Olgun Elicin

Current status and perspectives of interventional clinical trials for glioblastoma – analysis of ClinicalTrials.gov

The records of 208.777 (100%) clinical trials registered at ClinicalTrials.gov were downloaded on the 19th of February 2016. Phase II and III trials including patients with glioblastoma were selected for further classification and analysis. Based on the disease settings, trials were classified into three groups: newly diagnosed glioblastoma, recurrent disease and trials with no differentiation according to disease setting. Furthermore, we categorized trials according to the experimental interventions, the primary sponsor, the source of financial support and trial design elements. Trends were evaluated using the autoregressive integrated moving average model. Two hundred sixteen (0.1%) trials were selected for further analysis. Academic centers (investigator initiated trials) were recorded as primary sponsors in 56.9% of trials, followed by industry 25.9%. Industry was the leading source of monetary support for the selected trials in 44.4%, followed by 25% of trials with primarily academic financial support. The number of newly initiated trials between 2005 and 2015 shows a positive trend, mainly through an increase in phase II trials, whereas phase III trials show a negative trend. The vast majority of trials evaluate forms of different systemic treatments (91.2%). In total, one hundred different molecular entities or biologicals were identified. Of those, 60% were involving drugs specifically designed for central nervous system malignancies. Trials that specifically address radiotherapy, surgery, imaging and other therapeutic or diagnostic methods appear to be rare. Current research in glioblastoma is mainly driven or sponsored by industry, academic medical oncologists and neuro-oncologists, with the majority of trials evaluating forms of systemic therapies. Few trials reach phase III. Imaging, radiation therapy and surgical procedures are underrepresented in current trials portfolios. Optimization in research portfolio for glioblastoma is needed.

Up-front neck dissection followed by definitive (chemo)-radiotherapy in head and neck squamous cell carcinoma: Rationale, complications, toxicity rates, and oncological outcomes – A systematic review

BACKGROUND AND PURPOSE Lymph node metastases of head and neck cancer are considered one of the most negative prognostic factors. While outcomes and feasibility of chemo-radiotherapy ((C)RT) with or without adjuvant planned neck dissection (ND) in organ-preservation treatment strategy have been addressed, the role of ND before (C)RT, called up-front neck dissection (UFND), is not clearly established. This review provides a critical appraisal of UFND. MATERIAL AND METHODS Articles were identified with a systematic approach. Outcomes included post-UFND delay of (C)RT, surgical complications, radiation toxicity and oncologic outcome. RESULTS Fifteen studies met inclusion criteria, totaling 607 patients undergoing UFND. Part of the data suggest advantages toward less surgical complications compared with salvage ND, decreased serious acute radiation toxicity and better oncological outcomes when compared with (C)RT alone. The overall heterogeneity of the analyzed data does not allow a meta-analysis that provides high-quality evidence in favor or against UFND. CONCLUSIONS Due to lack of well-designed randomized trials, it is difficult to assess the role of UFND in organ-preserving (C)RT setting of head and neck cancer.

The latest prospects of investigational drugs for head and neck cancer

Squamous-cell cancer of the head and neck (SCCHN) is often diagnosed at advanced stages which require systemic treatments [1–4]. Current standards, both for curative and recurrent and/or metastatic (R/M) setting, involve cytotoxic chemotherapy agents (mainly platinum compounds), the EGFR inhibitor cetuximab, and the immune checkpoint inhibitors (ICIs) nivolumab and pembrolizumab (the latter two recently approved by the FDA, but not globally). The long-term survival rates are still low; and with the current treatment modalities, the upper limit of toxicity seems to be reached [5]. While we briefly focus on the current landscape of the clinical trials involving targeted drugs being investigated for the treatment of SCCHN, comprehensive information about the substances, their mechanisms of action, and results of previous trials can be obtained from recently published reviews [6–8]. Table 1 provides an overview of the agents which continued to be investigated in clinical trials in past 2 years. Worth to note, only 5% of the drugs, which show an anticancer activity in the early phases of development, later demonstrate a success in the phase III trials [9].

Salvage-Chirurgie bei Tumorrezidiven der Mundhöhle – Einfluss der vorherigen Behandlung und des Patientenalters

Tam S et al. Estimating Survival After Salvage Surgery for Recurrent Oral Cavity Cancer. JAMA Otolaryngol Head Neck Surg 2017; 143:685–690 LOKO-REGIONäRE REZIDIVE EINES PLATTENEPITHELKARZINOMS DER MUNDHöHLE SIND LEBENSBEDROHLICH UND EINE KLINISCHE HERAUSFORDERUNG. WELCHE ROLLE SPIELT IN DIESEN FäLLEN DIE SALVAGE-CHIRURGIE?

Outcomes in Advanced Head and Neck Cancer Treated with Up-front Neck Dissection prior to (Chemo)Radiotherapy.

Objective Our aim was to compare outcomes with and without up-front neck dissection prior to (chemo)radiotherapy in head and neck squamous cell carcinoma. Study Design Case series with chart review. Setting Tertiary referral center. Subjects and Methods Outcomes of oropharyngeal, laryngeal, and hypopharyngeal squamous cell carcinoma cases with neck lymph node metastases treated from January 2001 to March 2012 were analyzed. Due to imbalances in baseline characteristics between groups treated with (n = 129) and without (n = 95) up-front neck dissection, propensity score matching was performed. Results Median follow-up was 48 months (range, 12-148). With up-front neck dissection, the hazard ratio for the primary end point, disease-free survival, was 0.63 (95% confidence interval: 0.37-1.06, P = .08). Up-front neck dissection reduced acute grade ≥3 toxicity significantly when xerostomia was excluded (odds ratio: 0.40, 95% confidence interval: 0.20-0.82, P = .012). Conclusion Our results indicate less acute treatment toxicity without any significant difference in terms of oncologic outcome with up-front neck dissection prior to (chemo)radiotherapy as compared with (chemo)radiotherapy alone. Well-designed randomized trials are required to verify this result and further investigate the impact of this strategy on late toxicity and oncologic outcome.

Risk analysis for tracheostomy dependency in curatively treated laryngeal cancer with organ preservation

A tracheostomy has an enormous negative impact on the patients quality of life. The purpose of this study is to describe risk factors for permanent tracheostomies in patients undergoing curative organ‐preserving treatment of laryngeal cancer.

Primary tumor volume delineation in head and neck cancer: missing the tip of the iceberg?

BackgroundThe aim was to evaluate the geometric and corresponding dosimetric differences between two delineation strategies for head and neck tumors neighboring air cavities.MethodsPrimary gross and clinical tumor volumes (GTV and CTV) of 14 patients with oropharynx or larynx tumors were contoured using a soft tissue window (S). In a second strategy, the same volumes were contoured with an extension to include the parts which became visible on lung window (L). For the calculation of Hausdorff-distances (HD) between contoured volumes of the two strategies, triangular meshes were exported. Two radiotherapy plans with identical goals and optimization parameters were generated for each case. Plan_S were optimized on CTV_S, and Plan_L on CTV_L. The dose coverages of CTV_L and CTV_Δ (CTV_L minus CTV_S) were evaluated in Plan_S. OAR doses were compared among Plan_S and Plan_L.ResultsMedian three-dimensional HD for GTVs and CTVs were 5.7 (±2.6) and 9.3 (±2.8) mm, respectively. The median volume differences between structures contoured using L and S windows were 9% (±5%) and 9% (±4%) for GTV and CTV, respectively. In 13 out of 14 cases, Plan_S met the plan acceptance criteria for CTV_L. In 8 cases CTV_Δ was covered insufficiently in Plan_S. Mean and median differences in OAR dose-volume histogram parameters between Plan_S and Plan_L were within 3%.ConclusionFor the current practice in radiotherapy planning for head and neck cancer, the delineation of L-based volumes seems unnecessary. However, in special settings, where smaller or no PTV margins are used, this approach may play an important role for local control.

Current Role of Dacomitinib in Head and Neck Cancer

ABSTRACT Introduction: Recurrent and/or metastatic head and neck squamous cell carcinoma (HNSCC) has a dismal prognosis. With the emergence of monoclonal antibodies and tyrosine kinase inhibitors (TKI) targeting the epidermal growth factor receptor (EGFR), several drugs were developed and tested in HNSCC. To date, the monoclonal antibody cetuximab is the only approved therapy for curative and recurrent/metastatic patients. Other EGFR-targeting drugs either failed in the clinical trials or are still in the early phases of drug development and research. Areas covered: In this article, previously published data and ongoing studies regarding dacomitinib, a second-generation irreversible TKI, for the treatment of HNSCC are presented and discussed. Expert opinion: The current body of evidence is not mature enough to indicate the use of dacomitinib for the treatment of HNSCC in curative or in recurrent/metastatic settings. Phase II data suggest the potential of improved outcome in selected recurrent/metastatic HNSCC based on several biomarkers, which need to be evaluated in randomized phase III trials. Meanwhile, an ongoing phase I study is investigating dacomitinib’s optimal dosing combined with and without cisplatin in the curative concomitant chemoradiotherapy setting.