BACKGROUND: Treatment of cancer is increasingly more effective but is associated with short and long term side effects. Oral side effects remain a major source of illness despite the use of a variety of agents to prevent them. One of these side effects is oral mucositis (mouth ulcers). OBJECTIVES: To evaluate the effectiveness of prophylactic agents for oral mucositis in patients with cancer receiving treatment, compared with other potentially active interventions, placebo or no treatment. SEARCH STRATEGY: Electronic searches of Cochrane Oral Health Group and PaPaS Trials Registers (to 16 February 2011), CENTRAL (The Cochrane Library 2011, Issue 1), MEDLINE via OVID (1950 to 16 February 2011), EMBASE via OVID (1980 to 16 February 2011), CINAHL via EBSCO (1980 to 16 February 2011), CANCERLIT via PubMed (1950 to 16 February 2011), OpenSIGLE (1980 to 2005) and LILACS via the Virtual Health Library (1980 to 16 February 2011) were undertaken. Reference lists from relevant articles were searched and the authors of eligible trials were contacted to identify trials and obtain additional information. SELECTION CRITERIA: Randomised controlled trials of interventions to prevent oral mucositis in patients receiving treatment for cancer. DATA COLLECTION AND ANALYSIS: Information regarding methods, participants, interventions, outcome measures, results and risk of bias were independently extracted, in duplicate, by two review authors. Authors were contacted for further details where these were unclear. The Cochrane Collaboration statistical guidelines were followed and risk ratios calculated using random-effects models. MAIN RESULTS: A total of 131 studies with 10,514 randomised participants are now included. Overall only 8% of these studies were assessed as being at low risk of bias. Ten interventions, where there was more than one trial in the meta-analysis, showed some statistically significant evidence of a benefit (albeit sometimes weak) for either preventing or reducing the severity of mucositis, compared to either a placebo or no treatment. These ten interventions were: aloe vera, amifostine, cryotherapy, granulocyte-colony stimulating factor (G-CSF), intravenous glutamine, honey, keratinocyte growth factor, laser, polymixin/tobramycin/amphotericin (PTA) antibiotic pastille/paste and sucralfate. AUTHORS' CONCLUSIONS: Ten interventions were found to have some benefit with regard to preventing or reducing the severity of mucositis associated with cancer treatment. The strength of the evidence was variable and implications for practice include consideration that benefits may be specific for certain cancer types and treatment. There is a need for further well designed, and conducted trials with sufficient numbers of participants to perform subgroup analyses by type of disease and chemotherapeutic agent.

/pdf/interventions-for-treating-oral-mucositis-for-patients-with-wjcln0nmlw.pdf

Interventions for treating oral mucositis for patients with cancer receiving treatment.

Background Platinum-based concurrent chemoradiotherapy is the standard of care for patients with locoregionally advanced nasopharyngeal carcinoma. Additional gemcitabine and cisplatin indu...

https://www.nejm.org/doi/suppl/10.1056/NEJMoa1905287/suppl_file/nejmoa1905287_appendix.pdf

Gemcitabine and Cisplatin Induction Chemotherapy in Nasopharyngeal Carcinoma

The NCCN Guidelines for Head and Neck (H&N) Cancers provide treatment recommendations for cancers of the lip, oral cavity, pharynx, larynx, ethmoid and maxillary sinuses, and salivary glands. Recommendations are also provided for occult primary of the H&N, and separate algorithms have been developed by the panel for very advanced H&N cancers. These NCCN Guidelines Insights summarize the panel's discussion and most recent recommendations regarding evaluation and treatment of nasopharyngeal carcinoma.

/pdf/nccn-guidelines-insights-head-and-neck-cancers-version-1-4qsr2m8fm4.pdf

NCCN Guidelines Insights: Head and Neck Cancers, Version 1.2018

Purpose: To identify MRI-based radiomics as prognostic factors in patients with advanced nasopharyngeal carcinoma (NPC).Experimental Design: One-hundred and eighteen patients (training cohort: n = 88; validation cohort: n = 30) with advanced NPC were enrolled. A total of 970 radiomics features were extracted from T2-weighted (T2-w) and contrast-enhanced T1-weighted (CET1-w) MRI. Least absolute shrinkage and selection operator (LASSO) regression was applied to select features for progression-free survival (PFS) nomograms. Nomogram discrimination and calibration were evaluated. Associations between radiomics features and clinical data were investigated using heatmaps.Results: The radiomics signatures were significantly associated with PFS. A radiomics signature derived from joint CET1-w and T2-w images showed better prognostic performance than signatures derived from CET1-w or T2-w images alone. One radiomics nomogram combined a radiomics signature from joint CET1-w and T2-w images with the TNM staging system. This nomogram showed a significant improvement over the TNM staging system in terms of evaluating PFS in the training cohort (C-index, 0.761 vs. 0.514; P < 2.68 × 10-9). Another radiomics nomogram integrated the radiomics signature with all clinical data, and thereby outperformed a nomogram based on clinical data alone (C-index, 0.776 vs. 0.649; P < 1.60 × 10-7). Calibration curves showed good agreement. Findings were confirmed in the validation cohort. Heatmaps revealed associations between radiomics features and tumor stages.Conclusions: Multiparametric MRI-based radiomics nomograms provided improved prognostic ability in advanced NPC. These results provide an illustrative example of precision medicine and may affect treatment strategies. Clin Cancer Res; 23(15); 4259-69. ©2017 AACR.

https://clincancerres.aacrjournals.org/content/clincanres/23/15/4259.full.pdf

Radiomics Features of Multiparametric MRI as Novel Prognostic Factors in Advanced Nasopharyngeal Carcinoma

Purpose To establish the safety profile and antitumor activity of the anti-programmed death 1 receptor monoclonal antibody, pembrolizumab, in patients with recurrent or metastatic nasopharyngeal carcinoma (RM-NPC) that expressed programmed death-ligand 1 (PD-L1). Patients and Methods KEYNOTE-028 (NCT02054806) is a nonrandomized, multicohort, phase Ib trial of pembrolizumab in patients with PD-L1-positive advanced solid tumors. Key eligibility criteria for the NPC cohort included unresectable or metastatic disease, failure on prior standard therapy, and PD-L1 expression in 1% or more of tumor cells or tumor-infiltrating lymphocytes. Patients received pembrolizumab 10 mg/kg every 2 weeks up to 2 years or until disease progression or unacceptable toxicity. Primary end point was objective response rate (ORR) per investigator review. Tumor response was assessed according to Response Evaluation Criteria in Solid Tumors (RECIST; version 1.1) every 8 weeks for the first 6 months and every 12 weeks thereafter. Results Twenty-seven patients received pembrolizumab. Median age was 52.0 years (range, 18 to 68 years); 92.6% received prior therapies for RM-NPC; 70.4% had received three or more therapies. Partial response and stable disease were observed in seven and 14 patients, respectively, for an ORR of 25.9% (95% CI, 11.1 to 46.3) over a median follow-up of 20 months. ORR by central review was similar (26.3%). Drug-related adverse events that occurred in 15% or more of patients included rash (25.9%), pruritus (25.9%), pain (22.2%), hypothyroidism (18.5%), and fatigue (18.5%). Grade ≥ 3 drug-related adverse events occurred in eight patients (29.6%), and there was one drug-related death (sepsis). As of the data cutoff (June 20, 2016), two patients remained on pembrolizumab treatment. Conclusion Pembrolizumab demonstrated antitumor activity and a manageable safety profile in patients with RM-NPC.

https://ascopubs.org/doi/pdfdirect/10.1200/JCO.2017.73.3675

Safety and Antitumor Activity of Pembrolizumab in Patients With Programmed Death-Ligand 1-Positive Nasopharyngeal Carcinoma: Results of the KEYNOTE-028 Study.

https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(16)31388-5.pdf

Gemcitabine plus cisplatin versus fluorouracil plus cisplatin in recurrent or metastatic nasopharyngeal carcinoma: a multicentre, randomised, open-label, phase 3 trial

Head and neck cancer is the sixth most common malignant tumor worldwide, and squamous cell cancer of the head and neck accounts for more than 90% of head and neck cancers. In China, the incidence of oral cavity and pharyngolaryngeal cancer is 3.28 per 100,000 with a mortality of 1.37 per 100,000, and the incidence of nasopharyngeal cancer is 3.61 per 100,000 with a mortality was 1.99 per 100,000. In 2013, an expert consensus conference was held in China with the aim of establishing the optimum multimodality treatments that are applied in Chinese patients with squamous cell cancer of the head and neck. The experts, who met to review the literature and discuss and modify treatment strategies used in clinical practice in China, reached a consensus on the optimum therapy approaches, which, in general, combine surgery, radiotherapy, chemotherapy and targeted therapy. The experts strongly recommended that healthcare providers should integrate proper medical resources into a collaborative group involving specialists in several disciplines to agree upon and provide the most effective therapy for individual patients.

Comprehensive treatment of squamous cell cancer of head and neck: Chinese expert consensus 2013

A prospective, randomized, multi-center trial to investigate Actovegin in prevention and treatment of acute oral mucositis caused by chemoradiotherapy for nasopharyngeal carcinoma

With the advances of diagnostic imaging and radiation therapy technology, the limitations of the Chinese 1992 staging system for nasopharyngeal carcinoma (NPC) become obvious, and the revision of this system was clearly needed. On December 16, 2008, the Chinese Committee for Staging of Nasopharyngeal Carcinoma (CCSNPC) was inaugurated in Guangzhou, China, with the purpose of establishing a platform for the study of the Chinese staging system and ensuring the continuity of the work of NPC staging research. Data from published studies on staging of NPC were collected and reviewed. After extensive evaluation and discussion, the Chinese 2008 staging system for NPC, which was a consensus based on evidence-based medicine and revisions made on the Chinese 1992 staging system, was recommended by CCSNPC. Changes of the staging system including emphasizing the status of MRI in diagnosis and staging; classification of parapharyngeal involvement, cranial nerve involvement, and retropharyngeal lymph node involvement; and T classification in the new system were simplified as well. CCSNPC also proposed a new criterion of the N category. This review discusses the rationale and bases of our primary revisions of this system and proposes an updated system, named the Chinese 2008 staging system for NPC. Further investigations are needed to confirm the effectiveness as well as to provide basis for further improvement of this system.

/pdf/report-on-revision-of-the-chinese-1992-staging-system-for-m21fbq7cf4.pdf

Chong Zhao

Papers

Gemcitabine plus cisplatin versus fluorouracil plus cisplatin in recurrent or metastatic nasopharyngeal carcinoma: a multicentre, randomised, open-label, phase 3 trial

Comprehensive treatment of squamous cell cancer of head and neck: Chinese expert consensus 2013

A prospective, randomized, multi-center trial to investigate Actovegin in prevention and treatment of acute oral mucositis caused by chemoradiotherapy for nasopharyngeal carcinoma

Report on revision of the Chinese 1992 staging system for nasopharyngeal carcinoma