Person:

Yock, Torunn

Radiation-induced secondary malignancies are a significant, yet uncommon cause of morbidity and mortality among cancer survivors. Secondary malignancy risk is dependent upon multiple factors including patient age, the biological and genetic predisposition of the individual, the volume and location of tissue irradiated, and the dose of radiation received. Proton therapy (PRT) is an advanced particle therapy with unique dosimetric properties resulting in reduced entrance dose and minimal to no exit dose when compared with standard photon radiation therapy. Multiple dosimetric studies in varying cancer subtypes have demonstrated that PRT enables the delivery of adequate target volume coverage with reduced integral dose delivered to surrounding tissues, and modeling studies taking into account dosimetry and radiation cell biology have estimated a significantly reduced risk of radiation-induced secondary malignancy with PRT. Clinical data are emerging supporting the lower incidence of secondary malignancies after PRT compared with historical photon data, though longer follow-up in proton treated cohorts is awaited. This article reviews the current dosimetric and clinical literature evaluating the incidence of and risk factors associated with radiation-induced secondary malignancy following PRT.

Background: To precisely calculate skin dose and thus to evaluate the relationship between the skin dose and permanent alopecia for pediatric medulloblastoma patients treated with proton beams. Methods: The dosimetry and alopecia outcomes of 12 children with medulloblastoma (ages 4-15 years) comprise the study cohort. Permanent alopecia was assessed and graded after completion of the entire therapy. Skin threshold doses of permanent alopecia were calculated based on the skin dose from the craniospinal irradiation (CSI) plan using the concept of generalized equivalent uniform dose (gEUD) and accounting for chemotherapy intensity. Monte Carlo simulations were employed to accurately assess uncertainties due to beam range prediction and secondary particles. Results: Increasing the dose of the CSI field or the dose given by the boost field to the posterior fossa increased total skin dose delivered in that region. It was found that permanent alopecia could be correlated with CSI dose with a threshold of about 21 Gy (relative biological effectiveness, RBE) with high dose chemotherapy and 30 Gy (RBE) with conventional chemotherapy. Conclusions: Our results based on 12 patients provide a relationship between the skin dose and permanent alopecia for pediatric medulloblastoma patients treated with protons. The alopecia risk as assessed with gEUD could be predicted based on the treatment plan information.

Background: Thoracic and cardiac irradiation increases the risk of pulmonary and cardiovascular disease. In addition, radiation, often in combination with chemotherapy, can cause treatment-related pneumonitis. Previously, we showed that the common marker for cardiac damage, troponin T, was not elevated by chemoradiation [Lung Cancer 62:351–355, 2008]. In this study, we explore whether dose-volume metrics and biomarkers for cardiac damage, inflammation or angiogenesis could identify patients receiving thoracic radiation who would later have cardiac or pulmonary complications. Findings: To this end, we quantified cardiac biomarkers including c-reactive protein (cRP) as well as a panel of angiogenic and inflammatory molecules in thirty patients who received radiation therapy to the thorax with or without concurrent chemotherapy between May 2006 and May 2007. Serum was collected at baseline, 2 weeks into radiation treatment and at the completion of radiation therapy. Heart and lung dosimetric parameters and clinical risk factors were also examined, along with the monitoring of adverse pulmonary and cardiac events during follow-up. Contrary to our hypothesis, there was no correlation between serum biomarker levels and cardiac radiation dose. Similarly there was little association between lung dose-volume metrics and inflammatory or angiogenic biomarkers. Furthermore, there was no correlation with serum biomarkers and adverse pulmonary or cardiovascular events. Conclusion: Based on these data, acute elevations in serum biomarkers of cardiac damage, inflammation or angiogenesis should not be attributed to thoracic (chemo)radiation and elevations in such biomarkers of tissue damage should be further evaluated.

The increasing efficacy of pediatric cancer therapy over the past four decades has produced many long-term survivors that now struggle with serious treatment related morbidities affecting their quality of life. Radiation therapy is responsible for a significant proportion of these late effects, but a relatively new and emerging modality, proton radiotherapy hold great promise to drastically reduce these treatment related late effects in long term survivors by sparing dose to normal tissues. Dosimetric studies of proton radiotherapy compared with best available photon based treatment show significant dose sparing to developing normal tissues. Furthermore, clinical data are now emerging that begin to quantify the benefit in decreased late treatment effects while maintaining excellent cancer control rates.

Background/objectives The Pediatric Proton Consortium Registry (PPCR) was established to expedite proton outcomes research in the pediatric population requiring radiotherapy. Here, we introduce the PPCR as a resource to the oncology community and provide an overview of the data available for further study and collaboration. Design/methods A multi-institutional registry of integrated clinical, dosimetric, radiographic, and patient-reported data for patients undergoing proton radiation therapy was conceived in May 2010. Massachusetts General Hospital began enrollment in July of 2012. Subsequently, 12 other institutions joined the PPCR and activated patient accrual, with the latest joining in 2017. An optional patient-reported quality of life (QoL) survey is currently implemented at six institutions. Baseline health status, symptoms, medications, neurocognitive status, audiogram findings, and neuroendocrine testing are collected. Treatment details of surgery, chemotherapy, and radiation therapy are documented and radiation plans are archived. Follow-up is collected annually. Data were analyzed 25 September, 2017. Results: A total of 1,854 patients have consented and enrolled in the PPCR from October 2012 until September 2017. The cohort is 55% male, 70% Caucasian, and comprised of 79% United States residents. Central nervous system (CNS) tumors comprise 61% of the cohort. The most common CNS histologies are as follows: medulloblastoma (n = 276), ependymoma (n = 214), glioma/astrocytoma (n = 195), craniopharyngioma (n = 153), and germ cell tumors (n = 108). The most common non-CNS tumors diagnoses are as follows: rhabdomyosarcoma (n = 191), Ewing sarcoma (n = 105), Hodgkin lymphoma (n = 66), and neuroblastoma (n = 55). The median follow-up is 1.5 years with a range of 0.14 to 4.6 years. Conclusion: A large prospective population of children irradiated with proton therapy has reached a critical milestone to facilitate long-awaited clinical outcomes research in the modern era. This is an important resource for investigators both in the consortium and for those who wish to access the data for academic research pursuits.