The Differentiation between Progressive Disease and Treatment-Induced Effects with Perfusion-Weighted Arterial Spin-Labeling in High-Grade Gliomas.

BACKGROUND AND PURPOSE: Treatment-induced effects are difficult to differentiate from progressive disease in radiologically progressing diffuse gliomas after treatment. This retrospective, single-center cohort study investigated the diagnostic value of arterial spin-labeling perfusion in differentiating progressive disease from treatment-induced effects in irradiated patients with a high-grade glioma. MATERIALS AND METHODS: Adults with a high-grade glioma diagnosed between January 1, 2012, and December 31, 2018, with a new or increasing contrast-enhancing lesion after radiotherapy with or without chemotherapy and arterial spin-labeling were consecutively included. Arterial spin-labeling is part of the routine follow-up examinations of patients with a high-grade glioma. The outcomes of progressive disease or treatment-induced effects were defined after histologic or >6 weeks radiologic follow-up. Two neuroradiologists graded the arterial spin-labeling visually as negative (hypointense to gray matter) or positive (iso-/hyperintense). Additionally, the arterial spin-labeling signal intensity in the enhancing lesion was compared quantitatively with that in the contralateral normal brain. Diagnostic test properties and the Cohen κ inter- and intrarater reliability were determined. We present data according to the time after radiation therapy. RESULTS: We included 141 patients with 173 lesions (median age, 63 years). Ninety-four (54%) lesions showed treatment-induced effects, and 79 (46%), progressive disease. For visual analysis, the ORs of an arterial spin-labeling positive for progressive disease in the group with progression within 3, between 3 and 6, and after 6 months after radiation therapy were 0.65 (95% CI, 0.28-1.51; P = .319), 3.5 (95% CI, 0.69-17.89; P = .132), and 6.8 (95% CI, 1.48-32; P = .014). The areas under the curve were 0.456, 0.652, and 0.719. In quantitative analysis, the areas under the curve were 0.520, 0.588, and 0.587 in these groups. Inter- and intrarater reliability coefficients were 0.67 and 0.62. CONCLUSIONS: Arterial spin-labeling performed poorly in differentiating progressive disease from treatment-induced effects in high-grade gliomas within 6 months after radiation therapy, with fair performance after this period. Arterial spin-labeling may need to be combined with other imaging features and clinical information for better performance.

OX40 Agonist BMS-986178 Alone or in Combination With Nivolumab and/or Ipilimumab in Patients With Advanced Solid Tumors.

PURPOSE: This phase I/IIa study (NCT02737475) evaluated the safety and activity of BMS-986178, a fully human OX40 agonist IgG1 mAb, ± nivolumab and/or ipilimumab in patients with advanced solid tumors. PATIENTS AND METHODS: Patients (with non-small cell lung, renal cell, bladder, other advanced cancers) received BMS-986178 (20-320 mg) ± nivolumab (240-480 mg) and/or ipilimumab (1-3 mg/kg). The primary endpoint was safety. Additional endpoints included immunogenicity, pharmacodynamics, pharmacokinetics, and antitumor activity per RECIST version 1.1. RESULTS: Twenty patients received BMS-986178 monotherapy, and 145 received combination therapy in various regimens (including two patients receiving nivolumab monotherapy). With a follow-up of 1.1 to 103.6 weeks, the most common (≥5%) treatment-related adverse events (TRAEs) included fatigue, pruritus, rash, pyrexia, diarrhea, and infusion-related reactions. Overall, grade 3-4 TRAEs occurred in one of 20 patients (5%) receiving BMS-986178 monotherapy, six of 79 (8%) receiving BMS-986178 plus nivolumab, zero of two receiving nivolumab monotherapy, six of 41 (15%) receiving BMS-986178 plus ipilimumab, and three of 23 (13%) receiving BMS-986178 plus nivolumab plus ipilimumab. No deaths occurred. No dose-limiting toxicities were observed with monotherapy, and the MTD was not reached in either the monotherapy or the combination escalation cohorts. No objective responses were seen with BMS-986178 alone; objective response rates ranged from 0% to 13% across combination therapy cohorts. CONCLUSIONS: In this study, BMS-986178 ± nivolumab and/or ipilimumab appeared to have a manageable safety profile, but no clear efficacy signal was observed above that expected for nivolumab and/or ipilimumab.

Ecthyma gangrenosum caused by Pseudomonas aeruginosa in a patient with astrocytoma treated with chemotherapy.

Ecthyma gangrenosum, presenting as embolic lesions caused by Pseudomonas aeruginosa infection, has distinct pathognomonic features and a high mortality rate in patients with bacteremia, but when recognized early is easily treated. In this case report we describe this disseminated infection in an adult patient treated with chemotherapy for an astrocytoma.

Combined therapy for thyroid squamous cell carcinoma.

BACKGROUND.: Squamous carcinoma of the thyroid is a rare aggressive disease, resulting in poor prognosis. METHODS AND RESULTS.: We combined cisplatin with paclitaxel on a weekly basis as induction therapy, achieving a high cumulative dose, in a patient with squamous cell tumor of the thyroid with arterial encasement. After surgery, pathologic examination confirmed a complete resection of the primary tumor with clear margins, revealing a successful induction treatment with chemotherapy. CONCLUSIONS.: Our patient now has a recurrence-free survival of >20 months, longer than the mean survival described in the literature.

Ecthyma gangrenosum caused by Pseudomonas aeruginosa in a patient with astrocytoma treated with chemotherapy.

Ecthyma gangrenosum, presenting as embolic lesions caused by Pseudomonas aeruginosa infection, has distinct pathognomonic features and a high mortality rate in patients with bacteremia, but when recognized early is easily treated. In this case report we describe this disseminated infection in an adult patient treated with chemotherapy for an astrocytoma.