Optimal Supportive Care Research Articles

Exploring the dietary choices of Chinese women living with breast cancer in Vancouver, Canada

PurposeTo explore how Chinese Canadian patients with breast cancer make dietary choices and to understand their nutritional information needs in order to inform oncology healthcare providers about provision of optimal supportive care for this population.MethodsUsing interpretive description methodology, semi-structured interviews were conducted with first- and second-generation Chinese Canadian women aged 41–73 years living in Vancouver, Canada, who were diagnosed with breast cancer within the last 5 years. A follow-up focus group was held to validate emergent themes.ResultsNineteen women were interviewed; 6 participated in the focus group. Their accounts of dietary experiences following diagnosis focused on three areas: dietary change (including desired and implemented changes that participants believed would benefit their health), facilitators and barriers to dietary change, and information and resource needs. Dietary changes reported included avoiding or consuming greater amounts of certain foods, and taking traditional Chinese medicine (TCM) and natural health products. Barriers to desired dietary change included the interplay between food preferences and family and social life, work-life balance, and cost and availability of specialty foods. Support from family members, however, facilitated participants’ consumption of more whole and natural foods after their cancer diagnosis. Participants obtained food and nutrition information from a variety of sources but had difficulty determining the reliability and accuracy of information. They requested timely, credible, culturally-relevant, and easily accessible dietary information.ConclusionsOncology healthcare providers would benefit from increased understanding of the dietary practices, including TCM, of Chinese women living with breast cancer. To facilitate communication and improve quality of care, healthcare professionals should provide credible and culturally relevant diet-related information in a variety of forms.

Outcomes with nondose-dense chemotherapy for Ewing sarcoma: A practical approach for the developing world.

The current multidisciplinary approach in the treatment of Ewing sarcoma has improved cure rates, with contemporary dose-dense chemotherapy attaining 5-year event-free survival (EFS) of 73% in localized cases. Dose-intense and dose-dense chemotherapy is difficult in the majority of resource-limited settings with limited access to optimal supportive care. We report on patients with Ewing sarcoma treated on EFT-2001, a nondose-dense chemotherapy protocol. A retrospective analysis was conducted of patients (<15years) with Ewing sarcoma treated with curative intent during January 2013-June 2017 with an institutional ethics committee-approved nondose-dense protocol (EFT-2001). Local therapy was planned after 9-12weeks of chemotherapy with metastatic sites addressed with radiotherapy. The study assessed outcomes and prognostic factors. We analysed 200 patients with M:F ratio of 1.27:1 and metastases in 41 patients (20.5%). At a median follow up of 41.5months (range 4.5-81.8months), respective 3-year EFS and overall survival (OS) of the whole cohort is 65.3% (95% confidence interval [CI]: 58.1-71.7%) and 79.3% (95% CI: 72.8-84.5%); for localized and metastatic cohort, 70.9% (95% CI: 62.9-77.5%) and 82.8% (95% CI: 75.7-89.0%); and for metastatic cohort, 42.8% (95% CI: 28.0-58.6%) and 65.3% (95% CI: 47.7-78.3%). Presence of residual disease (morphologic/metabolic) on positron emission tomography-computed tomography scan done 3months post definitive radiotherapy (hazard ratio [HR] 7.92 [95% CI: 3.46-18.14]) and delay in any form of local control >4months (HR 3.42 [95% CI: 1.32-8.89]) affected outcomes. Nonrelapse mortality during treatment was 6.5%, mainly due to cardiomyopathy (3.0%) and bacterial sepsis (1.5%). Cardiotoxicity was seen in 11.5% of patients. Nondose-dense chemotherapy provides good outcomes with manageable toxicities in a multidisciplinary treatment approach, while reducing cumulative drug exposures in the developing world where dose-intense or dose-dense chemotherapy could potentially increase toxicity, and hence seems a feasible approach in resource-limited settings. Presence of any residual disease post definitive radiotherapy or delay in local control portends poor outcome.

Usefulness of Charlson Comorbidity Index to Predict Early Mortality and Overall Survival in Older Patients With Acute Myeloid Leukemia

IntroductionOlder adults with acute myeloid leukemia (AML) often have significant comorbidities. We hypothesized that greater comorbidity burden predicts worse 1-month mortality and overall survival (OS) in patients ≥60 years with AML. Materials and methodsWe included 50,668 patients ≥60 years diagnosed between 2004 and 2014 from the National Cancer Database; patients were divided into 3 groups with Charlson comorbidity index (CCI) 0, 1, and ≥2. Chi-square tests were used to examine the association between CCI and different variables. We used logistic regression and Cox proportional hazard models to determine predictors of 1-month mortality and OS, respectively. ResultsAmong the entire cohort, 65% had CCI 0, 24% had CCI 1, and 11% had CCI ≥2. Thirty-four percent did not receive chemotherapy. Patients with CCI 0 were more likely to receive chemotherapy, especially multiagent chemotherapy and undergo upfront hematopoietic cell transplantation. In multivariate analyses, 1-month mortality and OS were significantly worse with CCI 1 or ≥2, compared with CCI 0 in the entire cohort, as the subgroup of only those patients who received chemotherapy. Younger age, male gender, higher annual income, academic facility, longer travel distance, and acute promyelocytic leukemia were associated with improved OS. ConclusionIn one of the largest real-world studies of older adults with AML, we demonstrated that greater comorbidity, measured by higher CCI, independently predicted worse early mortality and OS in older patients with AML. Higher CCI was more common with increasing age and correlated with lower likelihood of receiving chemotherapy and hematopoietic cell transplantation. Whether optimal comorbidity management and supportive care may improve outcomes needs to be studied further.

"The Whole Game is Changing and You've Got Hope": Australian Perspectives on Treatment Decision Making in Spinal Muscular Atrophy.

The natural history and treatment of spinal muscular atrophy (SMA) is currently being transformed by the development and availability of novel therapies, with significant related changes in practice. This not only has important implications for the health and wellbeing of patients with SMA and their families, as well as improves the quality of care. The present study aimed to investigate the processes and factors that influence treatment and healthcare decisions for children and adults with SMA and their families and healthcare providers. Four focus groups comprising adults, or parents of children and adolescents, with SMA and an expert panel of healthcare providers (N = 25) explored experiences of SMA, its treatment and related decision making and expectations for future care. Group discussions were recorded and transcribed verbatim for thematic analysis using NVivo12.0. People with SMA, their families and healthcare providers described confronting complex healthcare decisions in the context of a rapidly changing SMA treatment environment. Across all groups, five key themes were identified: hope, yearning and searching, patient-centred care and support, community and a sense of connectedness and weighing up potential treatment benefits and costs. Essential to these themes was the notion of what it means to live with SMA and complexities relating to 'quality of life'. Identifying and more deeply understanding the factors that influence patient, family and healthcare providers' decision making regarding SMA treatment is an important first step in improving the quality of patient- and family-centred care and in informing clinical practice and future health policy incorporating personalized medicine and optimal supportive and mental health care.

National Cancer Control Program of Thailand.

Since 2000 cancer has been the leading cause of death in Thailand. In response to this challenge, the National Cancer Institute of Thailand (NCI), in collaboration with other bodies, has developed and promoted the National Cancer Control Program (NCCP) to provide appropriate policies and practice for the prevention, early detection and treatment of cancer, with optimal supportive care. With plans strongly supported by the Ministry of Public Health, the NCCP envisages integration into the health care system in 6 strategic areas: (1) cancer informatics; (2) primary prevention; (3) early detection; (4) treatment; (5) palliative care; and (6) cancer control research. For this purpose 7 regional cancer hospitals have been established to aid the NCI in conducting the NCCP. Cancer registration is a high priority, with 31.2% of the population now covered by quality registries. In primary prevention, there is a focus on awareness, lifestyle improvement, anti-smoking and alcohol control programs, vaccination, and Opisthorchis viverrini (OV) control. Screening programs for cervical, breast and colorectal cancer are underway to increase early detection. Priority is being given to facilities for chemotherapy and radiotherapy, as well as palliative care. Cancer control research encompasses international cooperation and participation in training programs, especially for development of cancer registration and other aspects of cancer control programs in South-East Asia, not least as an IARC Collaborating Center.

Efficacy and cost-utility of the eHealth self-management application 'Oncokompas', helping partners of patients with incurable cancer to identify their unmet supportive care needs and to take actions to meet their needs: a study protocol of a randomized controlled trial

BackgroundIncurable cancer does not only affect patients, it also affects the lives of their partners. Many partners take on caregiving responsibilities. The burden of these caregiving tasks are often associated with physical, psychological, and social difficulties and many partners have unmet supportive care needs. Oncokompas is an eHealth self-management application to support partners in finding and obtaining optimal supportive care, tailored to their quality of life and personal preferences. A randomized controlled trial will be carried out to determine the efficacy and cost-utility of Oncokompas.MethodsA total of 136 adult partners of patients with incurable cancer will be included. Partners will be randomly assigned to the intervention group, which directly gets access to Oncokompas, or the waiting-list control group, which gets access to Oncokompas after three months. The primary outcome measure is caregiver burden. Secondary outcome measures comprise self-efficacy, health-related quality of life, and costs. Measures will be assessed at baseline, two weeks after randomization, and three months after the baseline measurement.DiscussionThis study will result in evidence on the efficacy and cost-utility of Oncokompas among partners of patients with incurable cancer, which might lead to implementation of Oncokompas as a health service for partners of patients with incurable cancer.Trial registrationNetherlands Trial Register, NTR 7636. Registered on 23 November 2018.

Treatment effects of Chinese medicine (Yi-Qi-Qing-Jie herbal compound) combined with immunosuppression therapies in IgA nephropathy patients with high-risk of end-stage renal disease (TCM-WINE): study protocol for a randomized controlled trial

BackgroundIgA nephropathy (IgAN) is the most common glomerular disease worldwide. It has a high incidence in Asians and is more likely to progress to end-stage renal disease (ESRD). For high-risk IgAN, which is clinically characterized by massive proteinuria and renal dysfunction, however, there has been no international consensus on treatment options. Compared with other developed countries, IgAN patients in China are often found to have severe kidney function loss at initial diagnosis. Yi-Qi-Qing-Jie formula (YQF; a compound recipe of Chinese medicinal herbs) has shown potential renal protection in our previous clinical studies. To further confirm the efficacy and safety of YQF in the treatment of high-risk IgAN, we have designed a prospective double-blind randomized placebo-controlled trial.Methods/designThe TCM-WINE study is a single-center, prospective, double-blind randomized placebo-controlled trial. We plan to randomize 60 participants with biopsy-proven IgAN to a YQF combined group (YQF compound combined with prednisolone, and cyclophosphamide if necessary) or an immunosuppression group (placebo-YQF combined with prednisolone, and cyclophosphamide if necessary). The two groups will enter a 48-week in-trial treatment phase and receive post-trial follow-up until study completion (3 years). All patients will receive optimal supportive care. The primary composite outcome is defined as the first occurrence of a 40% decrease in estimated glomerular filtration rate (eGFR) from the baseline lasting for 3 months, initiating continuous renal replacement treatment, or death due to chronic kidney disease (CKD) during the 3-year study phase. The secondary endpoint events are defined as the mean annual eGFR decline rate (eGFR slope, ml/min per 1.73 m2 per year), which is calculated by the eGFR regression curve for each eligible patient, and proteinuria remission (prescribed as proteinuria < 0.5 g/day) at weeks 24, 36, and 48 during the in-trial phase. The remission rate of symptoms and inflammation status will be evaluated at week 48. Safety monitoring and assessment will be undertaken during the study.DiscussionThe TCM-WINE study will evaluate the effects and safety of YQF combined therapy compared with immunosuppression monotherapy on the basis of the optimal supportive treatment in high-risk IgAN. The evidence from this study will provide a novel, effective, and safe Chinese characteristic therapy for high-risk IgAN patients.Trial registrationClinicalTrials.gov, NCT03418779. Registered on 18 June 2018.

Pattern of care and epidemiology of brain metastasis over past 10 years: A retrospective study from tertiary cancer center

Background: In adults most common intracranial malignant lesion is brain metastasis, far outnumbering primary brain tumor. The most common primary site is lung cancer (18–64%), followed by breast (25–21%), malignant melanoma (4–16%), and colorectal cancer (2–12%). It is hypothesized that the incidence of brain metastasis might be increasing, as a result of increasing survival from recent advance in cancer treatment, more frequent brain screening for specific primary malignancy that known to have a higher prediction for brain metastasis and greater availability and use of magnetic resonance imaging (MRI) of brain. In clinical oncology, understanding brain metastasis is important, because it has profound effect on length of survival, quality of life, and in one-third to one-half of affected patients, they represent the direct cause of death despite current improvement in therapeutic approach. Epidemiological data of brain metastasis are lacking in India. Objectives: Aims of our retrospective analysis are to study epidemiology and pattern of care of brain metastasis over last one decade in Nil Ratan Sircar Medical College and Hospital, Kolkata. Materials and Methods: Between 2006 and December 2017, a total of 710 patients of brain metastasis treated in our department with palliative intent were analyzed retrospectively. New-onset neurological symptoms in a known case of cancer we always presumed that, symptoms were due to brain metastasis until proven otherwise. Hence, all patients presenting with acute neurological signs and symptoms underwent through clinical examination, contrast-enhanced (CE) computed tomography brain, and/or CEMRI of brain. Epidemiology, pattern of care, and outcome in the form of overall survival (OS) and disease-free survival were determined. Results: Fifty-seven percent patients were male. The median age was 62 years at the time of diagnosis. Lung carcinoma was most common primary site seen in 52% patients, followed by carcinoma breast second most common primary site, seen in 32% patients. Headache (73%) and motor weakness were most common presenting symptoms. Supratentorial location most common site, out of which parietal region is most common. The only small number of patients was offered best supportive care alone whereas majority of the patients were considered fit for palliative therapy. Treatment consisted of metastasectomy when possible and palliative whole-brain radiotherapy (WBRT) alone or followed by systemic therapy. Optimal supportive care in addition to chemotherapy or radiotherapy is given to all patients. A total of 254 patients were given blood product, erythropoietin, granulocyte-colony-stimulating factor following chemotherapy. Hospitalization required in 71% patients and tumor-related problem was most common cause (46%). Remaining patients were hospitalized for delivery WBRT or CCT. The median OS is 9 months. Patients with younger age and breast primary associated with better prognosis than lung primary. Conclusions: We can conclude that carcinoma lung in male and carcinoma breast in females was most common cause of brain metastasis. Because advance in palliative therapy, outcome of patients with brain metastasis has improved, and patients with brain metastasis benefit from palliative radiotherapy and chemotherapy and this treatment could be delivered easily on outpatients basis.

Occurrence and Resolution of Anthracycline Cardiotoxicity and Impact on Treatment Outcomes Among Children Treated on the AAML1031 Clinical Trial: A Report from the Children's Oncology Group

Background: Children treated for acute myeloid leukemia (AML) receive high doses of anthracyclines. Anthracycline cardiotoxicity causes significant short and long term morbidity and mortality, thus it is crucial to understand its risk factors, natural history, and impact on treatment outcome. Methods: Between June 2011 and September 2018, AAML1031 enrolled patients aged &amp;lt;30 years for treatment of de novo AML. Echocardiographic evaluations (echo) were required before each treatment course, at the end of protocol therapy, and at yearly intervals during off-protocol follow-up. The lowest shortening fraction (SF) and ejection fraction (EF) in each reporting period were prospectively collected. Cardiotoxicity was defined as SF &amp;lt;28% or EF &amp;lt;55% which represent the protocol-mandated thresholds at which anthracyclines were to be withheld. Higher-grade toxicity (SF &amp;lt;24%, EF &amp;lt;50%) consistent with grade 2 or higher left ventricular systolic dysfunction (grade 2+ LVSD) per CTCAE v3 definitions, and its resolution were also assessed. Resolution was defined as SF returning to baseline or &amp;gt;30% and EF returning to baseline or &amp;gt;60%. Resource utilization (RU) data for patients enrolled at hospitals contributing to the Pediatric Health Information Systems database (PHIS) were merged with AAML1031 study data. Cox regressions were used to assess risk factors for incident cardiotoxicity and recovery among cases, as well as to compare event-free (EFS) and overall survival (OS) in patients with and without cardiotoxicity. Poisson regressions were used to compare on-protocol RU. Cardiotoxicity was treated as a time-varying exposure introduced at time of documented onset in comparisons of EFS, OS and RU. Patients with high allelic ratio FLT3/ITD+ AML were excluded from analyses. Results: 1092 patients were treated on AAML1031 and included in the primary analyses. Echo compliance was high overall (mean ±sd: 74.5% ±19.6), but lower and more variable during off-protocol (mean ±sd: 58.1%, ±31.0) than on-protocol (mean ±sd: 90.6% ±19.5) reporting periods. Over a median follow-up of 3.5 years, 39% (n=428) of patients experienced protocol-defined cardiotoxicity, of whom 54% (n=232) suffered grade 2+ LVSD. Cumulative incidence was higher among patients randomized to receive bortezomib, non-infants, females, and patients with low risk disease who receive more cumulative anthracycline during frontline therapy (Table 1). Patients treated with dexrazoxane were less likely to develop cardiotoxicity. Among patients with grade 2+ LVSD, 49% experienced recovery of cardiac function within a median of 14 months (IQR: 9-20) from initial detection. High risk disease classification and dexrazoxane exposure were associated with LVSD recovery (Table 1). Both EFS (HR 1.23, 95% CI: 1.01-1.50) and OS (HR 1.45, 95% CI 1.15-1.84) were significantly worse in patients with cardiotoxicity meeting per-protocol thresholds for treatment modification. The magnitude of the association with EFS (HR 1.24, 95% CI: 0.98, 1.58) was similar when restricting to grade 2+ LVSD, but more pronounced for OS (HR 1.80, 95% CI 1.38, 2.34). A subset of 389 patients (23% suffered grade 2+ LVSD) were treated at PHIS hospitals and contributed to RU analyses. Cardiotoxicity was associated with greater cardiac ICU requirements, increased use of cardiac-directed interventions including antihypertensives, vasopressors, and heart failure medications, and reduced cardioprotection (Table 2). Conclusions: Echo compliance and cardiotoxicity rates were higher than previously described due in part to more frequent echoes and required reporting of raw echo results. Approximately 20% of pediatric AML patients on AAML1031 developed grade 2+ LVSD, only half of whom had documented resolution of LVSD. Dexrazoxane was strongly associated with reduced LVSD risk and potentially superior recovery. Our results offer further evidence that early cardiotoxicity decreases EFS/OS and that cumulative anthracycline dose is the principal predictor of LVSD. These data argue for comparative effectiveness studies of cardiac-directed interventions after LVSD, and identification of clinical and genetic risk factors for anthracycline cardiotoxicity and its recovery. Such studies may allow for anthracycline de-escalation in select patient populations. Work is ongoing to inform optimal supportive care practices for patients with LVSD using clinical data merged with PHIS. Disclosures Leger: Abbott: Research Funding; Jazz Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; BTG Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees.

ES23.04 Optimal Supportive Care During and After Concurrent Chemoradiotherapy and I/O

ES23.04 Optimal Supportive Care During and After Concurrent Chemoradiotherapy and I/O

810P - Phase I study of apatinib combined with POF (paclitaxel plus FOLFOX) in patients (pts) with treatment-naïve advanced gastric cancer (TNAGC)

BackgroundApatinib, is a novel, small molecule, selective VEGFR-2 TKI and is approved in China as third-line treatment for patients with AGC. Preclinical and clinical data suggests that apatinib may enhance the chemotherapeutic drugs cytotoxicity by inhibiting cell membrane–bound ATP-binding cassette transporters.POF is effective in pts with TNAGC reported in our phase II study. We evaluated the safety and efficacy of apatinib plus POF in TNAGC. MethodsThis was a phase I single center study with standard 3+3 design for pts with TNAGC. The primary endpoints are determining dose limiting toxicities (DLT) and maximum tolerated dose (MTD). Secondary endpoints include overall survival (OS), progression free survival (PFS), response rate (RR), and quality of life (QOL). Initial plan was to enroll pts in 5 escalating dose levels of apatinib (250/375/500/625/750mg daily) plus POF, consisted of paclitaxel 135mg/m2, followed by mFOLFOX6 omitted 5-Fu bolus, every 14 days repeated. Eligible pts had ECOG PS 0-1, age 18-70, and adequate organ function. DLT was any treatment-related hematologic ≥ grade 4 toxicity (except for neutropenia lasting for ≤ 5 days), or non-hematologic ≥ grade 3 toxicity (except for nausea and vomiting that could be improved with optimal supportive care, escalation of alkaline phosphatase). Results17 pts were treated in 5 different dl of apatinib plus POF (3 in each dl, except for 5 in dl 625mg). Median age was 55 years (range 25-69) with 76.5% male. All pts were evaluated for toxicity, but only 15 were evaluable for DLT. 2 pts in dl 625mg were replaced as they came off of study within 28 days (1 due to poor adherence to take apatinib as prescribed, 1 due to concealing his prior chemotherapy). Zero DLTs were observed at all dl. Only 3 pts had grade 3 neutropenia. The rest of toxicities were ≤ grade 2. Most frequent of toxicity were anemia (64.71%), hypoalbuminemia (58.82%), and neutropenia (47.06%). 11 pts were evaluable for response (8 PR [72.73%], 1 SD, 2 PD).5 pts have been on treatment > 6 months. ConclusionsApatinib can be safely administered up to 750mg daily combined with POF for pts with TNAGC.Phase II will begin after phase I completion and will evaluate efficacy of apatinib 750mg plus POF. Clinical trial identificationNCT03244774; Release date: August 10, 2017. Legal entity responsible for the studyRongbo Lin. FundingJiangsu HengRui Medicine Co., Ltd. DisclosureAll authors have declared no conflicts of interest.

Supportive care for hemostatic complications associated with pediatric leukemia: a national survey in Japan.

Optimal supportive care for disseminated intravascular coagulation (DIC) and hemostatic complications by asparaginase is indispensable for the successful treatment of pediatric leukemia. However, the situation regarding this type of care in Japan is unclear. We conducted a questionnaire-based survey at 155 institutions treating childhood leukemia in Japan. The questionnaire asked about the supportive care provided by each institution to acute leukemia patients with DIC and asparaginase-induced hemostatic alterations. Ninety-eight institutions responded. The most common diagnostic criteria for DIC were those established by the Japanese Ministry of Health and Welfare. Regardless of the etiology underlying DIC, recombinant human thrombomodulin and synthetic protease inhibitors were used as anticoagulation therapy by around 70% and 40% of institutions, respectively. Additionally, 92%, 93%, and 73% of institutions measured plasma antithrombin, fibrinogen, and D-dimer/fibrin degradation products, respectively, more than twice per week during induction therapy for acute lymphoblastic leukemia. Survey responses indicate that 95% and 24% of the institutions used antithrombin replacement and fresh-frozen plasma, respectively. Supportive care for DIC and/or asparaginase-induced hemostatic alterations at Japanese pediatric centers was intensive and differs markedly from protocols in other countries. The efficacy of supportive care should be evaluated prospectively in the setting of pediatric leukemia.

Diagnosing Microcystin Intoxication of Canines: Clinicopathological Indications, Pathological Characteristics, and Analytical Detection in Postmortem and Antemortem Samples.

In the summer of 2018, six dogs exposed to a harmful algal bloom (HAB) of Microcystis in Martin County Florida (USA) developed clinicopathological signs of microcystin (MC) intoxication (i.e., acute vomiting, diarrhea, severe thrombocytopenia, elevated alanine aminotransferase, hemorrhage). Successful supportive veterinary care was provided and led to survival of all but one patient. Confirmation of MC intoxication was made through interpretation of clinicopathological abnormalities, pathological examination of tissues, microscopy (vomitus), and analytical MC testing of antemortem/postmortem samples (vomitus, blood, urine, bile, liver, kidney, hair). Gross and microscopic examination of the deceased patient confirmed massive hepatic necrosis, mild multifocal renal tubular necrosis, and hemorrhage within multiple organ systems. Microscopy of a vomitus sample confirmed the presence of Microcystis. Three analytical MC testing approaches were used, including the MMPB (2-methyl-3-methoxy-4-phenylbutyric acid) technique, targeted congener analysis (e.g., liquid chromatography tandem-mass spectrometry of MC-LR), and enzyme-linked immunosorbent assay (ELISA). Total Adda MCs (as MMPB) were confirmed in the liver, bile, kidney, urine, and blood of the deceased dog. Urinalysis (MMPB) of one surviving dog showed a high level of MCs (32,000 ng mL−1) 1-day post exposure, with MCs detectable >2 months post exposure. Furthermore, hair from a surviving dog was positive for MMPB, illustrating another testable route of MC elimination in canines. The described cases represent the first use of urine as an antemortem, non-invasive specimen to diagnose microcystin toxicosis. Antemortem diagnostic testing to confirm MC intoxication cases, whether acute or chronic, is crucial for providing optimal supportive care and mitigating MC exposure.

Making a diagnosis in severe cutaneous drug hypersensitivity reactions.

Severe cutaneous adverse reactions (SCAR) are relatively uncommon but can be life-threatening. This review focuses on the nonanaphylactic (non-IgE-mediated) phenotypes of drug hypersensitivity, with specific reference to diagnosis and management of acute generalized exanthematous pustulosis (AGEP), drug reaction with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN). Here, we review recent guidelines on optimal supportive care as well as publications of interventional treatment for SJS/TEN, including various immunomodulating therapies, and management strategies for severe ocular disease with the use of amniotic membrane transplantation. In DRESS, long-term autoimmune sequelae are increasingly recognized and modify strategies for treatment of the acute episode. If the causative drug is not apparent from careful inspection of the drug exposure history, in-vitro diagnostics, HLA testing and skin testing before drug challenge testing may be considered and we present an algorithm for investigation of complex cases. Careful phenotypic analysis of the increasingly complex recognized patterns of SCAR facilitates the enhancement in our understanding of T-cell mediated drug hypersensitivity and allows the improvement of in-vitro diagnostic testing to minimize patient exposure to test substances in all but a very limited number of cases, thereby enhancing safety.

Management of patients with brain metastases from non-small cell lung cancer and adverse prognostic features: multi-national radiation treatment recommendations are heterogeneous

BackgroundDifferent management options exist for patients with brain metastases from non-small cell lung cancer (NSCLC), patients whose treatment with whole brain radiotherapy (WBRT) has become more controversial over the last decade. It is not trivial to find the optimal balance of over- versus undertreatment in these patients. Several recent trials, including the randomized QUARTZ trial now influence the decision to recommend or withhold WBRT for patients with unfavorable prognosis, and similarly, for favorable prognosis patients, the balance between radiosurgery alone or WBRT has become a nuanced decision. Additionally, the availability of intracranially active targeted agent for some subsets of these patients has added another layer of complexity to the decision-making.MethodsA multinational consortium of expert radiation oncologists was established with the aim of compiling treatment recommendations for challenging scenarios, in this case the choice between optimal supportive care (SC), WBRT and other types of radiation therapy (RT). We distributed 17 cases to 7 radiation oncologists who were allowed to involve coworkers to provide their treatment recommendations. The cases differed in extra- and intracranial disease extent, histology, age and other prognostic factors. Expert recommendations were tabulated with the aim of providing guidance.ResultsRegarding willingness to include the 17 patients in the QUARTZ trial, the rates of trial inclusion were low (range 0/7 to 3/7). Experts not recommending trial inclusion provided their treatment recommendations. These suggestions differed widely for most of the patients. It was not uncommon to see 3 or 4 different recommendations. In general, few (0–2) recommended SC. Some kind of local treatment was suggested by the majority of experts for all 17 patients. Commonly, stereotactic single-fraction radiosurgery (SRS) or stereotactic fractionated radiotherapy (SFRT) were recommended by many experts, also for patients with 5–7 lesions. The highest proportion of recommendations towards WBRT in any patient was 3/7. It was also quite common for patients with multiple metastases of varying size that experts suggested combinations of resection, post-operative SRS/SFRT and SRS/SFRT to intact lesions. Despite recommending active treatment, experts were often willing to include the patients in a hypothetical protocol investigating radiotherapy utilization in the last 30 days of life (assessment of factors predicting early death).ConclusionsWBRT was infrequently recommended. Even in patients with adverse prognostic features that raised the experts’ awareness of an increased risk for futile treatment near the end of life, SRS/SFRT were more often recommended than optimal supportive care, unless a patient decided to forego active treatment.

Adoption and implementation of a web-based self-management application \u201cOncokompas\u201d in routine cancer care: a national pilot study

PurposeA web-based self-management application “Oncokompas” was developed to monitor health-related quality of life and to support cancer survivors in finding and obtaining optimal supportive care. Access to this application is provided via a healthcare professional (HCP). The aim of this study was to explore the adoption and implementation of Oncokompas in routine clinical practice and to obtain insights in potentially relevant determinants of implementation.MethodsA pilot study was carried out among 65 hospitals throughout The Netherlands. HCPs filled out a questionnaire on the implementation of Oncokompas in their organization, consisting of study specific items and items based on the Measurement Instrument for Determinants of Innovations (MIDI). The MIDI comprises 29 determinants in four domains that predict the use of innovations: the innovation itself (Oncokompas), the user (HCP), the organization (hospital), and socio-political context.ResultsIn total, 20/65 eligible hospitals agreed to implement Oncokompas (adoption rate 31%). In these 20 adopting hospitals, the majority of the responding HCPs (72/205) in this study (44/61) indicated their patients were offered access to Oncokompas (implementation rate 72%). Comparing those HCPs who did and did not implement Oncokompas, the groups differed significantly on innovation-related (procedural clarity, complexity) and user-related determinants (importance of outcome expectations, professional obligation, social support, and self-efficacy).ConclusionsDuring this 1-year study, nationwide adoption rate of Oncokompas was at 31%, and subsequent implementation rate was at 72%. The results of this study contribute to further optimize interventions and strategies to adopt and implement (online) self-management applications in cancer care.

Induction Toxicities Are More Frequent in Young Adults Compared to Children Treated on the Children's Oncology Group (COG) First Relapse B-Lymphoblastic Leukemia Clinical Trial AALL1331

BackgroundCOG AALL1331 randomizes first relapse B-lymphoblastic leukemia (B-ALL) patients ages 1-30 years (yrs) to standard chemotherapy +/- blinatumomab after a common Induction (Block 1) based on the mitoxantrone arm of UKR3 ALL (Parker et al., 2010, n=103, age up to 18 years). Block 1 therapy consists of weekly vincristine, dexamethasone (days 1-5, and 15-19), pegaspargase (days 3 and 17), mitoxantrone (days 1,2) and intrathecal chemotherapy (based on CNS status) without blinatumomab.MethodsWe reviewed CTCAE4.0 grade 3-5 adverse events (AE) collected as per standard and expedited (AdEERS) reporting mechanisms during induction for all patients who completed Block 1 between December 2014 (study activation) and March 31, 2018. Cytopenias are universal and were excluded from reporting. For AE that occurred in greater than 5% of patients, we used Pearson's chi-squared tests to evaluate univariate associations between AE rates and age, sex, race/ethnicity, relapse site, peripheral blast count at relapse and duration of first remission (CR1).ResultsBlock 1 reporting was completed in 405 patients, 194 aged 1-9 yrs, 165 aged 10-18 yrs, and 46 aged 19-30 yrs, with median age of 10 yrs and a range of 1 to 26 yrs (Table 1). Grade 3-5 AE that occurred in more than 5% of patients are listed in Table 2, and notable associations are summarized in Table 1. Sixteen patients died (4.0%); 15 from infection/sepsis, 1 death NOS. Grades 3-5 infection occurred in 161/405 (39.8%) of patients. By univariate analysis, total infections and sepsis were more common in young adults who were 19-30 yrs (incidence of infections: 37.1%, 38.2%, and 56.5% in patients 1-9 yrs, 10-18 yrs, and 19-30 yrs, respectively, p=0.047 overall, and p=0.014 for <19 vs. 19-30; incidence of sepsis: 7.2%, 9.7%, and 23.9%, p=0.003 overall, and p=0.001 for <19 vs. 19-30). Infections occurred more frequently in patients with marrow relapse (p=0.007), shorter CR1 duration (p<0.001), and higher peripheral blast count at relapse (p=0.001). Lower rates of sepsis were seen in patients who were African American, Asian or other races/ethnicities as compared to Hispanic/Latino or Caucasians (p=0.035 overall, and p=0.006 for African American/Asian/other vs. Latino/Caucasians). Oral mucositis, hyperbilirubinemia and hyperglycemia were also more common in young adults. Interestingly, both gastrointestinal disorders and hypoalbuminemia were seen more frequently in females. Thrombotic events were very rare, seen in only 0.49% of patients.ConclusionsWe have prospectively studied a large cohort that includes both children and young adult patients with first relapse of B-ALL treated with UKR3 ALL four drug induction. Infection is the most common AE and cause of death. Risk of infection was associated with older age (young adults) and other high risk relapse features (marrow involvement, short first remission, high peripheral blast count). Young adult patients were also at higher risk of several other toxicities, highlighting the importance of optimal supportive care in this population. [Display omitted] DisclosuresRheingold:Pfizer: Research Funding.

Cyclophosphamide‐induced hemorrhagic cystitis in young patients with solid tumors: A single institution study

Although hemorrhagic cystitis (HC) is a significant complication in young patients who undergo chemotherapy with cyclophosphamide (CPA), risk factors and supportive care to prevent HC are unclear. This study attempted to identify optimal supportive care to prevent CPA-induced HC. Patients (<30-year-old) with malignant solid tumors who had been treated with CPA-containing chemotherapy in inpatient treatment were eligible. Vigorous hydration to increase urine output and intravenous 2-mercaptethane sulfonate (mesna) were used for prophylaxis of CPA-induced HC. We retrospectively analyzed 81 patients who had been treated with CPA-containing chemotherapy over (collectively) 486 cycles, and examined relationships between HC and various factors, especially CPA dosage, use of mesna, and fluid infusion volume/rate. HC occurred in four patients (4.9%) and five cycles (1%). When stratifying by doses and methods of administration of CPA, HC occurred in 3/323 low- and intermediate-dose (<1500mg/m2 /day) cycles and mesna was used in all three cycles with HC. Patients who were given mesna had a lower flow rate than those given hydration alone in the low- and intermediate-dose CPA (126 ± 25 vs 106 ± 16mL/m2 /h; P<0.01). All patients who received high-dose CPA (≥1500mg/m2 /day) were also given mesna and vigorous hydration (115 ± 16mL/m2 /h). Our supportive care measures may be effective in preventing CPA-induced HC. Patients who receive CPA doses<1500mg/m2 /day should get ≥125mL/m2 /h of infused fluid, regardless of mesna usage; those who receive of CPA ≥1500mg/m2 /day should also receive mesna and vigorous hydration.

Effect and moderators of exercise on fatigue in patients with cancer: Meta-analysis of individual patient data.

104 Background: Fatigue is a common and disabling complaint in patients with cancer and can be reduced by exercise. To further personalize exercise prescriptions, moderators of exercise effects on fatigue should be investigated. However, most randomized controlled trials (RCTs) are not adequately powered to identify heterogeneity in responses to exercise. Therefore, we conducted a meta-analysis using individual patient data (IPD) of exercise RCTs to investigate the effect and moderators of exercise on cancer-related fatigue. Methods: Within the Predicting OptimaL cAncer RehabIlitation and Supportive care (POLARIS) consortium, principal investigators of 34 exercise RCTs worldwide have shared their IPD, including in total 4366 cancer patients. A 1-step IPD meta-analysis, using a linear mixed-effect model with a random intercept on study was undertaken to investigate effect on fatigue. The result, a between-group difference in standardized z-scores, corresponds to a Cohen’s d effect size. An interaction term was included in the model to assess potential moderators including demographic (sex, age, marital status, education), clinical (body mass index, distant metastasis), intervention-related (timing, delivery mode, duration) and exercise-related (type, frequency, intensity, duration) characteristics. Results: Exercise significantly reduced fatigue (β = -0.17, 95% CI -0.22;-0.12). The effect was not moderated by demographic, clinical or exercise-related characteristics. Supervised exercise had significantly larger effects on fatigue than unsupervised exercise (βdifference= -0.18, 95%CI -0.28;-0.08). Compared to the control group, supervised exercise significantly improved fatigue (β = -0.23, 95%CI = -0.29;-0.17), while unsupervised exercise did not (β = -0.04, 95%CI = -0.13;0.04). Conclusions: Exercise significantly reduces cancer-related fatigue across subgroups formed on the basis of demographic and clinical characteristics. The effect of exercise is significantly larger when performed under supervision. Hence, exercise, and preferably supervised exercise, represents a viable intervention for the prevention and treatment of fatigue among patients with cancer.

‘Oncokompas’, a web-based self-management application to support patient activation and optimal supportive care: a feasibility study among breast cancer survivors

Background: Cancer survivors have to deal with symptoms related to cancer and its treatment. In Oncokompas, cancer survivors monitor their quality of life by completing patient reported outcome measures (PROMs), followed by personalized feedback, self-care advice, and supportive care options to stimulate patient activation. The aim of this study was to investigate feasibility and pretest–posttest differences of Oncokompas including a newly developed breast cancer (BC) module among BC survivors.Material and methods: A pretest–posttest design was used. Feasibility was investigated by means of adoption, usage, and satisfaction rates. Several socio-demographic and clinical factors, and health-related quality of life (HRQOL) were explored that might be associated with patient satisfaction. Barriers and facilitators of Oncokompas feasibility were investigated by evaluating nurse consultation reports. Differences in patient activation (Patient Activation Measure) and patient-physician interaction (Perceived Efficacy in Patient–Physician Interactions) before and after Oncokompas use were investigated.Results: In total, 101 BC survivors participated. Oncokompas had an adoption rate of 75%, a usage rate of 75–84%, a mean satisfaction score of 6.9 (range 0–10) and a Net Promoter Score (NPS) of −36 (range −100–100) (N = 68). The BC module had a mean satisfaction score of 7.6. BC survivors who received surgery including chemotherapy and/or radiotherapy were significantly more satisfied with Oncokompas than BC survivors with surgery alone (p = .013). Six facilitators and 10 barriers of Oncokompas feasibility were identified. After using Oncokompas, BC survivors scored significantly higher on patient activation (p = .007; r = .24), but not on patient-physician interaction (p = .75).Conclusion: Oncokompas including a BC module is considered feasible, but needs further optimization to increase user satisfaction. This study shows the value of tailoring eHealth applications for cancer survivors to their specific tumor type. Oncokompas including the BC module seems to improve patient activation among BC survivors.