Lukas Käsmann

Multimodal Anti-tumor Approaches Combined with Immunotherapy to Overcome Tumor Resistance in Esophageal and Gastric Cancer

Upper gastrointestinal malignancies are associated with a high disease burden worldwide, and esophageal and gastric cancers represent the most common entities. Given a lack of early characteristic symptoms and potent screening instruments, the majority of patients present with advanced disease at the time of diagnosis. Complete surgical resection is a first-line curative option, and multimodal approaches involving chemotherapy and radiotherapy further improve patient prognosis. However, response to standard adjuvant and neoadjuvant treatments remains low, and new strategies are warranted to increase tumor control rates. Immunotherapy is emerging in various cancer entities and may be successfully combined with standard therapeutic regimens to improve patient outcome. For the purpose of this review we aimed to assess combined approaches of immunotherapy and standard treatment options such as chemotherapy, radiotherapy and surgery. Current trials evaluating multimodal approaches with immunotherapy in esophageal and gastric cancer are evaluated.

Prophylactic cranial irradiation in small-cell lung cancer: update on patient selection, efficacy and outcomes

Over 10% of small-cell lung cancer (SCLC) patients have brain metastases (BM) at initial diagnosis; more than 50% will develop BM within 2 years. BM are detected in up to 80% of all patients at autopsy. After primary treatment, prophylactic cranial irradiation (PCI) has been established as standard of care in SCLC patients responding to initial therapy. Based on level I evidence, PCI significantly decreases the risk of intracranial relapse and shows a modest survival benefit after 3 years. However, the role of PCI in defined patient subgroups such as resected SCLC, elderly and extensive stage patients with access to magnetic resonance imaging surveillance and stereotactic radiotherapy is yet to be fully clarified. Furthermore, strategies to effective prevention of neurocognitive decline after PCI remain unclear. All these factors significantly impact treatment decision making and should be evaluated in prospective settings. New concepts such as hippocampal avoidance and drug neuroprotection prevent chronic neurocognitive effects reducing treatment-related side effects of PCI. The aim of this review is to present a summary and update of the latest evidence for patient selection, efficacy and outcome of PCI.

Chemoradiotherapy of stage III small-cell lung cancer: Can we further optimize multimodal treatment of N3 disease based on current evidence?

The NCCN guidelines recommend early concurrent hyperfractionated accelerated platin-based chemoradiotherapy (CRT) for limited stage small cell lung cancer (LS-SCLC); thoracic irradiation (TRT) starting with the first or second chemotherapy cycle as treatment standard in patients with UICC 8th edition stages I-IIIA-C. However, general adoption of hyperfractionated accelerated TRT in clinical routine remains relatively low. The recently published CONVERT trial demonstrated non-significant survival outcomes in the twice-daily vs. once-daily CRT arms. However, an unplanned analysis of the previously underrepresented subgroup of patients with N3 disease surprisingly showed a substantial survival benefit with a 2-year (40% vs. 18.8%) and 5-year survival (18.4% vs. 3.1%) in the twice-daily vs. once-daily groups, respectively (overall HR 2.67 95% CI 1.59-4.49; p=0.0002). Although unplanned, this aspect elicits further validation. This article is protected by copyright. All rights reserved.

Prophylactic Cranial Irradiation for Patients with Small Cell Lung Cancer in Germany: Pattern of Care Survey

Background/Aim: The general pattern of care regarding the application of prophylactic cranial irradiation (PCI) in small cell lung cancer (SCLC) patients in Germany has not been previously evaluated. This survey was conducted to assess patterns of care. Patients and Methods: Radiation oncology institutions in Germany were surveyed via an anonymous online questionnaire sent by e-mail to member institutions of the German Society for Radiation Oncology. Results: A total of 95 responses were received (29% response rate). Eighty-eight percent of all responders recommended a PCI total dose of 30Gy delivered in 15 daily fractions. Overall, 11 and 38% of the respondents applied PCI simultaneously with chemo- and radiotherapy, respectively. A quarter of respondents offered hippocampal-avoidance PCI and followed their patients with serial brain imaging. Conclusion: PCI with a total dose of 30 Gy in 15 daily fractions, without neuropsychological testing and hippocampus-avoidance, delivered after completion of primary multimodal treatment remains standard in Germany.