The potential impact of exercise upon symptom burden in adolescents and young adults undergoing cancer treatment.

PURPOSE: Adolescents and young adults (AYAs) experience vast symptom burden resulting from cancer treatment-related toxicities (TRTs). Evidence supports integrated exercise to mitigate several TRTs in other cohorts; however, evidence in AYAs is lacking. Conventional reporting of TRTs adopts a maximum grade approach failing to recognise the trajectory over time, of persistent, or lower grade toxicities. Alternatively, longitudinal analysis of toxicities over time (ToxT) may provide clinically meaningful summaries of this data. We evaluated the longitudinal impact of an exercise intervention on TRTs in AYAs undergoing cancer treatment. METHODS: A prospective, randomised trial allocated participants to a 10-week exercise intervention (EG) or control group (CG) undergoing usual care. Detailed information on TRTs was collected throughout the intervention. All TRTs were graded per the Common Terminology Criteria for Adverse Events (CTCAE v5.0). RESULTS: Forty-three (43) participants (63% male, mean age 21.1 years) were enrolled. When categorised to reflect the maximal worst grade experienced (Grade 0, Grade 1-2 and ≥ Grade 3), the CG reported an increased incidence of severe fatigue (≥ Grade 3) compared with the EG (p = 0.05). No other differences between groups were evident (p > 0.05). ToxT analysis of the four most common toxicities (fatigue, pain, nausea and mood disturbances) demonstrated no difference in the mean grade of each over time (p > 0.05). CONCLUSION: A 10-week exercise intervention reduces the severity of fatigue in AYAs undergoing treatment. While the ToxT approach provided insight into the toxicity profile, adequately powered studies are needed to better understand these differences within a homogenous sample. TRIAL REGISTRATION: (ACTRN12620000663954) 10th June 2020.

A randomised controlled trial investigating the ability for supervised exercise to reduce treatment-related decline in adolescent and young adult cancer patients.

INTRODUCTION: Exercise is recognised as integral in mitigating a myriad negative consequences of cancer treatment. However, its benefit within adolescent and young adult (AYA) cancer cohorts remains relatively under researched, and caution should be taken in extrapolating outcomes from adult and paediatric populations given AYA distinctly different physiological and psychosocial contexts. This study sought to evaluate the impact of an exercise intervention on mitigating the expected decline in fitness, strength, physical functioning, and quality of life (QOL) in AYA undergoing cancer treatment. METHODS: This prospective, randomised controlled trial (FiGHTINGF!T) allocated 43 participants (63% male, mean age 21.1 years) to a 10-week, multimodal, bi-weekly exercise intervention (EG) or control group (CG) undergoing usual care. Pre- and post-intervention assessments included cardiopulmonary exercise tests, one-repetition maximum (1RM) strength, functional tests, and QOL patient-reported outcome measures. Data were analysed via linear mixed models and regression. RESULTS: While no significant group differences (p > 0.05) were observed, neither group significantly declined (p > 0.05) in any outcome measure over the 10-week period. No significant (p˃0.05) strength or functional improvements were observed in the CG, though the EG demonstrated significant improvements in their 1RM leg press (p = 0.004) and chest press (p = 0.032), maximal push ups (p = 0.032), and global QOL (p = 0.011). The EG reported a significant increase in fatigue (p = 0.014), while the CG reported significant positive changes in anxiety measures (p = 0.005). CONCLUSION: The exercise intervention produced superior improvements in strength and global QOL, compared with the CG. Regardless of group allocation, enrolment in the exercise study appeared to mitigate the treatment-related decline expected in AYA undergoing cancer treatment.

Mycosis fungoides and Sézary syndrome: Australian clinical practice statement.

Primary cutaneous lymphomas represent a heterogeneous group of T- and B-cell lymphomas with distinct clinical presentations, histopathologic features, treatment approaches and outcomes. The cutaneous T-cell lymphomas, which include mycosis fungoides and Sézary syndrome, account for the majority of the cutaneous lymphomas. This Clinical Practice Statement is reflective of the current clinical practice in Australia. An expanded form of the Clinical Practice Statement (and updates), along with helpful patient resources and access to support groups, can be found at the following (http://www.australasianlymphomaalliance.org.au).

'It is a journey of discovery': living with myeloma.

PURPOSE: Although multiple myeloma (MM) is incurable, many people live with the disease for a number of years. Thus, understanding the effect of the disease and its therapies on the lives of those with MM is important. This qualitative study explores the impact of MM and its treatments on patients. METHODS: People with newly diagnosed or relapsed MM were recruited from a tertiary institution. Participants were interviewed using a semi-structured approach. The questions were designed to obtain insight into how participants viewed their diagnosis, treatment, and symptoms and how these had impacted on their lives. Data were analysed using a phenomenological approach. RESULTS: Fifteen people with MM with a mean age of 62 were recruited. Participants' mean time since diagnosis was 2.7 years and they had received a mean of 1.7 lines of therapy. The first major theme to emerge was lifestyle changes. Interviewees described MM as causing changes to all aspects of their lives, including substantial functional changes, as well as changes to employment, relationships, and their sense of self. The second major theme was 'adjust, adjust, adjust'. Alongside challenging life changes, participants described a range of practical, psychological, and relational approaches to adjusting to living with MM. CONCLUSION: This study highlights the importance of and the need for improved supportive care in patients with MM, ideally with a multidisciplinary approach. It also identifies the potential for further investigation of patient approaches to adjusting to MM and development of support strategies.

A pilot study of routine screening for distress by a nurse and psychologist in an outpatient haematological oncology clinic.

AIM: To explore the: 1) prevalence of distress, type of problems experienced by haematological patients, and referrals for supportive care; 2) effect of demographic and clinical variables on distress, and 3) effect on the time of health professionals conducting the screening in the ambulatory chemotherapy setting. METHODS: Participants completed the National Comprehensive Cancer Network Distress Thermometer and Problem List and had a follow-up screening discussion with a health professional. RESULTS: Of 68 participants, 40% reported significant distress (≥4) on the Distress Thermometer (mean 3.2, SD 2.4). All patients reported physical problems and 72% reported emotional problems-the major contributors to distress and to time spent with the health professional. Distress was unrelated to age, gender or cancer type. Patients were less likely to have significant distress at the end of treatment than at the beginning (OR=0.15, 95% CI: 0.03; 0.72,). Forty patients (59%) were referred to supportive services. The psychologist spent less time with patients compared to the nurse (18 vs 48min, p<0.001). The more emotional problems reported, the greater the time spent with the patient (rs=0.34, p=0.009). CONCLUSIONS: Nurses can appropriately screen for distress and address significant distress reported by haematology patients undergoing chemotherapy without over burdening the nurse or patient.

A randomised controlled trial comparing the effects of a 12-week supervised exercise versus usual care on outcomes in haematological cancer patients.

PURPOSE: Following treatment, haematological cancer (HEM) patients exhibit significant physical deconditioning and psychological distress. Exercise has been shown as a clinically effective and safe intervention for cancer patients, with the potential to reverse the deleterious effects following treatment. Our aim was to investigate the efficacy of a 12-week exercise rehabilitation on cancer-related fatigue (CRF) and associated outcomes in HEM patients post-treatment. METHODS: Patients with a HEM were recruited to participate in a 12-week exercise rehabilitation intervention post-treatment. Pre-, post- and follow-up assessments were conducted on outcome measures including CRF, quality of life (QoL), psychological distress, cardiovascular fitness, muscle strength (MS) and body composition. Patients were given tailored exercise programmes comprising aerobic and resistance exercises, carried out three times per week for 12 weeks in local gyms and clinics. Usual-care participants were offered a delayed, tailored 12-week exercise intervention after the initial study period. RESULTS: Thirty-seven patients (49 % recruitment rate) were randomly assigned to the 12-week exercise rehabilitation (n = 18) or usual care (n = 19) with a 91 % adherence to the exercise intervention. Following the exercise programme, significant improvements were seen in CRF (p = 0.01), cardiovascular fitness (p ≤ 0.001), QoL (p ≤ 0.001), MS (p ≤ 0.001) and body composition (p = 0.001), with moderate to large effects for all primary outcomes. Patient follow-up at 24 weeks demonstrated outcome maintenance in the exercise rehabilitation group and significant improvements in outcomes in usual-care patients following participation in a delayed exercise programme. There were no adverse reactions or study withdrawals. CONCLUSIONS: A 12-week exercise rehabilitation programme resulted in significant statistical (p ≤ 0.05) and clinical improvements in CRF and additional outcomes in HEM patients following treatment. Additionally, a 12-week delayed exercise programme showed similar significant improvements in patient outcomes. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12609000450213.

Differential gene expression analysis in early and late erythroid progenitor cells in ß-thalassaemia.

ß- thalassaemia is a disorder of globin gene synthesis resulting in reduced or absent production of the ß-globin chain in red blood cells. In this study, haematopoietic stem cells were isolated from the peripheral blood of six transfusion dependent ß-thalassaemia patients and six healthy controls. Following 7 and 14 d in culture, early- and late- erythroblasts were isolated and purified. No morphological difference in maturation was observed following 7 d in culture, while a delayed maturation was observed in the patient group after 14 d. Following RNA isolation and linear amplification, gene expression analyses were performed using microarray technology. The generated data were analysed by two methods: the BRB-ArrayTools platform and the Bioconductor platform using bead level data. Following 7 d culture, there was no difference in gene expression between the control and patient groups. Following 14 d culture, 384 differentially expressed genes were identified by either analysis. A subset of 90 genes was selected and the results were confirmed by Quantitative-Real-Time-polymerase chain reaction. Pathways shown to be significantly altered in the patient group include apoptosis, MAPKinase and the nuclear factor-κB pathway.

Romidepsin in peripheral and cutaneous T-cell lymphoma: mechanistic implications from clinical and correlative data.

Romidepsin is an epigenetic agent approved for the treatment of patients with cutaneous or peripheral T-cell lymphoma (CTCL and PTCL). Here we report data in all patients treated on the National Cancer Institute 1312 trial, demonstrating long-term disease control and the ability to retreat patients relapsing off-therapy. In all, 84 patients with CTCL and 47 with PTCL were enrolled. Responses occurred early, were clinically meaningful and of very long duration in some cases. Notably, patients with PTCL receiving romidepsin as third-line therapy or later had a comparable response rate (32%) of similar duration as the total population (38%). Eight patients had treatment breaks of 3.5 months to 10 years; in four of six patients, re-initiation of treatment led to clear benefit. Safety data show slightly greater haematological and constitutional toxicity in PTCL. cDNA microarray studies show unique individual gene expression profiles, minimal overlap between patients, and both induction and repression of gene expression that reversed within 24 h. These data argue against cell death occurring as a result of an epigenetics-mediated gene induction programme. Together this work supports the safety and activity of romidepsin in T-cell lymphoma, but suggests a complex mechanism of action.

Lymphoid neoplasm incidence by WHO subtype in Australia 1982-2006.

There are limited data characterizing the subtype-specific incidence of lymphoid neoplasms in the World Health Organization (WHO) Classification era. Data were obtained on all incident lymphoid neoplasms registered in Australia during 1982-2006. Subtypes were grouped using the InterLymph nested hierarchical classification, based on the 2008 WHO Classification. Temporal trends were examined using Joinpoint regression; average annual percentage change in incidence was computed. Multiple Poisson regression was used to compare incidence by sex and age. The incidence of all non-Hodgkin lymphoma (NHL) increased by 2.5%/year during 1982-1996 and was stable thereafter. During 1997-2006, several mature B- and natural killer (NK)-/T-cell NHL subtypes increased in incidence, including diffuse large B-cell (1.3%/year), follicular (2.5%/year), Burkitt (6.8%/year), marginal zone (13.2%/year), mantle cell (4.2%/year), peripheral T-cell lymphoma (4.7%/year) and plasmacytoma (7.1%/year). While chronic lymphocytic leukemia incidence was stable, small lymphocytic lymphoma incidence declined (8.1%/year). Hodgkin lymphoma (HL) incidence increased during 1997-2006 (2.2%/year), both classical (4.3%/year) and nodular lymphocyte predominant (12.1%/year) HL. Diagnostic artifact, evidenced by a sustained decline in the incidence of NHL not otherwise specified (NOS; 5.8%/year) and lymphoid neoplasms NOS (5.6%/year), limits the interpretation of temporal trends for some subtypes. A marked male predominance was observed for almost all subtypes. Incidence of mature B- and NK-/T-cell NHL subtypes increased sharply with age, except for Burkitt lymphoma/leukemia. For HL subtypes, a bimodal age distribution was only evident for nodular sclerosis HL. Variation in incidence patterns over time and by sex and age supports etiological differences between lymphoid neoplasm subtypes.

Positive patient experiences in an Australian integrative oncology centre.

BACKGROUND: The purpose of this study was to explore the experiences of cancer patients' utilising complementary and integrative therapies (CIT) within integrative oncology centres across Western Australia. METHODS: Across four locations 135 patients accessed CIT services whilst undergoing outpatient medical treatment for cancer. Of the 135 patients, 66 (61±12 y; female n=45; male n=21) agreed to complete a personal accounts questionnaire consisting of open-ended questions designed to explore patients' perceptions of CIT. All results were transcribed into nVivo (v9) and using thematic analysis, key themes were identified. RESULTS: Of the 66 participants, 100% indicated they would "recommend complementary therapies to other patients" and 92% stated "CIT would play a significant role in their future lifestyle". A mean score of 8±1 indicated an improvement in participants' perception of wellbeing following a CIT session. Three central themes were identified: empowerment, support and relaxation. Fourteen sub-themes were identified, with all themes clustered into a framework of multifaceted views held by cancer patients in relation to wellbeing, role of significant others and control. CONCLUSIONS: Exploration of patients' experiences reveals uniformly positive results. One of the key merits of the environment created within the centres is patients are able to work through their cancer journey with an increased sense of empowerment, without placing them in opposition to conventional medical treatment. In order to effectively target integrative support services it is crucial to explore the experiences of patients in their own words and use those forms of expression to drive service delivery.

Latitude gradients for lymphoid neoplasm subtypes in Australia support an association with ultraviolet radiation exposure.

Given the uncertainty surrounding solar ultraviolet radiation (UVR) exposure and risk of lymphoid neoplasms, we performed an ecological analysis of national Australian data for incident cases diagnosed between 2002 and 2006. Subtype-specific incidence was examined by latitude band (<29°S, 29-36°S, ≥37°S), a proxy for ambient UVR exposure, using multiple Poisson regression, adjusted for sex, age-group and calendar year. Incidence increased with distance from the equator for several mature B-cell non-Hodgkin lymphomas, including diffuse large B-cell [incidence rate ratio (IRR) = 1.37; 95% confidence interval (CI): 1.16-1.61 for latitude ≥37°S relative to <29°S], lymphoplasmacytic (IRR = 1.34; 95% CI: 1.12-1.61), mucosa-associated lymphoid tissue (IRR = 1.32; 95% CI: 0.97-1.80) and mantle cell lymphoma (IRR = 1.29; 95% CI: 1.05-1.58), as well as plasmacytoma (IRR = 1.52; 95% CI: 1.09-2.11) and plasma cell myeloma (IRR = 1.15; 95% CI: 1.03-1.27). A similar pattern was observed for several mature cutaneous T-cell neoplasms, including primary cutaneous anaplastic large cell lymphoma (IRR = 4.26; 95% CI: 1.85-9.84), mycosis fungoides/Sézary syndrome (IRR = 1.72; 95% CI: 1.20-2.46), and peripheral T-cell lymphoma not otherwise specified (NOS) (IRR = 1.53; 95% CI: 1.17-2.00). Incidence of mixed cellularity/lymphocyte-depleted (IRR = 1.60; 95% CI: 1.16-2.20) and nodular sclerosis Hodgkin lymphoma (IRR = 1.57; 95% CI: 1.33-1.85) also increased with distance from the equator. Many of these subtypes have a known association with infection or immune dysregulation. Our findings support a possible protective effect of UVR exposure on the risk of several lymphoid neoplasms, possibly through vitamin D-related immune modulation critical in lymphomagenesis.

Phase 2 trial of romidepsin in patients with peripheral T-cell lymphoma.

Romidepsin (depsipeptide or FK228) is a histone deacetylase inhibitor, one of a new class of agents active in T-cell lymphoma. A phase 2 trial was conducted in cutaneous (CTCL) and peripheral (PTCL) T-cell lymphoma. Major and durable responses in CTCL supported the approval of romidepsin for CTCL. Forty-seven patients with PTCL of various subtypes including PTCL NOS, angioimmunoblastic, ALK-negative anaplastic large cell lymphoma, and enteropathy-associated T-cell lymphoma were enrolled. All patients had received prior therapy with a median of 3 previous treatments (range 1-11); 18 (38%) had undergone stem-cell transplant. All patients were evaluated for toxicity; 2 patients discovered to be ineligible were excluded from response assessment. Common toxicities were nausea, fatigue, and transient thrombocytopenia and granulocytopenia. Complete responses were observed in 8 and partial responses in 9 of 45 patients, for an overall response rate of 38% (95% confidence interval 24%-53%). The median duration of overall response was 8.9 months (range 2-74). Responses were observed in various subtypes, with 6 responses among the 18 patients with prior stem-cell transplant. The histone deacetylase inhibitor romidepsin has single agent clinical activity associated with durable responses in patients with relapsed PTCL.

Characteristics and quality of life of patients presenting to cancer support centres: patient rated outcomes and use of complementary therapies.

BACKGROUND: In order to effectively target and provide individualised patient support strategies it is crucial to have a comprehensive picture of those presenting for services. The purpose of this study was to determine the characteristics and patient rated outcomes of individuals presenting to SolarisCare cancer support centres and their choices regarding complementary and integrated therapies (CIT). METHODS: A cohort with a current or previous cancer diagnosis aged 18 - 87 years presenting to a SolarisCare centre during a 5-day period completed a questionnaire. Four SolarisCare centres participated in the trial including regional and metropolitan locations. Outcomes included medical and demographic characteristics, CIT variables and patient rated outcomes (PROs) including quality of life (QoL). RESULTS: Of the 95 participants (70.3%) who completed the survey, the mean age was 60.5 years with 62% currently receiving treatment. Eighty percent of the sample had at least one other comorbid condition, with the most popular CIT being relaxation massage. Of the PROs, QoL was significantly lower than norms for the Australian population and other mixed cancer populations. No notable differences were seen between genders, however significantly poorer outcomes were found for the younger age group. Fifty percent of the population did not meet physical activity recommendations, and musculoskeletal symptoms explained between 25-27% of variance in QoL. CONCLUSIONS: A greater understanding of the health profiles of patients presenting to supportive care centres and their use of CIT, provides Western Australian health professionals with key information to ensure the safety of supportive care practices, as well as fosters optimal patient outcomes and enhances the integration of supportive care strategies within mainstream medical care.

Significant association between thyroid hormones and erythrocyte indices in euthyroid subjects.

OBJECTIVE: Hypothyroidism and hyperthyroidism are each associated with anaemia, but relationships between thyroid function and erythrocyte indices in euthyroid subjects have not been examined. The aim of this study was to examine these relationships in a community-based cohort. DESIGN, SUBJECTS AND MEASUREMENTS: Linear regression models with free T4, free T3 and TSH as predictors of erythrocyte indices and serum iron parameters were fitted to data from a cohort of 1179 participants in the 1994 Busselton health study and a subset of 1011 euthyroid participants. All models were adjusted for age, age(2), sex and an age-sex interaction. RESULTS: In the full cohort and euthyroid subset, there were significant, positive linear relationships between free T4 and each of haemoglobin, haematocrit and erythrocyte count (P < 0·01 for each), such that in euthyroid participants, each 1·0 pM increase in free T4 was associated with an increase in haemoglobin of 0·39 g/l. There were significant relationships between free T3 and each of haemoglobin, haematocrit and erythrocyte count (P < 0·001 for each), with the best model fits obtained using free T3(2), indicating curved relationships. TSH had a significant (P < 0·05) inverse relationship with serum iron and transferrin saturation in the full cohort and the euthyroid subset. Serum iron concentrations were lower in participants with subclinical hypothyroidism (n = 87) than euthyroid subjects [mean (SD) 15·9 (4·7) vs 18·4 (6·0) µM, P = 0·001]. CONCLUSION: In euthyroid subjects, small differences in thyroid function are associated with significant differences in erythrocyte indices.

Cutaneous intravascular anaplastic large T-cell lymphoma: a case report and review of the literature.

Intravascular lymphoma (IVL) is a rare subtype of extranodal lymphoma. In the 2008 WHO classification of tumors of the hematopoietic and lymphoid tissues intravascular large B-cell lymphoma is included as a distinct entity. IVL of T-cell type is not included as a diagnostic category and is only mentioned in passing by Nakamura et al. as "a different entity" in their discussion of intravascular large B-cell lymphoma. T-cell IVL is rare, the majority of cases being of natural killer/T-cell phenotype. Exceptionally rare is primary cutaneous intravascular anaplastic large T-cell lymphoma. We present such a case in an otherwise well 39-year-old female having disease limited to the skin established after detailed staging investigations. This is only the third such case described in the literature. We report the clinicopathological features of this case and also review previously documented cases of cutaneous intravascular anaplastic large cell lymphoma.

Test-retest reliability of the aerobic power index submaximal exercise test in cancer patients.

The purpose of this study was to investigate the reliability of the Aerobic Power Index (API) submaximal cardiorespiratory exercise test, as well as associated variables of oxygen uptake (ml·kg(-1)·min(-1)) and ratings of perceived exertion (RPE) in cancer patients who are generally unable to complete maximal or lengthy aerobic fitness tests. Twenty male and female participants (11 male; 9 female) aged between 18 and 70 y (mean = 53.28 ± 11. 82 y) were recruited with medical consent within 4 weeks of completing chemotherapy treatment for a lymphohaematopoietic cancer (LHC). Of the twenty recruited participants' 2 were excluded from analysis due to disease relapse or complications unrelated to testing occurring within the month following testing. Intra-class correlation coefficient (ICC) scores for power output (W·kg(-1)) and oxygen uptake (ml·kg(-1)·min(-1)) were highly reliable (R1 = 0.96 and 0.96, respectively) and the ICC for RPE was moderately reliable (R1 = 0.83). Technical error of measurement results for power output (W·kg(-1)), oxygen uptake (ml·kg(-1)·min(-1)) and RPE were 0.11W·kg(-1), 1.18 ml·kg(-1)·min(-1) and 1.0 respectively. A Pearson's product-moment correlation demonstrated a strong relationship between power output (W·kg(-1)) and oxygen uptake (ml·kg(-1)·min(-1)) for both trials (r = 0.93 and 0.89, respectively). Results demonstrate that the API test is a highly reliable protocol for use with a LHC population and can be considered a clinically feasible, safe and tolerable exercise test.

Risk of second cancer after lymphohematopoietic neoplasm.

People living with lymphohematopoietic neoplasms (LHNs) are known to have increased risks of second cancer; however, the incidence of second cancers after LHNs has not been studied extensively in Australia. The Australian Cancer Database was used to analyze site-specific risk of second primary cancer after LHNs in 127,707 patients diagnosed between 1983 and 2005. Standardized incidence ratios (SIRs) were calculated using population rates. Overall, patients with an LHN had nearly twice the risk of developing a second cancer compared to the Australian population. Among 40,321 patients with non-Hodgkin's lymphoma (NHL), there was over a fourfold significant increase in melanoma, Kaposi sarcoma, cancer of the lip, connective tissue and peripheral nerves, eye, thyroid, Hodgkin's disease (HD) and myeloid leukemia. Among 6,396 patients with HD, there was over a fourfold significant increase in melanoma, Kaposi sarcoma, cancer of the lip, oral cavity and pharynx, female breast, uterine cervix, testis, thyroid, NHL and myeloid leukemia. Among the 33,025 patients with lymphoid and myeloid leukemia, significant excess were seen for cancers of the lip, eye, connective tissue and peripheral nerves, NHL and HD. Among the 13,856 patients with plasma cell tumors, there was over fourfold significant increase for melanoma, cancer of the connective tissue and peripheral nerves and myeloid leukemia. Our findings provide evidence of an increased risk of cancer, particularly ultraviolet radiation- and immunosuppression-related cancers, after an LHN in Australia.