Predictors of specialized pediatric palliative care involvement and impact on patterns of end-of-life care in children with cancer

The quality of end of life care can be adversely affected by ICU admission and other intensive medical treatments. The objective of this retrospective cohort study was to link population-based clinical and health services databases to determine 1) which children with cancer access specialized pediatric palliative care (SPPC) and 2) the impact of accessing SPPC on the risk of experiencing high-intensity end-of-life care such as ICU admission during the last 30 days of life.
This study uses a combination of a provincial (Ontario) childhood cancer registry and health administrative data predicting the type of care received by a combination of billing codes, diagnostic codes, and SPPC databases. Children from 2000-2012 were categorized as having received either SPPC, generalized palliative care, or nor palliative care within 30 days of death.
572 children in total received care at one of the three institutions with SPPC teams and died during the period in which SPPC databases were available. 243 (42.5%) received care from SPPC team and 166 (29%) received SPPC for at least 30 days before death. 100 (17.5%) received general palliative care, which was based on not being in SPPC database but having physician billings for palliative care. 306 patients (53.5%) had no palliative care. SPPC involvement was significantly less likely for hematologic cancers, living in low-income areas, and living farther from treatment center. Accessing SPPC more than 30 days before death was associated with five-fold decreased odds of ICU admission and other high-intensity end-of-life care, including in-hospital death, whereas general palliative care had no impact.
Children who had SPPC or general palliative care for 30 days before death were counted as having no palliative care. Data did not include family preferences or goals of care. Difficult to generalize because health care systems and cultural attitudes about end-of-life care are variable.
SPPC but not general palliative care is associated with lower intensity care at end-of-life. Access to SPPC is uneven. Strong evidence to support the creation and timely involvement of SPPC teams.

Palliative Care Consultation Should Be Routine for All Children Who Enroll in a Phase I Trial

This is an excellent article written by physicians of the palliative care team at the Hospital for Sick Children describing why all pediatric oncology patients enrolled in a phase I trial should receive a palliative care consultation.

Fertility Preservation in Patients with Cancer: ASCO Clinical Practice Guideline Update Summary

ASCO first published evidence-based clinical practice guidelines on fertility preservation in 2006 with an update in 2013. This is the most recent iteration of the guideline which although it is adult focused, also applies to the pediatric population.
The guideline re-affirms some of the previous recommendations including a discussion of the possibility of infertility as early as possible before treatment starts, which is thought to reduced distress and improve quality of life. The discussion should be re-addressed after completion of therapy.
Options for post-pubertal males continue to include sperm cryopreservation, ideally done pre-treatment to ensure optimal quality. With technologies like IVF and intra-cytoplasmic sperm injection however, cryopreservation can still occur for patients on treatment if there is an urgency to begin therapy. Hormonal gonado-protection has not been shown to be effective. Testicular tissue cryopreservation and grafting of human testicular tissue remain experimental.
Options for women include embryo and oocyte cryopreservation. Oocyte preservation would be more feasible for a larger group of patients as it is no longer considered experimental. Flexible ovarian stimulation protocols can be initiated with less delay than previous and newer protocols including aromatase inhibitors would make stimulation feasible even for women with estrogen sensitive malignancies without an increase in their risk of cancer recurrence. Ovarian transposition during pelvic irradiation remains a viable option, although is not always successful due to scatter. There is conflicting evidence for GnRH agonists/ovarian suppression for fertility preservation. This can be considered when other methods are not feasible in young women. Perhaps most exciting is that while ovarian tissue cryopreservation remains experimental in North America, emerging data is very promising and some countries consider it nonexperimental. It is one of the best options for pediatrics and pre-pubertal patients. The safety of it in patients with leukemia is unknown.
Adult guidelines; limited options remain for pre-pubertal children.
A multitude of fertility preservation options exist for post-pubertal patients and should be discussed in a timely manner and on an ongoing basis. Exciting new data on the success of ovarian tissue transplantation may make this a viable option for a larger proportion of patients.

Risk of hepatitis B virus reactivation in patients treated with ibrutinib

Hepatitis B reactivation has been reported in patients with cancer receiving targeted therapies including mammalian target of rapamycin (mTOR) inhibitors, monoclonal antibodies and tyrosine kinase inhibitors. Ibrutinib is a Bruton tyrosine kinase inhibitor which affects B cell signalling, used in adult lymphomas (CLL, mantle cell lymphoma) and Pediatric non Hodgkin lymphoma.
This is a letter to the Editor which reports a 57 year old man with CLL who had a Hepatitis B reactivation nearly 4 years after starting on ibrutinib for progression of disease. The authors then looked at the group of patients who received Ibrutinib at Dana-Farber Cancer Institute between 2010 and 2016 to see what the incidence of Hepatitis B reactivation was for Ibrutinib.
2/71 patients developed Hepatitis B reactivation. One was the index patient described above and the other was a 75 year old man with CLL. The latter received antiviral therapy for Hepatitis B. Overall incidence was 9.5%.
The clinical significance of the infection or low level viraemia during ibrutinib treatment is unclear from this study of only two cases. There was a review of the literature with tyrosine kinase inhibitors and Hepatitis B reactivation in Hematology last year: https://www.ncbi.nlm.nih.gov/pubmed/28485688.
Hepatitis reactivation is an important consideration when using targeted therapies, even if infection was resolved prior to starting cancer therapy.

Cancer In The National Cancer Institute Inherited Bone Marrow Failure Syndrome Cohort After Fifteen Years Of Follow-Up

This study aimed to describe the incidence and characteristics of malignancy in patients with inherited bone marrow failure syndromes over a fifteen year duration. This was a prospective cohort study conducted by the National Cancer Institute. The Inherited Bone Marrow Syndrome Cohort was opened in Jan 2002 and continues to accrue participants. This cohort enrolled patients with Fanconi anemia, dyskeratosis congenita, Diamond-Blackfan anemia, and Shwachman-Diamond syndrome.
Patients (n=530) were enrolled in the cohort starting in 2002 with the aforementioned diagnoses of inherited bone marrow failure syndromes. Diagnosis was confirmed at the NCI. Demographic and outcome measures were then collected by parent/patient report and medical chart review. The ratio of expected to observed malignancy rates were calculated and adjusted for age, sex, race, and birth cohort.
Overall leukaemia was diagnosed at an incidence of 3% with DC, FA and SDS and 0% in the cohort with DBA. DC, FA and SDS had an increased risk of ALL and AML, but odds ratios were higher for AML. Solid tumours were diagnosed at an incidence of 5% DBA, 7% DC, 12% FA and 3% SDS. The cumulative incidence of solid tumors was close to 20% by age 65 in both DC and FA.
HSCT drastically left shifted the age of diagnosis of malignancy and increased the chances of secondary malignancy in FA (rate ratio 3.5) and DC (rate ratio 5).
For Fanconi Anemia patients developed head and neck squamous cell carcinomas (HNSCC), AML, vulvar SCC and brain tumors. For DC, patients reported HNSCC, AML and NHL. In DBA, patients developed lung, colon and cervical cancers. The SDS cohort was very small (n= 35) and there were two diagnoses of AML and cervical cancer.
The increased risk of both leukemias and solid tumors in all diagnostic groups were statistically significant.
This study was descriptive and therefore inferences cannot be made about the underlying causality of cancer predisposition in these syndromes. There was no analysis based on the genotype to cancer predisposition.
There could have been an enrolment bias in this study, with patients with more severe disease course being more likely to agree to participate.
This is the largest cohort study in terms of patient life years (enrolment and duration of study) to describe outcomes in inherited bone marrow failure syndromes. Patients with inherited bone marrow failure syndromes are at increased risk for leukemias and solid tumors. This risk is greatly increased and left shift (in terms of age of diagnosis) by bone marrow transplant, which is consistent with previously reported literature.
The specific types of malignancies are specific to the bone marrow failure syndrome and are described in this article. This is relevant to clinical practice in terms of surveillance of this patient population.

Platelet Transfusion for Patients With Cancer: American Society of Clinical Oncology Clinical Practice Guideline Update

This is review with recommendations for platelet transfusions in oncology patients (adult and pediatric).

Prediction of Ischemic Heart Disease and Stroke in Survivors of Childhood Cancer

The Childhood Cancer Survivor Study (CCSS) led to the largest cancer survivor follow-up cohort. It is based on data extracted from medical records and questionnaires that were sent to childhood cancer survivors (CCS). CCS have been shown to have a >10-fold increased risk of ischemic heart disease and stroke compared with siblings. This study developed a risk-prediction model using end-of-treatment data to risk stratify CCS and externally validate the model.
This manuscript used data from the CCSS from children diagnosed between 1970 and 1986 at 26 institutions in the United States and Canada (n=13,060). A random sample of siblings (n=4,023) served as comparison cohort. Two validation datasets were used: the SJLIFE cohort from St. Jude Children’s Research Hospital (led by the same team as the CCSS cohort) and the EKZ/ AMC cohort (unrelated group, n= 1,300 - 1,800 CCS). A set of variables with demographic and treatment data were tested for their association with ischemic heart disease and stroke.
Predictors of ischemic heart disease were male sex, neck or chest radiation; predictors for stroke were alkylator therapy, platinum agents, cranial and chest radiation. Two models were created: a simple model where cancer therapy–related exposures were categorized as yes or no only; and a standard model where clinical dose information was known. Risk scores were attributed and summed to create low-, moderate-, and high-risk groups. Low-risk groups had cumulative incidence risks of =15% of ischemic heart disease or stroke, respectively.
The cohorts used in this study were diagnosed three or more decades ago (training data set) or at least 15 years ago (validation data sets). Therefore, these findings might not be valid for modern treatment protocols. Particularly radiation was greatly reduced and application techniques changed within the last decades.
This study quantified risk factors for ischemic heart disease and stroke after childhood cancer treatment and compiled a prediction tool which might help estimate the risk for CCS (https://ccss.stjude.org/tools-and-documents/calculators-and-other-tools/ccss-cardiovascular-risk-calculator.html).

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