Little patients, big impacts: a narrative review of palliative and emergent radiotherapy for pediatric cancers.

BACKGROUND AND OBJECTIVE: The use of radiotherapy (RT) in the palliative and emergent settings for pediatric cancers is an under-utilized resource. Our objective was to provide an evidence-based review of the data to increase awareness of the benefit for this population along with providing guidance on pediatric specific treatment considerations for palliative care physicians, pediatric oncologists, and radiation oncologists. METHODS: A narrative review was performed querying PubMed, MEDLINE, ClinicalTrials.gov databases, and supplemented with review articles, survey studies, current and recent clinical trials. When limited data existed, well-designed retrospective and prospective studies in the adult setting were evaluated and expert opinion was provided from pediatric oncologists. KEY CONTENT AND FINDINGS: Pediatric specific treatment considerations include the use of anesthesia, impact of treatment on the developing child, and logistical challenges of RT. Treatment modality and dose selection are driven by histology and symptomatic site of pain, where we discuss detailed recommendations for hematologic, central nervous system, and solid tumors. For palliative RT, an underlying principle of searching for the lowest effective dose to balance response rate with minimal acute and late treatment related morbidity and logistical hardships is of paramount importance when caring for a pediatric patient. Lastly, we outline how to effectively communicate this option to patients and their caregivers. CONCLUSIONS: Palliative RT can be of valuable benefit in most settings for patients with pediatric cancer. There is an unmet need for prospective data to inform on dose-fractionation along with patient and caregiver reported outcomes.

Modeling the Risk of Hearing Loss From Radiation Therapy in Childhood Cancer Survivors: A PENTEC Comprehensive Review.

PURPOSE: The Pediatric Normal Tissue Effects in the Clinic (PENTEC) hearing loss (HL) task force reviewed investigations on cochlear radiation dose-response relationships and risk factors for developing HL. Evidence-based dose-response data are quantified to guide treatment planning. METHODS AND MATERIALS: A systematic review of the literature was performed to correlate HL with cochlear dosimetry. HL was considered present if a threshold exceeded 20 dB at any frequency. Radiation dose, ototoxic chemotherapy exposure, hearing profile including frequency spectra, interval to HL, and age at radiation therapy (RT) were analyzed. RESULTS: Literature was systematically reviewed from 1970 to 2021. This resulted in 739 abstracts; 19 met inclusion for meta-analysis, and 4 included data amenable to statistical modeling. These 4 studies included 457 cochleas at risk in patients treated with RT without chemotherapy, and 398 cochlea treated with chemotherapy. The incidence and severity of cochlear HL from RT exposure alone is related to dose and age. Risk of HL was <5% in cochlea receiving a mean dose ≤35 Gy but increased to 30% at 50 Gy. HL risk ranged from 25% to 40% in children under the age of 5 years at diagnosis, declining to 10% in older children for any radiation dose. Probability of similar severe HL occurred at doses 18.3 Gy higher for children <3 versus >3 years of age. High-frequency HL was most common, with average onset occurring 3.6 years (range, 0.4-13.2 years) after RT. Exposure to platinum-based chemotherapies added to the rates of HL at a given cochlear dose level, with 300 mg/m2 shifting the dose response by 7 Gy. CONCLUSIONS: In children treated with RT alone, risk of HL was low for cochlear dose <35 Gy and rose when dose exceeded 35 Gy without clear RT dose dependence. High-frequency HL was most prevalent, but all frequencies were affected. Children younger than 5 years were at highest risk of developing HL, although independent effects of dose and age were not fully elucidated. Future reports with more granular data are needed to better delineate time to onset of HL and the effects of chemoradiotherapy.

Feasibility of the Audio-Visual Assisted Therapeutic Ambience in Radiotherapy (AVATAR) System for Anesthesia Avoidance in Pediatric Patients: A Multicenter Trial.

PURPOSE: The Audio-Visual Assisted Therapeutic Ambience in Radiotherapy (AVATAR) system was the first published radiation therapy (RT)-compatible system to reduce the need for pediatric anesthesia through video-based distraction. We evaluated the feasibility of AVATAR implementation and effects on anesthesia use, quality of life, and anxiety in a multicenter pediatric trial. METHODS AND MATERIALS: Pediatric patients 3 to 10 years of age preparing to undergo RT at 10 institutions were prospectively enrolled. Children able to undergo at least 1 fraction of RT using AVATAR without anesthesia were considered successful (S). Patients requiring anesthesia for their entire treatment course were nonsuccessful (NS). The PedsQL3.0 Cancer Module (PedsQL) survey assessed quality of life and was administered to the patient and guardian at RT simulation, midway through RT, and at final treatment. The modified Yale Preoperative Anxiety Scale (mYPAS) assessed anxiety and was performed at the same 3 time points. Success was evaluated using the χ2 test. PedsQL and mYPAS scores were assessed using mixed effects models with time points evaluated as fixed effects and a random intercept on the subject. RESULTS: Eighty-one children were included; median age was 7 years. AVATAR was successful at all 10 institutions and with photon and proton RT. There were 63 (78%) S patients; anesthesia was avoided for a median of 20 fractions per patient. Success differed by age (P = .04) and private versus public insurance (P < .001). Both patient (P = .008) and parent (P = .006) PedsQL scores significantly improved over the course of RT for patients aged 5 to 7. Anxiety in the treatment room decreased for both S and NS patients over RT course (P < .001), by age (P < .001), and by S versus NS patients (P < .001). CONCLUSIONS: In this 10-center prospective trial, anesthesia avoidance with AVATAR was 78% in children aged 3 to 10 years, higher than among age-matched historical controls (49%; P < .001). AVATAR implementation is feasible across multiple institutions and should be further studied and made available to patients who may benefit from video-based distraction.

Progression of citation-based scholarly activity from postgraduate year one to postgraduate year two in a current resident class.

BACKGROUND: Recent work has demonstrated multiple measures of citation-based scholarly activity. Measures including Hirsch index (h-index), h-index limited to first author manuscripts (hf), h-index limited to first or second author only manuscripts (hs), and g-index have been associated with radiation oncology resident choice of academic versus private practice career. To date, there has been no evaluation of the progression of citation-based scholarly activity during residency. METHODS: A list of United States radiation oncology residents from the graduating class of 2022 [postgraduate year two (PGY-2) academic year of 2018-2019] was obtained through internet investigation. Citation-based scholarly activity was collected and calculated from searches of the Scopus bibliometric citation database for h-index, hf, hs, and g-index for each resident as previously described. Calculations were derived in June 2018 for the postgraduate year one (PGY-1) year, and in June 2019 for the PGY-2 year. Fisher's exact test was used for statistical analysis. RESULTS: Analysis of 195 residents from the 2022 class revealed that the citation-based scholarly activity significantly increased from PGY-1 to PGY-2 for h-index (2.6 to 3.2; P=0.047) and g-index (4.0 to 5.1; P=0.045), but not for hf (1.0 to 1.3; P=0.170) or hs (1.5 to 1.9; P=0.065). Underrepresented minority race/ethnicity (African-American/Hispanic) did not impact the significance of the h-index and g-index findings. CONCLUSIONS: From the PGY-1 to PGY-2 academic year, residents significantly increased in citation-based academic productivity, with an increase in the proportion of residents with a cited first-or-second author manuscript. Further study is necessary to determine how this trend persists in future years.

Optimal timing of radiotherapy following brain metastases surgery.

Background: There is growing evidence supporting the need for a short time delay before starting radiotherapy (RT) treatment postsurgery for most optimal responses. The timing of RT initiation and effects on outcomes have been evaluated in a variety of malignancies, but the relationship remains to be well established for brain metastasis. Methods: Retrospective study of 176 patients (aged 18-89 years) with brain metastases at a single institution (March 2009 to August 2018) who received RT following surgical resection. Time interval (≤22 and >22 days) from surgical resection to initiation of RT and any potential impact on patient outcomes were assessed. Results: Patients who underwent RT >22 days after surgical resection had a decreased risk for all-cause mortality of 47.2% (95% CI: 8.60, 69.5%). Additionally, waiting >40 days for RT after surgical resection more than doubled the risk of tumor progression; adjusted hazard ratio 2.02 (95% CI: 1.12, 3.64). Conclusions: Findings indicate that a short interval delay (>22 days) following surgical resection is required before RT initiation for optimal treatment effects in brain metastasis. Our timing of RT postsurgical resection data adds definition to current heterogeneity in RT timing, which is especially important for standardized clinical trial design and patient outcomes.

Evolution of the prevalence of pre-residency peer-reviewed publications among incoming junior residents.

Pre-residency peer-reviewed publications (PRP) have been associated with subsequent resident choice of academic versus private practice career. The evolution of PRP prevalence among radiation oncology resident classes has yet to be examined. A list of radiation oncology residents from the graduating classes of 2016 and 2022 were obtained, and PRP was compiled as the number of publications a resident had listed in PubMed as of the end of the calendar year of residency application. Statistical analysis was conducted using Fisher's exact test. Analysis of 163 residents from the 2016 class compared with 195 from the 2022 class revealed that the proportion of residents with zero PRP decreased from 46.6% to 23.6% between the 2016 to 2022 classes (p<0.0001), while that of residents with one PRP increased from 17.8% to 19.0% (p>0.05) and with at least two PRP increased from 35.6% to 57.4% (p<0.0001). Residents with a PhD were more likely to have at least two PRP in each class (p<0.0001). As with the class of 2016, there remained no significant difference in PRP by gender for the class of 2022. Over the past six years, PRP has become more prevalent among incoming radiation oncology residents. Residents in the class of 2016 were 180% less likely than the class of 2022 to have at least one PRP, and 60% less likely to have at least two PRP. These findings are indicative of the increasing pressure on medical students to enter residency with a publication background.

Gender-based analysis of pre-residency research productivity among a current United States radiation oncology resident class.

BACKGROUND: The increasing proportion of women in medicine has not been adequately reflected in the gender distribution of radiation oncology residents. The presence of at least one pre-residency peer-reviewed publication (PRP) has been associated with radiation oncology resident choice of academic over private practice career, with no significant gender difference in the likelihood of having a PRP (McClelland et al., 2017). We sought to pursue a gender-based analysis of PRP productivity in a current junior resident class. METHODS: A list of radiation oncology residents from the graduating class of 2022 (PGY-2 academic year of 2018-2019) was obtained through internet investigation. Research productivity was calculated using PRP number, defined as the number of a resident's publications listed in PubMed (pubmed.gov) through the calendar year of residency application (2016 for this class). RESULTS: Of 195 residents examined from the 2022 class, 61 (31%) were women, representing a nine percent increase from the resident class of 2016. Four-fifths of women had 1+ PRP, 31% had dual degrees, and 18% had a PhD. These percentages were comparable to their male counterparts, 73% with 1+ PRP, 28% with dual degrees, and 15% with a PhD. There were no statistically significant differences by gender in any of these benchmarks. CONCLUSIONS: While slower than the overall trend of increased female representation in medicine, the proportion of women in radiation oncology residency has increased by 0.9-1.5% annually over a recent six-year span. There remain no significant differences in PRP productivity, dual degree status, or PhD status by gender.

Concurrent Radiosurgery and Immune Checkpoint Inhibition: Improving Regional Intracranial Control for Patients With Metastatic Melanoma.

OBJECTIVES: The anti-CTLA-4 and antiprogrammed cell death-1 (PD-1) therapies have significantly improved survival of patients with metastatic melanoma. However, there is limited data regarding the interaction between immunotherapy (IT) and stereotactic radiosurgery (SRS) in patients with brain metastasis, particularly how combination therapy may affect toxicity and intracranial tumor control. METHODS: We retrospectively reviewed 26 patients with metastatic melanoma who received immune check point inhibitors and SRS for brain metastasis from 2011 to 2017. We evaluated lesions receiving SRS concurrently (within 30 days) and sequentially with IT. Overall survival (OS), local control (LC), and regional progression free survival (RPFS) were determined. RESULTS: In total, 26 patients and 90 lesions were treated using pembrolizumab, nivolumab and/or ipilimumab, sequentially, or concurrently with SRS. Median follow-up was 18.9 months (range, 4.9 to 62.3 mo). Median overall survival was 26.1 months. There were 3 local failures, but no significant difference between the 2 groups. Following concurrent SRS and immunotherapy, patients had a significantly longer period of intracranial progression free survival than those treated with nonconcurrent therapy, 19 months versus 3.4 months (P<0.0001). No grade 4-5 toxicities were observed. CONCLUSIONS: Patients with melanoma metastatic to brain treated with SRS and immune checkpoint inhibitors had favorable median survival of 26.1 months compared with historical controls. Patients receiving immunotherapy within 30 days of SRS had significantly improved regional intracranial progression free survival compared with patients receiving sequential therapy. Our findings suggest synergy between checkpoint inhibitor immunotherapy and radiosurgery. Further studies are needed to confirm these findings.

Cardiac Mortality in Children and Adolescents with Hodgkin's Lymphoma: A Surveillance, Epidemiology and End Results Analysis.

PURPOSE: The purpose of this study was to evaluate the risk of cardiac death in pediatric Hodgkin's lymphoma (HL) survivors and identify high-risk groups that may need additional surveillance. METHODS: The Surveillance, Epidemiology and End Results program database was queried to analyze the rates of radiation therapy (RT) use and cardiac-specific mortality (CSM) in HL patients, aged 0-21 years, treated from 1973 to 2007. Primary endpoint was cardiac mortality. RESULTS: A total of 6552 patients were included. Median follow-up was 12 years (range, 0-40). Median age at diagnosis was 17 years (range, 0-21). The majority were white (85.5%), from western states (41.2%), had nodular sclerosis HL (73.2%), presented with stage I or II disease (51.5%), and received RT (56.1%). Death from cardiac disease occurred in 114 patients (9.2% of all deaths). CSM for the entire cohort at 10-, 20-, and 30-year time points was 0.3%, 1.6%, and 5.0%, respectively. Median age at the time of cardiac death was 39 years (range, 18-58 years). Under multivariate analysis (MVA), adolescent patients (ages 13-21) had higher rates of CSM (hazard ratio [HR], 3.05; p = 0.005). Female gender (HR, 0.43; p < 0.001), patients treated from 1998 to 2007 (HR, 0.19; p = 0.018), and those with lymphocyte-rich histology (HR, 0.14; p = 0.047) had significantly lower rates of CSM. Use of RT was not associated with CSM under MVA (HR, 1.18, p = 0.452). CONCLUSION: The cumulative incidence of CSM in this population analysis of pediatric HL was 9.2%, with a steady decline over the past several decades. Adolescent patients at diagnosis and males were more likely to die of cardiac-related causes.

Obstetric referrals from a rural clinic to a community hospital in Honduras.

OBJECTIVES: referrals between health care facilities are important in low-resource settings, particularly in maternal and child health, to transfer pregnant patients to the appropriate level of obstetric care. Our aim was to characterise the obstetrical referrals from a rural clinic to a community referral hospital in Honduras, to identify barriers in effective transport/referral, and to describe subsequent patient outcomes. METHODS: we performed a descriptive retrospective study of patients referred during a 9-month period. We reviewed patient charts to review diagnosis, referral, and treatment times at both sites to understand the continuity of care. RESULTS: ninety-two pregnant patients were referred from the rural clinic to the community hospital. Twenty six pregnant patients (28%) did not have complete and accurate medical records and were excluded from the study. The remaining 66 patients were our study population. Of the 66 patients, 54 (82%) received antenatal care with an average of 5.5±2.4 visits. The most common diagnoses requiring referral were non-reassuring fetal status, hypertensive disorders of pregnancy, and preterm labour. The time spent in the rural clinic until transfer was 7.35±8.60 hours, and transport times were 4.42±1.07 hours. Of the 66 women transferred, 24 (36%) had different primary diagnoses and 16 (24%) had additional diagnoses after evaluation in the community hospital, whereas the remaining 26 (40%) had diagnoses that remained the same. No system was in place to give feedback to the referring clinic doctors regarding their primary diagnoses. CONCLUSIONS: our results demonstrate challenges seen in obstetric transport from a rural clinic to a community hospital in Honduras. Further research is needed for reform of emergency obstetric care management, targeting both healthcare personnel and medical referral infrastructure. The example of Honduras can be taken to motivate change in other resource-limited areas.