Marlen Haderlein

Increased skin and mucosal toxicity in the combination of vemurafenib with radiation therapy

BackgroundPalliative radiotherapy is often required for patients with metastatic malignant melanoma in the case of bone or brain metastases. Since BRAF inhibitor therapy is highly efficient in V600-mutated melanomas, there is hesitation to stop it during radiotherapy. Consequently, radiotherapy under simultaneous vemurafenib treatment is frequently needed.Case reportWe report the case of a patient receiving palliative radiotherapy of spinal bone metastases before and during vemurafenib therapy. The skin reactions were quantitatively scored using computer-assisted digital image evaluation.ResultsRadiotherapy without vemurafenib was tolerated very well, whereas radiotherapy under simultaneous vemurafenib treatment resulted in accentuated skin reactions. Furthermore, the patient developed dysphagia and had to be hospitalized for parenteral nutrition. In the quantitative analysis, there was a twofold increase in pigmentation and erythema of the irradiated skin area of the thoracic spine when vemurafenib was combined with radiotherapy compared with radiotherapy treatment alone. This is the first reported case of a patient showing no complications during radiotherapy without vemurafenib but remarkable skin and mucosal toxicity under concurrent vemurafenib therapy. Thus, a genetically conditioned individually elevated radiosensitivity can definitely be excluded. Compared with other reported cases, radiosensitization was not limited to the skin, but also affected the esophageal mucosa.ConclusionVemurafenib is a strong radiosensitizer. Patients receiving radiotherapy under simultaneous vemurafenib treatment should be monitored very closely.ZusammenfassungHintergrundBei Patienten mit metastasiertem Melanom ist die palliative Bestrahlung von Knochen- oder Hirnmetastasen häufig erforderlich. Da eine Therapie mit BRAF-Inhibitoren bei Patienten mit V600-mutierten Melanomen hoch effektiv ist, sollte man sie während einer Strahlentherapie nicht unterbrechen. Daher ist eine Strahlentherapie unter laufender Behandlung mit Vemurafenib häufig erforderlich.MethodenHier wird der Fall eines Patienten dargestellt, der palliative Bestrahlungen von Wirbelkörpermetastasen vor und während einer Behandlung mit Vemurafenib erhalten hat. Bei diesem Fallbericht wurde die Stärke der Hautreaktionen mit computerassistierter digitaler Bildanalyse quantitativ ausgewertet.ErgebnisDie Strahlentherapie ohne Vemurafenib wurde gut vertragen, wogegen es bei der Bestrahlung unter simultaner Vemurafenib-Therapie zu verstärkten Hautreaktionen kam. Darüber hinaus entwickelte der Patient eine Mukositis mit ausgeprägten Schluckbeschwerden, so dass er zur parenteralen Ernährung stationär aufgenommen werden musste. Verglichen zur alleinigen Bestrahlung waren Pigmentierung und Rötung in der quantitativen Auswertung bei der Kombination von Bestrahlung mit Vemurafenib auf das Doppelte erhöht. Dies ist der erste berichtete Fall eines Patienten, bei dem ohne Vemurafenib eine Strahlentherapie komplikationslos durchführbar war und in Kombination mit Vemurafenib Haut- und Schleimhauttoxizität auftraten. Daher kann eine genetisch bedingte individuell erhöhte Strahlenempfindlichkeit definitiv ausgeschlossen werden. Verglichen mit anderen berichteten Fällenbetraf die erhöhte Strahlenempfindlichkeit nicht nur die Haut, sondern auch die Schleimhaut des Ösophagus.SchlussfolgerungVemurafenib wirkt stark strahlensensibilisierend. Patienten, die unter simultaner Behandlung mit Vemurafenib bestrahlt werden, sollten engmaschig überwacht werden.

Single-cycle induction chemotherapy followed by chemoradiotherapy or surgery in patients with head and neck cancer: what are the best predictors of remission and prognosis?

There is controversy over the concept of function and organ preservation by chemotherapy/chemoradiation instead of surgery in locally advanced cancer of the larynx or pharynx. Tumor response to induction chemotherapy (ICT) can help in choosing between conservative and surgical treatment. This study compared 3 methods of assessing response to ICT: endoscopy, computed tomography, and 18F‐FDG‐PET/CT.

High-grade histology as predictor of early distant metastases and decreased disease-free survival in salivary gland cancer irrespective of tumor subtype.

The purpose of this study was to evaluate risk factors that influence overall survival (OS)/disease‐free survival (DFS)/locoregional recurrence‐free survival (LRFS), and distant metastases‐free survival (DMFS) in patients with high‐risk primary salivary gland carcinoma who underwent surgery and postoperative (chemo)radiotherapy with curative intention.

Spatial distribution of FoxP3+ and CD8+ tumour infiltrating T cells reflects their functional activity

Background Regulatory and cytotoxic T cells are key players in the hosts anticancer immune response. We studied the spatial distribution of FoxP+ and CD8+ cells to identify potential interactions. Methods In 202 patients 103 pre-radiochemotherapy biopsies and 153 post-radiochemotherapy tumour specimens of advanced rectal cancer were available and an immunohistochemical double staining of FoxP3+ and CD8+ tumour-infiltrating lymphocytes was performed to investigate cell density and cell-to-cell distances. Results FoxP3+ cells decreased after radiochemotherapy by a factor of 3 while CD8+ cells remained nearly unchanged. High epithelial (p=0.033) and stromal (p=0.009) FoxP3+ cell density was associated with an improved overall survival. Cell-to-cell distances of randomly distributed cells were simulated and compared to observed cell-to-cell distances. Observed distances shorter than the simulated, random distances were hypothesized to represent FoxP3+ cells actively interacting with CD8+ cells. Epithelial short distances were associated with a favourable prognosis while the opposite was true for the stromal compartment. Conclusion The analysis of cell-to-cell distances may offer a tool to predict outcome, maybe by identifying functionally active, interacting infiltrating inflammatory cells in different tumour compartments.

Ex Vivo Apoptosis in CD8+ Lymphocytes Predicts Rectal Cancer Patient Outcome.

Background. Apoptotic rates in peripheral blood lymphocytes can predict radiation induced normal tissue toxicity. We studied whether apoptosis in lymphocytes has a prognostic value for therapy outcome. Methods. Lymphocytes of 87 rectal cancer patients were ex vivo irradiated with 2 Gy, 8 Gy, or a combination of 2 Gy ionizing radiation and Oxaliplatin. Cells were stained with Annexin V and 7-Aminoactinomycin D and apoptotic and necrotic rates were analyzed by multicolor flow cytometry. Results. After treatment, apoptotic and necrotic rates in CD8+ cells are consistently higher than in CD4+ cells, with lower corresponding necrotic rates. Apoptotic and necrotic rates of CD4+ cells and CD8+ cells correlated well within the 2 Gy, 8 Gy, and 2 Gy and Oxaliplatin arrangements (p ≤ 0.009). High apoptotic CD8+ rates after 2 Gy, 8 Gy, and 2 Gy + Oxaliplatin treatment were prognostically favorable for metastasis-free survival (p = 0.009, p = 0.038, and p = 0.009) and disease-free survival (p = 0.013, p = 0.098, and p = 0.013). Conclusions. Ex vivo CD8+ apoptotic rates are able to predict the patient outcome in regard to metastasis-free or disease-free survival. Patients with higher CD8+ apoptotic rates in the peripheral blood have a more favorable prognosis. In addition to the prediction of late-toxicity by utilization of CD4+ apoptotic rates, the therapy outcome can be predicted by CD8+ apoptotic rates.

Bei Kopf-Hals-Karzinomen korreliert die Anzahl der bei Neck-Dissektion entnommenen Lymphknoten mit der Prognose

Hintergrund und Ziele Die Zahl der bei einer Neck-Dissektion (ND) entnommenen Lymphknoten (LK) bei Patienten mit Plattenepithelkarzinomen der Kopf-Hals-Region variiert stark zwischen den verschiedenen Behandlungszentren [1]. In vorangegangen Untersuchungen mit kleineren Fallzahlen wurde ein Zusammenhang zwischen der Anzahl der entnommenen LK und dem Gesamt(OS) bzw. krankheitsspezifischen Überleben (DFS) gefunden [2–4]. Ziel der hier kommentierten Arbeit war es, den Zusammenhang zwischen entnommener Lymphknotenanzahl und Letalität in einer großen, nationalen Kohorte retrospektiv zu validieren, und zwar unabhängig vom Behandlungszentrum.