Florian Huemer

Anti-Hu Antibody Associated Paraneoplastic Cerebellar Degeneration in Head and Neck Cancer

BackgroundParaneoplastic syndromes are most frequently associated with small cell lung carcinoma, hematologic and gynecologic malignancies while reports in head and neck cancer are rare.Case presentationWe present the case of a 60-year old female patient who developed paraneoplastic cerebellar degeneration upon locoregional recurrence of a poorly differentiated spindle cell carcinoma of the nasal cavity and paranasal sinus. The neurological symptoms, especially ataxia, stabilized after resection of tumor recurrence and concomitant chemoradiotherapy whereas anti-Hu-antibodies remained positive. Despite the unfavorable prognosis of paraneoplastic neurological disorders associated with onconeural antibodies, the patient achieved long-standing stabilization of neurological symptoms.ConclusionWe report the first patient with anti-Hu antibodies and paraneoplastic cerebellar degeneration associated with a spindle cell carcinoma of the head and neck. We recommend that evaluation of neurological symptoms in patients with this tumor entity should also include paraneoplastic syndromes as differential diagnoses and suggest early extensive screening for onconeural antibodies.

Extensive Leptomeningeal Intracranial and Spinal Metastases in a Patient with a Supratentorial Glioblastoma Multiforme, IDH-Wildtype

BACKGROUND Glioblastoma multiforme (GBM) is usually characterized by diffuse, infiltrative growth and local tumor progression. Extensive leptomeningeal metastases are rarely observed. It is unclear which GBMs are prone to this specific growth pattern and progression, and standardized salvage treatment protocols are unavailable. CASE DESCRIPTION In a 45-year-old man without focal neurologic deficit, a right temporal GBM, IDH-wildtype (biomarkers MGMT promoter methylation negative, Ki-67 proliferation rate 70%) was diagnosed. Gross tumor resection followed by concomitant and adjuvant radiotherapy and chemotherapy with temozolomide was performed. Routine follow-up imaging 8 months later showed a right parietal meningeal tumor. Resection confirmed a distant GBM, and next-generation sequencing revealed high tumor mutational burden, high-frequency microsatellite instability, and a pharmacologically targetable KIT mutation. Complete neuraxis imaging revealed multiple contrast-enhancing tumors in the craniocervical junction and levels C7, Th8-Th11, and S1. The craniocervical tumors and the cervical spine from C1-C2 were irradiated as palliative care, and second-line combined chemotherapy and antiangiogenic therapy with irinotecan and bevacizumab was initiated, which was later changed to an immune-checkpoint blockade with pembrolizumab in combination with bevacizumab owing to tumor progression. Tumor growth was slowed, but the patient eventually developed a progressive paraparesis. Subsequent KIT-targeting tyrosine kinase inhibitor therapy with imatinib was administered for a short time. The patient died 13.8 months after initial diagnosis. CONCLUSIONS High-risk genetic profiles for GBMs prone to develop extensive leptomeningeal metastases need to be identified. Guidelines on preemptive, complete neuraxis imaging in certain patients with GBM as well as treatment guidelines need to be developed.

Impact of antibiotic treatment on immune-checkpoint blockade efficacy in advanced non-squamous non-small cell lung cancer

Introduction Despite durable responses from immune-checkpoint blockade (ICB) in a subset of patients with advanced non-small cell lung cancer (NSCLC), the majority of patients do not derive benefit from this treatment. In this analysis we evaluated the impact of concomitant administration of antibiotics during initiation of ICB on clinical outcome. Methods Advanced non-squamous NSCLC patients receiving ICB as second- or later line between 2015 and 2017 at our tertiary cancer center in Salzburg (Austria) were included. Concomitant use of antibiotics was defined as administration of antibiotics within a time frame of one month before or one month after initiation of ICB (AB+-group). Results Of the 30 patients included, 11 (36.7%) received antibiotics one month before or one month after start of ICB (AB+-group). Median PFS on ICB was in favor of the AB--group (AB-: 3.1 months [95%CI: 3.0-16.3]; AB+: 2.9 months, [95%CI: 1.9-NA]; HR=0.46 [95%CI: 0.12-0.90], p=0.031). Furthermore, median OS was significantly longer in the AB--group (AB-: 15.1 months [95%CI: 11.1-NA]; AB+: 7.5 months [95%CI: 6.3-NA]; HR=0.31 [95%CI: 0.02-0.78], p=0.026). In a multivariate analysis, the antibiotic treatment status was identified as the only parameter statistically significantly associated with PFS (p=0.028) and OS (p=0.026). Conclusions Stratification of patients according to the antibiotic treatment status is warranted in future trials investigating ICB.

Overcoming Resistance Against HER2-Targeting Agents in Fifth-Line Therapy: Is There Still a Place for Bevacizumab in HER2+ Breast Cancer?

The role of bevacizumab in breast cancer is still controversial. Several phase III trials demonstrated an improvement in terms of progression-free survival (PFS) when bevacizumab was added to standard chemotherapy. On the downside, the toxicity rate was increased and no benefit in terms of overall survival (OS) was observed. For metastatic breast cancer positive for human epidermal growth factor receptor 2 (HER2), bevacizumab in combination with paclitaxel or capecitabine is still a valid and approved treatment option according to the European Medicines Agency (EMA). The American Food and Drug Administration (FDA), in contrast, withdrew approval for bevacizumab as first-line treatment in HER2 metastatic breast cancer. Recently, the results of the AVEREL trial, which investigated bevacizumab in combination with docetaxel and trastuzumab as first-line therapy in HER2þ breast cancer, were published. The primary endpoint of investigator-assessed PFS was not met although evaluation by an independent review committee indicated potential activity. There’s a striking variation of individual responses to bevacizumab-containing and an urgent need for biomarkers to select those patients who benefit from anti-angiogenic treatment. Here we report about a 55-year-old woman with HER2þ breast cancer highly symptomatic because of extensive pulmonary involvement. Despite heavy pretreatment, the combination of docetaxel, trastuzumab, and bevacizumab caused significant response. Because the patient had already progressed during both taxaneand trastuzumabbased therapy, a clear connection between treatment success and the addition of antievascular endothelial growth factor (VEGF) antibody can be shown.