Adverse Radiation Therapy Effects in the Treatment of Head and Neck Tumors.

Whether used as a single modality or as part of a combined approach, radiation therapy (RT) plays an essential role in the treatment of several head and neck malignancies. Despite the improvement in radiation delivery techniques, normal structures in the vicinity of the target area remain susceptible to a wide range of adverse effects. Given their high incidence, some of these effects are referred to as expected postradiation changes (eg, mucositis, sialadenitis, and edema), while others are considered true complications, meaning they should not be expected and can even represent life-threatening conditions (eg, radionecrosis, fistulas, and radiation-induced neoplasms). Also, according to their timing of onset, these deleterious effects can be divided into four groups: acute (during RT), subacute (within weeks to months), delayed onset (within months to years), and very delayed onset (after several years).The authors provide a comprehensive review of the most important radiation-induced changes related to distinct head and neck sites, focusing on their typical cross-sectional imaging features and correlating them with the time elapsed after treatment. Radiologists should not only be familiar with these imaging findings but also actively seek essential clinical data at the time of interpretation (including knowledge of the RT dose and time, target site, and manifesting symptoms) to better recognize imaging findings, avoid pitfalls and help guide appropriate management. © RSNA, 2022.

Letter to the editor: radiomics analysis for predicting pembrolizumab response in patients with advanced rare cancers.

A commentary on the original research article: 'Radiomics analysis for predicting pembrolizumab response in patients with advanced rare cancers'. Of note, the predictor selection process, the cross-validation method, along with the lack of final testing of the developed model with a separated data set may mask overfitting, overestimating performance metrics.

Involvement of Multiple Trigeminal Nerve Branches in IgG4-Related Orbital Disease.

PURPOSE: To describe the occurrence of multiple trigeminal nerves (TGNs) enlargement in patients with orbital IgG4-related disease. METHODS: Retrospective review of MRI findings and medical records of 6 patients (10 orbits) with orbital IgG4-related disease and enlargement of more than 1 TGN. Orbital biopsies were performed in all cases revealing the typical lymphoplasmacytic infiltrate with significant plasma cell positivity for IgG4 (IgG4+/IgG ratio ≥ 40%). Three experienced neuroradiologists reviewed the MRI sequences using a digital imaging viewer system (Horos, https://horosproject.org/). RESULTS: Bilateral involvement of at least 2 TGNs divisions was detected in all 6 patients. Enlargement of both V1 and V2 nerves was diagnosed in 5 patients, and in 3 cases, all TGN divisions were involved. V2 nerves were the most affected. In this division, all 12 infraorbital nerves were enlarged, followed by lesser palatines (10/83.3%), superior alveolar (10/83.3%), and zygomatic (6/50%). V1 and V3 nerves were less affected albeit 9 (75%) frontal branches (V1), and 50% of the inferior alveolar (V3) nerves were also enlarged. CONCLUSIONS: Widespread involvement of the TGN is an important feature of IgG4-related disease.

CT-based Radiomic Signatures for Predicting Histopathologic Features in Head and Neck Squamous Cell Carcinoma.

Purpose: To determine the performance of CT-based radiomic features for noninvasive prediction of histopathologic features of tumor grade, extracapsular spread, perineural invasion, lymphovascular invasion, and human papillomavirus status in head and neck squamous cell carcinoma (HNSCC). Materials and Methods: In this retrospective study, which was approved by the local institutional ethics committee, CT images and clinical data from patients with pathologically proven HNSCC from The Cancer Genome Atlas (n = 113) and an institutional test cohort (n = 71) were analyzed. A machine learning model was trained with 2131 extracted radiomic features to predict tumor histopathologic characteristics. In the model, principal component analysis was used for dimensionality reduction, and regularized regression was used for classification. Results: The trained radiomic model demonstrated moderate capability of predicting HNSCC features. In the training cohort and the test cohort, the model achieved a mean area under the receiver operating characteristic curve (AUC) of 0.75 (95% confidence interval [CI]: 0.68, 0.81) and 0.66 (95% CI: 0.45, 0.84), respectively, for tumor grade; a mean AUC of 0.64 (95% CI: 0.55, 0.62) and 0.70 (95% CI: 0.47, 0.89), respectively, for perineural invasion; a mean AUC of 0.69 (95% CI: 0.56, 0.81) and 0.65 (95% CI: 0.38, 0.87), respectively, for lymphovascular invasion; a mean AUC of 0.77 (95% CI: 0.65, 0.88) and 0.67 (95% CI: 0.15, 0.80), respectively, for extracapsular spread; and a mean AUC of 0.71 (95% CI: 0.29, 1.0) and 0.80 (95% CI: 0.65, 0.92), respectively, for human papillomavirus status. Conclusion: Radiomic CT models have the potential to predict characteristics typically identified on pathologic assessment of HNSCC.Supplemental material is available for this article.© RSNA, 2020.

Development and validation of radiomic signatures of head and neck squamous cell carcinoma molecular features and subtypes.

BACKGROUND: Radiomics-based non-invasive biomarkers are promising to facilitate the translation of therapeutically related molecular subtypes for treatment allocation of patients with head and neck squamous cell carcinoma (HNSCC). METHODS: We included 113 HNSCC patients from The Cancer Genome Atlas (TCGA-HNSCC) project. Molecular phenotypes analyzed were RNA-defined HPV status, five DNA methylation subtypes, four gene expression subtypes and five somatic gene mutations. A total of 540 quantitative image features were extracted from pre-treatment CT scans. Features were selected and used in a regularized logistic regression model to build binary classifiers for each molecular subtype. Models were evaluated using the average area under the Receiver Operator Characteristic curve (AUC) of a stratified 10-fold cross-validation procedure repeated 10 times. Next, an HPV model was trained with the TCGA-HNSCC, and tested on a Stanford cohort (N = 53). FINDINGS: Our results show that quantitative image features are capable of distinguishing several molecular phenotypes. We obtained significant predictive performance for RNA-defined HPV+ (AUC = 0.73), DNA methylation subtypes MethylMix HPV+ (AUC = 0.79), non-CIMP-atypical (AUC = 0.77) and Stem-like-Smoking (AUC = 0.71), and mutation of NSD1 (AUC = 0.73). We externally validated the HPV prediction model (AUC = 0.76) on the Stanford cohort. When compared to clinical models, radiomic models were superior to subtypes such as NOTCH1 mutation and DNA methylation subtype non-CIMP-atypical while were inferior for DNA methylation subtype CIMP-atypical and NSD1 mutation. INTERPRETATION: Our study demonstrates that radiomics can potentially serve as a non-invasive tool to identify treatment-relevant subtypes of HNSCC, opening up the possibility for patient stratification, treatment allocation and inclusion in clinical trials. FUND: Dr. Gevaert reports grants from National Institute of Dental & Craniofacial Research (NIDCR) U01 DE025188, grants from National Institute of Biomedical Imaging and Bioengineering of the National Institutes of Health (NIBIB), R01 EB020527, grants from National Cancer Institute (NCI), U01 CA217851, during the conduct of the study; Dr. Huang and Dr. Zhu report grants from China Scholarship Council (Grant NO:201606320087), grants from China Medical Board Collaborating Program (Grant NO:15-216), the Cyrus Tang Foundation, and the Zhejiang University Education Foundation during the conduct of the study; Dr. Cintra reports grants from São Paulo State Foundation for Teaching and Research (FAPESP), during the conduct of the study.

Monitoring optic chiasmatic-hypothalamic glioma volumetric changes by MRI in children under clinical surveillance or chemotherapy.

PURPOSE: Optic pathway gliomas represent 5% of pediatric brain tumors and are typically low-grade lesions. Because of their unpredictable clinical course, adequate treatment approaches have been controversial, involving surveillance, surgery, chemotherapy, and radiotherapy. In this study, we use volumetric imaging to compare evolution of optic chiasmatic-hypothalamic gliomas (OCHG) treated with and without chemotherapy, analyzing tumor volume variation during the overall period. METHODS: A total of 45 brain MRI were retrospectively analyzed for 14 patients with OCHG. Volumetric assessment of the lesions was performed by a neuroradiologist, using software DISPLAY. OCHG patients were allocated into two groups: group 1 (n = 8) who underwent chemotherapy and group 2 (n = 6) who did not receive chemotherapy. Outcome analysis was performed comparing tumor volume evolution of these two groups. RESULTS: The results showed a reduction of 4.4% of the volume of the lesions for group 1 after the end of chemotherapy, with an increase of 5.3% in volume in the late follow-up examination. For group 2, we found a slight reduction (5%) of the overall volume of the lesions, both with no statistical significance (p > 0.05). CONCLUSIONS: From the limited series analyzed in this study, no significant differences were observed in relation to the volume change of lesions treated or not treated with chemotherapy. Larger prospective clinical trials are needed to better evaluate the effect of chemotherapy and radiological response of OCHG.

Magnetic resonance imaging: dynamic contrast enhancement and diffusion-weighted imaging to identify malignant cervical lymph nodes.

OBJECTIVE: To examine the potential of two magnetic resonance imaging (MRI) techniques-dynamic contrast enhancement (DCE) and diffusion-weighted imaging (DWI)-for the detection of malignant cervical lymph nodes. MATERIALS AND METHODS: Using DCE and DWI, we evaluated 33 cervical lymph nodes. For the DCE technique, the maximum relative enhancement, relative enhancement, time to peak enhancement, wash-in rate, wash-out rate, brevity of enhancement, and area under the curve were calculated from a semi-quantitative analysis. For the DWI technique, apparent diffusion coefficients (ADCs) were acquired in the region of interest of each lymph node. Cystic or necrotic parts were excluded. All patients underwent neck dissection or node biopsy. Imaging results were correlated with the histopathological findings. None of the patients underwent neoadjuvant treatment before neck dissection. RESULTS: Relative enhancement, maximum relative enhancement, and the wash-in rate were significantly higher in malignant lymph nodes than in benign lymph nodes (p < 0.009; p < 0.05; and p < 0.03, respectively). The time to peak enhancement was significantly shorter in the malignant lymph nodes (p < 0.02). In the multivariate analysis, the variables identified as being the most capable of distinguishing between benign and malignant lymph nodes were time to peak enhancement (sensitivity, 73.7%; specificity, 69.2%) and relative enhancement (sensitivity, 89.2%; specificity, 69.2%). CONCLUSION: Although DCE was able to differentiate between benign and malignant lymph nodes, there is still no consensus regarding the use of a semi-quantitative analysis, which is difficult to apply in a clinical setting. Low ADCs can predict metastatic disease, although inflammatory processes might lead to false-positive results.

OBJETIVO: Examinar o potencial das imagens de contraste dinâmico (DCE-MRI) e difusão (DW-MRI) em ressonância magnética na detecção de linfonodos cervicais malignos. MATERIAIS E MÉTODOS: Foram realizadas DCE-MRI e DW-MRI em 33 linfonodos cervicais. Os valores de realce relativo máximo, realce relativo, tempo de pico, taxa de realce e lavagem, brevidade do realce e área sob a curva foram avaliados pela análise semiquantitativa (DCE-MRI). Os coeficientes de difusão aparente na DW-MRI foram obtidos na área de interesse. Foram excluídas partes císticas ou necróticas dos nódulos. Todos os pacientes foram submetidos a dissecção cervical ou a biópsia. Os resultados de imagem foram correlacionados com os achados patológicos. Nenhum paciente foi submetido a tratamento neoadjuvante antes da dissecção do pescoço. RESULTADOS: Realce relativo, realce relativo máximo e taxa de realce aumentaram nos nódulos malignos (p < 0,009, p < 0,05 e p < 0,03, respectivamente). O tempo de pico foi reduzido nos nódulos malignos (p < 0,02). A análise multivariada identificou tempo de pico (sensibilidade, 73,7%; especificidade, 69,2%) e realce relativo (sensibilidade, 89,2%; especificidade, 69,2%) como variáveis capazes de distinguir os nódulos benignos e malignos. CONCLUSÃO: Embora o DCE-MRI possa diferenciar os nódulos benignos e malignos, ainda não há consenso sobre a técnica de análise semiquantitativa, em razão de dificuldade de aplicação clínica. Valores baixos do coeficiente de difusão aparente podem predizer nódulo metastático, mas devem-se considerar também resultados falso-positivos, provavelmente secundários ao processo inflamatório.

Magnetic resonance imaging: dynamic contrast enhancement and diffusion-weighted imaging to identify malignant cervical lymph nodes / Uso do contraste dinâmico e da sequência de difusão em ressonância magnética na identificação de linfonodos cervicais malignos

Abstract Objective: To examine the potential of two magnetic resonance imaging (MRI) techniques-dynamic contrast enhancement (DCE) and diffusion-weighted imaging (DWI)-for the detection of malignant cervical lymph nodes. Materials and Methods: Using DCE and DWI, we evaluated 33 cervical lymph nodes. For the DCE technique, the maximum relative enhancement, relative enhancement, time to peak enhancement, wash-in rate, wash-out rate, brevity of enhancement, and area under the curve were calculated from a semi-quantitative analysis. For the DWI technique, apparent diffusion coefficients (ADCs) were acquired in the region of interest of each lymph node. Cystic or necrotic parts were excluded. All patients underwent neck dissection or node biopsy. Imaging results were correlated with the histopathological findings. None of the patients underwent neoadjuvant treatment before neck dissection. Results: Relative enhancement, maximum relative enhancement, and the wash-in rate were significantly higher in malignant lymph nodes than in benign lymph nodes (p < 0.009; p < 0.05; and p < 0.03, respectively). The time to peak enhancement was significantly shorter in the malignant lymph nodes (p < 0.02). In the multivariate analysis, the variables identified as being the most capable of distinguishing between benign and malignant lymph nodes were time to peak enhancement (sensitivity, 73.7%; specificity, 69.2%) and relative enhancement (sensitivity, 89.2%; specificity, 69.2%). Conclusion: Although DCE was able to differentiate between benign and malignant lymph nodes, there is still no consensus regarding the use of a semi-quantitative analysis, which is difficult to apply in a clinical setting. Low ADCs can predict metastatic disease, although inflammatory processes might lead to false-positive results.

Resumo Objetivo: Examinar o potencial das imagens de contraste dinâmico (DCE-MRI) e difusão (DW-MRI) em ressonância magnética na detecção de linfonodos cervicais malignos. Materiais e Métodos: Foram realizadas DCE-MRI e DW-MRI em 33 linfonodos cervicais. Os valores de realce relativo máximo, realce relativo, tempo de pico, taxa de realce e lavagem, brevidade do realce e área sob a curva foram avaliados pela análise semiquantitativa (DCE-MRI). Os coeficientes de difusão aparente na DW-MRI foram obtidos na área de interesse. Foram excluídas partes císticas ou necróticas dos nódulos. Todos os pacientes foram submetidos a dissecção cervical ou a biópsia. Os resultados de imagem foram correlacionados com os achados patológicos. Nenhum paciente foi submetido a tratamento neoadjuvante antes da dissecção do pescoço. Resultados: Realce relativo, realce relativo máximo e taxa de realce aumentaram nos nódulos malignos (p < 0,009, p < 0,05 e p < 0,03, respectivamente). O tempo de pico foi reduzido nos nódulos malignos (p < 0,02). A análise multivariada identificou tempo de pico (sensibilidade, 73,7%; especificidade, 69,2%) e realce relativo (sensibilidade, 89,2%; especificidade, 69,2%) como variáveis capazes de distinguir os nódulos benignos e malignos. Conclusão: Embora o DCE-MRI possa diferenciar os nódulos benignos e malignos, ainda não há consenso sobre a técnica de análise semiquantitativa, em razão de dificuldade de aplicação clínica. Valores baixos do coeficiente de difusão aparente podem predizer nódulo metastático, mas devem-se considerar também resultados falso-positivos, provavelmente secundários ao processo inflamatório.

Intraconal gauze mass: An unusual complication of orbital fracture repair - a case report.

Gossypiboma and textiloma are terms used to describe tumor-like masses caused by retained gauze or surgical sponges after any operation. It is a rare surgical complication, usually difficult to diagnose due to its variable clinical presentation and nonstandard radiological appearance. We describe here a rare case of orbital gossypiboma in a child after surgical correction of an orbital blowout fracture.

Perineural spread of malignant head and neck tumors: review of the literature and analysis of cases treated at a teaching hospital.

Perineural tumor spread refers to the migration of tumor cells along nerve tissues. It worsens the prognosis, increases the recurrence rate, and diminishes 5-year survival by up to 30%. It is an important finding on imaging tests employed in the staging of patients with head and neck cancers, because it cannot be assessed by the surgeon alone. Nevertheless, it is frequently overlooked. In this study, we reviewed the literature regarding the imaging and pathophysiological aspects of this type of dissemination. We also analyzed ten imaging tests, obtained from a teaching hospital in Brazil, in which there were radiological signs of perineural tumor spread.

Disseminação perineural de tumores refere-se à extensão de células tumorais ao longo do tecido dos nervos. Acarreta um pior prognóstico, aumenta a taxa de recorrência e diminui a expectativa de vida em cinco anos em até 30%. É um achado importante em exames de imagem quando se estadia pacientes com cânceres de cabeça e pescoço, já que não pode ser avaliado somente pelo cirurgião. Todavia, é uma alteração que frequentemente passa despercebida. No presente estudo, revisamos trabalhos científicos da literatura médica sobre os achados de imagem e os aspectos fisiopatológicos desse tipo de disseminação e analisamos 10 exames de imagem com sinais radiológicos de disseminação perineural oriundos de um hospital-escola brasileiro.

Perineural spread of malignant head and neck tumors: review of the literature and analysis of cases treated at a teaching hospital / Disseminação perineural de tumores malignos de cabeça e pescoço: revisão da literatura e análise de casos de um hospital-escola

Abstract Perineural tumor spread refers to the migration of tumor cells along nerve tissues. It worsens the prognosis, increases the recurrence rate, and diminishes 5-year survival by up to 30%. It is an important finding on imaging tests employed in the staging of patients with head and neck cancers, because it cannot be assessed by the surgeon alone. Nevertheless, it is frequently overlooked. In this study, we reviewed the literature regarding the imaging and pathophysiological aspects of this type of dissemination. We also analyzed ten imaging tests, obtained from a teaching hospital in Brazil, in which there were radiological signs of perineural tumor spread.

Resumo Disseminação perineural de tumores refere-se à extensão de células tumorais ao longo do tecido dos nervos. Acarreta um pior prognóstico, aumenta a taxa de recorrência e diminui a expectativa de vida em cinco anos em até 30%. É um achado importante em exames de imagem quando se estadia pacientes com cânceres de cabeça e pescoço, já que não pode ser avaliado somente pelo cirurgião. Todavia, é uma alteração que frequentemente passa despercebida. No presente estudo, revisamos trabalhos científicos da literatura médica sobre os achados de imagem e os aspectos fisiopatológicos desse tipo de disseminação e analisamos 10 exames de imagem com sinais radiológicos de disseminação perineural oriundos de um hospital-escola brasileiro.

Lacrimal Gland Involvement in Blepharophimosis-Ptosis-Epicanthus Inversus Syndrome.

PURPOSE: To describe the involvement of the lacrimal gland (LG) in blepharophimosis-ptosis-epicanthus inversus syndrome (BPES). DESIGN: Observational, cross-sectional study. PARTICIPANTS: Twenty-one patients with BPES (10 female, 11 male) aged on average 15 years (range, 2-39 years), from 3 Brazilian medical centers and 1 Portuguese medical center. METHODS: Patients had their ocular surface evaluated with slit-lamp biomicroscopy, and tear production quantified with the Schirmer test I. The LG volumes were measured on computed tomography (CT) scans in the BPES sample and in a group of age-matched subjects imaged for nonorbital diseases. Sixteen patients were screened for mutations in the FOXL2 gene. MAIN OUTCOME MEASURES: Lacrimal meniscus height, Schirmer test I, presence of superficial punctate keratopathy (SPK), LG volume, and molecular analysis of the FOXL2 gene. RESULTS: Absence of LG was detected bilaterally in 9 patients (42.8%) and unilaterally in 2 patients (9.5%). When considering only patients with measurable LG, the median volume was 0.22 cm3 in the right eye (range, 0.06-0.36 cm3) and 0.24 cm3 in the left eye (range, 0.08-0.34 cm3). These values were significantly lower than those for the age-matched controls (median = 0.54 right eye and 0.53 left eye; P < 0.05). There was a significant association between deficiency of tear production and LG volume reduction and agenesis. Molecular analysis of the FOXL2 gene revealed the presence of 8 distinct mutations, 4 of them novel ones. A significant reduction of LG size or agenesis was associated with mutations affecting protein size (due to underlying changes in the stop codon location) or the DNA-binding forkhead domain (Fisher exact test, P = 0.021). In 3 probands, the underlying genetic defect was not found. CONCLUSIONS: This is the first study reporting LG volumes in BPES, describing a significant number of patients with LG agenesis. The association between alacrima and BPES is not incidental, and a thorough evaluation of tear production is recommended especially if ptosis surgery is planned.

Hyperostosis Following Orbital Exenteration.

PURPOSE: To describe CT scan findings following orbital exenteration in 27 patients and to identify the factors involved in the development of post exenteration hyperostosis. METHODS: Noncomparative case series. The authors reviewed the charts of 27 patients ranging in age from 33 to 99 years, who underwent unilateral exenteration at King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia and at the School of Medicine of Ribeirão Preto, University of São Paulo, Brazil. Data regarding patient demographics, surgical procedure, clinical diagnosis, and preoperative and postoperative CT imaging of the orbits were obtained. The relationship between hyperostosis and postoperative time, gender, age, adjuvant radiotherapy, and cavity coverage was evaluated by multivariate stepwise logistic regression. RESULTS: Seventeen (73.9 %) orbits had postoperative orbital hyperostosis. No soft tissue masses were detected in the affected orbits except in 2 cases with tumor recurrence. The only factor associated with hyperostosis was immediate intraoperative socket rehabilitation (odds ratio = 0.13, 95% confidence interval: 0.01-0.89). There was an 87.0% lower chance of hyperostosis in patients whose socket was covered with musculocutaneous flaps. Sequential CT scans showed that orbital hyperostosis followed a specific pattern. Initially, bone thickening appeared as either uniform or undulating endo-osteal minimal thickening along the roof and then on the lateral and medial walls. More advanced hyperostosis had a laminated/lamellated appearance progressing to homogeneous and diffuse circumferential bone thickening. New bone formation and bone overgrowth were late findings. Hyperostosis extended to involve the adjacent facial bone, more obviously on the maxilla. Some patients had minimal thickening of the adjacent frontal and squamous temporal bone. Over-pneumatization of the paranasal sinuses was evident in all cases of hyperostosis. CONCLUSIONS: Development of hyperostosis following exenteration is not rare. Radiologists and surgeons should be aware of the need to monitor the orbital healing process closely to avoid misdiagnoses of tumor recurrence/radionecrosis or infection. Obliteration of the orbital cavity with musculocutaneous flaps significantly reduces the chances of bone hyperostosis.

Giant dacryocystocele and congenital alacrimia in lacrimo-auriculo-dento-digital syndrome.

The lacrimo-auriculo-dento-digital syndrome, also known as Levy-Hollister syndrome, is a rare multiple congenital dysplasia characterized by malformation of the lacrimal apparatus and by aural, dental, and digital anomalies. Since the first report in 1973, different clinical findings such as urogenital malformations and facial dysmorphism have been described in the affected patients, showing that the phenotypic spectrum of the syndrome is broad. The authors report for the first time an association among giant dacryocystocele, alacrima, and agenesis of the lacrimal puncta in a patient with lacrimo-auriculo-dento-digital syndrome.

Orbital invasion by squamous cell carcinoma arising in multiple epidermoid cysts.

Epidermal or epidermoid cysts usually are benign, solitary-growing masses located in the mid- or lower dermis. They are believed to derive from pilosebaceous units and are lined with an epidermis-like epithelium including a granular cell layer. The occurrence of multiple epidermal cysts on the scalp of nonsyndromic patients is extremely rare. Although the presence of squamous cell carcinoma in the wall of an isolated epidermoid cysts is well documented in the dermatological literature,, the authors are not aware of any article in the English literature describing orbital invasion by a carcinoma developed in isolated or multiple epidermoid cysts.