Salvage boron neutron capture therapy for pediatric patients with recurrent diffuse midline glioma.

PURPOSE: Pediatric diffuse malignant glioma located in the brainstem was officially named "diffuse midline glioma" (DMG) by the World Health Organization in 2016. For this disease, radical surgery is not beneficial, and the only major treatment strategy is radiotherapy. However, the dose limitations to brainstem tissue mean that treatment by radiotherapy can only control and not eradicate the tumors, and there is no effective treatment for recurrence, resulting in short overall survival of 6-12 months. This paper reports our experience with boron neutron capture therapy (BNCT), a new treatment process, and its efficacy in treating children with recurrent DMG. METHODS: From September 2019 to July 2022, we treated 6 children affected by recurrent DMG. With the collaboration of Taipei Veteran General Hospital (TVGH) and National Tsing-Hua University (NTHU), each patient received two sessions of BNCT within 1 month. RESULTS: Among the six patients, three showed partial response and the rest had stable disease after the treatment. The overall survival and recurrence-free survival duration after treatment were 6.39 and 4.35 months, respectively. None of the patients developed severe side effects, and only one patient developed brain necrosis, which was most likely resulted from previous hypofractionated radiotherapy received. CONCLUSION: BNCT elicited sufficient tumor response with low normal tissue toxicity; it may benefit vulnerable pediatric patients with DMG.

Progressive muscle loss is an independent predictor for survival in locally advanced oral cavity cancer: A longitudinal study.

BACKGROUND AND PURPOSE: To investigate the association between progressive muscle loss and survival outcomes of patients with advanced-stage oral squamous cell carcinoma (OSCC) undergoing surgery and adjuvant (chemo)radiotherapy. METHODS: We analyzed the computed tomography (CT) scans of 155 patients with stage III-IVB OSCC at baseline, at simulation CT for radiotherapy, and at 3- and 9-months post-treatment. Skeletal muscle index (SMI) was measured using CT at the C3 vertebral level. The predictors of overall survival (OS) and recurrence-free survival (RFS) were evaluated using Cox regression models. RESULTS: The median follow-up period was 75.0 months. Fifty-one patients (32.9%) developed recurrence, with the median time from the fourth CT to recurrence being 9.1 months. The SMI progressively decreased from baseline to simulation CT by 1.1% (p = 0.006), to 3 months post-treatment by 5.1% (p < 0.001), and to 9 months post-treatment by 15.6% (p < 0.001) in patients developing recurrence. Patients without recurrence lost SMI at the simulation CT by 0.7% (p = 0.001) and at 3 months post-treatment by 2.1% (p < 0.001); their SMI returned to the baseline level at 9 months post-treatment. SMI changes were weakly correlated with changes in body mass index (BMI) (Spearman ρ, 0.13; p = 0.11). In multivariate analysis, SMI changes (per 5% decrease) were independently associated with significantly worse OS (hazard ratio: 1.88, 95% confidence interval: 1.58-2.23; p < 0.001) and RFS (hazard ratio: 1.89, 95% confidence interval: 1.61-2.20; p < 0.001). CONCLUSION: Progressive muscle loss was independently associated with worse survival outcomes in patients with stage III-IVB OSCC. Muscle loss might not be detected by changes in BMI.

Sarcopenia and Systemic Inflammation Synergistically Impact Survival in Oral Cavity Cancer.

OBJECTIVES: Sarcopenia and systemic inflammation can affect survival of advanced-stage oral squamous cell carcinoma (OSCC) patients; however, their reciprocal associations with survival outcomes are yet to be investigated. STUDY DESIGN: Retrospective review at a tertiary cancer center. METHODS: Patients with stage III-IVB OSCC that underwent surgery and (chemo)radiotherapy at our institution between 2010 and 2015 were reviewed. Skeletal muscle index (SMI) was assessed using computed tomography scans at the C3 vertebra. Sarcopenia was defined at the lowest sex-specific tertile for SMI. Systemic inflammation was estimated using the modified Glasgow prognostic score (mGPS), which ranges from 0 to 2 based on serum C-reactive protein and albumin levels. The predictors of overall survival (OS) were evaluated using Cox regression models. RESULTS: A total of 174 patients were included in the study. The cut-off values for sarcopenia were set at SMI <52.4 cm2 /m2 (men) and < 36.2 cm2 /m2 (women) corresponding to the lowest sex-specific tertile. An mGPS 1-2 was independently associated with sarcopenia (odds ratio: 2.05; 95% confidence interval: 1.06-3.97; P = .03). On multivariate analysis for OS, sarcopenia and mGPS 1-2 independently predicted OS (hazard ratio: 2.12; 95% confidence interval: 1.17-3.85; P = .01 and hazard ratio: 7.85; 95% confidence interval: 3.7-16.65; P < .001, respectively). Patients with both sarcopenia and mGPS 1-2 (vs. neither) had worse OS (hazard ratio: 16.80; 95% confidence interval: 6.01-46.99; P < .001). CONCLUSIONS: Sarcopenia and systemic inflammation may exert a negative synergistic prognostic impact in advanced-stage OSCC patients. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:E1530-E1538, 2021.

Over expression of CDK4 and MDM2 in a patient with recurrent ALK-negative mediastinal inflammatory myofibroblastic tumor: A case report.

RATIONALE: The diagnosis of anaplastic lymphoma kinase (ALK)-negative inflammatory myofibroblastic tumors (IMT) remains challenging because of their morphological resemblance with spindle cell sarcoma with myofibroblastic characteristics. PATIENT CONCERNS: A 69-year-old female patient presented with loco-regional recurrent IMT several times within 8 years after primary treatment and neck lymph node metastasis 3.5 years after last recurrence. DIAGNOSIS: The primary, recurrence, and lymph node metastasis lesions were diagnosed as ALK-negative IMTs based on the histopathological features. INTERVENTIONS: Biopsy samples were obtained during repeated surgeries and evaluated for genomic alterations during first and recurrent presentations. The evaluation was done using pathway-driven massive parallel sequencing, and genomic alterations between primary and recurrent tumors were compared. OUTCOMES: Copy number gains and overexpression of mouse double minute 2 homolog (MDM2) and cyclin dependent kinase 4 (CDK4) were observed in the primary lesion, and additional gene amplification of Discoidin Domain Receptor Tyrosine Kinase 2 (DDR2), Succinate Dehydrogenase Complex II subunit C (SDHC), and thyroid stimulating hormone receptor (TSHR) Q720H were found in the recurrent tumors. Metastases to the neck lymph node were observed 3.5 years after recurrence. LESSONS: Our results indicated genetic evolution in a microscopically benign condition and highlighted the importance of molecular characterization of fibro-inflammatory lesions of uncertain malignant potential.

Image-guided study of inter-fraction and intra-fraction set-up variability and margins in reverse semi-decubitus breast radiotherapy.

BACKGROUND: This study aimed to evaluate the inter-fraction set-up error and intra-fraction motion during reverse semi-decubitus (RSD) breast radiotherapy, and to determine a planning target volume (PTV) margin. MATERIAL AND METHODS: Pre- and post-treatment cone-beam computed tomography (CBCT) scans were prospectively acquired at fractions 1, 4, 7, 8, 11, and 14 for 30 patients who underwent RSD breast radiotherapy. Online correction for initial set-up error greater than 5 mm or 2° was performed and post-correction CBCT was acquired. An off-line analysis was performed to quantify initial and residual inter-fraction set-up errors and intra-fraction motion in three-dimensions. Patient inter-fraction errors were analysed for time trends during the course of radiotherapy. PTV margins were calculated from the systematic and random errors. RESULTS: The initial inter-fraction population systematic errors were 1.8-3.3 mm (translation) and 0.5° (rotation); random errors were 1.8-2.1 mm (translation) and 0.3-0.5° (rotation). After online correction, the residual inter-fraction population systematic errors were 1.2-1.8 mm (translation) and 0.3-0.4° (rotation); random errors were 1.4-1.6 mm (translation) and 0.3-0.4° (rotation). Intra-fraction population systematic and random errors were ≤ 1.3 mm (translation) and ≤ 0.2° (rotation). The magnitude of inter-fraction set-up errors in the anterior-posterior direction, roll, and yaw were significantly correlated with higher body weight and body mass index (BMI). The inter-fraction set-up error did not change significantly as a function of time during the course of radiotherapy. The magnitude of intra-fraction motion was not correlated with patient characteristics and treatment time. The total PTV margins accounting for pre-correction and intra-fraction errors were 6.5-10.2 mm; those accounting for post-correction and intra-fraction errors were 4.7-6.3 mm. CONCLUSIONS: CBCT is an effective modality to evaluate and improve the inter-fraction set-up reproducibility in RSD breast radiotherapy, particularly for patients with higher BMI. Intra-fraction motion was minimal during RSD breast radiotherapy.

Guideline and preliminary clinical practice results for dose specification and target delineation for postoperative radiotherapy for oral cavity cancer.

BACKGROUND: Surgery followed by radiotherapy (RT) is indicated for patients with high-risk oral cavity cancer (OCC). Based on multi-institutional reports, we developed a guideline for postoperative RT for patients with OCC. METHODS: A multidisciplinary OCC team was recruited to develop a questionnaire concerning details of risk-factor categorization, target delineation, and dose specification. Thirty-one radiation oncologists from 18 institutions completed the questionnaire, and data were subjected to extensive review to establish the guideline by expert meeting. In this study, we also report the results for patients treated in accordance with the guideline at our institution between 2007 and 2011. RESULTS: Forty-one patients received RT compatible with this guideline with a median 26.8-month follow-up. Thirty-two patients (78%) remained disease-free, 6 (15%) developed locoregional recurrence (4 in-field, 1 marginal, and 1 out-field) and 4 (10%) developed distant metastasis. The overall 2-year survival rate was 86.7%. CONCLUSION: This guideline is promising and should be validated and refined in further clinical practice.

Comparison of radiotherapy strategies for locally advanced hypopharyngeal cancer after resection and ileocolic flap reconstruction.

CONCLUSION: IMRT provided better conformity, less toxicity and better function restoration for advanced hypopharyngeal carcinoma after major surgery with ileocolic flap reconstruction. OBJECTIVES: To compare the results of adjuvant conventional radiotherapy (2DRT) with intensity modulated radiation therapy (IMRT) for locally advanced hypopharyngeal cancer after resection and ileocolic free flap reconstruction and to design treatment plans for those two modalities plus 3D conformal radiotherapy (3DCRT) for dose distribution comparison. METHODS: 13 locally advanced hypopharyngeal cancer patients were enrolled, 8 treated with 2DRT and 5 with IMRT. Different plans were planned for 3 IMRT-treated patients for comparing dose distribution. RESULTS: After major surgery, patients treated with IMRT had less toxicity and better functional restoration than those with 2DRT. IMRT and 3DCRT both showed lower dose to the spinal cord than did 2DRT. Only IMRT showed reduced dose to ileocolic flap.