RESUMO
PURPOSE: When a pregnant woman is diagnosed with cancer, she faces complex and unique challenges while navigating both obstetric and oncological care. Despite often being the primary support for women diagnosed with cancer during pregnancy (CDP), little is known about the experiences of their partners. We undertook an in-depth exploration of the experiences of partners of women diagnosed with CDP in Australia. METHODS: Semi-structured interviews were conducted with partners of women diagnosed with CDP treated in Australia. Interviews explored partners' inclusion in decision making and communication with health professionals and their own coping experiences. Data were analysed thematically. RESULTS: Data from interviews with 12 male partners (N = 12) of women diagnosed with CDP were analysed. Two unique themes relevant to partners were identified: 'Partners require support to adjust to changing roles and additional burdens' and 'Treating the couple as a team facilitates agency and coping, but partners' needs are placed second by all'. CONCLUSION: Partners of women diagnosed with CDP commonly experience unique stressors and a substantial shift in previously established roles across multiple domains including medical advocacy, household coordination and parenting. Partners' coping is interlinked with how the woman diagnosed with CDP is coping. Inclusion of partners in treatment decisions and communications, and considering partners' wellbeing alongside that of the woman with CDP, is likely to be supportive for partners. In turn, this is likely to enhance the quality of support that women diagnosed with CDP receive from their partners.
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Adaptação Psicológica , Pesquisa Qualitativa , Cônjuges , Humanos , Feminino , Gravidez , Adulto , Masculino , Cônjuges/psicologia , Austrália , Complicações Neoplásicas na Gravidez/psicologia , Complicações Neoplásicas na Gravidez/terapia , Neoplasias/psicologia , Entrevistas como Assunto , Tomada de Decisões , Apoio SocialRESUMO
BACKGROUND: Studies on the efficacy of rituximab in primary CNS lymphoma (PCNSL) reported conflicting results. Our international randomized phase 3 study showed that the addition of rituximab to high-dose methotrexate, BCNU, teniposide, and prednisolone (MBVP) in PCNSL was not efficacious in the short term. Here we present long-term results after a median follow-up of 82.3 months. METHODS: One hundred and ninety-nine eligible newly diagnosed, nonimmunocompromised patients with PCNSL aged 18-70 years with WHO performance status 0-3 was randomized between treatment with MBVP chemotherapy with or without rituximab, followed by high-dose cytarabine consolidation in responding patients, and reduced-dose WBRT in patients agedâ ≤â 60 years. Event-free survival was the primary endpoint. Overall survival rate, neurocognitive functioning (NCF), and health-related quality of life (HRQoL) were additionally assessed, with the IPCG test battery, EORTC QLQ-C30 and QLQ-BN20 questionnaires, respectively. RESULTS: For event-free survival, the hazard ratio was 0.85, 95% CI 0.61-1.18, Pâ =â .33. Overall survival rate at 5 years for MBVP and R-MBVP was 49% (39-59) and 53% (43-63) respectively. In total, 64 patients died in the MBVP arm and 55 in the R-MBVP arm, of which 69% were due to PCNSL. At the group level, all domains of NCF and HRQoL improved to a clinically relevant extent after treatment initiation, and remained stable thereafter up to 60 months of follow-up, except for motor speed which deteriorated between 24 and 60 months. Although fatigue improved initially, high levels persisted in the long term. CONCLUSIONS: Long-term follow-up confirms the lack of added value of rituximab in addition to MBVP and HD-cytarabine for PCNSL.
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Neoplasias do Sistema Nervoso Central , Linfoma , Humanos , Metotrexato/uso terapêutico , Rituximab/uso terapêutico , Teniposídeo/uso terapêutico , Carmustina/uso terapêutico , Linfoma/terapia , Prednisolona/uso terapêutico , Qualidade de Vida , Terapia Combinada , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias do Sistema Nervoso Central/patologia , Citarabina/uso terapêuticoRESUMO
PURPOSE: Radiation-induced meningiomas (RIM) are the most common secondary neoplasm post cranial radiotherapy, yet optimal surveillance and treatment strategies remain contentious. Herein, we report the clinical outcomes and radiological growth rate of RIM, diagnosed in a cohort of survivors undergoing MRI screening, with the objective of informing clinical guidelines and practice. MATERIALS AND METHODS: Long-term survivors of paediatric or young-adult malignancies, diagnosed with RIM between 1990 and 2015, were identified. Absolute (AGR) and relative (RGR) volumetric growth rates were calculated. Rapid growth was defined as AGR > 2 cm3/year or AGR > 1 cm3/year and RGR ≥ 30% RESULTS: Fifty-two patients (87 RIM) were included. Median age at first RIM diagnosis was 33.9 (range,13.8-54.1) years. Seventy-seven (88%) RIM were asymptomatic at detection. Median follow-up time from first RIM detection was 11 (range, 0.6-28) years. Median absolute and relative volumetric growth rates were 0.05 (IQR 0.01-0.11) cm3 and 26 (IQR 7-79) % per year, respectively. Two (3.3%) RIM demonstrated rapid growth. Active surveillance was adopted for 67 (77%) RIM in 40 patients. Neurological sequelae due to RIM progression were reported in 5% of patients on active surveillance. Surgery was performed for 33 RIM (30 patients): 18 (54.5%) at diagnosis and 15 (45.5%) after active surveillance. Histopathology was WHO Grade 1 (85.2%), 2 (11.1%), 3 (3.7%). Following resection, 10-year local recurrence rate was 12%. During follow-up, 19 (37%) survivors developed multiple RIM. CONCLUSIONS: Asymptomatic RIM are typically low-grade tumours which exhibit slow growth. Active surveillance appears to be a safe initial strategy for asymptomatic RIM, associated with a low rate of neurological morbidity.
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Neoplasias Meníngeas , Meningioma , Humanos , Adulto Jovem , Criança , Adolescente , Adulto , Pessoa de Meia-Idade , Meningioma/radioterapia , Meningioma/cirurgia , Conduta Expectante , Estudos Retrospectivos , Sobreviventes , Progressão da DoençaRESUMO
Lymphoma in pregnancy (LIP) presents unique clinical, social and ethical challenges; however, the evidence regarding this clinical scenario is limited. We conducted a multicentre retrospective observational study reporting on the features, management, and outcomes of LIP in patients diagnosed between January 2009 and December 2020 at 16 sites in Australia and New Zealand for the first time. We included diagnoses occurring either during pregnancy or within the first 12 months following delivery. A total of 73 patients were included, 41 diagnosed antenatally (AN cohort) and 32 postnatally (PN cohort). The most common diagnoses were Hodgkin lymphoma (HL; 40 patients), diffuse large B-cell lymphoma (DLBCL; 11) and primary mediastinal B-cell lymphoma (PMBCL; six). At a median follow up of 2.37 years, the 2- and 5-year overall survival (OS) for patients with HL were 91% and 82%. For the combined DLBCL and PMBCL group, the 2-year OS was 92%. Standard curative chemotherapy regimens were successfully delivered to 64% of women in the AN cohort; however, counselling regarding future fertility and termination of pregnancy were suboptimal, and a standardised approach to staging lacking. Neonatal outcomes were generally favourable. We present a large multicentre cohort of LIP reflecting contemporary practice and identify areas in need of ongoing research.
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Doença de Hodgkin , Linfoma Difuso de Grandes Células B , Gravidez , Recém-Nascido , Humanos , Feminino , Resultado do Tratamento , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Doença de Hodgkin/terapia , Doença de Hodgkin/tratamento farmacológico , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Estudos Retrospectivos , Rituximab/uso terapêuticoRESUMO
Lymphoma in pregnancy is a rare and challenging diagnosis that complicates â¼1:6000 pregnancies; posing a series of unique therapeutic, social, and ethical challenges to the patient, her family, and the medical professionals involved. These difficulties are compounded by the paucity of real-world data on the management of LIP, and a lack of relevant support systems for women in this setting. We conducted a retrospective multicenter qualitative study, interviewing women aged ≥18 years of age diagnosed with Hodgkin (HL) or non-Hodgkin lymphoma (NHL) during pregnancy or within 12 months postpartum, between 1 January 2009 and 31 December 2020 from 13 Australasian sites. Semi-structured telephone interviews were conducted, recorded, and analyzed using QSR Int NVivo 12 Pro (March 2020, USA) to quantify salient themes. Of the 32 women interviewed, 20 (63%) were diagnosed during pregnancy (16, 34, and 13% in the 1st, 2nd, and 3rd trimesters, respectively), while 12 (37%) were diagnosed post-partum. Women recalled that their chief concerns at diagnosis were the welfare of their child (n = 13, 41%) and a fear of dying (n = 9, 28%). Perceived diagnostic delay attributed to pregnancy was reported by 41% of participants. Other key themes were communication, educational materials, psychosocial supports, and oncofertility issues. To our knowledge this is the first report capturing the lived experiences of survivors of lymphoma during pregnancy, affording a unique opportunity to consider the management, psychosocial supports, and delivery of care to meet the needs of these women.What is the NEW aspect of your work? To our knowledge, this is the first report capturing and analyzing the healthcare experiences of survivors of Lymphoma in Pregnancy (LIP).What is the CENTRAL finding of your work? Women valued clear and empathic communication, provision of tailored educational materials, access to psychosocial supports (particularly childcare and financial supports), and timely oncofertility management in their healthcare journey.What is (or could be) the SPECIFIC clinical relevance of your work? Women's personal accounts of positive and negative experiences of LIP care provide insights into their specific concerns and needs which can shape healthcare policy and development of a specific framework for managing and supporting patients with LIP (and other cancers).
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Linfoma não Hodgkin , Neoplasias , Humanos , Gravidez , Criança , Feminino , Adolescente , Adulto , Lactente , Diagnóstico Tardio , Medo , Estudos RetrospectivosRESUMO
Platelets have been shown to enhance the survival of lymphoma cell lines. However, it remains unclear whether they play a role in lymphoma. Here, we investigated the potential role of platelets and/or megakaryocytes in the progression of Eµ-myc lymphoma. Eµ-myc tumor cells were transplanted into recipient wild-type (WT) control, Mpl-/-, or TpoTg mice, which exhibited normal, low, and high platelet and megakaryocyte counts, respectively. TpoTg mice that underwent transplantation exhibited enhanced lymphoma progression with increased white blood cell (WBC) counts, spleen and lymph node weights, and enhanced liver infiltration when compared with WT mice. Conversely, tumor-bearing Mpl-/- mice had reduced WBC counts, lymph node weights, and less liver infiltration than WT mice. Using an Mpl-deficient thrombocytopenic immunocompromised mouse model, our results were confirmed using the human non-Hodgkin lymphoma GRANTA cell line. Although we found that platelets and platelet-released molecules supported Eµ-myc tumor cell survival in vitro, pharmacological inhibition of platelet function or anticoagulation in WT mice transplanted with Eµ-myc did not improve disease outcome. Furthermore, transient platelet depletion or sustained Bcl-xL-dependent thrombocytopenia did not alter lymphoma progression. Cytokine analysis of the bone marrow fluid microenvironment revealed increased levels of the proinflammatory molecule interleukin 1 in TpoTg mice, whereas these levels were lower in Mpl-/- mice. Moreover, RNA sequencing of blood-resident Eµ-myc lymphoma cells from TpoTg and WT mice after tumor transplantation revealed the upregulation of hallmark gene sets associated with an inflammatory response in TpoTg mice. We propose that the proinflammatory microenvironment in TpoTg mice promotes lymphoma progression.
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Linfoma , Trombocitopenia , Camundongos , Animais , Humanos , Megacariócitos/metabolismo , Receptores de Trombopoetina , Plaquetas/metabolismo , Trombocitopenia/genética , Linfoma/genética , Microambiente TumoralRESUMO
Melanoma is one of the most common cancers diagnosed in New Zealand, and New Zealand has one of the highest rates of melanoma incidence and mortality in the world. Monitoring by Environmental Health Intelligence NZ (EHINZ) has found a recent sharp decline in melanoma mortality rates in New Zealand. Since 2014 and 2015 (with 376 and 378 melanoma deaths, respectively), melanoma deaths have declined to 362 deaths in 2016, 308 deaths in 2017, and 296 deaths in 2018. We believe that two new PD-1 inhibitor drug treatments introduced in New Zealand in 2016-nivolumab (Opdivo, BMS) and pembrolizumab (Keytruda, MSD)-may have contributed to this decrease in melanoma mortality. Other factors are unlikely to have had such a major effect, with the drop unlikely due to random variation, and no major changes in melanoma registrations or melanoma thickness at diagnosis over the past decade. While our monitoring of the time trend is descriptive only, and cannot attribute causality, it does suggest a recent decrease in melanoma mortality rates at the population level. These national-level statistics reflect both what might be expected in the New Zealand situation with the introduction of PD-1 inhibitor treatments, based on clinical trials, and what oncologists are seeing at an individual level. Further studies could investigate this observational finding, to confirm whether PD-1 inhibitor drug treatments are having an impact on melanoma mortality and survival rates in New Zealand.
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Inibidores de Checkpoint Imunológico , Melanoma , Humanos , Incidência , Melanoma/epidemiologia , Nova Zelândia/epidemiologia , Nivolumabe/uso terapêuticoRESUMO
BACKGROUND: The development of Bruton's tyrosine kinase inhibitors (BTKi) for the treatment of chronic lymphocytic leukaemia (CLL) has provided a highly effective and relatively non-toxic alternative to conventional chemotherapy. Some studies have shown that BTKi can also lead to improvements in T cell immunity in patients despite in vitro analyses suggesting an immunosuppressive effect of BTKi on T cell function. METHODS: In this study, we examined both the in vitro effect and long-term in vivo effect of two clinically available BTKi, ibrutinib and zanubrutinib. Additional in vitro assessments were undertaken for a third BTKi, acalabrutinib. Immune subset phenotyping, cytokine secretion, T cell degranulation and proliferation assays were performed on peripheral blood mononuclear cells isolated from untreated CLL patients, and CLL patients on long-term (> 12 months) BTKi treatment. RESULTS: Similar to prior studies we observed that long-term BTKi treatment normalises lymphocyte subset frequency and reduces PD-1 expression on T cells. We also observed that T cells from patients taken prior to BTKi therapy showed an abnormal hyper-proliferation pattern typical of senescent T cells, which was normalised by long-term BTKi treatment. Furthermore, BTKi therapy resulted in reduced expression of the T cell exhaustion markers PD-1, TIM3 and LAG3 in late generations of T cells undergoing proliferation. CONCLUSIONS: Collectively, these findings indicate that there are critical differences between the in vitro effects of BTKi on T cell function and the effects derived from long-term BTKi exposure in vivo. Overall long-term exposure to BTKi, and particularly ibrutinib, resulted in improved T cell fitness in part due to suppressing the abnormal hyper-proliferation of CLL T cells and the associated development of T cell senescence.
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Leucemia Linfocítica Crônica de Células B , Adenina/análogos & derivados , Proliferação de Células , Humanos , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Leucócitos Mononucleares , Piperidinas , Inibidores de Proteínas Quinases , Linfócitos TRESUMO
OBJECTIVES: To identify features enhancing the quality of healthcare experiences for women with gestational cancer, and explore the impact of the heterogeneous Australian healthcare system on those experiences. METHODS: Semi-structured, qualitative interviews were conducted with women diagnosed with any cancer during pregnancy in the last five years. Recruitment occurred during 2018-2019 via social media and professional, clinical and community networks. Questions related to women's experiences of their healthcare, wellbeing and psychosocial needs. Interviews were analysed thematically. RESULTS: Study participants (n = 23) received treatment in the private sector (n = 10), public sector (n = 8), or both (n = 5). Five interview themes were found: Control over healthcare; Trust in clinicians, hospitals and systems; Coordination of care; An uncommon diagnosis; Holistic, future-oriented care. Women were most likely to have had a positive healthcare experience when (a)care was well-coordinated and adjusted to meet their unique needs/challenges, and (b)women perceived their care went beyond their immediate medical needs and encompassed future psychosocial wellbeing, including preparation for postpartum challenges. CONCLUSION: Existing 'usual care' in the public and/or private sector for both the pregnancy and the cancer is insufficient to meet these women's needs. Prioritising psychological wellbeing including psychosocial needs, and communication and planning around fertility and postnatal challenges are essential for this population.
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Atenção à Saúde , Neoplasias , Austrália , Feminino , Humanos , Gravidez , Pesquisa QualitativaAssuntos
Neoplasias , Poder Familiar , Criança , Estudos de Viabilidade , Humanos , Neoplasias/terapia , Relações Pais-Filho , PaisRESUMO
Cancer therapy related cardiac dysfunction (CTRCD) is an area of increasing focus, particularly during the survivorship period, for paediatric, adolescent and adult cancer survivors. With the advent of immunotherapy and targeted therapy, there is a new set of mechanisms from which paediatric and young adult patients with cancer may suffer cardiovascular injury. Furthermore, cardiovascular disease is the leading cause of morbidity and mortality in the survivorship period. The recently established Australian Cardio-Oncology Registry is the largest and only population-based cardiotoxicity database of paediatric and adolescent and young adult oncology patients in the world, and the first paediatric registry that will document cardiotoxicity caused by chemotherapy and novel targeted therapies using a prospective approach. The database is designed for comprehensive data collection and evaluation of the Australian practice in terms of diagnosis and management of CTRCD. Using the Australian Cardio-Oncology Registry critical clinical information will be collected regarding predisposing factors for the development of CTRCD, the rate of subclinical left ventricular dysfunction and transition to overt heart failure, further research into protectant molecules against cardiac dysfunction and aid in the discovery of which genetic variants predispose to CTRCD. A health economic arm of the study will assess the cost/benefit of both the registry and cardio-oncology clinical implementation. Finally, an imaging arm will establish if exercise cardiac magnetic resonance imaging and VO2 max testing is a more sensitive predictor of cardiac reserve in paediatric and adolescent and young adult oncology patients exposed to cardiac toxic therapies.
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Antineoplásicos , Neoplasias , Adolescente , Antineoplásicos/uso terapêutico , Austrália/epidemiologia , Cardiotoxicidade/epidemiologia , Criança , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/epidemiologia , Nova Zelândia/epidemiologia , Sistema de RegistrosRESUMO
The phase 2 portion of this open-label phase 2/3 study assessed the efficacy and safety of blinatumomab as second salvage for aggressive relapsed or refractory (r/r) aggressive B-cell non-Hodgkin lymphoma (B-NHL) following platinum-based first salvage chemotherapy. Forty-one patients with aggressive disease (32% relapsed; 68% refractory) enrolled and received stepwise blinatumomab (9-28-112 µg/day) in a 70-day cycle 1 and an optional 28-day cycle 2; 19 (46%) completed cycle 1 and 3 (7%) completed cycle 2. The overall response rate after 12 weeks was 37%, including 9 (22%) complete metabolic responses. Eight (20%) patients (all responders) subsequently received stem cell transplants. Grade ≥3 adverse events were reported in 29 (71%) patients. Grade 3 cytokine release syndrome occurred in one patient. Grade 3 neurologic events occurred in 10 (24%) patients; all resolved. Blinatumomab monotherapy appears effective as second salvage therapy in patients with r/r aggressive B-NHL. Trial registration: NCT02910063.
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Linfoma não Hodgkin , Terapia de Salvação , Adulto , Anticorpos Biespecíficos , Protocolos de Quimioterapia Combinada Antineoplásica , Linfócitos B , Humanos , Linfoma não Hodgkin/tratamento farmacológico , Recidiva Local de NeoplasiaRESUMO
OBJECTIVE: To explore the communication and resource needs of mothers diagnosed with breast cancer treated with curative intent in communicating with their young children and to identify gaps in the resources and support provided to these women. METHODS: Data were collected via semi-structured telephone interviews from 13 mothers who were diagnosed with breast cancer while parenting a young child (age 3-12 years), and 10 health professionals in Victoria, Australia. Data were analysed qualitatively using the Framework Method. RESULTS AND CONCLUSION: Mothers and health professionals prioritised communication with children about the cancer diagnosis; however, health professionals and mothers differed in their views of parents' communication needs both in terms of the nature of the support/information needed and the delivery of this support/information. Mothers wanted easily accessible resources that were both instructive and practical. Mothers also emphasised quality over quantity of support. Health professionals were mostly aware of mothers' needs, however, emphasised less instructive support and information. This study highlights the need for improved coordination and tailoring of psychosocial resources and supports for these parents and families communicating about a cancer diagnosis with their young children.
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Neoplasias da Mama/psicologia , Comunicação , Pessoal de Saúde/psicologia , Recursos em Saúde , Mães/psicologia , Adulto , Atitude Frente a Saúde , Neoplasias da Mama/diagnóstico , Criança , Pré-Escolar , Feminino , Humanos , Pessoa de Meia-Idade , Poder Familiar/psicologia , Psico-Oncologia , Pesquisa Qualitativa , VitóriaRESUMO
Novel strategies, such as chemosensitization with targeted agents, that build on the success of standard immunochemotherapy show promise for the treatment of non-Hodgkin lymphoma (NHL). Here, we report a phase 1b study investigating dose escalation of the BCL2 inhibitor, venetoclax, in combination with rituximab or obinutuzumab and cyclophosphamide, doxorubicin, vincristine, and prednisone (R-/G-CHOP) chemotherapy in B-cell NHL. Objectives included safety assessment and determination of a recommended phase 2 dose (RP2D). Fifty-six patients were enrolled, most with follicular lymphoma (43%) or diffuse large B-cell lymphoma (DLBCL; 32%). Dose-limiting toxicities were reported in 3/14 patients at the first venetoclax dose (200 mg/d), after which dosing was changed from daily to 10 days per cycle and escalated to 800 mg. A further reduction to 5 days per cycle occurred at the 800-mg dose level in the G-CHOP arm. Cytopenias were predominant among grade 3/4 events and reported at a higher rate than expected, particularly in the G-CHOP arm; however, safety was manageable. Overall response rates were 87.5% (R-CHOP and G-CHOP combinations); complete response (CR) rates were 79.2% and 78.1%, respectively. Most double-expressor (BCL2+ and MYC+) DLBCL patients (87.5%; n = 7/8) achieved CR. Although the maximum tolerated dose was not reached, the RP2D for venetoclax with R-CHOP was established at 800 mg days 4 to 10 of cycle 1 and days 1 to 10 of cycles 2 to 8; higher doses were not explored, and this dosing schedule demonstrated an acceptable safety profile. This regimen is subsequently being evaluated in first-line DLBCL in the phase 2 portion of the study. This trial was registered at www.clinicaltrials.gov as #NCT02055820.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Compostos Bicíclicos Heterocíclicos com Pontes/uso terapêutico , Linfoma não Hodgkin/tratamento farmacológico , Sulfonamidas/uso terapêutico , Idoso , Anticorpos Monoclonais Humanizados/uso terapêutico , Ciclofosfamida/uso terapêutico , Intervalo Livre de Doença , Doxorrubicina/uso terapêutico , Feminino , Humanos , Linfoma não Hodgkin/mortalidade , Masculino , Dose Máxima Tolerável , Pessoa de Meia-Idade , Prednisona/uso terapêutico , Rituximab/uso terapêutico , Vincristina/uso terapêuticoRESUMO
BACKGROUND: The prognosis for primary CNS lymphoma has improved with the use of high-dose methotrexate-based chemotherapy, but patient outcomes remain poor. Rituximab, a chimeric monoclonal antibody that targets the CD20 cell surface protein, has substantial activity in systemic CD20-positive diffuse large B-cell lymphoma, but its efficacy in primary CNS lymphoma is unknown and low penetration of the large rituximab molecule through the blood-brain barrier could limit its effect. We aimed to investigate the addition of rituximab to a high-dose methotrexate-based chemotherapy regimen in patients with newly diagnosed primary CNS lymphoma. METHODS: This intergroup, multicentre, open-label, randomised phase 3 study was done at 23 hospitals in the Netherlands, Australia, and New Zealand. Non-immunocompromised patients aged 18-70 years with newly diagnosed primary CNS lymphoma were randomly assigned (1:1) to receive methotrexate-based chemotherapy with or without intravenous rituximab. We used a web-based randomisation system with stratification by centre, age, and Eastern Cooperative Oncology Group-WHO performance status, and a minimisation procedure. All group assignment was open label and neither investigators nor patients were masked to allocation. All patients were treated with two 28-day cycles of induction chemotherapy, consisting of intravenous methotrexate 3 g per m2 on days 1 and 15, intravenous carmustine 100 mg per m2 on day 4, intravenous teniposide 100 mg per m2 on days 2 and 3, and oral prednisone 60 mg per m2 on days 1-5, with (R-MBVP) or without (MBVP) intravenous rituximab 375 mg per m2 on days 0, 7, 14, and 21 in cycle one and days 0 and 14 in cycle two. Patients with response at the end of induction subsequently received high-dose cytarabine and, in patients aged 60 years or younger, low-dose whole-brain radiotherapy. The primary endpoint was event-free survival, with events defined as not reaching complete response or complete response unconfirmed at the end of treatment, or progression or death after response; analysis was adjusted for age and performance score. Patients were analysed on a modified intention-to-treat basis. This trial is registered with the Nederlands Trial Register, number NTR2427, and the Australian New Zealand Clinical Trials Registry, number ACTRN12610000908033. The trial was closed on May 27, 2016, after achieving complete accrual, and follow-up is ongoing. FINDINGS: Between Aug 3, 2010, and May 27, 2016, we recruited 200 patients (109 men and 91 women; median age was 61 years [IQR 55-67]). We randomly assigned 100 patients to MBVP and 99 patients to R-MBVP. One patient was randomly assigned to the R-MBVP group but found to be ineligible because of an incorrect diagnosis and was excluded from all analyses. After a median follow-up of 32·9 months (IQR 23·9-51·5), 98 patients had had an event (51 in the MBVP group and 47 in the R-MBVP group), of whom 79 had died (41 in the MBVP group and 38 in the R-MBVP group). Event-free survival at 1 year was 49% (95% CI 39-58) in the MBVP group (no rituximab) and 52% (42-61) in the R-MBVP group (with rituximab; hazard ratio 1·00, 95% CI 0·70-1·43, p=0·99). Grade 3 or 4 adverse events occurred in 58 (58%) patients in the MBVP group and 63 (64%) patients in the R-MBVP group, with infections (24 [24%] patients receiving MBVP vs 21 [21%] patients receiving R-MBVP), haematological toxicity (15 [15%] vs 12 [12%]), and nervous system disorders (ten [10%] vs 15 [15%]) being the most common. Life-threatening or fatal serious adverse events occurred in 12 (12%) patients in the MBVP group and ten (10%) patients in the R-MBVP group, and five (5%) patients in the MBVP group and three (3%) in the R-MBVP group died from treatment-related causes. INTERPRETATION: We found no clear benefit of addition of rituximab to methotrexate, carmustine, teniposide, and prednisone chemotherapy in primary CNS lymphoma. Therefore, the results of this study do not support the use of rituximab as a component of standard treatment in primary CNS lymphoma. FUNDING: Roche, the Dutch Cancer Society, and Stichting STOPhersentumoren.
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Antimetabólitos Antineoplásicos/administração & dosagem , Antineoplásicos Imunológicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias do Sistema Nervoso Central/tratamento farmacológico , Linfoma/tratamento farmacológico , Metotrexato/administração & dosagem , Rituximab/administração & dosagem , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
Understanding how cancer and cancer therapies affect the immune system is integral to the rational application of immunotherapies. Flow cytometry is the gold standard method of peripheral blood immune cell profiling. However, the requirement for viable cells can limit its applicability, especially in studies of retrospective clinical cohorts. We aimed to determine if gene expression, analysed using the NanoString platform, could be used to quantify the immune populations present in cryopreserved peripheral blood mononuclear cell (PBMC) samples from patients with chronic lymphocytic leukaemia. Cell abundance scores derived from gene expression analysis were significantly correlated with the population frequency quantified by flow cytometry for all subsets analysed, including T cells, NK cells and Monocytes. This study demonstrates that gene expression analysis can be applied to cryopreserved PBMC and provides a concordant and complementary understanding of the immune profile to flow cytometry.
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Citometria de Fluxo , Perfilação da Expressão Gênica , Regulação Leucêmica da Expressão Gênica/imunologia , Imunofenotipagem , Leucemia Linfocítica Crônica de Células B/imunologia , Leucócitos Mononucleares/imunologia , Proteínas de Neoplasias/imunologia , Idoso , Criopreservação , Feminino , Humanos , Leucemia Linfocítica Crônica de Células B/patologia , Leucócitos Mononucleares/patologia , MasculinoRESUMO
Developing environmental health indicators is challenging and applying a conceptual framework and indicator selection criteria may not be sufficient to prioritise potential indicators to monitor. This study developed a new approach for prioritising potential environmental health indicators, using the example of the indoor environment for New Zealand. A three-stage process of scoping, selection, and design was implemented. A set of potential indicators (including 4 exposure indicators and 20 health indicators) were initially identified and evaluated against indicator selection criteria. The health indicators were then further prioritised according to their public health impact and assessed by the five following sub-criteria: number of people affected (based on environmental burden of disease statistics); severity of health impact; whether vulnerable populations were affected and/or large inequalities were apparent; whether the indicator related to multiple environmental exposures; and policy relevance. Eight core indicators were ultimately selected, as follows: living in crowded households, second-hand smoke exposure, maternal smoking at two weeks post-natal, asthma prevalence, asthma hospitalisations, lower respiratory tract infection hospitalisations, meningococcal disease notifications, and sudden unexpected death in infancy (SUDI). Additionally, indicators on living in damp and mouldy housing and children's injuries in the home, were identified as potential indicators, along with attributable burden indicators. Using public health impact criteria and an environmental burden of disease approach was valuable in prioritising and selecting the most important health impacts to monitor, using robust evidence and objective criteria.
Assuntos
Poluição do Ar em Ambientes Fechados/estatística & dados numéricos , Exposição Ambiental/análise , Saúde Ambiental/normas , Habitação/normas , Saúde Pública/normas , Criança , Saúde Ambiental/estatística & dados numéricos , Feminino , Habitação/estatística & dados numéricos , Humanos , Nova Zelândia , Saúde Pública/estatística & dados numéricos , Fatores SocioeconômicosRESUMO
BACKGROUND: Few studies have documented the outcomes of superior labral anterior-posterior (SLAP) repairs in baseball players. Furthermore, the results of these previous studies varied widely and were based on small numbers of patients. Hypothesis/Purpose: The purpose was to report return-to-play (RTP) rates and validated subjective outcome scores for baseball players after SLAP repair. It was hypothesized that RTP rates and outcomes would be significantly different between pitchers and nonpitchers, as well as among baseball levels. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: A series of 216 baseball players was identified who had isolated SLAP repair or SLAP repair with debridement of partial-thickness (<25%) rotator cuff tear at our surgical centers. Patients were contacted by phone a minimum of 2 years after surgery and asked questions about their ability to RTP. Patients were also asked questions to complete the Western Ontario Shoulder Instability Index (WOSI), Veteran's RAND 12-Item Health Survey (VR-12), and Kerlan-Jobe Orthopaedic Clinic (KJOC) questionnaires. Statistical equivalence in RTP rate, VR-12, and WOSI scores was determined between players with and without concomitant rotator cuff debridement using 2 one-sided tests and risk difference measures. Differences in RTP were tested among baseball levels (high school, college, professional) and positions (pitcher vs nonpitcher) using chi-square analyses ( P < .05). Differences in outcomes scores were compared using t tests and analyses of variance ( P < .05). RESULTS: Of the 216 baseball players, 133 were reached by phone for follow-up interview (mean, 78 months; range, 27-146 months). Overall, 62% successfully returned to play. There were no differences in RTP rates or subjective outcomes among baseball levels or between procedures. RTP rates were 59% for pitchers and 76% for nonpitchers ( P = .060). Subjectively, the percentage of patients who felt the same or better at follow-up compared to preinjury was significantly higher among nonpitchers (66%) than pitchers (43%). There was no difference in KJOC scores between the pitchers (75.3 ± 19.4) and nonpitchers (76.2 ± 17.4) who successfully returned to play, although these scores were well below the minimum desired score of 90 for healthy baseball players. CONCLUSION: SLAP repair should continue to be considered as an option for SLAP tear treatment only after nonsurgical management has failed. Some players may be able to return to baseball after SLAP repair, although regaining preinjury health and performance is challenging.