Antoinette Anazodo

Online group-based cognitive-behavioural therapy for adolescents and young adults after cancer treatment: a multicenter randomised controlled trial of Recapture Life-AYA.

BackgroundA cancer diagnosis is 2.9 times more likely to occur during the adolescent and young adult years than in younger children. This spike in incidence coincides with a life stage characterised by psychological vulnerability as young people strive to attain numerous, critical developmental milestones. The distress young people experience after cancer treatment seriously jeopardises their ability to move into well-functioning adulthood.Methods/DesignThis article presents the protocol of the Recapture Life study, a phase II three-arm randomised controlled trial designed to evaluate the feasibility and efficacy of a new intervention in reducing distress and improving quality of life for adolescent and young adult cancer survivors. The novel intervention, “ReCaPTure LiFe” will be compared to a both a wait-list, and a peer-support group control. Ninety young people aged 15–25 years who have completed cancer treatment in the past 1–6 months will be recruited from hospitals around Australia. Those randomised to receive Recapture Life will participate in six, weekly, 90-minute online group sessions led by a psychologist, involving peer-discussion around cognitive-behavioural coping skills (including: behavioural activation, thought challenging, communication and assertiveness skills training, problem-solving and goal-setting). Participants randomised to the peer-support group control will receive non-directive peer support delivered in an identical manner. Participants will complete psychosocial measures at baseline, post-intervention, and 12-months post-intervention. The primary outcome will be quality of life. Secondary outcomes will include depression, anxiety, stress, family functioning, coping, and cancer-related identity.DiscussionThis article reviews the empirical rationale for using group-based, online cognitive-behavioural therapy in young people after cancer treatment. The potential challenges of delivering skills-based programs in an online modality are highlighted, and the role of both peer and caregiver support in enhancing the effectiveness of this skills-based intervention is also discussed. The innovative videoconferencing delivery method Recapture Life uses has the potential to address the geographic and psychological isolation of adolescents and young adults as they move toward cancer survivorship. It is expected that teaching AYAs coping skills as they resume their normal lives after cancer may have long-term implications for their quality of life.Trial RegistrationACTRN12610000717055

Cardiac or cardiopulmonary transplantation in childhood cancer survivors: an increasing need?

Childhood cancer patients now have an excellent survival rate. Anthracyclines and radiation have contributed to this success, unfortunately at a cost. Both modalities are cardiotoxic and in some cases this is fatal unless treated by cardiac transplantation. This population-based study investigates the requirement for transplantation, patient demographics and transplant outcomes. Childhood cancer survivors requiring a subsequent cardiac or cardiopulmonary transplant were identified by record linkage between the National Registry Childhood Tumours (NRCT) and United Kingdom Transplant registry (UKT). The clinical details were obtained from the treatment centres for confirmed matches. Forty-three patients were identified as requiring cardiac transplantation: 36 underwent transplantation, 4 died while waiting and 3 were removed from the list. Their childhood cancers included 21 haematopoietic and 22 solid tumours diagnosed at a median age of 3.00 years (range 0.11-13.92 years). All patients were treated with anthracyclines (210-750 mg/m(2)) and 15 received cardiac radiation. The median age at cardiac transplantation was 14.80 years (range 3.26-23.92 years) and actuarial survival for the 36 who underwent cardiac transplantation was 74% and 67% at 5 and 10 years, respectively. A further three patients underwent heart/lung transplantation: all three died from transplant-related causes. Cardiac transplantation is a realistic option for cancer survivors, with survival rates comparable with those of other cardiac recipients. This study demonstrates that, over three decades, there has been an increased requirement for cardiac transplantation among childhood cancer survivors. Future planning for long term survivors needs to take this into account.

Creating a Global Community of Practice for Oncofertility

Fertility preservation in the cancer setting, known as oncofertility, is a field that requires cross-disciplinary interaction between physicians, basic scientists, clinical researchers, ethicists, lawyers, educators, and religious leaders. Funded by the National Institutes of Health, the Oncofertility Consortium (OC) was formed to be a scientifically grounded, transparent, and altruistic resource, both intellectual and monetary, for building this new field of practice capable of addressing the unique needs of young patients with cancer. The OC has expanded its attention to include other nonmalignant conditions that can threaten fertility, and the work of the OC now extends around the globe, involving partners who together have created a community of shared effort, resources, and practices. The OC creates materials that are translated, disseminated, and amended by all participants in the field, and local programs of excellence have developed worldwide to accelerate the pace and improve the quality of oncofertility research and practice. Here we review the global oncofertility programs and the capacity building activities that strengthen these research and clinical programs, ultimately improving patient care.

Outcomes of haematopoietic stem cell transplantation for inherited metabolic disorders: a report from the Australian and New Zealand Children's Haematology Oncology Group and the Australasian Bone Marrow Transplant Recipient Registry.

We report a retrospective analysis of 53 haematopoietic stem cell transplants for inherited metabolic disorders performed at ANZCHOG transplant centres between 1992 and 2008. Indications for transplant included Hurler syndrome, ALD, and MLD. The majority of transplants utilized unrelated donor stem cells (66%) with 65% of those being unrelated cord blood. Conditioning therapy was largely myeloablative, with Bu plus another cytotoxic agent used in 89% of recipients. Primary graft failure was rare, occurring in three patients, all of whom remain long‐term survivors following the second transplant. The CI of grade II‐IV and grade III‐IV acute GVHD at day +100 was 39% and 14%, respectively. Chronic GVHD occurred in 17% of recipients. TRM was 12% at day +100 and 19% at one yr post‐transplant. OS at five yr was 78% for the cohort, 73% for patients with ALD and 83% for patients with Hurler syndrome. There was no statistically significant difference in overall survival between unrelated marrow and unrelated cord blood donor groups. The development of interstitial pneumonitis was an independent variable shown to significantly impact on TRM and OS. In summary, we report a large cohort of patients with inherited metabolic disorders with excellent survival post‐allogeneic transplant.

Clinician Provision of Oncofertility Support in Cancer Patients of a Reproductive Age: A systematic review

The emerging discipline of oncofertility advocates for the timely provision of fertility information and referral for fertility preservation to all cancer patients of reproductive age (<45 years). A systematic review was undertaken on the clinician provision of oncofertility support to determine whether cancer patients are having their support needs adequately met by staff.

Survey of Fertility Preservation Options Available to Patients With Cancer Around the Globe

Purpose Oncofertility focuses on providing fertility and endocrine-sparing options to patients who undergo life-preserving but gonadotoxic cancer treatment. The resources needed to meet patient demand often are fragmented along disciplinary lines. We quantify assets and gaps in oncofertility care on a global scale. Methods Survey-based questionnaires were provided to 191 members of the Oncofertility Consortium Global Partners Network, a National Institutes of Health–funded organization. Responses were analyzed to measure trends and regional subtleties about patient oncofertility experiences and to analyze barriers to care at sites that provide oncofertility services. Results Sixty-three responses were received (response rate, 25%), and 40 were analyzed from oncofertility centers in 28 countries. Thirty of 40 survey results (75%) showed that formal referral processes and psychological care are provided to patients at the majority of sites. Fourteen of 23 respondents (61%) stated that some fertility preservation services are not offered because of cultural and legal barriers. The growth of oncofertility and its capacity to improve the lives of cancer survivors around the globe relies on concentrated efforts to increase awareness, promote collaboration, share best practices, and advocate for research funding. Conclusion This survey reveals global and regional successes and challenges and provides insight into what is needed to advance the field and make the discussion of fertility preservation and endocrine health a standard component of the cancer treatment plan. As the field of oncofertility continues to develop around the globe, regular assessment of both international and regional barriers to quality care must continue to guide process improvements.Purpose Oncofertility focuses on providing fertility and endocrine-sparing options to patients who undergo life-preserving but gonadotoxic cancer treatment. The resources needed to meet patient demand often are fragmented along disciplinary lines. We quantify assets and gaps in oncofertility care on a global scale. Methods Survey-based questionnaires were provided to 191 members of the Oncofertility Consortium Global Partners Network, a National Institutes of Health–funded organization. Responses were analyzed to measure trends and regional subtleties about patient oncofertility experiences and to analyze barriers to care at sites that provide oncofertility services. Results Sixty-three responses were received (response rate, 25%), and 40 were analyzed from oncofertility centers in 28 countries. Thirty of 40 survey results (75%) showed that formal referral processes and psychological care are provided to patients at the majority of sites. Fourteen of 23 respondents (61%) stated that some fertility preservation services are not offered because of cultural and legal barriers. The growth of oncofertility and its capacity to improve the lives of cancer survivors around the globe relies on concentrated efforts to increase awareness, promote collaboration, share best practices, and advocate for research funding. Conclusion This survey reveals global and regional successes and challenges and provides insight into what is needed to advance the field and make the discussion of fertility preservation and endocrine health a standard component of the cancer treatment plan. As the field of oncofertility continues to develop around the globe, regular assessment of both international and regional barriers to quality care must continue to guide process improvements.

Improving fertility preservation for girls and women by coupling oocyte in vitro maturation with existing strategies.

Background Advances in the treatment of cancer have resulted in a significant increase in cancer survival rates over the past two decades. Therefore, there is an increasing demand to prevent or decrease the loss of fertility in young female cancer patients who are facing life-preserving, but fertility-destroying, chemo or radiation therapy. Fertility preservation covers a range of clinical approaches and laboratory technologies, many of which are still experimental. Ovarian hyperstimulation and multiple oocyte collection, as per a full IVF cycle, offers cancer patients the best chance of preserving their fertility. Therefore, this is often the first line of treatment for cancer patients, providing good pregnancy outcomes. However, a full IVF stimulation cycle is not suitable for certain cohorts of patients undergoing cancer treatment, such as prepubertal girls, patients who have estrogen-sensitive cancers or those who have insufficient time for a full IVF cycle (∼2 weeks). Ovarian tissue is increasingly being collected from cancer patients and cryopreserved for fertility preservation purposes. Ovarian tissue preservation has been practiced for many decades despite the fact that, until recently, the prospects of generating a pregnancy from this material have been very limited. Recently, there has been encouraging successes using tissue-transplantation approaches with now >60 healthy children born. Oocyte in vitro maturation (IVM) is a procedure that involves the collection of immature oocytes from minimally unstimulated ovaries followed by their maturation in the laboratory before being fertilized or stored. IVM is used to treat infertility. There are significant opportunities to improve fertility preservation by coupling differing variants of IVM to existing fertility preservation strategies.

Inconsistencies and time delays in site-specific research approvals hinder collaborative clinical research in Australia

The aim of this study was to describe the time and documentation needed to gain ethics and governance approvals in Australian states with and without a centralised ethical review system.

A novel BRD4-NUT fusion in an undifferentiated sinonasal tumor highlights alternative splicing as a contributing oncogenic factor in NUT midline carcinoma.

NUT midline carcinoma (NMC) is a fatal cancer that arises in various tissues along the upper midline of the body. The defining molecular feature of NMC is a chromosomal translocation that joins (in the majority of cases) the nuclear testis gene NUT (NUTM1) to the bromodomain protein family member 4 (BRD4) and thereby creating a fusion oncogene that disrupts cellular differentiation and drives the disease. In this study, we report the case of an adolescent NMC patient presenting with severe facial pain, proptosis and visual impairment due to a mass arising from the ethmoid sinus that invaded the right orbit and frontal lobe. Treatment involved radical resection, including exenteration of the affected eye with the view to consolidate treatment with radiation therapy; however, the patient experienced rapid tumor progression and passed away 79 days post resection. Molecular analysis of the tumor tissue identified a novel in-frame BRD4-NUT transcript, with BRD4 exon 15 fused to the last 124 nucleotides of NUT exon 2 (BRD4-NUT ex15:ex2Δnt1–585). The partial deletion of NUT exon 2 was attributed to a mid-exonic genomic breakpoint and the subsequent activation of a cryptic splice site further downstream within the exon. Inhibition of the canonical 3′ acceptor splice site of NUT intron 1 in cell lines expressing the most common NMC fusion transcripts (PER-403, BRD4-NUT ex11:ex2; PER-624, BRD4-NUT ex15:ex2) induced alternative splicing from the same cryptic splice site as identified in the patient. Detection of low levels of an in-frame BRD4-NUT ex11:ex2Δnt1–585 transcript in PER-403 confirmed endogenous splicing from this alternative exon 2 splice site. Although further studies are necessary to assess the clinical relevance of the increasing number of variant fusions described in NMC, the findings presented in this case identify alternative splicing as a mechanism that contributes to this pathogenic complexity.

Pregnancy Outcomes After a Breast Cancer Diagnosis: A Systematic Review and Meta-analysis

Abstract Improvements in local and systemic treatment, along with earlier diagnoses through breast awareness and screening, have led to increases in survival and a decline in breast cancer (BC) recurrence. To the best of our knowledge, no meta‐analysis has yet focused on pregnancy outcomes after BC treatment. Hence, our research group explored the reproductive outcomes (pregnancy, miscarriage, termination of pregnancy, live births) after BC treatment. The Embase, MEDLINE, PubMed, and Scopus databases were searched. Studies were included that reported on pregnancy and reproductive outcomes after treatment of BC. A meta‐analysis of 16 studies with subgroup analyses was conducted. In the matched cohort and case‐control studies (n = 1287), subgroup analysis showed that women who had received systemic therapy after surgery had an overall pooled estimate of 14% (95% confidence interval [CI], 0.12‐0.16; I2 = 95.4%) of becoming pregnant. Of those who became pregnant, 12% (95% CI, 0.08‐0.16; I2 = 65.9%) experienced a miscarriage. For the population‐based studies (n = 711), the estimated pooled pregnancy rate was 3% (95% CI, 0.02‐0.03; I2 = 85.1%) for women who became pregnant after BC treatment. The pregnancy rate after BC treatment for survivors was on average 40% lower than the general population pregnancy rate. Women with BC should be informed about the subsequent adverse effects of BC and its treatments on conception. With the increasing trend for women to defer childbirth to later in life, provision of fertility‐related information, access to fertility preservation, and fertility‐related psychosocial support should be offered to women of a reproductive age before they begin BC treatment.