Ophthalmologic adverse events in childhood head and neck rhabdomyosarcoma survivors treated according to four different local treatment strategies

Introduction: Ophthalmological adverse events (OAEs) are known to frequently occur following local treatment for pediatric head and neck rhabdomyosarcoma (HNRMS). The exact nature of these OAEs and the burden they put on survivors is less well described. Moreover, it is suspected there might be differences in the prevalence and nature of OAEs depending on local treatment strategy applied: external beam radiation therapy with photons, external beam radiation therapy with protons, macroscopically radical surgery combined with brachytherapy, or microscopically radical surgery combined with external beam radiation therapy. Methods: We cross-sectionally assessed 98 HNRMS survivors with long (median 9 years) follow-up time, according to a predefined list of OAEs based on the Common Terminology Criteria for Adverse Events system. We added information from chart reviews on the nature and management of all OAEs scored grade ≥1. We describe the prevalence of OAEs for the different tumor sites and treatment strategies separately. Results: OAEs occurred following treatment of all HNRMS sites. The most frequently observed OAEs are eyelid abnormalities, dry eyes, and cataracts. Sixty-two percent of survivors had several different OAEs simultaneously. In 27 % of survivors additional (surgical) treatment of OAEs was required during follow-up. The patterns observed suggest a possible relationship between OAE type and treatment strategy. Conclusion: OAEs in HNRMS survivors confer a high burden of chronic toxicity. The simultaneous occurrence of multiple OAEs in individual survivors present a particularly challenging clinical scenario and demand specific expertise. We propose a standardized screening scheme to detect possible OAEs in asymptomatic survivors based on primary tumor localization

Facial deformation following treatment for pediatric head and neck rhabdomyosarcoma; the difference between treatment modalities. Results of a trans-Atlantic, multicenter cross-sectional cohort study

Background: The four different local therapy strategies used for head and neck rhabdomyosarcoma (HNRMS) include proton therapy (PT), photon therapy (RT), surgery with radiotherapy (Paris-method), and surgery with brachytherapy (AMORE). Local control and survival is comparable; however, the impact of these different treatments on facial deformation is still poorly understood. This study aims to quantify facial deformation and investigates the differences in facial deformation between treatment modalities. Methods: Across four European and North American institutions, HNRMS survivors treated between 1990 and 2017, more than 2 years post treatment, had a 3D photograph taken. Using dense surface modeling, we computed facial signatures for each survivor to show facial deformation relative to 35 age–sex–ethnicity-matched controls. Additionally, we computed individual facial asymmetry. Findings: A total of 173 HNRMS survivors were included, survivors showed significantly reduced facial growth (p <.001) compared to healthy controls. Partitioned by tumor site, there was reduced facial growth in survivors with nonparameningeal primaries (p =.002), and parameningeal primaries (p ≤.001), but not for orbital primaries (p =.080) All patients were significantly more asymmetric than healthy controls, independent of treatment modality (p ≤.001). There was significantly more facial deformation in orbital patients when comparing RT to AMORE (p =.046). In survivors with a parameningeal tumor, there was significantly less facial deformation in PT when compared to RT (p =.009) and Paris-method (p =.007). Interpretation: When selecting optimal treatment, musculoskeletal facial outcomes are an expected difference between treatment options. These anticipated differences are currently based on clinicians’ bias, expertise, and experience. These data supplement clinician judgment with an objective analysis highlighting the impact of patient age and tumor site between existing treatment options

Ki-67 Staining Is a Strong Predictor of Distant Metastasis and Mortality for Men With Prostate Cancer Treated With Radiotherapy Plus Androgen Deprivation: Radiation Therapy Oncology Group Trial 92–02

Purpose The Ki-67 staining index (Ki67-SI) has been associated with prostate cancer patient outcome; however, few studies have involved radiotherapy (RT) -treated patients. The association of Ki67-SI to local failure (LF), biochemical failure (BF), distant metastasis (DM), cause-specific death (CSD) and overall death (OD) was determined in men randomly assigned to short term androgen deprivation (STAD) + RT or long-term androgen deprivation (LTAD) + RT. Patients and Methods There were 537 patients (35.5%) on Radiation Therapy Oncology Group (RTOG) 92-02 who had sufficient tissue for Ki67-SI analysis. Median follow-up was 96.3 months. Ki67-SI cut points of 3.5% and 7.1% were previously found to be related to patient outcome and were examined here in a Cox proportional hazards multivariate analysis (MVA). Ki67-SI was also tested as a continuous variable. Covariates were dichotomized in accordance with stratification and randomization criteria. Results Median Ki67-SI was 6.5% (range, 0% to 58.2%). There was no difference in the distribution of patients in the Ki-67 analysis cohort (n = 537) and the other patients in RTOG 92-02 (n = 977) by any of the covariates or end points tested. In MVAs, Ki67-SI (continuous) was associated with LF (P = .08), BF (P = .0445), DM (P < .0001), CSD (P < .0001), and OD (P = .0094). When categoric variables were used in MVAs, the 3.5% Ki67-SI cut point was not significant. The 7.1% cut point was related to BF (P = .09), DM (P = .0008), and CSD (P = .017). Ki67-SI was the most significant correlate of DM and CSD. A detailed analysis of the hazard rates for DM in all possible covariate combinations revealed subgroups of patients treated with STAD + RT that did not require LTAD. Conclusion Ki67-SI was the most significant determinant of DM and CSD and was also associated with OD. The Ki67-SI should be considered for the stratification of patients in future trials