Relationship between the brain radiation dose for the treatment of childhood cancer and the risk of long-term cerebrovascular mortality

9017 Background: This study describes the frequencies of and risk factors for altered oral health and dental development in pediatric patients who have survived childhood cancer. Methods: We identified 8,522 participants and 2,831 siblings in the CCSS with information on dental health. Dental outcomes of treatment and socioeconomic-demographic (SED) data, were analyzed using univariate and multivariate logistic regression models to estimate odds ratios (OR). Results: Survivors included 4,249 females (49.9%), 7,367 white non-Hispanic (86.5%). Median age at cancer diagnosis, 6.8y (range, 0–20 y); time from diagnosis to interview, 31.4 y (range, 17–54 y). Overall, 30% of survivors self-reported ≥ 1 oral-dental abnormality: microdontia (10%), hypodontia (8%), > 5 caries (55%), root stunting (6%), enamel hypoplasia (13%), gingivitis (7%). Compared to siblings, survivors were at increased risk of ≥ 1 oral-dental abnormalities when adjusted for SED (OR = 2.0, p<0.001). Increased risk of abnormalities was associated with being female (p<0.001) or white non-Hispanic (p=0.001), having an income < $20K (p=0.001) or lower education (p=0.004), and lack of health insurance (p=0.02). Patients with central nervous system tumors, neuroblastoma and soft tissue sarcoma had highest risk of abnormality (all P-values < 0.001). In multivariate models adjusted for SED, radiation dose to jaw, and exposure to increasing doses of alkylating agents increased risk of oral-dental abnormalities (radiation dose = 20 Gy OR = 5.6, p < 0.001; alkylating agent score OR=1.6, p<0.0001). Conclusions: Childhood cancer therapy results in adverse long- term oral-dental sequelae and is associated with specific treatment factors. No significant financial relationships to disclose.

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Radiation dose and long term risk of cardiac pathology following radiotherapy and anthracyclin for a childhood cancer

Radiotherapy and Oncology ◽

10.1016/j.radonc.2006.08.020 ◽

2006 ◽

Vol 81 (1) ◽

pp. 47-56 ◽

Cited By ~ 28

Author(s):

Laurence Guldner ◽

Nadia Haddy ◽

François Pein ◽

Ibrahima Diallo ◽

Akthar Shamsaldin ◽

...

Keyword(s):

Radiation Dose ◽

Childhood Cancer ◽

Cardiac Pathology

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Correlation of long-term pulmonary injury with radiation dose distribution in childhood cancer survivors

Practical Radiation Oncology ◽

10.1016/j.prro.2011.07.003 ◽

2012 ◽

Vol 2 (3) ◽

pp. 237-240 ◽

Cited By ~ 1

Author(s):

Rajkumar Venkatramani ◽

Arthur J. Olch ◽

Leo Mascarenhas ◽

Susanne Yoon ◽

Batul Suterwala ◽

...

Keyword(s):

Radiation Dose ◽

Cancer Survivors ◽

Childhood Cancer ◽

Dose Distribution ◽

Childhood Cancer Survivors ◽

Pulmonary Injury

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Role of Cancer Treatment in Long-Term Overall and Cardiovascular Mortality After Childhood Cancer

Journal of Clinical Oncology ◽

10.1200/jco.2008.20.2267 ◽

2010 ◽

Vol 28 (8) ◽

pp. 1308-1315 ◽

Cited By ~ 297

Author(s):

Markhaba Tukenova ◽

Catherine Guibout ◽

Odile Oberlin ◽

Françoise Doyon ◽

Abdeddahir Mousannif ◽

...

Keyword(s):

United Kingdom ◽

Radiation Dose ◽

Childhood Cancer ◽

Cardiovascular Mortality ◽

Standardized Mortality Ratio ◽

Average Dose ◽

Cardiac Mortality ◽

The United Kingdom

Purpose The purpose of this study was to assess the role of treatment in long-term overall and cardiovascular mortality after childhood cancer. Patients and Methods We studied 4,122 5-year survivors of a childhood cancer diagnosed before 1986 in France and the United Kingdom. Information on chemotherapy was collected, and the radiation dose delivered to the heart was estimated for 2,870 patients who had received radiotherapy. Results After 86,453 person-years of follow-up (average, 27 years), 603 deaths had occurred. The overall standardized mortality ratio (SMR) was 8.3-fold higher (95% CI, 7.6-fold to 9.0-fold higher) in relation to the general populations in France and the United Kingdom. Thirty-two patients had died as a result of cardiovascular diseases (ie, 5.0-fold [95% CI, 3.3-fold to 6.7-fold] more than expected). The risk of dying as a result of cardiac diseases (n = 21) was significantly higher in individuals who had received a cumulative anthracycline dose greater than 360 mg/m2 (relative risk [RR], 4.4; 95% CI, 1.3 to 15.3) and in individuals who received an average radiation dose that exceeded 5 Gy (RR, 12.5 and 25.1 for 5 to 14.9 Gy and > 15 Gy, respectively) to the heart. A linear relationship was found between the average dose of radiation to the heart and the risk of cardiac mortality (estimated excess RR at 1 Gy, 60%). Conclusion This study is the first, to our knowledge, to establish a relationship between the radiation dose received by the heart during radiotherapy for a childhood cancer and long-term cardiac mortality. This study also confirms a significant excess risk of cardiac mortality associated with a high cumulative dose of anthracyclines.

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Subsequent neoplasm risk associated with rare variants in DNA repair and clinical radiation sensitivity syndrome genes: A report from the Childhood Cancer Survivor Study.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.10028 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. 10028-10028

Author(s):

Lindsay M. Morton ◽

Danielle M Karyadi ◽

Steven Hartley ◽

Megan Frone ◽

Joshua N Sampson ◽

...

Keyword(s):

Dna Repair ◽

Radiation Dose ◽

Cancer Survivors ◽

Childhood Cancer ◽

Rare Variants ◽

Childhood Cancer Survivors ◽

Radiation Sensitivity ◽

Dna Break ◽

Double Strand Dna

10028 Background: Radiotherapy for childhood cancer is associated with strikingly elevated risk for developing subsequent neoplasms (SNs). Whether mutations in DNA repair and radiation sensitivity genes modulate SN risks is largely unknown. Methods: We conducted whole-exome sequencing in 5105 long-term childhood cancer survivors of European descent (mean follow-up = 32.7 years). SnpEff and ClinVar identified potentially damaging rare variants in 476 DNA repair or radiation sensitivity genes. Conditional logistic regression assessed SN risk associated with these variants aggregated by gene or pathway (N = 155 with ≥5 carriers). Controls were matched on sex, childhood cancer type and diagnosis age, radiation dose to the SN site, and survival. Exact p-values were calculated by permutation. Analyses used all survivors or subsets stratified on radiation dose. Results: A total of 1108 (21.7%) survivors developed at least one SN type known to be related to ionizing radiation exposure (e.g., breast cancer, basal cell carcinoma, meningioma, thyroid cancer, sarcoma). Radiation-related SN risk was associated with homologous recombination (HR) gene variants for SN sites that received > 0- < 10 Gy (20.9% cases, 11.0% controls; odds ratio [OR] = 2.20, 95% confidence interval [CI] 1.52-3.18; P = 1.41x10-4), most notably for FANCM (3.1% cases, 0.5% controls; OR = 9.91, 95%CI 3.73-26.4; P = 2.85x10-4). For radiation-related SNs at sites with higher doses (≥10 Gy), associations were not observed for the HR pathway (14.4% cases, 12.4% controls, P = 0.17) but were observed for two individual genes implicated in double-strand DNA break repair, EXO1 (1.8% cases, 0.4% controls; OR = 6.50, 95%CI 3.49-12.1; P = 7.43x10-4) and NEIL3 (0% cases, 1.0% controls; P = 3.23x10-4). Conclusions: In this discovery study, we identified dose-specific novel associations between SN risk after radiotherapy for childhood cancer and potentially damaging rare variants in genes involved in double-strand DNA break repair, particularly HR. If replicated, these results could impact long-term screening of childhood cancer survivors and risk-benefit assessments of treatment approaches.

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The Acute Effect of Alcohol on Various Memory Processes

Journal of Psychophysiology ◽

10.1027/0269-8803/a000038 ◽

2010 ◽

Vol 24 (4) ◽

pp. 249-252 ◽

Cited By ~ 7

Author(s):

Márk Molnár ◽

Roland Boha ◽

Balázs Czigler ◽

Zsófia Anna Gaál

Keyword(s):

Low Dose ◽

Short Term Memory ◽

Acute Effect ◽

Long Term Memory ◽

Term Memory ◽

Memory Processes ◽

Different Types ◽

The Brain ◽

Legal Consequences

This review surveys relevant and recent data of the pertinent literature regarding the acute effect of alcohol on various kinds of memory processes with special emphasis on working memory. The characteristics of different types of long-term memory (LTM) and short-term memory (STM) processes are summarized with an attempt to relate these to various structures in the brain. LTM is typically impaired by chronic alcohol intake but according to some data a single dose of ethanol may have long lasting effects if administered at a critically important age. The most commonly seen deleterious acute effect of alcohol to STM appears following large doses of ethanol in conditions of “binge drinking” causing the “blackout” phenomenon. However, with the application of various techniques and well-structured behavioral paradigms it is possible to detect, albeit occasionally, subtle changes of cognitive processes even as a result of a low dose of alcohol. These data may be important for the consideration of legal consequences of low-dose ethanol intake in conditions such as driving, etc.

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Supplemental Material for Relations Between Posttraumatic Stress and Posttraumatic Growth in Long-Term Survivors of Childhood Cancer: A Report From the Childhood Cancer Survivor Study

Health Psychology ◽

10.1037/hea0000076.supp ◽

2014 ◽

Keyword(s):

Childhood Cancer ◽

Posttraumatic Growth ◽

Posttraumatic Stress ◽

Cancer Survivor ◽

Childhood Cancer Survivor ◽

Childhood Cancer Survivor Study ◽

Survivors Of Childhood Cancer ◽

Long Term Survivors

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Moving past the vaccine/autism controversy - to examine potential vaccine neurological harms

International Journal of Risk & Safety in Medicine ◽

10.3233/jrs-200052 ◽

2020 ◽

pp. 1-15

Author(s):

Peter R. Breggin

Keyword(s):

Neurological Disorders ◽

Developmental Disorder ◽

Physical Symptoms ◽

Psychosocial Disorders ◽

The Us ◽

Potential Vaccine ◽

Research And Education ◽

The Brain ◽

New Vaccines

BACKGROUND: The vaccine/autism controversy has caused vast scientific and public confusion, and it has set back research and education into genuine vaccine-induced neurological disorders. The great strawman of autism has been so emphasized by the vaccine industry that it, and it alone, often appears in authoritative discussions of adverse effects of the MMR and other vaccines. By dismissing the chimerical vaccine/autism controversy, vaccine defenders often dismiss all genuinely neurological aftereffects of the MMR (measles, mumps, and rubella) and other vaccines, including well-documented events, such as relatively rare cases of encephalopathy and encephalitis. OBJECTIVE: This report explains that autism is not a physical or neurological disorder. It is not caused by injury or disease of the brain. It is a developmental disorder that has no physical origins and no physical symptoms. It is extremely unlikely that vaccines are causing autism; but it is extremely likely that they are causing more neurological damage than currently appreciated, some of it resulting in psychosocial disabilities that can be confused with autism and other psychosocial disorders. This confusion between a developmental, psychosocial disorder and a physical neurological disease has played into the hands of interest groups who want to deny that vaccines have any neurological and associated neuropsychiatric effects. METHODS: A review of the scientific literature, textbooks, and related media commentary is integrated with basic clinical knowledge. RESULTS: This report shows how scientific sources have used the vaccine/autism controversy to avoid dealing with genuine neurological risks associated with vaccines and summarizes evidence that vaccines, including the MMR, can cause serious neurological disorders. Manufacturers have been allowed by the US Food and Drug Administration (FDA) to gain vaccine approval without placebo-controlled clinical trials. CONCLUSIONS: The misleading vaccine autism controversy must be set aside in favor of examining actual neurological harms associated with vaccines, including building on existing research that has been ignored. Manufacturers of vaccines must be required to conduct placebo-controlled clinical studies for existing vaccines and for government approval of new vaccines. Many probable or confirmed neurological adverse events occur within a few days or weeks after immunization and could be detected if the trials were sufficiently large. Contrary to current opinion, large, long-term placebo-controlled trials of existing and new vaccines would be relatively easy and safe to conduct.

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