Liquid biopsy using cfDNA to predict radiation therapy response in solid tumors

Purpose@#This study explored the potential feasibility of cell-free DNA (cfDNA) in monitoring treatment response through the measurement of chromosomal instabilities using I-scores in the context of radiation therapy (RT) for other solid tumors. @*Materials and Methods@#This study enrolled 23 patients treated with RT for lung, esophageal, and head and neck cancer. Serial cfDNA monitoring was performed before RT, 1 week after RT, and 1 month after RT. Low-depth whole-genome sequencing was done using Nano kit and NextSeq 500 (Illumina Inc.). To measure the extent of genome-wide copy number instability, I-score was calculated. @*Results@#Pretreatment I-score was elevated to more than 5.09 in 17 patients (73.9%). There was a significant positive correlation between the gross tumor volume and the baseline I-score (Spearman rho = 0.419, p = 0.047). The median I-scores at baseline, post-RT 1 week (P1W), and post-RT 1 month (P1M) were 5.27, 5.13, and 4.79, respectively. The I-score at P1M was significantly lower than that at baseline (p = 0.002), while the difference between baseline and P1W was not significant (p = 0.244). @*Conclusion@#We have shown the feasibility of cfDNA I-score to detect minimal residual disease after RT in patients with lung cancer, esophageal cancer, and head and neck cancer. Additional studies are ongoing to optimize the measurement and analysis of I-scores to predict the radiation response in cancer patients.

Higher thoracic radiation dose is beneficial in patients with extensive small cell lung cancer

PURPOSE: The effectiveness of thoracic radiation therapy (TRT) in extensive-stage small cell lung cancer (ES-SCLC) patients is increasingly reported, but there is no definite consensus on its application. The aim of this study was to identify factors associated with better outcomes of TRT among patients with ES-SCLC, focusing on whether a higher TRT dose could improve treatment outcome. MATERIALS AND METHODS: The medical records of 85 patients with ES-SCLC who received TRT between January 2008 and June 2017 were retrospectively reviewed. Eligibility criteria were a biological effective dose with α/β = 10 (BED) higher than 30 Gy₁₀ and completion of planned radiotherapy. RESULTS: During a median follow-up of 5.3 months, 68 patients (80.0%) experienced disease progression. In univariate analysis, a BED >50 Gy₁₀ was a significant prognostic factor for overall survival (OS; 40.8% vs. 12.5%, p = 0.006), progression-free survival (PFS; 15.9% vs. 9.6%, p = 0.004), and intrathoracic PFS (IT-PFS; 39.3% vs. 20.5%, p = 0.004) at 1 year. In multivariate analysis, a BED >50 Gy₁₀ remained a significant prognostic factor for OS (hazard ratio [HR] = 0.502; 95% confidence interval [CI], 0.287–0.876; p = 0.015), PFS (HR = 0.453; 95% CI, 0.265–0.773; p = 0.004), and IT-PFS (HR = 0.331; 95% CI, 0.171–0.641; p = 0.001). Response to the last chemotherapy was also associated with better OS in both univariate and multivariate analysis. CONCLUSION: A TRT dose of BED >50 Gy₁₀ may be beneficial for patients with ES-SCLC. Further studies are needed to select patients who will most benefit from high-dose TRT.

Presumptive Diagnosis of Recurrent Herpes-induced Anterior Uveitis with Acute Hypopyon

PURPOSE: We report an unusual case of presumptive diagnosis of herpes-induced anterior uveitis with acute hypopyon after trauma. CASE SUMMARY: A 82-year-old male was diagnosed with herpes keratitis due to dendritic keratitis in the left eye, and the lesion disappeared after antiviral treatment. However, 1 year later, the patient visited again with visual loss, pain, and tearing of the left eye after trauma. At the examination, best-corrected visual acuity was counting fingers and the intraocular pressure was 27 mmHg in the left eye. Slit-lamp examination revealed corneal epithelial erosion, moderate corneal edema, and prominent inflammation with 2 mm high hypopyon in the anterior chamber. We thought that bacterial endophthalmitis had rapidly progressed after trauma, so we performed bacterial cultures and an intravitreal antibiotics injection. Considering the clinical manifestations of lesions and herpes keratitis in the past, we could not exclude herpes virus infection. Cultures were negative and the symptoms improved, so the antiviral treatment was gradually reduced and stopped at 2 months. However, recurrence was observed on day 5 after stopping antiviral therapy. We therefore assumed that recurrent herpes virus caused anterior uveitis, and then, antiviral and steroid therapy was resumed. The patient subsequently showed improvement in his symptoms and recovered his visual acuity. CONCLUSIONS: When acute hypopyon is observed in the anterior chamber after trauma, not only bacterial iritis and endophthalmitis but also viral-induced anterior uveitis should be considered in the differential diagnosis.

The Neuro-ophthalmic Presentation of Intracranial Aneurysms

PURPOSE: To investigate the neuro-ophthalmic diagnosis and clinical manifestations of intracranial aneurysm. METHODS: A retrospective survey of 33 patients who were diagnosed with intracranial aneurysm and underwent neuro-ophthalmic examination from April 2008 to December 2016. Frequency of the first diagnosis of intracranial aneurysm in ophthalmology, neuro-ophthalmic diagnosis, location of intracranial aneurysm, examination of intracranial aneurysm rupture, and neurologic prognosis of Terson's syndrome patients were analyzed by image examination, neurosurgery, and ophthalmology chart review. RESULTS: Of the 33 patients, most patients (n = 31, 94%) were diagnosed with intracranial aneurysm at the neurosurgical department and only 2 patients were diagnosed initially at the ophthalmology department. Causes and association were: Terson's syndrome (n = 10, 30%), third cranial nerve palsy (n = 10, 30%), internclear ophthalmoplegia (n = 4, 12%), visual field defect (n = 3, 9%), optic atrophy (n = 3, 9%), sixth cranial nerve palsy (n = 2, 6%), and nystagmus (n = 1, 3%). The location of intracranial aneurysms were: anterior communicating artery (n = 13, 39%), medial communicating artery (n = 12, 36%), and posterior communicating artery (n = 5, 15%). Ten of 33 patients had Terson's syndrome, and 6 patients (60%) with Terson's syndrome had apermanent neurological disorder such as agnosia, gait disorder and conduct disorder. CONCLUSIONS: Third cranial nerve palsy was the most common neuro-ophthalmic disease in patients presenting with intracranial aneurysm. The neuro-ophthalmic prognoses for those diseases were relatively good, but, if Terson's syndrome was present, neurological disorders (agnosia, gait disorder, conduct disorder) were more likely to remain after treatment.

Bilateral Macular Infarction in Primary Antiphospholipid Syndrome

PURPOSE: We report a rare case of bilateral macular infarction as an ocular presenting sign of primary antiphospholipid syndrome. CASE SUMMARY: A 29-year-old woman who had undergone a cesarean section for chorioamnionitis in the department of Obsterics was referred to the department of ophthalmology for bilateral visual loss. At examination, best-corrected visual acuity (BCVA) of the right eye was counting fingers, and for the left was 0.05. Fundus examination revealed extensive macular edema and cotton-wool spots in both eyes. We performed hematologic tests including thrombophilia examination. Antinuclear antibody and rheumatoid factor were negative but lupus anticoagulant presented high titers on two occasions 12 weeks apart. She was administered sub-Tenon's injections of triamcinolone acetonide 50 mg/week in both eyes under the diagnosis of bilateral macular arteriolar occlusion in primary antiphospholipid syndrome. Her BCVA remained 0.025 in her right eye and improved to 0.125 in her left eye. CONCLUSIONS: Macular infarction is an uncommon but severe complication of antiphospholipid syndrome. Early and regular fundus exam in patients with antiphospholipid syndrome is necessary to avoid progression of severe ocular complications.

A Case of Acute Interstitial Keratitis in a Patient with Acquired Syphilis

PURPOSE: To report a case of acute interstitial keratitis as the first clinical sign in a patient with latent syphilis. CASE SUMMARY: A 23-year-old female presented with visual impairment and discomfort in her right eye that developed 3 days earlier. The visual acuity in the right eye was 20/200 and corrected to 20/100, and slit lamp examination showed round sub-epithelial opacification in the central cornea with stromal edema and neovascularization on the cornea of the right eye. Whole body tests including serological tests were performed. Under the suspicion of acute interstitial keratitis, topical antibiotics and steroids were applied 4 times a day initially. Serological tests were reactive for venereal disease research laboratory test (VDRL). Under the suspicion of acute interstitial keratitis due to syphilis, fluorescent treponemal antibody absorption test IgM/IgG (FTA-ABS IgM/IgG) was performed; a positive result for FTA-ABS IgG led to diagnosis of acute interstitial keratitis with latent syphilis. During treatment, systemic doxycycline 200 mg for 4 weeks with topical antibiotics and steroids were administered, the opacity and edema of the cornea regressed after 2 weeks of treatment, and visual acuity in the patient's right eye improved to 20/20. CONCLUSIONS: We report an unusual case of acute interstitial keratitis as the first clinical manifestation of latent syphilis in an immunocompetent patient.