Specifying WHO Recommendation: Moving toward Disease-Specific Guidelines

Introduction: The World Health Organization (WHO) explicitly recommends the integration of palliative care (PC) early in the disease trajectory as part of the WHO definition of PC. Our comprehensive cancer center decided: (1) to include this recommendation in the administrative directives for principles of cancer care and (2) to establish a PC hospital support team. The evaluation of this approach revealed that patients with lung cancer still received PC rather late in the course of the disease. Therefore, we decided to additionally develop disease-specific standard operating procedures (SOPs) to try to overcome these deficiencies. The first SOP was completed for patients with lung cancer. Standard Operating Procedure (Consensus SOP): Specifically, the SOP states that: Specialized PC is recommended regularly for all lung cancer patients without curative treatment options, specifically patients with (i) metastasized and inoperable or (ii) locally advanced and inoperable or (iii) relapsing lung cancer. Integration of PC is recommended simultaneously to starting tumor-specific therapy. In this context, initial PC should be delivered to the patient at the same place as specific treatment, which is the interdisciplinary outpatient unit of the Center of Integrated Oncology (CIO) or an oncological ward. Discussion: This SOP for the first time presents disease-specific guidelines for PC integration into comprehensive (lung) cancer therapy by (1) defining green flags for early integration of PC and (2) recommending PC parallel to initiation of anticancer therapy. Furthermore, clear definitions are provided to delineate PC assignments. Such disease-specific algorithms should be helpful to further reduce uncertainty about the way PC can be integrated early in the course of the disease

Neoadjuvant chemoimmunotherapy as a potential therapeutic option in NSCLC UICC stage IIIA with multilevel N2 disease

Lung Cancer is still one of the leading causes for cancer related death worldwide. The determina-tion of an adequate therapeutic approach requests a precise staging, which contains computed to-mography (CT) of the thorax, positron emission tomography computed tomography (PET-CT), cerebral magnetic resonance imaging (cMRI) and pulmonary function testing as well as the pa-tient's opinion. In UICC stages I and II, if there is functional operability and technical resectabil-ity, the treatment of choice is primary surgery followed by adjuvant therapy depending on lymph node status, while patients in the metastatic stage IV, or with locally advanced, nonresectable dis-ease are more likely to receive definitive chemoradiation therapy. The UICC Stage III (8th edi-tion) combines a heterogeneous group of patients that remains the focus of discussion regarding the optimal therapeutic regimen, which ranges from primary surgical care to a neoadjuvant ther-apeutic approach, to definitive conservative treatment. Since March 2020, we have been treating a patient on an interdisciplinary basis who initially had a UICC stage IIIA multilevel N-2 pul-monary adenocarcinoma and finally underwent successful surgery after a very good response to neoadjuvant chemoimmunotherapy. Our latest follow-up showed no evidence of recurrence. Sim-ilar to current ongoing studies our case shows, that neoadjuvant immunotherapy is a reasonable alternative to conventional neoadjuvant chemotherapy

HBsAg-negative/anti-HBc-positive patients treated with rituximab: prophylaxis or monitoring to prevent hepatitis B reactivation?

Rituximab (RTX) has been classified as a drug associated with a high risk for hepatitis B virus (HBV) reactivation in HbsAg-negative/anti-HBc-positive patients. However, data on frequency of HBV reactivation are limited especially for RTX monotherapy. Several new recommendations for screening, monitoring and prophylactic antiviral treatment have been published recently. Here, we report the real-life experience in the management and reactivation rate of HbsAg-negative/anti-HBc-positive patients treated with RTX with or without chemotherapy from a large cohort and discuss our results in the light of updated recommendations

Induction therapy with Erlotinib (E) and Gemcitabine/Platinum (GP) in stage III NSCLC

Background: In 2004 we started a phase II trial in non-small lung cancer (NSCLC), stage III, with erlotinib followed by a combination with a platinum-based doublet in unselected patients to identify molecular subgroups benefitting from an EGFR targeting approach. Patients and methods: Induction with erlotinib (E, 150 mg, d1-42) was followed by three cycles of gemcitabine (G, 1250 mg/m², d1+d8, q3w) and cisplatin (P, 80 mg/m², d1, q3w). Patients with at least stable disease after E were treated with a GP + E combination. Induction was followed by surgery and radiation. The trial was conducted as a prospective, multi-center, open label, exploratory phase II study to determine pathological response rate (pRR), as well as secondary endpoints disease free survival (DFS) and overall survival (OS). Results: Of 38 prescreened patients 16 were included in the main study. Due to slow recruitment the study had to be terminated early. Combination of E and GP was well tolerated, surgery was feasible after induction therapy in 12 of 16 patients, 7/12 (58%) patients had a major pathological response (MPR). Median overall survival for patients with MPR was 57.7 months (confidence interval (CI), 37.4 to 78.0; n = 7) and for patients without MPR 11.9 months (CI, 6.4 to 17.4; n = 5). 2/16 patients had an epidermal growth factor receptor (EGFR) mutation. Conclusion: Before discovery of distinct molecular mechanisms in NSCLC our study was an attempt to identify clinical and pathological subgroups that would benefit from E induction. Two patients with an EGFR mutation were identified. MPR was a predictor of long term disease free and overall survival

A Genomics-Based Classification of Human Lung Tumors

We characterized genome alterations in 1255 clinically annotated lung tumors of all histological subgroups to identify genetically defined and clinically relevant subtypes. More than 55% of all cases had at least one oncogenic genome alteration potentially amenable to specific therapeutic intervention, including several personalized treatment approaches that are already in clinical evaluation. Marked differences in the pattern of genomic alterations existed between and within histological subtypes, thus challenging the original histomorphological diagnosis. Immunohistochemical studies confirmed many of these reassigned subtypes. The reassignment eliminated almost all cases of large cell carcinomas, some of which had therapeutically relevant alterations. Prospective testing of our genomics-based diagnostic algorithm in 5145 lung cancer patients enabled a genome-based diagnosis in 3863 (75%) patients, confirmed the feasibility of rational reassignments of large cell lung cancer, and led to improvement in overall survival in patients with EGFR-mutant or ALK-rearranged cancers. Thus, our findings provide support for broad implementation of genome-based diagnosis of lung cancer