The Effect of Health Insurance on Pediatric Cancer Survival: An Analysis of Children Evaluated for Radiation Therapy in Diverse Multicenter Health Systems.

BACKGROUND: Understanding the role of health insurance in cancer survival in a diverse population of pediatric radiation oncology patients could help to identify patients at risk of adverse outcomes. MATERIALS AND METHODS: Data were collected from cancer patients evaluated for radiation therapy, age < 19, diagnosed from January 1990 to August 2019. Predictors of recurrence-free survival (RFS) and overall survival (OS) were analyzed by univariable and multivariable Cox regression. Variables included health insurance, diagnosis type, sex, race/ethnicity, and socioeconomic status deprivation index. RESULTS: The study included 459 patients with a median diagnosis age of 9 years. Demographic breakdown was 49.5% Hispanic, 27.2% non-Hispanic White, and 20.7% non-Hispanic Black. There were 203 recurrences and 86 deaths observed over a median follow-up of 2.4 years. Five-year RFS was 59.8% (95% CI, 51.6, 67.0) versus 36.5% (95% CI, 26.6, 46.6), and 5-year OS was 87.5% (95% CI, 80.9, 91.9) versus 71.0% (95% CI, 60.3, 79.3) in private pay insurance versus Medicaid/Medicare, respectively. Multivariable showed Medicaid/Medicare patients experienced a 54% higher risk of recurrence (hazard ratio: 1.54, 95% CI, 1.08, 2.20) and 79% higher risk of death (hazard ratio: 1.79, 95% CI, 1.02, 3.14) than privately insured patients. CONCLUSIONS: Significant disadvantages in RFS and OS were identified in radiation oncology patients with Medicaid/Medicare insurance, even after adjusting for clinical and demographic variables.

Effects of Cancer Treatment on the Education and Cognition of South Florida Pediatric Cancer Survivors.

Purpose As pediatric cancer survival rates have exponentially increased in the past decade, with the vast majority surviving five years or more, the long-term impacts of treatment on the quality of survivorship must be explored. This study examines the effects of pediatric cancer treatment regimens on education outcomes among a demographically diverse regional population. The primary objective is to identify potential factors that may impact the educational and cognitive quality of life in this population.  Methods Four hundred sixty-eight pediatric oncology patients diagnosed at age <20 between January 1990 - August 2019 and treated for cancer with radiation therapy at a large public or a multi-center private hospital in South Florida were identified. A novel survey available in English and Spanish was electronically distributed at least three times to each patient from August 2020 - July 2021 via email, phone call, and text message. Variables relating to demographics, treatment, cognitive impairment, and school re-entry were collected through the survey and electronic medical record review. Descriptive statistical analysis was performed.  Results Of the patients, 10.5% responded to the survey (26 male, 21 female, two unidentified sex). The mean age was 8.9 years old (range 0-20) at diagnosis, 24.0 years old (range 8-39) at the time of survey completion, and 55.1% self-identified as Hispanic. Nearly one-quarter of respondents (22.4%) were unable to correctly identify the treatment modalities they received; Hispanic self-identifying patients were 1.75 times more likely than non-Hispanic patients to incorrectly report the treatment modalities received. One-quarter (26.5%) of respondents reported long-term cognitive deficits post-treatment, of which, over three-quarters (76.9%) identified as Hispanic.  Conclusion This study illuminates patients' perspectives on their long-term cognitive impacts after pediatric cancer treatment. Given the diverse study population, ethnic disparities in post-treatment survivorship were explored. A substantial subset of Hispanic participants was unable to correctly identify their treatment regimen, and a disproportionately large group of Hispanic patients experienced cognitive long-term cognitive deficits, suggesting that ethnic disparities play a critical role in post-treatment survivorship. Further research on prioritizing educational intervention during and after treatment is essential to improving both the quality and equity of survivorship among pediatric oncology patients.

Long-term outcomes of patients with conjunctival extranodal marginal zone lymphoma.

Comprehensive information on clinical features and long-term outcomes of primary conjunctival extranodal marginal zone lymphoma (PCEMZL) is scarce. We present a large single-institution retrospective study of 72 patients. The median age was 64 years, and 63.9% were female. Stage I was present in 87.5%. Radiation therapy (RT) alone was the most common treatment (70.8%). Complete response (CR) was 87.5%, and 100% in RT-treated patients. With a median follow-up of 6.7 years, relapse/progression and death occurred in 19.4% each, with one relapse within the RT field. The 10-year progression-free survival (PFS) and overall survival (OS) were 68.4% (95% CI 52.8%-79.8%) and 89.4% (95% CI 77.4%-95.2%), respectively. The 10-year rate for time to progression from diagnosis was 22.5% (95% CI 11.6%-35.7%). The 10-year PFS and OS of MALT-IPI 0 versus 1-2 were 83.3% versus 51.3%, (p = .022) and 97.6% versus 76.6%, (p = .0052), respectively. The following characteristics were associated with shorter survival: age > 60 years (PFS: HR = 2.93, 95% CI 1.08-7.95; p = .035, OS: HR = 9.07, 95% CI 1.17-70.26; p = .035) and MALT-IPI 1-2 (PFS: HR = 2.67, 95% CI 1.12-6.31; p = .027, OS: HR = 6.64, 95% CI 1.45-30.37; p = .015). CR following frontline therapy was associated with longer PFS (HR = 0.13, 95% CI 0.04-0.45; p = .001), but not OS. Using the Fine and Gray regression model with death without relapse/progression as a competing risk, RT and CR after frontline therapy were associated with lower risk of relapse (SHR = 0.34, 95% CI 0.12-0.96 p = .041 and SHR = 0.11, 95% CI 0.03-0.36; p < .001, respectively). Patients with PCEMZL treated with frontline RT exhibit excellent long-term survival, and the MALT-IPI score appropriately identifies patients at risk for treatment failure.

A Novel Mechanism of High Dose Radiation Sensitization by Metformin.

Introduction: Metformin, the most widely used treatment for diabetes, is lethal to cancer cells and increases in toxicity when used in combination with radiation. In addition to various molecular and metabolic mechanisms that have been previously proposed, the studies presented provide evidence of an additional, novel mechanism of sensitization following high dose radiotherapy; the magnitude of sensitization depends on the microenvironmental levels of glucose and oxygen which are in turn affected by high dose radiation. Methods: Cancer cells (A549 and MCF7) were studied in vitro under various controlled conditions. Endpoints included clonogenic cell survival and ROS expression measured by DHE and DCFDA. CD1 nu/nu athymic mice implanted with A549 cells received metformin alone (200 mg/kg, i.p.), radiation alone (15 Gy) or a combination of metformin and radiation; the effect of treatment sequence on efficacy was assessed by tumor growth delay and histology. In a separate set of experiments, tumor blood flow was measured using a tracer clearance technique using SPECT after the administration of metformin alone, radiation alone and the combined treatment. Results: In vivo, metformin provided equally effective tumor growth delay when given 24 h after radiation as when given 1 h or 4 h before radiation, an observation not previously reported and, in fact, unexpected based on published scientific literature. When drug followed radiation, the tumors were histologically characterized by massive cellular necrosis. In vitro, cancer cells when glucose depleted and/or hypoxic were preferentially killed by metformin, in a drug dose dependent manner. A549 cells exposed to 5.0 mM of metformin was reduced seven fold in survival when in a glucose deprived as compared to a low-glucose medium (0 vs. 1.0 g/L). Finally, using a SPECT detector to follow the washout of a radioactive tracer, it was shown that a high single dose of radiosurgery (15 Gy) could dramatically inhibit blood flow and presumably diminish glucose and oxygen. Discussion: Insight into the best timing of drug and radiation administration is gained through an understanding of the mechanisms of interaction. A new mechanism of metformin sensitization by high dose radiation is proposed based on the blood flow, glucose and oxygen.