RESUMO
BACKGROUND: Chemotherapy-induced peripheral neurotoxicity (CIPN) affects the quality of life of cancer survivors. However, the impact of pain on symptom burden remains undefined. This study aimed to define differences in the clinical symptom profile of patients with painful and nonpainful CIPN. PATIENTS AND METHODS: A total of 579 participants (median age, 59 years [IQR, 19 years]; F=66%) were assessed cross-sectionally 6 months posttreatment. CIPN severity was graded using multiple methods, including patient-reported outcome measures, a clinically graded scale (NCI-CTCAE), and a neurologic examination score. Participants were classified into subgroups based on patient symptom report, with painful CIPN characterized by the presence of shooting/burning pain, and nonpainful CIPN characterized by the presence of numbness or tingling without shooting/burning pain. Behavioral changes were assessed via structured patient interview regarding symptom impact on sleep, exercise, and treatment-seeking. RESULTS: Among 579 participants, 24% (n=140) reported painful CIPN, 48% (n=280) reported nonpainful CIPN, and 28% (n=159) had no CIPN. Participants with painful CIPN demonstrated higher CIPN severity than those with nonpainful CIPN across multiple measures, including NCI-CTCAE, neurologic grading, and patient report (all P<.05). Participants with painful CIPN were more likely to report that their symptoms affected their ability to exercise (P=.007), produced sleep impairment, and increased treatment-seeking behavior due to their symptoms (both P<.001) compared with participants with nonpainful CIPN. CONCLUSIONS: Overall, participants with painful CIPN reported higher scores across all CIPN severity measures, including behavioral changes. This study underlines the need for accurate identification of different CIPN subgroups in hopes of informing better treatment and rehabilitation options for cancer survivors with painful CIPN.
Assuntos
Antineoplásicos , Neoplasias , Doenças do Sistema Nervoso Periférico , Humanos , Pessoa de Meia-Idade , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Doenças do Sistema Nervoso Periférico/diagnóstico , Antineoplásicos/efeitos adversos , Carga de Sintomas , Qualidade de Vida , Dor/etiologia , Dor/diagnóstico , Neoplasias/complicações , Neoplasias/tratamento farmacológicoRESUMO
BACKGROUND: CD73 upregulation in tumors leads to local immunosuppression. This phase I, first-in-human study evaluated oleclumab (MEDI9447), an anti-CD73 human IgG1λ monoclonal antibody, alone or with durvalumab in patients with advanced colorectal cancer (CRC), pancreatic ductal adenocarcinoma (PDAC), or epidermal growth factor receptor-mutant non-small-cell lung cancer (NSCLC). METHODS: Patients received oleclumab 5-40 mg/kg (dose-escalation) or 40 mg/kg (dose-expansion) intravenously every 2 weeks (Q2W), alone (escalation only) or with durvalumab 10 mg/kg intravenously Q2W. RESULTS: 192 patients were enrolled, 66 during escalation and 126 (42 CRC, 42 PDAC, 42 NSCLC) during expansion. No dose-limiting toxicities occurred during escalation. In the monotherapy and combination therapy escalation cohorts, treatment-related adverse events (TRAEs) occurred in 55 and 54%, respectively, the most common being fatigue (17 and 25%). In the CRC, PDAC, and NSCLC expansion cohorts, 60, 57, and 45% of patients had TRAEs, respectively; the most common were fatigue (15%), diarrhea (9%), and rash (7%). Free soluble CD73 and CD73 expression on peripheral T cells and tumor cells showed sustained decreases, accompanied by reduced CD73 enzymatic activity in tumor cells. Objective response rate during escalation was 0%. Response rates in the CRC, PDAC, and NSCLC expansion cohorts were 2.4% (1 complete response [CR]), 4.8% (1 CR, 1 partial response [PR]), and 9.5% (4 PRs), respectively; 6-month progression-free survival rates were 5.4, 13.2, and 16.0%. CONCLUSIONS: Oleclumab ± durvalumab had a manageable safety profile, with pharmacodynamic activity reflecting oleclumab's mechanism of action. Evidence of antitumor activity was observed in tumor types that are generally immunotherapy resistant. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov, NCT02503774; date of registration, July 17, 2015.
Assuntos
Antineoplásicos , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Anticorpos Monoclonais/uso terapêutico , Antineoplásicos/uso terapêutico , Fadiga/induzido quimicamenteRESUMO
BACKGROUND: Chemotherapy-induced peripheral neurotoxicity (CIPN) is a common complication of cancer treatment that produces functional disability. Increasingly, patient-reported outcome measures (PROMs) are used to assess CIPN, providing a broader symptom perspective than clinician-graded scales. Understanding when a reported change in CIPN symptoms meets the threshold for clinical significance is challenging. This study aimed to provide interpretation guidelines for validated CIPN PROMs, and thereby enable estimation of thresholds to identify clinically relevant symptoms. METHODS: Patients commencing neurotoxic cancer treatments were assessed at 3 timepoints: baseline, midtreatment, and end-of-treatment. Trajectory of CIPN development was assessed by means of CIPN PROMs, EORTC Quality of Life - Chemotherapy-Induced Peripheral Neuropathy questionnaire (QLQ-CIPN20), and Functional Assessment of Cancer Therapy/Gynecologic Oncology Group - Neurotoxicity questionnaire (FACT/GOG-NTX). Thresholds were estimated for CIPN PROMs using the NCI CTCAE sensory neuropathy scale as the clinical anchor by midtreatment and end-of-treatment. Patients were assigned to a clinical change group according to CIPN development: either no development; grade 1 neuropathy (minimally important difference [MID]); or grade 2 neuropathy (clinically important difference). Distribution-based estimates (SD, 0.5) were also evaluated as supportive evidence. RESULTS: In total, 406 patients were recruited to the study, of whom 62% (n=199/320) developed CIPN by midtreatment and 80% (n=274/343) by end-of-treatment. Anchor-based MID estimates by midtreatment were 5.06 (95% CI, 4.26-5.86) for the QLQ-CIPN20 and 3.54 (95% CI, 2.87-4.20) for the FACT/GOG-NTX. End-of-treatment MIDs were estimated to be 7.32 (95% CI, 6.23-8.40) for the QLQ-CIPN20 and 4.84 (95% CI, 3.98-5.70) for the FACT/GOG-NTX. Distribution-based MID estimations yielded lower values than anchor-based methods, at 3.73 for the QLQ-CIPN20 and 2.64 for the FACT/GOG-NTX at midtreatment and 5.52 for the QLQ-CIPN20 and 3.64 for the FACT/GOG-NTX at end-of-treatment. CONCLUSIONS: Findings from the present series aid meaningful interpretation for commonly used validated CIPN PROMs and provide thresholds that serve as guidance on how to interpret score changes, which will be useful for design and evaluation of clinical trials and clinical practice.
Assuntos
Antineoplásicos , Neoplasias , Doenças do Sistema Nervoso Periférico , Humanos , Feminino , Antineoplásicos/efeitos adversos , Neoplasias/tratamento farmacológico , Qualidade de Vida , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Doenças do Sistema Nervoso Periférico/diagnóstico , Doenças do Sistema Nervoso Periférico/terapia , Inquéritos e Questionários , Medidas de Resultados Relatados pelo PacienteRESUMO
PURPOSE: Sleep problems are commonly reported by cancer survivors; however, knowledge of the impact of chemotherapy-induced peripheral neurotoxicity (CIPN) on sleep quality remains limited. In this study, we explored the impact of CIPN on sleep quality, as well as identified clinical characteristics associated with poor sleep quality. METHODS: Participants were assessed cross-sectionally post-neurotoxic chemotherapy. CIPN severity was graded using a range of questionnaires that assessed CIPN severity and quality of life, as well as neurological grading scales. Sleep quality was assessed using a self-rated questionnaire (Pittsburgh Sleep Quality Index, PSQI). Participants with poor sleep quality were further grouped according to whether sleep impairment was due to CIPN or other factors. RESULTS: Among 77 participants who reported CIPN, 75% (n = 58) reported poor sleep quality. Of those, 41% (n = 24) reported CIPN as contributing to sleep impairment, while 59% (n = 34) reported other causes. Participants with CIPN-induced sleep impairments had higher CIPN severity across all outcome measures, as well as greater neuropathic pain (all p < 0.05). Furthermore, participants with CIPN-induced sleep impairments reported worse impact of neuropathy on physical and social functioning, as well as emotional well-being (all p < 0.05). CONCLUSIONS: Participants with CIPN-induced poor sleep quality reported worse scores across all CIPN severity measures. This emphasises the negative impacts of CIPN symptoms on quality of life of chemotherapy-treated patients and highlights the importance of sleep quality assessment in cancer survivors.
Assuntos
Antineoplásicos , Síndromes Neurotóxicas , Transtornos do Sono-Vigília , Humanos , Qualidade de Vida , Síndromes Neurotóxicas/epidemiologia , Síndromes Neurotóxicas/etiologia , Sono , Transtornos do Sono-Vigília/induzido quimicamente , Transtornos do Sono-Vigília/epidemiologia , Antineoplásicos/efeitos adversosRESUMO
Fanconi anaemia due to biallelic loss of BRCA2 (Fanconi anaemia subtype D1) is traditionally diagnosed during childhood with cancer rates historically reported as 97% by 5.2 years. This report describes an adult woman with a history of primary ovarian failure, who was diagnosed with gastrointestinal adenocarcinoma and BRCA2-associated Fanconi anaemia at 23 years of age, only after she suffered severe chemotherapy toxicity. The diagnostic challenges include atypical presentation, initial false-negative chromosome fragility testing and variant classification. It highlights gastrointestinal adenocarcinoma as a consideration for adults with biallelic BRCA2 pathogenic variants with implications for surveillance. After over 4 years, the patient has no evidence of gastrointestinal cancer recurrence although the tumour was initially considered only borderline resectable. The use of platinum-based chemotherapy, to which heterozygous BRCA2 carriers are known to respond, may have had a beneficial anticancer effect, but caution is advised given its extreme immediate toxicity at standard dosing. Fanconi anaemia should be considered as a cause for women with primary ovarian failure of unknown cause and referral to cancer genetic services recommended when there is a family history of cancer in the hereditary breast/ovarian cancer spectrum.
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Adenocarcinoma , Neoplasias da Mama , Anemia de Fanconi , Proteína BRCA2/genética , Anemia de Fanconi/diagnóstico , Anemia de Fanconi/genética , Anemia de Fanconi/patologia , Feminino , Predisposição Genética para Doença , Humanos , FenótipoRESUMO
To summarise the prognostic value of patient-reported outcomes (PROs) in advanced gastro-oesophageal (GO) cancer. We systematically searched multiple databases using search terms related to advanced GO cancer, PRO and prognosis. Studies examining the relationship between baseline PROs and prognosis were included. Two reviewers independently screened articles and extracted data on study design, survival and associations between PROs and survival, in both univariable and multivariable analyses. QUIPS was used for quality assessment. From 3004 studies screened, seven studies were eligible, comprising PRO data from 2761 of 3408 (81%) participants. Median survival times ranged from 4.5 to 9.5 months. Among participants with oesophageal squamous cell carcinoma (SCC), physical functioning, social functioning and fatigue (QLQ-C30) were associated with overall survival (OS) in one univariable analysis. Among three studies of participants with adenocarcinoma, univariable analyses revealed associations between OS and global quality of life (QOL), physical functioning, role functioning and social functioning; two studies showed association with pain. There was an association between emotional functioning, fatigue, lack of mobility, lack of self-care, appetite loss/anorexia and OS in one study. One multivariable analysis among participants with oesophageal SCC showed physical and social functioning was associated with OS. Among participants with adenocarcinoma, multivariable analyses showed associations between OS and physical functioning/lack of mobility, appetite loss/anorexia (three studies), global QOL, role functioning/lack of self-care, pain (two studies) and social functioning (one study). Physical functioning, role functioning, social functioning, pain, anorexia and global QOL were associated with OS in advanced GO cancer.
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Adenocarcinoma , Neoplasias Esofágicas , Neoplasias Gástricas , Humanos , Prognóstico , Qualidade de Vida/psicologia , Anorexia , Neoplasias Esofágicas/terapia , Dor , Medidas de Resultados Relatados pelo Paciente , Fadiga/epidemiologia , Fadiga/etiologiaRESUMO
OBJECTIVE: To report treatment patterns and survival outcomes of patients with relapsed and refractory metastatic germ cell tumours (GCTs) treated with high-dose chemotherapy (HDCT) and autologous stem-cell transplantation in low-volume specialized centres within the widely dispersed populations of Australia and New Zealand between 1999 and 2019. PATIENTS AND METHODS: We conducted a retrospective analysis of 111 patients across 13 institutions. Patients were identified from the Australasian Bone Marrow Transplant Recipient Registry. We reviewed treatment regimens, survival outcomes, deliverability and toxicities. Primary endpoints included overall (OS) and progression-free survival (PFS). Cox proportional hazards models were used to test the association of survival outcomes with patient and treatment factors. RESULTS: The median (range) age was 30 (14-68) years and GCT histology was non-seminomatous in 84% of patients. International Prognostic Factors Study Group (IPFSG) prognostic risk category was very low/low, intermediate, high and very high in 18%, 36%, 25% and 21% of patients, respectively. Salvage conventional-dose chemotherapy (CDCT) was administered prior to HDCT in 59% of patients. Regimens included paclitaxel, ifosfamide, carboplatin and etoposide (50%), carboplatin and etoposide (CE; 28%), carboplatin, etoposide and ifosfamide (CEI; 6%), carboplatin, etoposide and cyclophosphamide (CEC; 5%), CEC-paclitaxel (6%) and other (5%). With a median follow-up of 4.4 years, the 1-, 2- and 5-year PFS rates were 62%, 57% and 52%, respectively, and OS rates were 73%, 65% and 61%, respectively. There were five treatment-related deaths. Progression on treatment occurred in 17%. In a univariable analysis, worse International Germ Cell Cancer Collaborative Group (IGCCCG) and IPFSG prognostic groups were associated with inferior survival outcomes. An association of inferior survival was not found with the number of high-dose cycles received nor when HDCT was delivered after salvage CDCT. CONCLUSION: This large dual-national registry-based study reinforces the efficacy and deliverability of HDCT for relapsed and refractory metastatic GCT in low-volume specialized centres in Australia and New Zealand, with survival outcomes comparable to those found in international practice.
Assuntos
Neoplasias Embrionárias de Células Germinativas , Neoplasias Testiculares , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carboplatina , Intervalo Livre de Doença , Etoposídeo/uso terapêutico , Humanos , Ifosfamida/uso terapêutico , Masculino , Pessoa de Meia-Idade , Neoplasias Embrionárias de Células Germinativas/tratamento farmacológico , Paclitaxel/uso terapêutico , Estudos Retrospectivos , Terapia de Salvação , Neoplasias Testiculares/patologiaRESUMO
BACKGROUND: Cancer patients treated with neurotoxic chemotherapy are at risk of developing neurological symptoms that can impact functional capacity and quality of life. However, there are no standardised pathways to assess and manage chemotherapy-induced peripheral neurotoxicity (CIPN). This study aimed to determine consensus on statements regarding a CIPN assessment and management clinical pathway. METHODS: A CIPN clinical pathway (CIPN-path) was developed and reviewed by an expert multi-disciplinary panel and consumers. Agreement with 18 statements regarding four content themes (pretreatment review, screening and assessment, management and referral, and CIPN-path feasibility) were assessed by 70 Australian respondents (68 health professionals, 2 consumers), using a 2-stage Delphi survey process to reach consensus. Respondents rated statements using a 5-point Likert scale to determine the level of agreement, with consensus defined as ≥ 80% of respondents agreeing with each statement. RESULTS: The consensus was reached for 14 of 18 items after stage 1 and all items after stage 2. Feedback was obtained for all items to refine the CIPN-path. There was an agreement on important characteristics of the CIPN-path, including pretreatment screening, regular patient-reported assessment, and a stepped-care approach to investigating and managing symptom burden. There was a lack of agreement on who should oversee CIPN assessment, which may differ according to the structure and resources of each site. CONCLUSIONS: There was an overall agreement concerning the CIPN-path to assess and manage CIPN, which may be adapted accordingly to the resources of each clinic. The CIPN-path may assist teams across different health services in identifying CIPN symptoms, aiding decision-making, and reducing morbidity from CIPN.
Assuntos
Antineoplásicos , Síndromes Neurotóxicas , Doenças do Sistema Nervoso Periférico , Antineoplásicos/efeitos adversos , Austrália , Consenso , Procedimentos Clínicos , Humanos , Síndromes Neurotóxicas/tratamento farmacológico , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Doenças do Sistema Nervoso Periférico/diagnóstico , Doenças do Sistema Nervoso Periférico/terapia , Qualidade de VidaRESUMO
AIM: To evaluate a web-based tool for estimating and explaining three scenarios for expected survival time to people with advanced cancer (patients), their family members (FMs), and other healthcare professionals (HCPs). METHODS: Thirty-three oncologists estimated the "median survival of a group of similar patients" for patients seeking quantitative prognostic information. The web-based tool generated worst-case, most likely, and best-case scenarios for survival based on the oncologist's estimate. Oncologists presented the scenarios to each patient and provided a printed summary to patients, FMs, and HCPs. Attitudes to the information were assessed by questionnaires. Observed survival for each patient was compared with the oncologist's estimated survival and the three scenarios. RESULTS: Prognosis was discussed with 222 patients: median age 67 years; 61% male; most common primary sites pancreas 15%, non-small-cell lung 15%, and colorectal 12%. The median (range) for observed survival times was 9 months (0.5-43) and for oncologist's estimated survival times was 12 months (2-96). Ninety-one percent of patients, 91% of FMs, and 84% of HCPs agreed that it was helpful having life expectancy explained as three scenarios. The majority (77%) of patients judged the information presented about their life expectancy to be the same or better than they had expected before the consultation. The survival estimates met a priori criteria for calibration, precision, and accuracy. CONCLUSIONS: Patients, FMs, and HCPs found it helpful to receive personalized prognostic information formatted as three scenarios for survival. It was feasible, acceptable, and safe to use a web-based resource to do this.
Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Neoplasias , Idoso , Atenção à Saúde , Família , Feminino , Humanos , Expectativa de Vida , Masculino , Neoplasias/terapia , PrognósticoRESUMO
PURPOSE: To summarise what is currently known about the psychosocial morbidity, experiences, and needs of people with cancer and their informal caregivers, who live in rural or regional areas of developed countries. METHODS: Eligible studies dating from August 2010 until May 2021 were identified through several online databases, including MEDLINE, EMBASE, PsychINFO, and RURAL (Rural and Remote Health Database). Results were reported according to the PRISMA guidelines and the protocol was registered on PROSPERO (CRD42020171764). RESULTS: Sixty-five studies were included in this review, including 20 qualitative studies, 41 quantitative studies, and 4 mixed methods studies. Qualitative research demonstrated that many unique psychosocial needs of rural people remain unmet, particularly relating to finances, travel, and accessing care. However, most (9/19) quantitative studies that compared rural and urban groups reported no significant differences in psychosocial needs, morbidity, or quality of life (QOL). Five quantitative studies reported poorer psychosocial outcomes (social and emotional functioning) in urban cancer survivors, while three highlighted poorer outcomes (physical functioning, role functioning, and self-reported mental health outcomes) in the rural group. CONCLUSION: Recent research shows that rural people affected by cancer have unique unmet psychosocial needs relating to rurality. However, there was little evidence that rural cancer survivors report greater unmet needs than their urban counterparts. This contrasts to the findings from a 2011 systematic review that found rural survivors consistently reported worse psychosocial outcomes. More population-based research is needed to establish whether uniquely rural unmet needs are due to general or cancer-specific factors.
Assuntos
Neoplasias , Qualidade de Vida , Cuidadores , Humanos , Neoplasias/terapia , População Rural , SobreviventesRESUMO
PURPOSE: Chemotherapy-induced peripheral neuropathy (CIPN) is an adverse event of cancer treatment that can affect sensory, motor, or autonomic nerves. Assessment of autonomic neuropathy is challenging, with limited available tools. Accordingly, it is not routinely assessed in chemotherapy-treated patients. In this study, we aimed to examine whether electrochemical skin conductance (ESC) via Sudoscan, a potential measure of autonomic function, associates with subjective and objective measures of CIPN severity and autonomic neuropathy. METHODS: A cross-sectional assessment of patients who completed neurotoxic chemotherapy 3-24 months prior was undertaken using CIPN patient-reported outcomes (EORTC-QLQ-CIPN20), clinically graded scale (NCI-CTCAE), neurological examination score (TNSc), autonomic outcome measure (SAS), and Sudoscan. Differences in CIPN severity between participants with or without ESC dysfunction were investigated. Linear regression analyses were used to identify whether ESC values could predict CIPN severity. RESULTS: A total of 130 participants were assessed, with 93 participants classified with CIPN according to the clinically graded scale (NCI-CTCAE/grade ≥ 1), while 49% demonstrated hands or feet ESC dysfunction (n = 46). Participants with ESC dysfunction did not significantly differ from those with no dysfunction on multiple CIPN severity measures (clinical-grade, patient-report, neurological examination), and no differences on the autonomic outcome measure (SAS) (all p > 0.0063). Linear regression analyses showed that CIPN could not be predicted by ESC values. CONCLUSIONS: The inability of ESC values via Sudoscan to predict clinically-graded and patient-reported CIPN or autonomic dysfunction questions its clinical utility for chemotherapy-treated patients. The understanding of autonomic neuropathy with chemotherapy treatment remains limited and must be addressed to improve quality of life in cancer survivors.
Assuntos
Antineoplásicos , Neoplasias , Doenças do Sistema Nervoso Periférico , Humanos , Qualidade de Vida , Antineoplásicos/efeitos adversos , Estudos Transversais , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Doenças do Sistema Nervoso Periférico/diagnósticoRESUMO
BACKGROUND: Clinical pathways (CPs) are intended to standardise and improve care but do not always produce positive outcomes, possibly because they were not adapted to suit the specific context in which they were enacted. This qualitative study aimed to explore staff perspectives of implementation of a CP for routine screening, assessment, referral and management of anxiety and depression (the ADAPT CP) for patients with cancer, focussing on perceived feasibility of the CP and negotiated adaptations made during the implementation phase. METHODS: The ADAPT CP was implemented in 12 urban and regional oncology services in Australia. Services were randomised to receive core versus enhanced implementation strategies. Core sites received support until implementation commencement and could access progress reports. Enhanced sites received proactive, ongoing support during the 12-month implementation. Purposively selected staff were interviewed prior to implementation (n = 88) and 6 months later, half-way through the implementation period (n = 89). Monthly meetings with lead multi-disciplinary teams at the eight enhanced sites were recorded. Data were thematically analysed. RESULTS: Six overarching themes were identified: ADAPT is of high value; timing for introducing the CP and screening is difficult; online screening is challenging; a burden too much; no-one to refer patients to; and micro-logistics are key. While early screening was deemed desirable, diverse barriers meant this was complex, with adaptations made to time and screening location. Online screening prompted by email, seen as time-saving and efficient, also proved unsuccessful in some services, with adaptations made to in-clinic or phone screening, or repeated email reminders. Staff negative attitudes to ADAPT, time constraints, and perceived poor fit of ADAPT to work roles and flows, all impacted implementation, with key tasks often devolving to a few key individuals. Nevertheless, services remained committed to the ADAPT CP, and worked hard to create, review and adapt strategies to address challenges to optimise success. CONCLUSIONS: This study demonstrates the interactive nature of health service change, with staff actively engaging with, forming views on, and problem-solving adaptations of the ADAPT CP to overcome barriers. Obtaining staff feedback is critical to ensure health service change is sustainable, meaningful and achieves its promise of improving patient outcomes. TRIAL REGISTRATION: The study was registered prospectively with the ANZCTR on 22/3/2017. Trial ID ACTRN12617000411347.
Assuntos
Procedimentos Clínicos , Neoplasias , Ansiedade/diagnóstico , Ansiedade/terapia , Transtornos de Ansiedade , Depressão/diagnóstico , Depressão/terapia , Estudos de Viabilidade , Humanos , Neoplasias/terapiaRESUMO
BACKGROUND: Anxiety and depression screening and management in cancer settings occurs inconsistently in Australia. We developed a clinical pathway (ADAPT CP) to promote standardized assessment and response to affected patients and enhance uptake of psychosocial interventions. Health professional education is a common strategy utilised to support implementation of practice change interventions. We developed an interactive on-line education program to support staff communication and confidence with anxiety/depression screening and referral prior to the ADAPT CP being implemented in 12 oncology services participating in the ADAPT CP cluster randomised controlled trial (CRCT). The aim of this research was to assess acceptability and uptake of the education program. Patient Involvement: Although the wider ADAPT Program included patient consumers on the Steering Committee, in the context of this research consumer engagement included health professionals working in oncology. These consumers contributed to resource development. METHODS: Development was informed by oncology and communication literature. The five online modules were pilot tested with 12 oncology nurses who participated in standardised medical simulations. Acceptability and uptake were assessed across the 12 Oncology services participating in the ADAPT CRCT. RESULTS: During pilot testing the online training was reported to be acceptable and overall communication and confidence improved for all participants post training. However, during the ADAPT CRCT uptake was low (7%; n = 20). Although those who accessed the training reported it to be valuable, competing demands and the online format reportedly limited HPs' capacity and willingness to undertake training. CONCLUSIONS: This interactive on-line training provides strategies and communication skills for front-line staff to guide important conversations about psychosocial screening and referral. Building workforce skills, knowledge and confidence is crucial for the successful implementation of practice change interventions. However, despite being acceptable during pilot testing, low uptake in real world settings highlights that organisational support and incentivisation for frontline staff to undertake training are critical for wider engagement. A multimodal approach to delivery of training to cater for staff preferences for face to face and/or online training may maximise uptake and increase effectiveness of training interventions. TRIAL REGISTRATION: Pilot study ACTRN12616001490460 (27/10/2016). ADAPT RCT ACTRN12617000411347(22/03/2017).
Assuntos
Transtornos de Ansiedade , Depressão , Ansiedade/diagnóstico , Ansiedade/terapia , Comunicação , Depressão/diagnóstico , Depressão/terapia , Humanos , Projetos PilotoRESUMO
Pancreatic ductal adenocarcinoma (PDAC) is the most frequent pancreatic cancer type, characterized by a dismal prognosis due to late diagnosis, frequent metastases, and limited therapeutic response to standard chemotherapy. Circulating tumor cells (CTCs) are a rare subset of tumor cells found in the blood of cancer patients. CTCs has the potential utility for screening, early and definitive diagnosis, prognostic and predictive assessment, and offers the potential for personalized management. However, a gold-standard CTC detection and enrichment method remains elusive, hindering comprehensive comparisons between studies. In this review, we summarize data regarding the utility of CTCs at different stages of PDAC from early to metastatic disease and discuss the molecular profiling and culture of CTCs. The characterization of CTCs brings us closer to defining the specific CTC subpopulation responsible for metastasis with the potential to uncover new therapies and more effective management options for PDAC.
Assuntos
Biomarcadores Tumorais/sangue , Carcinoma Ductal Pancreático , Células Neoplásicas Circulantes/metabolismo , Neoplasias Pancreáticas , Carcinoma Ductal Pancreático/sangue , Carcinoma Ductal Pancreático/diagnóstico , Carcinoma Ductal Pancreático/terapia , Humanos , Neoplasias Pancreáticas/sangue , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/terapia , PrognósticoRESUMO
BACKGROUND: Chemotherapy-induced peripheral neurotoxicity (CIPN) is a major adverse effect of cancer treatment. However, its impact remains poorly understood. This study aimed to investigate the impact associated with CIPN on the lives of cancer survivors. PATIENTS AND METHODS: A volunteer sample of 986 individuals who had received neurotoxic chemotherapy completed an anonymous, cross-sectional survey. Outcomes assessed included CIPN symptoms, pain, neuropathic pain, quality of life (QoL), physical activity, and comorbid health conditions via the Self-Administered Comorbidity Questionnaire. RESULTS: Respondents had a mean age of 58 years (SD, 10.7), and 83.2% were female. Most were treated for breast (58.9%) or colorectal cancer (13.5%); had received docetaxel (32.7%), paclitaxel (31.6%), or oxaliplatin (12.5%); and had completed treatment 3.6 ± 3.5 years previously. We found that 76.5% of respondents reported current CIPN. Respondents reporting severe CIPN had poorer QoL, more comorbidities, and higher body mass index, and more often received multiple neurotoxic chemotherapies than those with mild CIPN. Respondents who completed the survey ≤1 year after completing chemotherapy did not differ in reported CIPN or pain compared with respondents who completed chemotherapy ≥6 years earlier. However, respondents who completed chemotherapy ≥6 years earlier reported better QoL. Multivariable linear regression analyses revealed predictors of CIPN severity as follows: F(7, 874) = 64.67; P<.001; R2 = 0.34, including pain (ß = -0.36; P<.001), burning pain (ß = 0.25; P<.001), sex (male sex associated with greater CIPN: ß = 0.14; P<.001), years since completing chemotherapy (shorter time associated with greater CIPN; ß = -0.10; P<.001), age (ß = 0.80; P=.006), number of comorbid conditions (ß = 0.07; P=.02), and body mass index (ß = 0.07; P=.02). CONCLUSIONS: Respondents with a high CIPN symptom burden experienced poorer general health and QoL. Improvements in CIPN may be more likely soon after treatment. However, improvements in QoL may occur over time in those with chronic symptoms. CIPN seems to have lasting impacts on cancer survivors, and understanding risk factors is important to enable the design of further preventive and therapeutic management strategies.
Assuntos
Antineoplásicos , Sobreviventes de Câncer , Neoplasias , Doenças do Sistema Nervoso Periférico , Antineoplásicos/efeitos adversos , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/complicações , Neoplasias/tratamento farmacológico , Neoplasias/epidemiologia , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Doenças do Sistema Nervoso Periférico/epidemiologia , Qualidade de VidaRESUMO
PURPOSE: Patient-reported outcome measures (PROMs) are useful clinical tools to recognise symptoms, patient needs and their severity. Whilst PROMs are routinely utilised in integrative oncology (IO) and supportive care (SC) services to improve patient care, they are not as common in general oncology. We explored our patients' symptom burden, the approach taken by clinicians to identify and manage patient needs, and barriers and facilitators to using PROMs in an Australian tertiary comprehensive cancer centre to inform wider implementation of PROMs. METHODS: From 2017 to 2018, PROM data collected for patients accessing IO and SC was retrospectively analysed. Semi-structured interviews with oncology doctors and nurses explored their approach to patient needs assessment and their use of PROMs. RESULTS: A total of 404 patients completed the Edmonton Symptom Assessment Scale (ESAS). The most frequently identified symptoms were sleep disturbance, fatigue and lack of wellbeing. Symptom clusters included drowsiness, fatigue and shortness of breath; anxiety and depression; sleep and pain; appetite and nausea. In total, 9 nurse consultants, 5 surgeons, 7 medical and 5 radiation oncologists were interviewed. Most participants took an intuitive approach to identifying and managing patient needs and did not routinely use PROMs. Perceived risks, barriers and facilitators to using PROMS are presented. CONCLUSIONS: High and complex symptom burden was found in our IO and SC patient population, reinforcing the need for screening. Whilst wider clinical use of PROMs within the hospital may improve clinical outcomes, the barriers and facilitators identified by Health Care Professionals (HCPs) need to be addressed before implementing PROMs more broadly.
Assuntos
Avaliação das Necessidades , Medidas de Resultados Relatados pelo Paciente , Austrália , Humanos , Estudos Retrospectivos , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Kaposi's sarcoma is an uncommon complication in renal transplant patients, and typically presents with cutaneous lesions on the lower extremities. Penile involvement has been reported only rarely. Management of cutaneous-limited disease is primarily reduction of immunosuppression and conversion to an mTOR-inhibitor, whereas the treatment of disseminated disease in transplant patients is more variable. CASE PRESENTATION: A 75-year-old male, originally from Somalia, received a deceased-donor kidney transplant for diabetic and hypertensive nephropathy. Seven months post-transplant he presented with lower limb lesions, oedema and bilateral deep vein thromboses. He then developed a fast-growing painful lesion on his penile shaft. A biopsy of this lesion confirmed KS, and a PET scan demonstrated disseminated disease in the lower extremities, penis and thoracic lymph nodes. His tacrolimus was converted to sirolimus, and his other immunosuppression was reduced. He was treated with single agent paclitaxel chemotherapy in view of his rapidly progressing, widespread disease. The penile lesion completely resolved, and the lower extremity lesions regressed significantly. His kidney allograft function remained stable throughout treatment. CONCLUSION: This case illustrates a rare presentation of an uncommon post-transplant complication and highlights the need for a high index of suspicion of KS in transplant patients presenting with atypical cutaneous lesions. It serves to demonstrate that the use of single agent paclitaxel chemotherapy, switch to an mTORi and reduction in immunosuppression where possible produces excellent short-term outcomes, adding to the body of evidence for this management strategy in disseminated Kaposi's sarcoma.
Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Transplante de Rim , Paclitaxel/uso terapêutico , Neoplasias Penianas/tratamento farmacológico , Complicações Pós-Operatórias/tratamento farmacológico , Sarcoma de Kaposi/tratamento farmacológico , Idoso , Humanos , MasculinoRESUMO
BACKGROUND: Clinical pathways (CPs) can improve health outcomes, but to be sustainable, must be deemed acceptable and appropriate by staff. A CP for screening and management of anxiety and depression in cancer patients (the ADAPT CP) was implemented in 12 Australian oncology services for 12 months, within a cluster randomised controlled trial of core versus enhanced implementation strategies. This paper compares staff-perceived acceptability and appropriateness of the ADAPT CP across study arms. METHODS: Multi-disciplinary lead teams at each service tailored, planned, championed and implemented the CP. Staff at participating services, purposively selected for diversity, completed a survey and participated in an interview prior to implementation (T0), and at midpoint (6 months: T1) and end (12 months: T2) of implementation. Interviews were recorded, transcribed and thematically analysed. RESULTS: Seven metropolitan and 5 regional services participated. Questionnaires were completed by 106, 58 and 57 staff at T0, T1 and T2 respectively. Eighty-eight staff consented to be interviewed at T0, with 89 and 76 at T1 and T2 (response rates 70%, 66% and 57%, respectively). Acceptability/appropriateness, on the quantitative measure, was high at T0 (mean of 31/35) and remained at that level throughout the study, with no differences between staff from core versus enhanced services. Perceived burden was relatively low (mean of 11/20) with no change over time. Lowest scores and greatest variability pertained to perceived impact on workload, time and cost. Four major themes were identified: 1) Mental health is an important issue which ADAPT addresses; 2) ADAPT helps staff deliver best care, and reduces staff stress; 3) ADAPT is fit for purpose, for both cancer care services and patients; 4) ADAPT: a catalyst for change. Opposing viewpoints are outlined. CONCLUSIONS: This study demonstrated high staff-perceived acceptability and appropriateness of the ADAPT CP with regards to its focus, evidence-base, utility to staff and patients, and ability to create change. However, concerns remained regarding burden on staff and time commitment. Strategies from a policy and managerial level will likely be required to overcome the latter issues. TRIAL REGISTRATION: The study was registered prospectively with the ANZCTR on 22/3/2017. Trial ID ACTRN12617000411347. https://www.anzctr.org.au/ .
Assuntos
Depressão , Neoplasias , Ansiedade/diagnóstico , Ansiedade/etiologia , Ansiedade/terapia , Transtornos de Ansiedade , Austrália , Procedimentos Clínicos , Depressão/diagnóstico , Depressão/etiologia , Depressão/terapia , Humanos , Neoplasias/complicações , Neoplasias/terapiaRESUMO
PURPOSE: The causal link between chemotherapy and cognitive impairment is unclear. We studied testicular cancer patients' objective and subjective cognitive function longitudinally, comparing a surgery group with a surgery + chemotherapy group, addressing prior methodological issues using a computerized test to limit assessment issues, and controlling for confounding variables. METHODS: Prospectively, of 145 patients from 16 centres with sufficient data, n = 61 receiving surgery + chemotherapy (etoposide and cisplatin ± bleomycin, BEP/EP; or single agent carboplatin) were compared to n = 41 receiving surgery alone. CogHealth assessed six objective cognitive tasks. The Cognitive Failures Questionnaire assessed self-perceived cognitive dysfunction. The Functional Assessment of Chronic Illness Therapy-Fatigue and the Hospital Anxiety and Depression Scale assessed psychological influences. Linear mixed models compared changes from baseline (< 6 months post-surgery/pre-chemotherapy) to follow-up (12-18 months post-baseline), controlling covariates. RESULTS: There were no significant interaction effects for five objective cognitive function tasks suggesting that changes over time were not due to group membership. However, psychomotor function (controlling for age) and physical well-being were significantly worse for the chemotherapy versus the surgery group at baseline, with groups converging by follow-up. Groups showed no differences in subjective cognitive dysfunction. The chemotherapy group showed higher anxiety, poorer functional well-being and worse fatigue compared to the surgery-only group at baseline, but not by follow-up. For both groups, emotional well-being, functional well-being and anxiety significantly improved over time. CONCLUSION: No substantive differences in objective or subjective cognitive dysfunction in either group persisted 12-18 months post-baseline. Patients undergoing chemotherapy for testicular cancer differ from findings in breast cancer populations. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: ACTRN12609000545268.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carboplatina/efeitos adversos , Cognição/efeitos dos fármacos , Disfunção Cognitiva/induzido quimicamente , Neoplasias Testiculares/tratamento farmacológico , Neoplasias Testiculares/psicologia , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bleomicina/administração & dosagem , Bleomicina/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/psicologia , Carboplatina/uso terapêutico , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Etoposídeo/administração & dosagem , Etoposídeo/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Neoplasias Testiculares/cirurgiaRESUMO
OBJECTIVES: To generate Australian general population reference values for the EORTC Quality of Life Questionnaire for cancer patients (QLQ-C30); to compare Australian values with published EORTC general population reference values, and to explore associations between socio-demographic and health characteristics and QLQ-C30 subscale scores. DESIGN: Analysis of responses to cross-sectional, online survey (QLQ-C30), March 2015 - February 2016, and supplementary health-related and socio-demographic questions. SETTING, PARTICIPANTS: 1979 people quota-sampled from a national online survey panel to be representative of the Australian general population by age and sex. MAIN OUTCOME MEASURES: Mean QLQ-C30 subscale scores, adjusted for socio-demographic characteristics and comorbid conditions, by sex and age group. RESULTS: Data for 1821 participants were analysed (92% completion rate); 924 (50.7%) were women. Higher psychological distress was associated with worse outcomes on all QLQ-C30 subscales. Better self-reported general health was associated with better global quality of life and better functioning (except cognitive functioning), and less fatigue, pain, dyspnoea and insomnia. Having arthritis or rheumatism was associated with poorer global quality of life, and poorer physical, role and social functioning, and with more fatigue, pain, insomnia, diarrhoea, and financial difficulties. Although differences between Australian QLQ-C30 subscale scores and EORTC general population values were clinically trivial, the Australian values are more accurate benchmarks for QLQ-C30 results from Australians with cancer. CONCLUSIONS: Our Australian QLQ-C30 reference values provide normative benchmarks that facilitate interpretation of data for Australians with cancer in terms of burden of disease and its treatment. In survivorship studies and studies without pre-disease baseline data, comparisons with reference values can indicate the extent to which people have returned to better levels of health.