Dose-Effect Analysis of Early Changes in Orbital Bone Morphology After Radiation Therapy for Rhabdomyosarcoma

Purpose: In survivors of orbital embryonal rhabdomyosarcoma (ERMS), late effects include facial deformation and asymmetry. We sought to quantify orbital asymmetry in ERMS survivors and characterize the dose effect of radiation to the orbital bones. Methods and Materials: We evaluated the most recent follow-up magnetic resonance imaging (MRI) in 17 children (≤21 years old) with stage 1 group III orbital ERMS treated with proton therapy between 2007 and 2018. For all patients, the orbital socket volumes were calculated and compared with the contralateral, unirradiated orbital socket. Patient age, orbital tumor quadrant, and the radiation dose delivered to the major orbital bones (maxillary, frontal, and zygomatic bones) were recorded and correlated with the orbital socket volume difference. Results: The mean age at diagnosis was 5.4 years old (range, 1.1-9.7 years). All patients received a prescription dose of 45 GyRBE. The mean time interval between radiation and MRI was 2.9 years (range, 0.8-3.2 years). The mean age at most recent MRI was 8.4 years (range, 2.3-12.9 years). In 16 of 17 patients, the volume of the ipsilateral orbit was significantly smaller than the contralateral orbit on follow-up MRI (P ≤ .0001). In one patient with nonviable tumor in situ, the irradiated orbit was larger. The volume difference increased with follow-up time and did not correlate with age at treatment or age at MRI. A dose >40 GyRBE to all bones of the orbital rim was associated with a significant decrease in orbital volume (P 40 GyRBE to either the frontal, maxillary, or zygomatic bone was not. Conclusions: Despite the dosimetric precision of proton therapy, orbital asymmetry will develop after >40 GyRBE to multiple bones of the orbital rim. These data may be used to guide treatment planning and counsel patients on expected cosmesis

Medication Use During Pregnancy and Lactation in a Dutch Population

Background: Medication use during pregnancy and lactation can be unavoidable, but knowledge on safety for the fetus or breastfed infant is limited among patients and healthcare providers. Research aim: This study aimed to determine (a) the prevalence of medication use in pregnant and lactating women in a tertiary academic center, (b) the types and safety of these medicines, and (c) the influence of medication use on initiation of breastfeeding. Methods: This study used a cross-sectional survey among women (N = 292) who underwent high-risk or low-risk deliveries. Data about their use of prescribed, over-the-counter, and homeopathic medication during pregnancy were obtained through a structured interview, followed by a questionnaire during lactation. Safety was classified according to the risk classification system from the Dutch Teratological Information Service. Results: Overall, 95.5% of participants used medication. One third of participants used at least one medicine with an unknown risk for the fetus. Teratogenic medication was used by 6.5% of participants, whereas 29.5% used medication with a (suspected) pharmacological effect on the fetus. Lactation was initiated by 258 (88.7%) participants, of which 84.2% used medication while breastfeeding. In 3.8% of participants, this medication was classified unsafe, but none used medication with an unknown risk. One-third of the nonlactating participants decided not to initiate breastfeeding because of medication use. In 70% of participants, this decision was appropriate. Conclusion: The prevalence of overall use of medication in Dutch pregnant and lactating women admitted to a tertiary center was high. There is an urgent need for pharmacometric studies for determination of the safe use of the most frequently used medicines during pregnancy or lactation

Patient-reported outcomes in childhood head and neck rhabdomyosarcoma survivors and their relation to physician-graded adverse events—A multicenter study using the FACE-Q Craniofacial module

Introduction: Adverse events (AE) of treatment are prevalent and diverse in head and neck rhabdomyosarcoma (HNRMS) survivors. These AEs are often reported by physicians; however, patients' perceptions of specific AE are not well known. In this study, we explored patient-reported outcomes measuring appearance, health-related quality of life (HRQOL), and facial function in HNRMS survivors. Second, we assess the relationship between physician grading of AE and patient reporting. Materials and Methods: Survivors of pediatric HNRMS, diagnosed between 1993 and 2017, who were at least 2 years after completing treatment were invited to an outpatient clinic as part of a multicenter cross-sectional cohort study. At the outpatient clinics, survivors aged ≥8 years filled out the FACE-Q Craniofacial module; a patient-reported outcome instrument measuring issues specific to patients with facial differences. AE were systematically assessed by a multidisciplinary team based on the Common Terminology Criteria of Adverse Events system. Results: Seventy-seven survivors with a median age of 16 years (range 8–43) and median follow-up of 10 years (range 2–42) completed the questionnaire and were screened for AEs. Patient-reported outcomes varied widely between survivors. Many survivors reported negative consequences: 82% on appearance items, 81% on HRQOL items, and 38% on facial function items. There was a weak correlation between physician-scored AEs and the majority of patient-reported outcomes specific for those AEs. Conclusions: Physician-graded AEs are not sufficient to provide tailored care for HNMRS survivors. Findings from this study highlight the importance of incorporating patient-reported outcome measures in survivorship follow-up

Psychometric Validation of the FACE-Q Craniofacial Module for Facial Nerve Paralysis

Background: Systematic reviews have identified the need for a patient-reported outcome measure for facial nerve paralysis (FNP). The aim of this study was to determine the psychometric properties of FACE-Q Craniofacial module scales when used in a combined sample of children and older adults with FNP. Methods: Data were collected between December 2016 and December 2019. We conducted qualitative interviews with children and adults with FNP. FACE-Q data were collected from patients aged 8 years and older with FNP. Rasch measurement theory analysis was used to examine the reliability and validity of the relevant scales in the FNP sample. Results: Twenty-five patients provided 2052 qualitative codes related to appearance, physical, psychological, and social function. Many patient concerns were common across age. The field-test sample included 235 patients aged 8-81 years. Of the 13 scales examined, all 122 items had ordered thresholds and good item fit to the Rasch model. For 12 scales, person separation index values were ≥0.79 and Cronbach's alpha values were ≥0.82. The 13th scale's reliability values were ≥0.71. Conclusion: The FACE-Q Craniofacial module scales described in this study can be used to collect and compare evidence-based outcome data from children and adults with FNP

An overview of radiological manifestations of acquired dental developmental disturbances in paediatric head and neck cancer survivors

OBJECTIVES: In paediatric cancer survivors treated with chemotherapy and radiotherapy therapy, late effects on dental development are quite common. Oral radiologists are not familiar with the radiographic images of these specific dental consequences of chemotherapy and radiotherapy. With the goal of educating colleagues, to raise awareness of the needs of survivors, and to identify directions for future research, we present dental radiographs of survivors treated for head and neck rhabdomyosarcoma with chemotherapy and radiotherapy. Also, based on the survivors reviewed, a radiographic inventory of commonly found late dental developmental effects seen in conjunction with treatment is presented. METHODS: Panoramic radiographic findings of five illustrative cases are presented, from a group of 42 survivors of head and neck rhabdomyosarcoma treated at the Academic Medical Center Amsterdam, The Netherlands over the past 25 years. RESULTS: Five cases showing dental developmental disorders are presented. These cases show an association of the location of the radiation field and the developmental stage of the teeth with the severity of the effect on dental development. We also report an inventory of severe and moderate effects of chemotherapy and radiotherapy on the development of molars and anterior teeth. CONCLUSIONS: This paper presents five cases and a radiographic inventory to illustrate disturbances of dental development associated with chemotherapy and radiotherapy in children. Medical and dental professionals involved in the treatment of cancer survivors are relatively unaware of the dental consequences of radiation therapy and the age dependency of specific regional effects. These effects can be severe, with great impact on quality of life. Further research in this area could help improve planning of radiation therapy for children, potentially preventing or limiting dental or maxillofacial sequelae

Facial asymmetry in head and neck rhabdomyosarcoma survivors

Radiotherapy is essential for achieving and maintaining local control in head and neck rhabdomyosarcoma (HNRMS) patients. However, radiotherapy may cause outgrowth disturbances of facial bone and soft tissue, resulting in facial asymmetry. The aim of this study was to develop a method to visualize and measure facial asymmetry in HNRMS survivors using three-dimensional (3D) imaging techniques. Facial deformity was evaluated in a multidisciplinary clinical assessment of 75 HNRMS survivors, treated with external beam radiotherapy (EBRT, n = 26) or Ablative surgery, MOulage brachytherapy, and REconstruction (AMORE, n = 49). Individual facial asymmetry was measured using 3D photogrammetry and expressed in a raw asymmetry index and a normalized sex-age-ethnicity-matched asymmetry signature weight. Facial asymmetry was also compared between British and Dutch controls and between survivors and their matched controls. Facial asymmetry was more pronounced with increasing age (P < 0.01) in British controls compared with Dutch controls (P = 0.04). Survivors developed more facial asymmetry than matched controls (P < 0.001). The clinical assessment of facial deformity correlated with the raw asymmetry index (r = 0.60, P < 0.001). 3D imaging can be used for objective measurement of facial asymmetry in HNRMS survivors. The raw asymmetry index correlated with a clinical assessment of facial deformity. Comparisons between treatment groups seemed inappropriate given the differences in facial asymmetry between British and Dutch controls. In future studies, pretreatment images could act as matched controls for posttreatment evaluatio

AMORE treatment as salvage treatment in children and young adults with relapsed head-neck rhabdomyosarcoma

Background and purpose: Survival after relapse of head and neck rhabdomyosarcoma (HNRMS) after prior external beam radiotherapy (EBRT) is poor, since options for adequate local treatment are often lacking. In this study we describe our experience with salvage AMORE in patients with relapsed HNRMS after prior EBRT. Materials and methods: Patients with relapsed HNRMS after prior EBRT in which salvage AMORE treatment was considered feasible were analysed; this includes patients with parameningeal, head and neck non-parameningeal and orbital localization. AMORE treatment consisted of Ablative surgery, MOuld technique brachytherapy and surgical REconstruction. Results: In total 18 patients received salvage AMORE treatment; nine patients had relapsed parameningeal (PM) RMS, two patients had relapsed head and neck non-parameningeal RMS (HN-nonPM) and seven patients had relapsed orbital RMS. Local control rate was 67% and 5-year overall survival was 54% (95% confidence interval: 31–78%); 3/9 patients with PM RMS, 0/2 patients with HN-nonPM RMS and 6/7 patients with orbital RMS were alive after a median follow-up of 8.6 years. One patient with PM RMS survived more than 5 years after which he died from a secondary cancer. Six patients developed a local relapse (of which one patient also developed a distant metastasis) and two patients developed distant metastases. Conclusions: Salvage AMORE treatment is a feasible and effective local therapy approach even after prior EBRT. Since salvage AMORE treatment is sometimes the only curative option in patient with relapsed HNRMS, we encourage physicians to consider salvage AMORE treatment for patients with relapsed HNRMS after prior EBRT

FACE-Q craniofacial module: Part 2 Psychometric properties of newly developed scales for children and young adults with facial conditions

Background: The FACE-Q Craniofacial Module is a patient-reported outcome measure designed for patients aged 8 to 29 years with conditions associated with a facial difference. In part 1, we describe the psychometric findings for the original CLEFT-Q scales tested in patients with cleft and noncleft facial conditions. The aim of this study was to examine psychometric performance of new FACE-Q Craniofacial Module scales. Methods: Data were collected between December 2016 and December 2019 from patients aged 8 to 29 years with conditions associated with a visible or functional facial difference. Rasch measurement theory (RMT) analysis was used to examine psychometric properties of each scale. Scores were transformed from 0 (worst) to 100 (best) for tests of construct validity. Results: 1495 participants were recruited with a broad range of conditions (e.g., birthmarks, facial paralysis, craniosynostosis, craniofacial microsomia, etc.) RMT analysis resulted in the refinement of 7 appearance scales (Birthmark, Cheeks, Chin, Eyes, Forehead, Head Shape, Smile), two function scales (Breathing, Facial), and an Appearance Distress scale. Person separation index and Cronbach alpha values met criteria. Three checklists were also formed (Eye Function, and Eye and Face Adverse Effects). Significantly lower scores on eight of nine scales were reported by participants whose appearance or functional difference was rated as a major rather than minor or no difference. Higher appearance distress correlated with lower appearance scale scores. Conclusion: The FACE-Q Craniofacial Module scales can be used to collect and compare patient reported outcomes data in children and young adults with a facial condition

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