Project description:A randomized, open-label, phase 2, multicenter clinical trial was conducted to evaluate the efficacy and safety of the addition of a recombinant human endostatin adenovirus (E10A) to cisplatin and paclitaxel in patients with advanced head and neck squamous cell carcinoma or nasopharyngeal carcinoma. Patients with locally advanced or metastatic head and neck squamous cell carcinoma or nasopharyngeal carcinoma not suitable for operation or radiotherapy were randomly assigned to receive E10A plus chemotherapy every 3 weeks for a maximum of six cycles or to receive chemotherapy only. One hundred and thirty-six eligible patients were randomly assigned. The addition of E10A did not significantly improve the objective response rate (29.9 versus 39.7%, P = 0.154). However, patients who received endostatin had longer progression-free survival (7.03 versus 3.60 months, P = 0.006; hazard ratio: 0.55). The combination of E10A with chemotherapy benefited prior chemotherapy-treated patients and those who received three to four treatment cycles (6.50 versus 3.43 months, P = 0.003; 8.27 versus 4.27 months, P = 0.018; respectively). The overall disease control rate significantly increased from 80.6% in the control group to 92.6% in the test group (P = 0.034). Except for fever, no adverse events were associated with the E10A treatment. In summary, E10A plus chemotherapy is a safe and effective therapeutic approach in patients with advanced head and neck squamous cell carcinoma or nasopharyngeal carcinoma.
Project description:These NCCN Guidelines Insights focus on recent updates to the 2015 NCCN Guidelines for Head and Neck (H&N) Cancers. These Insights describe the different types of particle therapy that may be used to treat H&N cancers, in contrast to traditional radiation therapy (RT) with photons (x-ray). Research is ongoing regarding the different types of particle therapy, including protons and carbon ions, with the goals of reducing the long-term side effects from RT and improving the therapeutic index. For the 2015 update, the NCCN H&N Cancers Panel agreed to delete recommendations for neutron therapy for salivary gland cancers, because of its limited availability, which has decreased over the past 2 decades; the small number of patients in the United States who currently receive this treatment; and concerns that the toxicity of neutron therapy may offset potential disease control advantages.
Project description:The authors present the application of the reduced order constrained optimization (ROCO) method, previously successfully applied to the prostate and lung sites, to the head-and-neck (H&N) site, demonstrating that it can quickly and automatically generate clinically competitive IMRT plans. We provide guidelines for applying ROCO to larynx, oropharynx, and nasopharynx cases, and report the results of a live experiment that demonstrates how an expert planner can save several hours of trial-and-error interaction using the proposed approach.The ROCO method used for H&N IMRT planning consists of three major steps. First, the intensity space of treatment plans is sampled by solving a series of unconstrained optimization problems with a parameter range based on previously treated patient data. Second, the dominant modes in the intensity space are estimated by dimensionality reduction using principal component analysis (PCA). Third, a constrained optimization problem over this basis is quickly solved to find an IMRT plan that meets organ-at-risk (OAR) and target coverage constraints. The quality of the plan is assessed using evaluation tools within Memorial Sloan-Kettering Cancer Center (MSKCC)'s treatment planning system (TPS).The authors generated ten H&N IMRT plans for previously treated patients using the ROCO method and processed them for deliverability by a dynamic multileaf collimator (DMLC). The authors quantitatively compared the ROCO plans to the previously achieved clinical plans using the TPS tools used at MSKCC, including DVH and isodose contour analysis, and concluded that the ROCO plans would be clinically acceptable. In our current implementation, ROCO H&N plans can be generated using about 1.6 h of offline computation followed by 5-15 min of semiautomatic planning time. Additionally, the authors conducted a live session for a plan designated by MSKCC performed together with an expert H&N planner. A technical assistant set up the first two steps, which were performed without further human interaction, and then collaborated in a virtual meeting with the expert planner to perform the third (constrained optimization) step. The expert planner performed in-depth analysis of the resulting ROCO plan and deemed it to be clinically acceptable and in some aspects superior to the clinical plan. This entire process took 135 min including two constrained optimization runs, in comparison to the estimated 4 h that would have been required using traditional clinical planning tools.The H&N site is very challenging for IMRT planning, due to several levels of prescription and a large, variable number (6-20) of OARs that depend on the location of the tumor. ROCO for H&N shows promise in generating clinically acceptable plans both more quickly and with substantially less human interaction.
Project description:In this study, we investigated the consensus gene modules in head and neck cancer (HNC) and cervical cancer (CC). We used a publicly available gene expression dataset, GSE6791, which included 42 HNC, 14 normal head and neck, 20 CC and 8 normal cervical tissue samples. To exclude bias because of different human papilloma virus (HPV) types, we analyzed HPV16-positive samples only. We identified 3824 genes common to HNC and CC samples. Among these, 977 genes showed high connectivity and were used to construct consensus modules. We demonstrated eight consensus gene modules for HNC and CC using the dissimilarity measure and average linkage hierarchical clustering methods. These consensus modules included genes with significant biological functions, including ATP binding and extracellular exosome. Eigengen network analysis revealed the consensus modules were highly preserved with high connectivity. These findings demonstrate that HPV16-positive head and neck and cervical cancers share highly preserved consensus gene modules with common potentially therapeutic targets.
Project description:Head and neck squamous cell carcinoma is the sixth most common cancer worldwide and despite advances in treatment over the last years, there is still a relapse rate of 50%. New therapeutic agents are awaited to increase the survival of patients. DNA repair targeted agents in combination with standard DNA damaging therapies are a recent evolution in cancer treatment. These agents focus on the DNA damage repair pathways in cancer cells, which are often involved in therapeutic resistance. Interesting targets to overcome these cancer defense mechanisms are: PARP, DNA-PK, PI3K, ATM, ATR, CHK1/2, and WEE1 inhibitors. The application of DNA targeted agents in head and neck squamous cell cancer showed promising preclinical results which are translated to multiple ongoing clinical trials, although no FDA approval has emerged yet. Biomarkers are necessary to select the patients that can benefit the most from this treatment, although adequate biomarkers are limited and validation is needed to predict therapeutic response.
Project description:Checkpoint inhibitors have recently gained FDA approval for the treatment of cisplatin-resistant recurrent and metastatic head and neck squamous cell carcinoma (HNSCC) by outperforming standard of care chemotherapy and inducing durable responses in a subset of patients. These monoclonal antibodies unleash the patient's own immune system to target cancer cells. HNSCC is a good target for these agents as there is ample evidence of active immunosurveillance in the head and neck and a number of immune evasion mechanisms by which HNSCCs form progressive disease including via the PD-1/PD-L1 axis. As HNSCCs typically possess a moderately high mutation burden, they should express numerous mutation-derived antigen targets for immune detection. However, with response rates less than 20% in clinical trials, there is a need for biomarkers to screen patients as well as clinical trials evaluating novel combinations to improve outcomes. The aim of this review is to provide historical and mechanistic context for the use of checkpoint inhibitors in head and neck cancer and provide a perspective on the role of novel checkpoints, biomarkers, and combination therapies that are evolving in the near term for patients with HNSCC.
Project description:Head and neck cancers (HNCs) encompass a heterogeneous group of cancers between the mouth and larynx. Familial clustering in HNCs has been described, but how it influences individual sites and to which extent known risk factors, such as human papilloma virus (HPV) infection, may contribute is not well established. We employed standardized incidence ratios (SIRs) to estimate familial risks for HNC with same (concordant) and different (discordant) cancers among first-degree relatives using data from the Swedish Cancer Registry from 1958 to 2018. Incidence for male and female oropharyngeal cancer increased close to four-fold in the past 39 years. Familial HNC was found in 3.4% of the study population, with an overall familial SIR of 1.78. Patients with concordant nasopharyngeal cancer showed a high risk of 23.97, followed by hypopharyngeal cancer (5.43). The husbands of wives with cervical cancer had an increased risk of oropharyngeal cancer. Nasopharyngeal cancers lacked associations with lifestyle or HPV associated cancers, suggesting a role for germline genetics, which was also true for the high-risk families of three HNC patients. In the Swedish population with low smoking levels, HPV is becoming a dominant risk factor, emphasizing the need for sexual hygiene and HPV vaccination.
Project description:Although surgical resection has been the primary treatment modality of solid tumors for decades, surgeons still rely on visual cues and palpation to delineate healthy from cancerous tissue. This may contribute to the high rate (up to 30%) of positive margins in head and neck cancer resections. Margin status in these patients is the most important prognostic factor for overall survival. In addition, second primary lesions may be present at the time of surgery. Although often unnoticed by the medical team, these lesions can have significant survival ramifications. We hypothesize that real-time fluorescence imaging can enhance intraoperative decision making by aiding the surgeon in detecting close or positive margins and visualizing unanticipated regions of primary disease. The purpose of this study was to assess the clinical utility of real-time fluorescence imaging for intraoperative decision making. Methods: Head and neck cancer patients (n = 14) scheduled for curative resection were enrolled in a clinical trial evaluating panitumumab-IRDye800CW for surgical guidance (NCT02415881). Open-field fluorescence imaging was performed throughout the surgical procedure. The fluorescence signal was quantified as signal-to-background ratios to characterize the fluorescence contrast of regions of interest relative to background. Results: Fluorescence imaging was able to improve surgical decision making in 3 cases (21.4%): identification of a close margin (n = 1) and unanticipated regions of primary disease (n = 2). Conclusion: This study demonstrates the clinical applications of fluorescence imaging on intraoperative decision making. This information is required for designing phase III clinical trials using this technique. Furthermore, this study is the first to demonstrate this application for intraoperative decision making during resection of primary tumors.
Project description:Radiotherapy is a common treatment modality in the management of head and neck malignancies. In select clinical scenarios of well-lateralized tumors, radiotherapy can be delivered to the primary tumor or tumor bed and the ipsilateral nodal regions, while intentional irradiation of the contralateral neck is omitted. Proton beam therapy is an advanced radiotherapy modality that allows for the elimination of exit-dose through nontarget tissues such as the oral cavity. This dosimetric advantage is apt for unilateral treatments. By eliminating excess dose to midline and contralateral organs at risk and conforming dose around complex anatomy, proton beam therapy can reduce the risk of iatrogenic toxicities. Currently, there is no level I evidence comparing proton beam therapy to conventional photon radiation modalities for unilateral head and neck cancers. However, a growing body of retrospective and prospective evidence is now available describing the dosimetric and clinical advantages of proton beam therapy. Subsequently, the intent of this clinical review is to summarize the current evidence supporting the use of proton beam therapy in unilateral irradiation of head and neck cancers, including evaluation of disease site-specific evidence, unique challenging clinical scenarios, and ongoing clinical trials.