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PurposeTo evaluate the performance of a model-based optimisation process for volumetric modulated arc therapy applied to prostate cancer in a multicentric cooperative group. The RapidPlan (RP) knowledge-based engine was tested for the planning of Volumetric modulated arc therapy with RapidArc on prostate cancer patients. The study was conducted in the frame of the German RapidPlan Consortium (GRC).Methods and materials43 patients from one institute of the GRC were used to build and train a RP model. This was further shared with all members of the GRC plus an external site from a different country to increase the heterogeneity of the patient’s sampling. An in silico multicentric validation of the model was performed at planning level by comparing RP against reference plans optimized according to institutional procedures. A total of 60 patients from 7 institutes were used.ResultsOn average, the automated RP based plans resulted fully consistent with the manually optimised set with a modest tendency to improvement in the medium-to-high dose region. A per-site stratification allowed to identify different patterns of performance of the model with some organs at risk resulting better spared with the manual or with the automated approach but in all cases the RP data fulfilled the clinical acceptability requirements. Discrepancies in the performance were due to different contouring protocols or to different emphasis put in the optimization of the manual cases.ConclusionsThe multicentric validation demonstrated that it was possible to satisfactorily optimize with the knowledge based model patients from all participating centres. In the presence of possibly significant differences in the contouring protocols, the automated plans, though acceptable and fulfilling the benchmark goals, might benefit from further fine tuning of the constraints. The study demonstrates that, at least for the case of prostate cancer patients, it is possibile to share models among different clinical institutes in a cooperative framework.

Purpose: While naïve T cells circulate between peripheral blood and lymph nodes, memory effector T cells acquire certain surface molecules that enable them to travel to peripheral tissues and exert their effector function. We analyzed whether deficient numbers of effector-type T cells within the malignant effusion might contribute to tumor escape from immunosurveillance.Experimental Design: We analyzed the expression of a broad range of adhesion molecules and chemokine receptors (CD62L, CD56, CCR4, CCR5, CCR7, CXCR3, CLA, and integrin ␣4␤7) on tumor-associated lymphocytes in effusions and peripheral blood lymphocytes of patients with malignant ascites (n ‫؍‬ 11) or malignant pleural effusion (n ‫؍‬ 16). A tumor-associated lymphocyte:peripheral blood lymphocyte ratio was calculated as an indicator for homing of lymphocytes into the effusions and was compared with patients with nonmalignant ascites (n ‫؍‬ 17).Results: Patients with malignancies show an increased enrichment of T cells expressing the phenotype of "naïve" (CD62L؉ and CD45RA؉CCR7؉), "central memory" (CD45RA-CCR7؉), and type 2-polarized (CCR4؉) T cells within their effusions. In contrast, enrichment of "effector"-type (CD45RA-CCR7؊ or CD45RA؉CCR7؊) and presumably type 1-polarized T cells (CCR5؉) at the tumor site is deficient. The same is true for natural killer cells and potentially cytotoxic CD56؉ T cells.Conclusions: Here we show for the first time that patients with malignant effusions show a deficient enrichment of T cells expressing the phenotype of type-1-polarized effector T cells at the tumor site. This mechanism is likely to contribute to the escape of tumor cells from immunosurveillance.

With the outbreak of the COVID-19 pandemia, routine clinical work was immediately, deeply, and sustainably impacted in Germany and worldwide. The infrastructure of almost all hospitals is currently redirected to provide a maximum of intensive care resources, including the necessary staff. In parallel, routine as well as emergency clinical care for all patients in need has to be secured. This challenge becomes particularly evident in cancer care. In order to maintain adequate oncological care at all levels of provision and to conduct especially curative and intensive treatments with a maximum of safety, continuous adaption of the oncology care system has to be ensured. Intensive communication with colleagues and patients is needed as is consequent expert networking and continuous reflection of the own developed strategies. In parallel, it is of high importance to actively avoid cessation of innovation in order not to endanger the continuous improvement in prognosis of cancer patients. This includes sustained conduction of clinical trials as well as ongoing translational research. Here, we describe measures taken at the University Cancer Center Hamburg (UCCH) – a recognized comprehensive oncology center of excellence – during the COVID-19 crisis. We aim to provide support and potential perspectives to generate a discussion basis on how to maintain high-end cancer care during such a crisis and how to conduct patients safely into the future.

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