = 0.01). Hypogonadism and low-AMH were related to treatment burden. CONCLUSION: Twenty years after treatment of CL, female CLSs' attempts of pregnancy initiation are mostly successful, while males seem at higher risk of infertility. Hypogonadism is a problem in 10% of the male CLSs. Based on AMH levels, POF is a risk in 20% of the female CLSs. The clinical significance of AMH reflecting true probability of fertility needs further research in cancer survivors.


Assuntos
Gônadas/fisiologia , Hipogonadismo/diagnóstico , Infertilidade/diagnóstico , Linfoma/terapia , Complicações Neoplásicas na Gravidez , Adolescente , Adulto , Criança , Pré-Escolar , Estudos Transversais , Feminino , Hormônio Foliculoestimulante/metabolismo , Seguimentos , Humanos , Hipogonadismo/metabolismo , Infertilidade/metabolismo , Hormônio Luteinizante/metabolismo , Linfoma/complicações , Linfoma/metabolismo , Masculino , Gravidez , Insuficiência Ovariana Primária/diagnóstico , Insuficiência Ovariana Primária/metabolismo , Prognóstico , Sobreviventes , Testosterona/metabolismo , Adulto Jovem
16.
BJS Open ; 6(2)2022 03 08.
Artigo em Inglês | MEDLINE | ID: mdl-35257140

RESUMO

BACKGROUND: Improvement in survival from pancreatic ductal adenocarcinoma (PDAC) has been reported in trial settings but is less explored in unselected cohorts. The aim of this study was to assess trends in provision of treatments and survival in Norway over a 15-year period following the implementation of hepato-pancreato-biliary (HPB) multidisciplinary teams, centralization of surgery, and implementation of modern chemotherapy (CTx) regimens. METHODS: A population-based observational study was conducted by analysing all patients diagnosed with PDAC between 2004 and 2018 using coupled data from the Cancer Registry of Norway and the National Patient Registry. RESULTS: A total of 10 630 patients were identified, of whom 1492 (14.0 per cent) underwent surgical resection. The resection rate, median age of those resected, and provision of perioperative CTx all increased over time. Median overall survival after resection improved from 16.0 months in the period 2004 to 2008 to 25.1 months in the period 2014 to 2018 (P < 0.001). For non-resected patients there was a rise in the provision of palliative chemotherapy, but little survival gain over time (median overall survival for 2004 to 2008 was 3.2 months versus 4.2 months for 2014 to 2018; P < 0.001). The rate of patients who did not receive any tumour-directed treatment (neither CTx nor surgery) was 44.3 per cent (2481 of 5603 patients) and decreased from 52.9 per cent in 2010 to 37.9 per cent in 2018 (P < 0.001). The median overall survival for all patients with PDAC increased from 3.7 months for 2004 to 2008 to 5.8 months for 2014 to 2018 (P < 0.001). CONCLUSION: Survival after resection increased substantially, as did national resection rates. Little development in the provision of CTx or survival was observed for non-resected patients.


Assuntos
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Carcinoma Ductal Pancreático/cirurgia , Quimioterapia Adjuvante , Humanos , Pancreatectomia , Neoplasias Pancreáticas/cirurgia , Neoplasias Pancreáticas
17.
Acta Oncol ; 50(5): 653-9, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21261507

RESUMO

PURPOSE: Survivors after malignant lymphoma are at high risk of late effects. In order to take full responsibility for their own health they need knowledge about their diagnosis, treatment and risk of late effects. We assessed such knowledge in adult survivors of childhood malignant lymphoma. MATERIAL AND METHODS: In 2007-2009 128 five-year survivors after childhood malignant lymphoma participated in a national cross-sectional questionnaire-based survey combined with clinical examination. [Males: 69, females: 59, treatment period 1970-2000, median age (range) at diagnosis: 14 years (0-18), at survey: 32 years (19-55), Hodgkin lymphoma (HL): 84, Non-Hodgkin lymphoma (NHL): 44]. Prior to the clinical examination a semi-structured interview on the survivors' knowledge was conducted by a study nurse. The individual survivors' responses were compared with his/her medical record. RESULTS: One hundred and twenty one reported their diagnosis correctly, seven reported that they had cancer, but could not specify malignant lymphoma. Thirty-three could not differentiate between HL and NHL. One hundred and twenty three reported their treatment modalities correctly (radiotherapy vs. chemotherapy vs. combined). Eighty-five (66%) were not aware of any risks for late effects. The remaining 43 listed at least one of the following late effects; infertility, heart-problems, impaired dental status, hypothyroidism, breast cancer, reduced muscle growth, fatigue and reduced memory or concentration. Thirty-seven survivors who provided additional comments reported that they had received some information about risk of late effects from their therapists. Age at diagnosis or educational level were not associated with knowledge about possible late effects while treatment period was. CONCLUSIONS: Norwegian long-term survivors of childhood malignant lymphomas are showing improved level of knowledge of their diagnosis and treatment modalities during the last decade. Still, independent of age at diagnosis and level of education, they are insufficiently aware of their risk of late effects.


Assuntos
Conscientização/fisiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Linfoma/reabilitação , Lesões por Radiação , Sobreviventes , Adolescente , Adulto , Idade de Início , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Criança , Pré-Escolar , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/psicologia , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Lactente , Recém-Nascido , Linfoma/epidemiologia , Linfoma/terapia , Masculino , Pessoa de Meia-Idade , Lesões por Radiação/complicações , Lesões por Radiação/epidemiologia , Lesões por Radiação/psicologia , Fatores de Risco , Sobreviventes/psicologia , Sobreviventes/estatística & dados numéricos , Fatores de Tempo , Adulto Jovem
18.
Trials ; 21(1): 303, 2020 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-32241299

RESUMO

BACKGROUND: Several publications have addressed the need for a systematic integration of oncological care focused on the tumor and palliative care (PC) focused on the patient with cancer. The exponential increase in anticancer treatments and the high number of patients living longer with advanced disease have accentuated this. Internationally, there is now a persuasive argument that introducing PC early during anticancer treatment in patients with advanced disease has beneficial effects on symptoms, psychological distress, and survival. METHODS: This is a national cluster-randomized trial (C-RCT) in 12 Norwegian hospitals. The trial investigates effects of early, systematic integration of oncology and specialized PC in patients with advanced cancer in six intervention hospitals compared with conventional care in six. Hospitals are stratified on the size of local catchment areas before randomization. In the intervention hospitals, a three-part complex intervention will be implemented. The backbone of the intervention is the development and implementation of patient-centered care pathways that contain early, compulsory referral to PC and regular and systematic registrations of symptoms. An educational program must be completed before patient inclusion. A total of 680 patients with advanced cancer and one caregiver per patient are included when patients come for start of last line of chemotherapy, defined according to national treatment guidelines. Data registration, clinical variables, and patient- and caregiver-reported outcomes take place every 2 months for 1 year or until death. The primary outcome is use of chemotherapy in the last 3 months of life by comparing the proportion of patients who receive this in the intervention and control groups. Primary outcome is use of chemotherapy in the last 3 months before death, i.e. number of patients. Secondary outcomes are initiation, discontinuation and number of cycles, last 3 months of life, administration of other medical interventions in the last month of life, symptom burden, quality of life (QoL), satisfaction with information and follow-up, and caregiver health, QoL, and satisfaction with care. DISCUSSION: Results from this C-RCT will be used to raise the awareness about the positive outcomes of early provision of specialized palliative care using pathways for patients with advanced cancer receiving medical anticancer treatment. The long-term clinical objective is to integrate these patient-centered pathways in Norwegian cancer care. The specific focus on the patient and family and the organization of a predictable care trajectory is consistent with current Norwegian strategies for cancer care. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03088202. Registered on 23 March 2017.


Assuntos
Neoplasias/terapia , Cuidados Paliativos/métodos , Educação de Pacientes como Assunto/métodos , Cuidado Transicional , Adaptação Psicológica , Cuidadores/educação , Cuidadores/psicologia , Conhecimentos, Atitudes e Prática em Saúde , Pessoal de Saúde/educação , Humanos , Oncologia , Estudos Multicêntricos como Assunto , Neoplasias/patologia , Neoplasias/psicologia , Noruega , Satisfação do Paciente , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Encaminhamento e Consulta , Fatores de Tempo
19.
J Adolesc Young Adult Oncol ; 6(3): 470-476, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28837384

RESUMO

BACKGROUND: The increased incidence of physical and psychosocial adverse health outcomes (AHOs) in childhood lymphoma survivors (CLSs) is well known, but these AHOs' association with self-reported general health is rarely described. AIM: We explored this association among long-term CLSs. METHODS: In 124 CLSs (Hodgkin: 81; non-Hodgkin: 43; median age: 33 years), physical AHOs were graded based on slightly modified common toxicity criteria for adverse effects (CTCAE)-4 recommendations (Grade 0-3). Psychosocial AHOs (pain, work inability, fatigue, and mental distress) were mainly assessed by validated patient-reported questionnaires (Grade 0-2). The results were related to contemporary self-reported general health. Statistical significance: p < 0.01. RESULTS: At least one physical AHO was found in 120 CLSs, being of Grades 1, 2, and 3, respectively, in 43, 43, and 34 survivors. The prevalence of psychosocial AHOs (Grades 1 or 2) was 63%, being Grade 2 in 62 CLSs. The CLSs described their general health as significantly reduced compared with controls, with the greatest reduction for survivors in whom physical AHOs were combined with moderate to severe psychosocial AHOs. CONCLUSION: Psychosocial more than physical AHOs impact on CLSs' current self-reported general health. Clinicians responsible for follow-up of CLSs should be aware of the strong reduction of contemporary general health by Grade 2 psychosocial AHOs. The study challenges the use of the physician-assessed CTCAE-4 categories in long-term cancer survivors and emphasizes the need to develop instruments, which reflect both physical and psychosocial AHOs in these individuals.


Assuntos
Sobreviventes de Câncer/psicologia , Sobreviventes de Câncer/estatística & dados numéricos , Nível de Saúde , Linfoma/diagnóstico , Linfoma/epidemiologia , Linfoma/reabilitação , Autorrelato , Adolescente , Adulto , Idade de Início , Criança , Pré-Escolar , Emprego/psicologia , Emprego/estatística & dados numéricos , Fadiga/epidemiologia , Fadiga/etiologia , Feminino , Humanos , Incidência , Linfoma/psicologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estresse Psicológico/epidemiologia , Estresse Psicológico/etiologia , Inquéritos e Questionários , Adulto Jovem
20.
BMC Res Notes ; 10(1): 214, 2017 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-28619116

RESUMO

BACKGROUND: Given the risk of developing acute and long-term adverse effects in patients receiving cisplatin-based chemotherapy for testicular cancer (TC), risk-reducing interventions, such as physical activity (PA), may be relevant. Limited knowledge is available on the challenges met when conducting PA intervention trials in patients with TC during and shortly after chemotherapy. The aims of the present feasibility study are therefore to determine patient recruitment, compliance and adherence to a PA intervention. RESULTS: Patients with metastatic TC referred to cisplatin-based chemotherapy were eligible. They followed an individual low-threshold PA intervention, including counseling from a personal coach during and 3 months after chemotherapy. Outcomes were recruitment rate, compliance rate and adherence to the intervention including preferences for type of PA and barriers for PA. During 8 months 12 of 18 eligible patients were invited, all consented, but three dropped out. Walking and low intensity activities were preferred and nausea and feeling unwell were the most often reported barriers towards PA. DISCUSSION: In order to achieve adequate recruitment, compliance and complete data in future PA intervention trials, close cooperation with treating physicians, individual PA plans and availability of personalized coaching are required. Trial registration NCT01749774, November 2012, ClinicalTrials.gov.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cisplatino/uso terapêutico , Aconselhamento , Exercício Físico/fisiologia , Seminoma/terapia , Neoplasias Testiculares/terapia , Adulto , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Náusea/fisiopatologia , Cooperação do Paciente/psicologia , Cooperação do Paciente/estatística & dados numéricos , Seleção de Pacientes , Medicina de Precisão , Estudos Prospectivos , Seminoma/patologia , Seminoma/psicologia , Neoplasias Testiculares/patologia , Neoplasias Testiculares/psicologia , Resultado do Tratamento
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