The role of radiation therapy in palliative care of children with advanced cancer: Clinical outcomes and patterns of care.

BACKGROUND: There are few published data to guide the use and timing of palliative radiation therapy (RT) in children. We aimed to determine the clinical outcomes of palliative RT in children and the relationship with palliative care and hospice referrals. PROCEDURE: A retrospective chart review was performed on all patients younger than 18 years who received palliative RT in our clinic from January 2005 to January 2015. RESULTS: In the specified time period, 50 children underwent 83 courses of palliative RT. Median survival after treatment was 124 days (range, 1-1141 days). Fifteen courses were delivered to children in the last 30 days of life (dol). Palliative RT was successful in 89% of courses delivered before the last 30 dol versus 28% of courses delivered in the last 30 dol (p < 0.0001, Fisher's exact test). At the time of data collection, 43 children were deceased. Altogether, 88% of children who received palliative RT were also referred to our institution's pediatric palliative care team or to hospice at some time in their course. Of the children who died, 74% were referred to hospice and 34% were on hospice while receiving palliative RT. For children not already on hospice, the median time to hospice referral was 96 days after the last fraction (range, 0-924 days). CONCLUSIONS: Palliative RT is effective in children with advanced cancer, although less so in the last 30 dol. With careful care coordination and multidisciplinary collaboration, RT can be successfully integrated into supportive and end-of-life care for children with advanced cancer.

Simultaneous radiotherapy and superficial hyperthermia for high-risk breast carcinoma: a randomised comparison of treatment sequelae in heated versus non-heated sectors of the chest wall hyperthermia.

PURPOSE: In vitro data demonstrate that heat-induced radiosensitisation is maximised if hyperthermia and radiotherapy are given simultaneously, with the radiation fraction delivered midway through a hyperthermia session, rather than sequentially. The long-term normal tissue toxicity of full-dose simultaneous thermoradiotherapy is unknown. MATERIALS AND METHODS: Patients with locally advanced breast cancer (T3, T4 or more than three involved nodes or local recurrence), no prior radiotherapy, received between four and eight sessions of simultaneous thermoradiotherapy. Hyperthermia always included the primary tumour site. In addition an electively heated sector (EHS) was included. The EHS was randomised to either medial or lateral to the tumour site, with the other side an irradiated but unheated control. As per our usual practice, patients received surgery and/or chemotherapy prior to radiotherapy. Radiation doses were 46-50 Gy followed by a boost of ≤16 Gy at 1.8-2 Gy per fraction. EHS and control sectors received the same dose. RESULTS: A total of 57 evaluable cases with average follow-up of 79 months experienced two local and two nodal recurrences. There was no significant difference in ≥grade 2 toxicity for heated versus control sectors (LR χ(2 )= 0.78, p = 0.38) with no relationship between number of hyperthermia sessions and toxicity (LR χ(2 )= 2.90, p = 0.09). CONCLUSIONS: Simultaneous full-dose thermoradiotherapy for breast cancer is feasible and well tolerated, with no significant difference in late toxicity between electively heated and unheated control sectors. All patients had hyperthermia to the primary tumour site with excellent local control.

How do children and parents make decisions about pediatric clinical research?

Little is known about how children and parents make decisions regarding pediatric research. To provide data, we surveyed children aged 7 to 14 years who were enrolled in clinical research or receiving clinical care for cancer or asthma at one of 7 sites, and a parent or guardian. The present manuscript reports data on the respondents' attitudes and experiences regarding the child's involvement in making clinical care and research decisions. Of 117 parent-child pairs invited to participate, 81 completed the survey (response rate=69.2%). Pediatric respondents reported that their decisions regarding research enrollment were influenced primarily by a desire to benefit themselves, and to help others. In the research group, 90.5% of pediatric respondents believed they should be involved in making research enrollment decisions, whereas only 61.5% of the adult respondents believed children should be involved in making these decisions. These findings highlight the potential for disagreement within families regarding children's involvement in making decisions about research enrollment. Investigators should be aware of and find ways to address these disagreements when soliciting assent from children.

Medical decision making for patients without surrogates.

Patients who lose decision-making capacity and lack advance directives and next of kin present a quandary for physicians. Current mechanisms for making treatment decisions for these patients rely on decision makers, such as courts, public guardians, committees, and physicians, who typically do not have sufficient knowledge to predict the patients' preferences. Thus, these mechanisms likely yield decisions that are inconsistent with patients' treatment preferences in many cases. A population-based treatment indicator is a computer-based tool that predicts which treatment a given patient would prefer based on the treatment preferences of similar patients in similar situations. A recent analysis suggests that a population-based treatment indicator could predict patient preferences as accurately as patient-appointed surrogates and next of kin. This analysis suggests that a population-based treatment indicator may provide a mechanism to respect the treatment preferences of patients without surrogates and ensure that their treatment preferences are respected as much as the preferences of patients who have surrogates. Collection of data on patients' treatment preferences, especially those without surrogates, incorporation of these data into a treatment indicator, and exploration of ways to implement this approach for patients without surrogates are called for.

Cerebrospinal fluid biomarkers versus glasgow coma scale and glasgow outcome scale in pediatric traumatic brain injury: the role of young age and inflicted injury.

The Glasgow Coma Scale (GCS) and Glasgow Outcome Scale (GOS) are widely used clinical scoring systems to measure the severity of neurologic injury after traumatic brain injury (TBI), but have recognized limitations in infants and small children. Cerebrospinal fluid (CSF) concentrations of neuron-specific enolase (NSE) and S100B show promise as markers of brain injury. We hypothesized that the initial GCS and 6-month GOS scores would be inversely associated with CSF NSE and/or S100B concentrations after severe pediatric TBI. Using banked CSF obtained during ongoing studies of pediatric TBI, NSE and S100B were determined in CSF collected within 24 h of trauma from 88 infants and children with severe TBI (GCS < or = 8) versus 20 non-injured controls. Victims of inflicted (iTBI) and non-inflicted TBI (nTBI) showed similar (>10-fold) increases in both NSE and S100B versus control. Both markers showed overall significant, inverse correlation with GCS and GOS scores. In subgroup analysis, both markers correlated significantly with GCS and GOS scores only in older (>4 years) victims of nTBI; no correlation was found for patients < or =4 years old or victims of iTBI. While confirming the overall correlations between GCS/GOS score and CSF NSE and S100B seen in prior studies, we conclude that these clinical and CSF biomarkers of brain injury do not correlate in children < or =4 years of age and/or victims of iTBI. Although further, prospective study is warranted, these findings suggest important limitations in our current ability to assess injury severity in this important population.

Building a palliative radiation oncology program: From bedside to B.E.D.

A growing body of evidence supports the integration of palliative care with standard cancer treatments. In these situations, patients often experience a better quality of life, better quality of care, decreased cost, and, in some cases, improved survival with the addition of palliative care services to traditional treatment pathways. In this manuscript, we explore the integration of radiation oncology at palliative care. First, we discuss the impetus for change at Vanderbilt University and the inception of Vanderbilt's inpatient Palliative Radiation Oncology Service at Vanderbilt. Second, we discuss the growth of palliative care and how this invites innovative collaborative care delivery models. As you will see, this mutually beneficial relationship expands new service lines, brings radiation oncology interventions and expertise to more patients seen by palliative care specialists, and improves overall care for some of the sickest, most vulnerable patients in the health care system. As we move away from fee-for-service and toward bundled and global-based strategies, there will be further emphasis on supportive and palliative care services at the end of life. Understanding how radiation oncology can evolve is ever more relevant.

F2-isoprostane and neuron-specific enolase in cerebrospinal fluid after severe traumatic brain injury in infants and children.

It has been hypothesized that oxidative stress plays an important role in mediating secondary damage after traumatic brain injury (TBI). To study the relationship between lipid peroxidation, clinical variables, and neuronal damage in pediatric TBI, we measured levels of F2-isoprostane, a marker of lipid peroxidation, and neuron-specific enolase (NSE), a marker of neuronal damage, in serial cerebrospinal fluid (CSF) samples from 23 infants and children with severe TBI (Glasgow Coma Scale score <8). These were compared to CSF samples from 10 uninjured pediatric controls. On d1 after injury, F2-isoprostane was increased 6-fold vs. control (36.59+/-8.96 pg/ml vs. 5.64+/-8.08 pg/ml, p=0.0035) and NSE was increased 10-fold (100.62+/-17.34 ng/ml vs. 8.63+/-2.76 ng/ml, p=0.0002). Multivariate analysis of F2-isoprostane levels and selected clinical variables showed a trend toward an inverse association with time after injury (p=0.0708). Multivariate analysis of NSE levels and selected variables showed a positive association between d1 NSE and F2-isoprostane (p=0.0426). CSF F2-isoprostane increases early after TBI in infants and children and is correlated with NSE, supporting a role for oxidative stress in the evolution of secondary damage early after severe TBI in infants and children.