Memento for interprofessional learning

The vast increase of technical, diagnostic, and treatment possibilities and deepened understanding of molecular biology has revolutionized diagnosis and treatment of cancer and thus has great impact on pathology. Different professionals are responsible for proper evaluation of the results and their translating into an accurate diagnosis and appropriate treatment. Next to expertise, a close interaction between clinical molecular biologists, pathologists, and oncologists is required; it is crucial that these professionals speak “the same language.” Key to this is communication skills and creating possibilities for collaboration in a meaningful context. Here, we present an interprofessional, educational workshop model and we describe the parameters that contribute to effective learning by specialists

Daily practice in guideline adherence to adjuvant chemotherapy in stage III colon cancer and predictors of outcome

Introduction: Although guidelines recommend adjuvant chemotherapy for stage III colon cancer patients, many patients do not receive adjuvant chemotherapy. The aim of this study was to identify reasons for guideline non-adherence and assess the effect on patient outcomes in a multicenter cohort of stage III colon cancer patients who received surgery plus adjuvant chemotherapy or surgery alone. Methods: Patients who underwent surgery between 2007 and 2017 were included. Reasons for non-adherence were determined. Propensity score analyses with inverse probability weighting were performed to adjust for confounding factors. Cox proportional hazards regression and risk stratified analyses were performed to assess the association of guideline adherence and other potential predictors with recurrence free survival (RFS). Results: Data of 575 patients were included of whom 61% received adjuvant chemotherapy. In 87 of 222 patients (39%) who did not receive adjuvant chemotherapy, no reason was documented. Only age was predictive for receiving chemotherapy. Patients who received adjuvant chemotherapy had longer RFS (HR 0.42, 95%CI 0.29–0.62, p &lt; 0.001). High T- and N-stage were associated with poorer RFS HR 2.0 (95%CI 1.58–2.71, p &lt; 0.001) and HR 2.19 (95%CI 1.60–2.99, p &lt; 0.001) respectively. Risk groups were identified with distinct prognosis and treatment effect and a nomogram is presented to visualize individualized RFS differences. Conclusion: This study shows considerable variation in guideline adherence to adjuvant chemotherapy and poor documentation on reasons for non-adherence. Optimizing adherence and gaining insight in reasons for non-adherence is advocated as this can lead to significant RFS benefit, especially in patients with high T-and N-stage tumors.</p

Clonality analysis for antigen receptor genes:Preliminary results from the biomed-2 concerted action PL 96-3936

The diagnosis of lymphoproliferative disorders is based on histopathology and immunophenotyping, and most cases can be concluded without further techniques. However, in a number of cases the differential diagnosis between a reactive process and malignant lymphoma is difficult, and molecular techniques can be helpful. In particular, assessment of clonality is a useful adjunct, because mature lymphocytes have rearranged immunoglobulin or T-cell antigen receptor genes, and thus almost all malignant lymphomas have a clonal rearrangement of at least 1 of these antigen receptor genes. Assessment of clonality can be performed using Southern blot analysis with several restriction enzymes and many different probes. This is a reliable method, but it requires large amounts of high-molecular-weight DNA and is time-consuming. Several different polymerase chain reaction (PCR)-based methods have been described, generally using consensus primers for only a few of the rearranged loci. This method is rapid but less reliable, because incomplete rearrangements can be missed and also because mutations in the regions of primer annealing can cause negative results. This is especially common in lymphomas of germinal center (GC) origin and also to a lesser extent in post-GC lymphomas. We therefore decided to develop and test new primer sets for all relevant loci of the B-cell and T-cell receptor genes

Clonality analysis for antigen receptor genes:Preliminary results from the biomed-2 concerted action PL 96-3936

The diagnosis of lymphoproliferative disorders is based on histopathology and immunophenotyping, and most cases can be concluded without further techniques. However, in a number of cases the differential diagnosis between a reactive process and malignant lymphoma is difficult, and molecular techniques can be helpful. In particular, assessment of clonality is a useful adjunct, because mature lymphocytes have rearranged immunoglobulin or T-cell antigen receptor genes, and thus almost all malignant lymphomas have a clonal rearrangement of at least 1 of these antigen receptor genes. Assessment of clonality can be performed using Southern blot analysis with several restriction enzymes and many different probes. This is a reliable method, but it requires large amounts of high-molecular-weight DNA and is time-consuming. Several different polymerase chain reaction (PCR)-based methods have been described, generally using consensus primers for only a few of the rearranged loci. This method is rapid but less reliable, because incomplete rearrangements can be missed and also because mutations in the regions of primer annealing can cause negative results. This is especially common in lymphomas of germinal center (GC) origin and also to a lesser extent in post-GC lymphomas. We therefore decided to develop and test new primer sets for all relevant loci of the B-cell and T-cell receptor genes

Chemotherapy, bevacizumab, and cetuximab in metastatic colorectal cancer.

Contains fulltext : 79995.pdf (publisher's version ) (Open Access)BACKGROUND: Fluoropyrimidine-based chemotherapy plus the anti-vascular endothelial growth factor (VEGF) antibody bevacizumab is standard first-line treatment for metastatic colorectal cancer. We studied the effect of adding the anti-epidermal growth factor receptor (EGFR) antibody cetuximab to a combination of capecitabine, oxaliplatin, and bevacizumab for metastatic colorectal cancer. METHODS: We randomly assigned 755 patients with previously untreated metastatic colorectal cancer to capecitabine, oxaliplatin, and bevacizumab (CB regimen, 378 patients) or the same regimen plus weekly cetuximab (CBC regimen, 377 patients). The primary end point was progression-free survival. The mutation status of the KRAS gene was evaluated as a predictor of outcome. RESULTS: The median progression-free survival was 10.7 months in the CB group and 9.4 in the CBC group (P=0.01). Quality-of-life scores were lower in the CBC group. The overall survival and response rates did not differ significantly in the two groups. Treated patients in the CBC group had more grade 3 or 4 adverse events, which were attributed to cetuximab-related adverse cutaneous effects. Patients treated with cetuximab who had tumors bearing a mutated KRAS gene had significantly decreased progression-free survival as compared with cetuximab-treated patients with wild-type-KRAS tumors or patients with mutated-KRAS tumors in the CB group. CONCLUSIONS: The addition of cetuximab to capecitabine, oxaliplatin, and bevacizumab resulted in significantly shorter progression-free survival and inferior quality of life. Mutation status of the KRAS gene was a predictor of outcome in the cetuximab group. (ClinicalTrials.gov number, NCT00208546.

Platinum-based drugs disrupt STAT6-mediated suppression of immune responses against cancer in humans and mice

Tumor microenvironments feature immune inhibitory mechanisms that prevent T cells from generating effective antitumor immune responses. Therapeutic interventions aimed at disrupting these inhibitory mechanisms have been shown to enhance antitumor immunity, but they lack direct cytotoxic effects. Here, we investigated the effect of cytotoxic cancer chemotherapeutics on immune inhibitory pathways. We observed that exposure to platinum-based chemotherapeutics markedly reduced expression of the T cell inhibitory molecule programmed death receptor-ligand 2 (PD-L2) on both human DCs and human tumor cells. Downregulation of PD-L2 resulted in enhanced antigen-specific proliferation and Th1 cytokine secretion as well as enhanced recognition of tumor cells by T cells. Further analysis revealed that STAT6 controlled downregulation of PD-L2. Consistent with these data, patients with STAT6-expressing head and neck cancer displayed enhanced recurrence-free survival upon treatment with cisplatin-based chemoradiation compared with patients with STAT6-negative tumors, demonstrating the clinical relevance of platinum-induced STAT6 modulation. We therefore conclude that platinum-based anticancer drugs can enhance the immunostimulatory potential of DCs and decrease the immunosuppressive capability of tumor cells. This dual action of platinum compounds may extend their therapeutic application in cancer patients and provides a rationale for their use in combination with immunostimulatory compounds