RESUMEN
BACKGROUND: KRAS mutations in metastatic colorectal cancer (mCRC) are used as predictive biomarkers to select therapy with EGFR monoclonal antibodies (mAbs). Other factors may be significant determinants of benefit. METHODS: Individual patient data from randomised trials with a head-to-head comparison between EGFR mAb versus no EGFR mAb (chemotherapy alone or best supportive care) in mCRC, across all lines of therapy, were pooled. Overall survival (OS) and progression-free survival (PFS) were compared between groups. Treatment effects within the predefined KRAS biomarker subsets were estimated by adjusted hazard ratio (HRadj) and 95% confidence interval (CI). EGFR mAb efficacy was measured within the KRAS wild-type subgroup according to BRAF and NRAS mutation status. In both KRAS wild-type and mutant subgroups, additional factors that could impact EGFR mAb efficacy were explored including the type of chemotherapy, line of therapy, age, sex, tumour sidedness and site of metastasis. RESULTS: 5675 patients from 8 studies were included, all with known mCRC KRAS mutation status. OS (HRadj 0.90, 95% CI 0.84-0.98, p = 0.01) and PFS benefit (HRadj 0.73, 95% CI 0.68-0.79, p < 0.001) from EGFR mAbs was observed in the KRAS wild-type group. PFS benefit was seen in patients treated with fluorouracil (HRadj 0.75, 95% CI 0.68-0.82) but not with capecitabine-containing regimens (HRadj 1.04, 95% CI 0.86-1.26) (pinteraction = 0.002). Sidedness also interacted with EGFR mAb efficacy, with survival benefit restricted to left-sided disease (pinteraction = 0.038). PFS benefits differed according to age, with benefits greater in those under 70 (pinteraction = 0.001). The survival benefit was not demonstrated in those patients with mutations found in the KRAS, NRAS or BRAF genes. The presence of liver metastases interacted with EGFR mAb efficacy in patients with KRAS mutant mCRC (pinteraction = 0.004). CONCLUSION: The benefit provided by EGFR mAbs in KRAS WT mCRC is associated with left-sided primary tumour location, younger patient age and absence of NRAS or BRAF mutations. Survival benefit is observed with fluorouracil but not capecitabine. Exploratory results support further research in KRAS mutant mCRC without liver metastases.
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Neoplasias del Colon , Neoplasias Colorrectales , Neoplasias Hepáticas , Neoplasias del Recto , Humanos , Anticuerpos Monoclonales/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Proteínas Proto-Oncogénicas B-raf/genética , Proteínas Proto-Oncogénicas p21(ras)/genética , Fluorouracilo , Neoplasias del Colon/tratamiento farmacológico , Neoplasias del Recto/tratamiento farmacológico , Receptores ErbB/genética , Neoplasias Hepáticas/tratamiento farmacológico , Mutación , CetuximabRESUMEN
Immune thrombocytopenia (ITP) was reported as a rare complication of COVID-19 vaccines. We conducted a retrospective single-center analysis of all ITP cases detected in 2021 and compared the quantity with the pre-vaccination years, from 2018 to 2020. In 2021, a two-fold increase in ITP cases was identified compared to previous years; 11 of 40 cases (27.5%) were considered COVID-19-vaccine related. Our study highlights an increase in ITP cases at our institution, probably related to COVID-19 vaccinations. Further studies are needed to investigate this finding globally.
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Vacunas contra la COVID-19 , COVID-19 , Púrpura Trombocitopénica Idiopática , Trombocitopenia , Humanos , COVID-19/epidemiología , COVID-19/prevención & control , Vacunas contra la COVID-19/efectos adversos , Programas de Inmunización , Incidencia , Púrpura Trombocitopénica Idiopática/inducido químicamente , Púrpura Trombocitopénica Idiopática/epidemiología , Estudios Retrospectivos , Trombocitopenia/inducido químicamente , Trombocitopenia/epidemiología , Vacunación/efectos adversosRESUMEN
BACKGROUND: Atypical EGFR mutations occur in 10%-30% of non-small-cell lung cancer (NSCLC) patients with EGFR mutations and their sensitivity to classical epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKI) is highly heterogeneous. Patients harboring one group of uncommon, recurrent EGFR mutations (G719X, S768I, L861Q) respond to EGFR-TKI. Exon 20 insertions are mostly insensitive to EGFR-TKI but display sensitivity to exon 20 inhibitors. Clinical outcome data of patients with very rare point and compound mutations upon systemic treatments are still sparse to date. PATIENTS AND METHODS: In this retrospective, multicenter study of the national Network Genomic Medicine (nNGM) in Germany, 856 NSCLC cases with atypical EGFR mutations including co-occurring mutations were reported from 12 centers. Clinical follow-up data after treatment with different EGFR-TKIs, chemotherapy and immune checkpoint inhibitors were available from 260 patients. Response to treatment was analyzed in three major groups: (i) uncommon mutations (G719X, S7681, L861Q and combinations), (ii) exon 20 insertions and (iii) very rare EGFR mutations (very rare single point mutations, compound mutations, exon 18 deletions, exon 19 insertions). RESULTS: Our study comprises the largest thus far reported real-world cohort of very rare EGFR single point and compound mutations treated with different systemic treatments. We validated higher efficacy of EGFR-TKI in comparison to chemotherapy in group 1 (uncommon), while most exon 20 insertions (group 2) were not EGFR-TKI responsive. In addition, we found TKI sensitivity of very rare point mutations (group 3) and of complex EGFR mutations containing exon 19 deletions or L858R mutations independent of the combination partner. Notably, treatment responses in group 3 (very rare) were highly heterogeneous. Co-occurring TP53 mutations exerted a non-significant trend for a detrimental effect on outcome in EGFR-TKI-treated patients in groups 2 and 3 but not in group 1. CONCLUSIONS: Based on our findings, we propose a novel nNGM classification of atypical EGFR mutations.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Receptores ErbB , Medicina Genómica , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Mutación , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/uso terapéutico , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: Improved, multimodal treatment strategies have been shown to increase cure rates in cancer patients. Those who survive cancer as a child, adolescent or young adult (CAYA), are at a higher risk for therapy-, or disease-related, late or long-term effects. The CARE for CAYA-Program has been developed to comprehensively assess any potential future problems, to offer need-based preventative interventions and thus to improve long-term outcomes in this particularly vulnerable population. METHODS: The trial is designed as an adaptive trial with an annual comprehensive assessment followed by needs stratified, modular interventions, currently including physical activity, nutrition and psycho-oncology, all aimed at improving the lifestyle and/or the psychosocial situation of the patients. Patients, aged 15-39 years old, with a prior cancer diagnosis, who have completed tumour therapy and are in follow-up care, and who are tumour free, will be included. At baseline (and subsequently on an annual basis) the current medical and psychosocial situation and lifestyle of the participants will be assessed using a survey compiled of various validated questionnaires (e.g. EORTC QLQ C30, NCCN distress thermometer, PHQ-4, BSA, nutrition protocol) and objective parameters (e.g. BMI, WHR, co-morbidities like hyperlipidaemia, hypertension, diabetes), followed by basic care (psychological and lifestyle consultation). Depending on their needs, CAYAs will be allocated to preventative interventions in the above-mentioned modules over a 12-month period. After 1 year, the assessment will be repeated, and further interventions may be applied as needed. During the initial trial phase, the efficacy of this approach will be compared to standard care (waiting list with intervention in the following year) in a randomized study. During this phase, 530 CAYAs will be included and 320 eligible CAYAs who are willing to participate in the interventions will be randomly allocated to an intervention. Overall, 1500 CAYAs will be included and assessed. The programme is financed by the innovation fund of the German Federal Joint Committee and will be conducted at 14 German sites. Recruitment began in January 2018. DISCUSSION: CAYAs are at high risk for long-term sequelae. Providing structured interventions to improve lifestyle and psychological situation may counteract against these risk factors. The programme serves to establish uniform regular comprehensive assessments and need-based interventions to improve long-term outcome in CAYA survivors. TRIAL REGISTRATION: Registered at the German Clinical Trial Register (ID: DRKS00012504, registration date: 19th January 2018).
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Cuidados Posteriores/métodos , Supervivientes de Cáncer/psicología , Adolescente , Adulto , Cuidados Posteriores/organización & administración , Niño , Depresión/psicología , Depresión/terapia , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/complicaciones , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/prevención & control , Ejercicio Físico/fisiología , Femenino , Humanos , Estilo de Vida , Masculino , Neoplasias/complicaciones , Neoplasias/psicología , Evaluación Nutricional , Medicina Preventiva/métodos , Medicina Preventiva/organización & administración , Factores de Riesgo , Encuestas y Cuestionarios , Factores de Tiempo , Adulto JovenRESUMEN
Tumor cells always exhibit differences to normal cells. These differences can be recognized by the immune system, enabling the destruction of tumor cells by T cells, as was impressively demonstrated by the success of immune checkpoint inhibition, e.g., in malignant melanoma. Many cancers, however, do not respond to this kind of therapy. In these cases, vaccination against tumor antigens could be very helpful. Nevertheless, all of the efforts made in this respect during the past 30 years have been virtually futile. With current knowledge and technology there is new hope.
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Antígenos de Neoplasias/inmunología , Vacunas contra el Cáncer/uso terapéutico , Melanoma/inmunología , Neoplasias/inmunología , Vacunas contra el Cáncer/inmunología , Humanos , Melanoma/prevención & control , Neoplasias/prevención & control , Neoplasias/terapia , Linfocitos T/inmunología , VacunaciónRESUMEN
The European Society for Medical Oncology (ESMO) consensus conference on testicular cancer was held on 3-5 November 2016 in Paris, France. The conference included a multidisciplinary panel of 36 leading experts in the diagnosis and treatment of testicular cancer (34 panel members attended the conference; an additional two panel members [CB and K-PD] participated in all preparatory work and subsequent manuscript development). The aim of the conference was to develop detailed recommendations on topics relating to testicular cancer that are not covered in detail in the current ESMO Clinical Practice Guidelines (CPGs) and where the available level of evidence is insufficient. The main topics identified for discussion related to: (1) diagnostic work-up and patient assessment; (2) stage I disease; (3) stage II-III disease; (4) post-chemotherapy surgery, salvage chemotherapy, salvage and desperation surgery and special topics; and (5) survivorship and follow-up schemes. The experts addressed questions relating to one of the five topics within five working groups. Relevant scientific literature was reviewed in advance. Recommendations were developed by the working groups and then presented to the entire panel. A consensus vote was obtained following whole-panel discussions, and the consensus recommendations were then further developed in post-meeting discussions in written form. This manuscript presents the results of the expert panel discussions, including the consensus recommendations and a summary of evidence supporting each recommendation. All participants approved the final manuscript.
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Oncología Médica/normas , Recurrencia Local de Neoplasia/prevención & control , Neoplasias de Células Germinales y Embrionarias/terapia , Guías de Práctica Clínica como Asunto , Neoplasias Testiculares/terapia , Cuidados Posteriores/métodos , Cuidados Posteriores/normas , Supervivientes de Cáncer/psicología , Quimioradioterapia Adyuvante/métodos , Quimioradioterapia Adyuvante/normas , Conferencias de Consenso como Asunto , Europa (Continente) , Humanos , Masculino , Oncología Médica/métodos , Terapia Neoadyuvante/métodos , Terapia Neoadyuvante/normas , Recurrencia Local de Neoplasia/epidemiología , Estadificación de Neoplasias , Neoplasias de Células Germinales y Embrionarias/diagnóstico , Neoplasias de Células Germinales y Embrionarias/patología , Orquiectomía/psicología , Cuidados Paliativos/métodos , Cuidados Paliativos/normas , Pronóstico , Calidad de Vida , Factores de Riesgo , Terapia Recuperativa/métodos , Terapia Recuperativa/normas , Sociedades Médicas/normas , Supervivencia , Neoplasias Testiculares/diagnóstico , Neoplasias Testiculares/patología , Testículo/diagnóstico por imagen , Testículo/patología , Testículo/cirugíaRESUMEN
Background: Bone metastases (BM) are rare in germ cell tumor (GCT) patients. Systematic data on risk factors, treatment and outcome are largely lacking. Patients and methods: A database created by an international consortium including 123 GCT patients with BM at primary diagnosis was retrospectively analysed. Survival estimates were calculated by the method of Kaplan-Meier and compared by log-rank testing. Cox regression analysis was applied for risk factor analyses. Results: In our cohort of patients, BM at primary diagnosis more often affected multiple sites (61%) and BM as the only metastatic site were scarce (9%). Histology was non-seminoma in 77% and seminoma in 23% of patients. After a median follow-up of 18 months (range, 0-228), estimated median PFS and OS were 21 (range, 0-225) and 98 months (95%CI, 36-160), respective 2-year PFS and OS rates were 34% and 45%. Negative prognosticators in univariate analysis were a mediastinal primary (PFS; HR 1.92; 95%CI, 1.05-3.50; OS; HR 2.16; 95%CI, 1.14-4.09) and the presence of liver and/or brain metastases (PFS; HR 1.89; 95%CI, 1.13-3.17; OS; HR 1.91; 95%CI, 0.024) Seminomatous histology was the strongest predictor for favorable PFS (multivariate Cox regression; HR, 0.32; P=0.011) with respective 2-year PFS and OS rates of 68% and 75% compared with 24% and 36% for non-seminoma patients. Conclusions: Outcome of GCT patients with primary metastatic bone disease is particularly poor in non-seminoma patients, even worse than the expected outcomes of the general IGCCCG 'poor prognosis' group. This series does not indicate that mutlimodal treatment improves the prognosis over stage-adapted chemotherapy alone, however, the statistical power of these results is limited due to low patient numbers in each specific subgroup.
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Neoplasias Óseas/patología , Neoplasias Encefálicas/patología , Neoplasias de Células Germinales y Embrionarias/patología , Seminoma/patología , Adulto , Anciano , Neoplasias Óseas/epidemiología , Neoplasias Óseas/secundario , Neoplasias Encefálicas/epidemiología , Neoplasias Encefálicas/secundario , Supervivencia sin Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Neoplasias de Células Germinales y Embrionarias/epidemiología , Pronóstico , Sistema de Registros , Estudios Retrospectivos , Factores de Riesgo , Seminoma/epidemiología , Resultado del TratamientoAsunto(s)
Seminoma , Neoplasias Testiculares , Estudios de Seguimiento , Humanos , Masculino , Estadificación de Neoplasias , Orquiectomía , Seminoma/diagnóstico , Seminoma/patología , Seminoma/terapia , Neoplasias Testiculares/diagnóstico , Neoplasias Testiculares/patología , Neoplasias Testiculares/terapiaRESUMEN
BACKGROUND: Risk models of chemotherapy-induced (CIN) and febrile neutropenia (FN) have to date focused on determinants measured at the start of chemotherapy. We extended this static approach with a dynamic approach of CIN/FN risk modeling at the start of each cycle. DESIGN: We applied predictive modeling using multivariate logistic regression to identify determinants of CIN/FN episodes and related hospitalizations and chemotherapy disturbances (CIN/FN consequences) in analyses at the patient ('ever' during the whole period of chemotherapy) and cycle-level (during a given chemotherapy cycle). Statistical dependence of cycle data being 'nested' under patients was managed using generalized estimation equations. Predictive performance of each model was evaluated using bootstrapped c concordance statistics. RESULTS: Static patient-level risk models of 'ever' experiencing CIN/FN adverse events and consequences during a planned chemotherapy regimen included predictors related to history, risk factors, and prophylaxis initiation and intensity. Dynamic cycle-level risk models of experiencing CIN/FN adverse events and consequences in an upcoming cycle included predictors related to history, risk factors, and prophylaxis initiation and intensity; as well as prophylaxis duration, CIN/FN in prior cycle, and treatment center characteristics. CONCLUSIONS: These 'real-world evidence' models provide clinicians with the ability to anticipate CIN/FN adverse events and their consequences at the start of a chemotherapy line (static models); and, innovatively, to assess risk of CIN/FN adverse events and their consequences at the start of each cycle (dynamic models). This enables individualized patient treatment and is consistent with the EORTC recommendation to re-appraise CIN/FN risk at the start of each cycle. Prophylaxis intensity (under-, correctly-, or over-prophylacted relative to current EORTC guidelines) is a major determinant. Under-prophylaxis is clinically unsafe. Over-prophylaxis of patients administered chemotherapy with intermediate or low myelotoxicity levels may be beneficial, both in patients with and without risk factors, and must be validated in future studies.
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Biosimilares Farmacéuticos/efectos adversos , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/patología , Neutropenia Febril/patología , Filgrastim/administración & dosificación , Adulto , Anciano , Biosimilares Farmacéuticos/administración & dosificación , Neutropenia Febril/inducido químicamente , Femenino , Filgrastim/efectos adversos , Factor Estimulante de Colonias de Granulocitos/metabolismo , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Modelos Estadísticos , Factores de RiesgoRESUMEN
BACKGROUND: Multimodality treatment improves the chance of survival but increases the risk for long-term side effects in young cancer survivors, so-called" Adolescents and Young Adults"(AYAs). Compared to the general population AYAs have a 5 to 15-fold increased risk of cardiovascular morbidity. Thus, improving modifiable lifestyle risk factors is of particular importance. METHODS: The INAYA trial included AYAs between 18 and 39 years receiving an intensified individual nutrition counseling at four time points in a 3-month period based on a 3-day dietary record. At week 0 and 12 AYAs got a face-to-face counseling, at week 2 and 6 by telephone. Primary endpoint was change in nutritional behavior measured by Healthy Eating Index - European Prospective Investigation into Cancer and Nutrition (HEI-EPIC). RESULTS: Twenty-three AYAs (11 female, 12 male, median age 20 years (range 19-23 years), median BMI: 21.4 kg/m2 (range: 19.7-23.9 kg/m2) after completion of cancer treatment for sarcoma (n = 2), carcinoma (n = 2), blastoma (n = 1), hodgkin lymphoma (n = 12), or leukemia (n = 6) were included (median time between diagnosis and study inclusion was 44 month). The primary endpoint was met, with an improvement of 20 points in HEI-EPIC score in 52.2 % (n = 12) of AYAs. At baseline, median HEI-EPIC score was 47.0 points (range from 40.0 to 55.0 points) and a good, moderate and bad nutritional intake was seen in 4.3, 73.9 and 21.7 % of AYAs. At week 12, median HEI-EPIC improved significantly to 65.0 points (range from 55.0 to 76.0 points) (p ≤ 0.001) and a good, moderate and bad nutritional intake was seen in 47.8, 52.2 and 0 % of AYAs. No change was seen in quality of life, waist-hip ratio and blood pressure. CONCLUSION: Intensified nutrition counseling is feasible and seem to improve nutritional behavior of AYAs. Further studies will be required to demonstrate long-term sustainability and confirm the results in a randomized design in larger cohorts. TRIAL REGISTRATION: Clinical trial identifier DRKS00009883 on DRKS.
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Neoplasias/epidemiología , Evaluación Nutricional , Estado Nutricional , Adolescente , Adulto , Biomarcadores , Índice de Masa Corporal , Niño , Conducta Alimentaria , Femenino , Humanos , Masculino , Neoplasias/diagnóstico , Calidad de Vida , Sobrevivientes , Relación Cintura-Cadera , Adulto JovenRESUMEN
INTRODUCTION: Despite similar residual factor VIII activity, patients with haemophilia A (HA) show significant interindividual variability with regard to bleeding frequency and severity, suggesting that additional factors modulate thrombin generation and fibrin deposition. Protein disulphide isomerase (PDI) is an abundant oxidoreductase that exerts pleiotropic effects in primary and secondary haemostasis and contributes to thrombosis and vascular inflammation. AIM: We conducted a pilot study to explore a potential role of platelet PDI in patients with HA. METHODS: Expression and release of platelet PDI were studied by flow cytometry and enzyme-linked immunosorbent assay, respectively. RESULTS: Compared to healthy male controls (n = 12), patients with HA (n = 24) showed significantly increased expression of PDI antigen on ADP- or TRAP-6-, but not on buffer-treated platelets, a finding that could not be explained by enhanced platelet activation, as indicated by expression of the α-granule protein, CD62P (P-selectin). While platelet agonists did not affect PDI secretion in healthy male controls, increased levels of PDI antigen were found in supernatants of TRAP-6-treated platelets from patients with HA. Importantly, in two patients with exceedingly high TRAP-6-induced PDI release over baseline, findings were consistent when platelets were isolated and stimulated on a separate occasion. No obvious association was found between platelet PDI and bleeding phenotype in this patient cohort. CONCLUSION: Agonist-induced expression and release of platelet PDI were increased in patients with HA. Larger studies are needed to clarify if variations in this platelet response contribute to the diversity in bleeding frequency and severity among patients with congenital factor VIII deficiency.
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Plaquetas/metabolismo , Hemofilia A/metabolismo , Proteína Disulfuro Isomerasas/metabolismo , Adulto , Femenino , Citometría de Flujo , Humanos , Masculino , Proyectos PilotoRESUMEN
INTRODUCTION: In haemophilia, clinical outcomes are mainly determined by the severity of clotting factor deficiency, treatment regimen, availability of clotting factor concentrate and age. Information about the relevance of patient-related factors such as education, social status or impact of the disease on the patient's life is scarce. AIM: To assess the impact of social status and disease-related impairment of certain aspects of the patient's life on clinical and psychosocial outcomes in patients with inherited bleeding disorders (PWBD). METHODS: Consecutive patients of a single centre were assessed by questionnaires on social status and quality of life (SF-36). Social status was defined by school and professional education, employment and financial income of patients as well as school education of their parents. RESULTS: Fifty-seven PWBD (mean age, 38 ± 16 years) were enrolled, 60% were treated on-demand; PWBD had a median number of 2.5 (0-34) annual bleeds and a median orthopaedic joint score of 6 (0-38). No significant differences were found for clinical and psychosocial outcomes across social status groups. More than half of the patients reported that haemophilia had an impact on their school education, childhood and leisure activities. Patients with a high impact of haemophilia on their lives were less satisfied with their lives (P < 0.002), reported worse quality of life in all domains of the SF-36, had a worse joint score (P < 0.024) and reported more pain (P < 0.013). CONCLUSION: The perceived impact of haemophilia on patients' lives seems to have a stronger impact on clinical and psychosocial outcomes than patients' actual social status.
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Hemofilia A/psicología , Enfermedades de von Willebrand/psicología , Adulto , Femenino , Hemofilia A/terapia , Humanos , Masculino , Resultado del Tratamiento , Enfermedades de von Willebrand/terapiaRESUMEN
PURPOSE: This prospective study aimed to determine the extent to which cancer patients experience loss of dignity during primary cancer care (baseline) and at 3-month follow-up and the contribution of positive social support and detrimental social interactions on loss of dignity at follow-up. METHODS: At baseline, we enrolled N = 270 cancer patients (advanced cancer 57 %) undergoing oncological treatment. At follow-up, n = 178 patients (72 %) participated. Patients completed the following questionnaires: sense of dignity item (SDI), physical problem list of the NCCN Distress Thermometer, Illness-Specific Social Support Scale (SSUK), Patient Health Questionnaire (PHQ-9), and Generalized Anxiety Disorder Questionnaire (GAD-7). We conducted ordinal regression analyses controlling for age, gender, tumor stage, number of physical symptoms, depression, and anxiety. RESULTS: At baseline, 18 % of the patients experienced moderate to extreme loss of dignity (follow-up 23 %, p = 0.27). Detrimental interactions significantly predicted loss of dignity (OR = 1.42, 95 % CI 1.06-1.90) in a model including positive support (OR = 1.10, 95 % CI 0.82-1.49), depression (OR = 1.55, 95 % CI 0.96-2.51), and anxiety (OR = 1.20, 95 % CI 0.83-1.74). Items in relation to detrimental interactions with significant others such as "made you feel like you couldn't take care of yourself" (r = 0.29, p < 0.001) and "felt uncomfortable in illness conversations" (r = 0.24, p = 0.002) showed the highest associations with perceived loss of dignity. CONCLUSION: Loss of dignity was a frequent problem in our mixed cancer patient sample. Detrimental interactions that weaken the sense of dignity may result from discrepancies with patients' needs for autonomy and security. Tailoring social support to attachment-related patient needs may help to conserve patients' sense of dignity.
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Ansiedad/psicología , Depresión/psicología , Relaciones Interpersonales , Neoplasias/psicología , Apoyo Social , Adulto , Anciano , Ansiedad/etiología , Depresión/etiología , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Neoplasias/complicacionesRESUMEN
BACKGROUND: Integrins are involved in tumour progression and metastasis, and differentially expressed on colorectal cancer (CRC) cells. Abituzumab (EMD 525797), a humanised monoclonal antibody targeting integrin αν heterodimers, has demonstrated preclinical activity. This trial was designed to assess the tolerability of different doses of abituzumab in combination with cetuximab and irinotecan (phase I) and explore the efficacy and tolerability of the combination versus that of cetuximab and irinotecan in patients with metastatic CRC (mCRC) (phase II part). METHODS: Eligible patients had KRAS (exon 2) wild-type mCRC and had received prior oxaliplatin-containing therapy. The trial comprised an initial safety run-in using abituzumab doses up to 1000 mg combined with a standard of care (SoC: cetuximab plus irinotecan) and a phase II part in which patients were randomised 1 : 1 : 1 to receive abituzumab 500 mg (arm A) or 1000 mg (arm B) every 2 weeks combined with SoC, or SoC alone (arm C). The primary end point was investigator-assessed progression-free survival (PFS). Secondary end points included overall survival (OS), response rate (RR) and tolerability. Associations between tumour integrin expression and outcomes were also assessed. RESULTS: Phase I showed that abituzumab doses up to 1000 mg were well tolerated in combination with SoC. Seventy-three (arm A), 71 (arm B) and 72 (arm C) patients were randomised to the phase II part. Baseline characteristics were balanced. PFS was similar in the three arms: arm A versus SoC, hazard ratio (HR) 1.13 [95% confidence interval (CI) 0.78-1.64]; arm B versus SoC, HR 1.11 (95% CI 0.77-1.61). RRs were also similar. A trend toward improved OS was observed: arm A versus SoC, HR 0.83 (95% CI 0.54-1.28); arm B versus SoC, HR 0.80 (95% CI 0.52-1.25). Grade ≥3 treatment-emergent adverse events were observed in 72%, 78% and 67% of patients. High tumour integrin αvß6 expression was associated with longer OS in arms A [HR 0.55 (0.30-1.00)] and B [HR 0.41 (0.21-0.81)] than in arm C. CONCLUSION: The primary PFS end point was not met, although predefined exploratory biomarker analyses identified subgroups of patients in whom abituzumab may have benefit. The tolerability of abituzumab combined with cetuximab and irinotecan was acceptable. Further study is warranted. CLINICALTRIALS.GOV IDENTIFIER: NCT01008475.
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Anticuerpos Monoclonales Humanizados/uso terapéutico , Antineoplásicos/uso terapéutico , Camptotecina/análogos & derivados , Neoplasias Colorrectales/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos Monoclonales Humanizados/efectos adversos , Antineoplásicos/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Camptotecina/efectos adversos , Camptotecina/uso terapéutico , Cetuximab , Neoplasias Colorrectales/mortalidad , Supervivencia sin Enfermedad , Receptores ErbB/antagonistas & inhibidores , Femenino , Humanos , Integrina alfaV/biosíntesis , Integrina alfaV/inmunología , Irinotecán , Masculino , Persona de Mediana Edad , Proteínas Proto-Oncogénicas/genética , Proteínas Proto-Oncogénicas p21(ras) , Proteínas ras/genéticaRESUMEN
PURPOSE: Patients with cancer frequently experience chemotherapy-induced anaemia (CIA) and iron deficiency. Erythropoiesis-stimulating agents (ESAs), iron supplementation and blood transfusions are available therapies. This study evaluated routine practice in CIA management. METHODS: Medical oncologists and/or haematologists from nine European countries (n=375) were surveyed on their last five cancer patients treated for CIA (n=1,730). Information was collected on tests performed at diagnosis of anaemia, levels of haemoglobin (Hb), serum ferritin and transferrin saturation (TSAT), as well as applied anaemia therapies. RESULTS: Diagnostic tests and therapies for CIA varied across Europe. Anaemia and iron status were mainly assessed by Hb (94%) and ferritin (48%) measurements. TSAT was only tested in 14%. At anaemia diagnosis, 74% of patients had Hb ≤ 10 g/dL, including 15% with severe anaemia (Hb <8 g/dL). Low-iron levels (ferritin ≤ 100 ng/mL) were detected in 42% of evaluated patients. ESA was used in 63%of patients, blood transfusions in 52 % and iron supplementation in 31% (74% oral, 26% intravenous iron). Only 30% of ESA-treated patients received a combination of ESA and iron supplementation. Blood transfusions formed part of a regular anaemia treatment regimen in 76% of transfused patients. Management practices were similar in 2009 and 2011. CONCLUSION: Management of anaemia and iron status in patients treated for CIA varies substantially across Europe. Iron status is only assessed in half of the patients. In contrast to clinical evidence, iron treatment is under utilised and mainly based on oral iron supplementation. Implementation of guidelines needs to be increased to minimize the use of blood transfusions.
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Anemia/inducido químicamente , Anemia/terapia , Antineoplásicos/efectos adversos , Hematínicos/uso terapéutico , Neoplasias/tratamiento farmacológico , Anemia/sangre , Anemia/diagnóstico , Antineoplásicos/uso terapéutico , Femenino , Ferritinas/sangre , Hemoglobinas/metabolismo , Humanos , Quimioterapia de Inducción , Hierro/administración & dosificación , Masculino , Persona de Mediana Edad , Neoplasias/sangreRESUMEN
BACKGROUND: In relapsed or refractory (RR) metastatic germ cell cancer (GCC), high-dose (HD) chemotherapy (CTX) plus autologous stem cell transplantation is considered the standard of care. Limited data exist regarding the efficacy of HD-CTX following conventionally dosed salvage regimens (CDRs). This analysis explores and contrasts the efficacy of HD-CTX as the first or subsequent salvage regimen. PATIENTS AND METHODS: Data were retrospectively collected to explore the efficacy of HD-CTX administered as the first (group A) or subsequent salvage CTX (group B) after a CDR. The primary endpoint was OS from the time of HD-CTX. Associations of survival, overall response rate (ORR), and toxicity with clinical characteristics were explored using stratified Kaplan-Meier and Cox regression models. RESULTS: Overall, 283 patients with GCC were included from 11 international centers, with 159 patients (56%) in group A and 124 patients (44%) in group B. The first salvage treatment was administered between 1998 and 2022, with a median follow-up of 27.0 [standard deviation (SD) 46.2] months for group A and 17.0 (SD 48.5) months for group B. The median OS from HD-CTX treatment initiation was not reached in group A, compared with 25 months in group B (P = 0.00027), associated with 2- and 5-year OS rates of 74% and 63% (group A) versus 53% and 37% (group B), respectively. When administered as the first salvage treatment, HD-CTX was associated with a higher ORR (79% versus 60%; P = 0.013) and lower nonhematologic grade ≥3 toxicity rate (78% versus 97%; P < 0.001). Concerning risk factor analysis for the total cohort, the International Prognostic Factors Study Group score was the only independent predictor of OS in multivariable analysis (P = 0.006). CONCLUSIONS: When administered as the initial salvage treatment or after CDR, HD-CTX exhibits curative potential for patients with RR GCC. The efficacy and safety outcomes were more favorable when HD-CTX was conducted as the first salvage treatment line.
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Neoplasias de Células Germinales y Embrionarias , Terapia Recuperativa , Humanos , Terapia Recuperativa/métodos , Masculino , Neoplasias de Células Germinales y Embrionarias/tratamiento farmacológico , Estudios Retrospectivos , Adulto , Persona de Mediana Edad , Recurrencia Local de Neoplasia/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Adulto Joven , Resultado del Tratamiento , FemeninoRESUMEN
BACKGROUND: The aim of our analysis is to further characterise the prognostic relevance of early tumour shrinkage (TS) during VEGF-targeted therapy in mRCC, in order to explore whether this could define a group of patients with long-term survivorship. METHODS: A hundred patients were stratified into five subgroups according to their change of tumour size with first treatment evaluation: -100% to -60%; -59% to -30% and -29% to 0% TS or gain of tumour size from 1% to 19% and ≤20% or occurrence of new lesions (i.e., progressive disease). RESULTS: The median PFS and OS were 10.4 months and 28.2 months, respectively. The median OS stratified according to the subgroups as described above was 77.4, 33.5, 26.9, 30.0 and 14.3 months, respectively. Multivariate analysis revealed early TS as a prognostic marker (P=0.021; HR 1.624). CONCLUSION: The extent of TS defines a small proportion of patients with an excellent prognosis. Larger studies are warranted to define the relationship of long-term survivorship and extent of TS with targeted therapies.
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Antineoplásicos/uso terapéutico , Carcinoma de Células Renales/tratamiento farmacológico , Carcinoma de Células Renales/patología , Neoplasias Renales/tratamiento farmacológico , Neoplasias Renales/patología , Factor A de Crecimiento Endotelial Vascular/metabolismo , Inhibidores de la Angiogénesis/efectos adversos , Inhibidores de la Angiogénesis/uso terapéutico , Antineoplásicos/efectos adversos , Carcinoma de Células Renales/metabolismo , Supervivencia sin Enfermedad , Femenino , Humanos , Neoplasias Renales/metabolismo , Masculino , Persona de Mediana Edad , Terapia Molecular Dirigida , Metástasis de la Neoplasia , Pronóstico , Inhibidores de Proteínas Quinasas/efectos adversos , Inhibidores de Proteínas Quinasas/uso terapéutico , Análisis de Supervivencia , Resultado del TratamientoAsunto(s)
Anemia Ferropénica/terapia , Hematínicos/administración & dosificación , Hierro/administración & dosificación , Oncología Médica/normas , Neoplasias/complicaciones , Anemia Ferropénica/sangre , Anemia Ferropénica/diagnóstico , Anemia Ferropénica/etiología , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Biosimilares Farmacéuticos/administración & dosificación , Biosimilares Farmacéuticos/normas , Transfusión de Eritrocitos/efectos adversos , Transfusión de Eritrocitos/métodos , Transfusión de Eritrocitos/normas , Europa (Continente) , Hematínicos/normas , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Trasplante de Células Madre Hematopoyéticas/métodos , Trasplante de Células Madre Hematopoyéticas/normas , Humanos , Oncología Médica/métodos , Neoplasias/sangre , Neoplasias/terapia , Sociedades Médicas/normas , Terapias en Investigación/efectos adversos , Terapias en Investigación/métodos , Terapias en Investigación/normas , Resultado del TratamientoRESUMEN
In November 2011, the Third European Consensus Conference on Diagnosis and Treatment of Germ-Cell Cancer (GCC) was held in Berlin, Germany. This third conference followed similar meetings in 2003 (Essen, Germany) and 2006 (Amsterdam, The Netherlands) [Schmoll H-J, Souchon R, Krege S et al. European consensus on diagnosis and treatment of germ-cell cancer: a report of the European Germ-Cell Cancer Consensus Group (EGCCCG). Ann Oncol 2004; 15: 1377-1399; Krege S, Beyer J, Souchon R et al. European consensus conference on diagnosis and treatment of germ-cell cancer: a report of the second meeting of the European Germ-Cell Cancer Consensus group (EGCCCG): part I. Eur Urol 2008; 53: 478-496; Krege S, Beyer J, Souchon R et al. European consensus conference on diagnosis and treatment of germ-cell cancer: a report of the second meeting of the European Germ-Cell Cancer Consensus group (EGCCCG): part II. Eur Urol 2008; 53: 497-513]. A panel of 56 of 60 invited GCC experts from all across Europe discussed all aspects on diagnosis and treatment of GCC, with a particular focus on acute and late toxic effects as well as on survivorship issues. The panel consisted of oncologists, urologic surgeons, radiooncologists, pathologists and basic scientists, who are all actively involved in care of GCC patients. Panelists were chosen based on the publication activity in recent years. Before the meeting, panelists were asked to review the literature published since 2006 in 20 major areas concerning all aspects of diagnosis, treatment and follow-up of GCC patients, and to prepare an updated version of the previous recommendations to be discussed at the conference. In addition, â¼50 E-vote questions were drafted and presented at the conference to address the most controversial areas for a poll of expert opinions. Here, we present the main recommendations and controversies of this meeting. The votes of the panelists are added as online supplements.