Recent advances in the treatment of oral ulcerative mucositis from clinical and basic perspectives.

BACKGROUND: Oral ulcerative mucositis (OUM) is common in patients with cancer, particularly in those undergoing chemoradiation therapy. The effective management of OUM is crucial for continuous cancer care and patient well-being. Recent studies have advanced our understanding of the causes, leading to clinical trials toward novel treatments. This review focuses on the contemporary therapeutic landscape, and provides the latest insights into the mechanisms of mucosal healing and pain. HIGHLIGHTS: Management strategies for oral ulcerative mucositis in patients with cancer include maintaining good oral hygiene, reducing mucosal irritation against radiation, and using various topical analgesic treatments, including herbal medicines. However, the current management practices have limitations that necessitate the development of more efficacious and novel treatments. Molecular research on transient receptor potential (TRP) channels in the oral mucosa is crucial for understanding the mechanisms of wound healing and pain in patients with OUM. Targeting TRP subfamily V member 3 (V3) and TRPV4 can enhance wound healing through re-epithelialization. The suppression of TRPV1, TRPA1, and TRPV4 may be effective in alleviating OUM-induced pain. CONCLUSION: Research advancements have improved our understanding and potentially led to novel treatments that offer symptomatic relief. This progress highlights the importance of collaborations between clinical researchers and scientists in the development of innovative therapies.

Nursing management of patients receiving interstitial brachytherapy for head and neck malignancies.

Brachytherapy is a type of radiation therapy in which the radioactive source is directly delivered to the tumor and is used to treat a variety of malignancies. Although the local control effect of brachytherapy is higher than that of external beam radiation therapy (EBRT), it is often the case that brachytherapy is more invasive than conventional EBRT. As a result, patients receiving head and neck brachytherapy confront several physical, nutritional, and pain management issues. The nurses caring for patients with head and neck cancer receiving high-dose rate interstitial brachytherapy (ISBT) should have a thorough understanding of radiation therapy principles, technology, applicator management, and the acute and chronic side effects of ISBT. However, there are no appropriate textbooks or review articles regarding nursing care for head and neck patients undergoing ISBT. The purpose of this article is to provide radiation oncologists and nurses who want to start head and neck ISBT with a comprehensive guide regarding nursing care and to help the wide spread of this treatment strategy.

The combination of volumetric arc radiation therapy and boost high-dose rate interstitial brachytherapy for T3N2c tongue cancer: a technical report.

Currently, tongue cancers are primarily managed by surgery, and interstitial brachytherapy is only recommended for a selected group of early state T1-2N0 patients who refuse surgery or are medically inoperable. In this report, a case with T3N2cM0 tongue cancer who has been effectively treated by the combination of concurrent chemoradiotherapy involving volumetric arc therapy and boost high-dose rate interstitial brachytherapy is presented. Of course, surgery remains the main treatment strategy for tongue cancer patients; however, the authors believe that if volumetric arc therapy is carefully planned to reduce the mandible dose as much as possible and high-dose rate interstitial brachytherapy with a mouthpiece that protects the mandible is combined, it is possible to treat T3N2 disease, and this can be considered for patients who want to preserve organ function.

J-SUPPORT research policy for oral mucositis associated with cancer treatment.

BACKGROUND: Oral mucositis is one of the main areas of research in supportive and palliative care of cancer patients. However, the methodology of prospective clinical trials on oral mucositis has not been established, despite its uniqueness. Here, we propose a novel research policy on oral mucositis, including an implementable set of recommendations for researchers conducting clinical trials. METHODS: The first draft was developed by an expert panel of six specialists from the Japanese Supportive, Palliative, and Psychosocial Care Study Group. A provisional draft was developed after review by the following medical societies: the Japanese Association of Supportive Care in Cancer, the Japanese Association of Oral Supportive Care in Cancer, the Japanese Cancer Association, and the receipt of public comments. RESULTS: The research policy on oral mucositis mainly consists of the following components: (i) definition of oral mucositis; (ii) characteristics of oral mucositis; (iii) characteristics of oral mucositis research; (iv) target population for oral mucositis research; (v) endpoints and assessment measures in oral mucositis; (vi) eligibility criteria; (vii) research design; (viii) minimally recommended intervention in oral mucositis research as a supplement. The final policy (Ver1.0) was completed on August 16, 2021. CONCLUSIONS: This policy may serve as a significant reference for planning and conducting clinical trials for the management of oral mucositis.

Effects of an oral mucosa protective formulation on chemotherapy- and/or radiotherapy-induced oral mucositis: a prospective study.

BACKGROUND: Oral mucositis (OM) associated with cancer treatment not only impairs patients' quality of life but also causes treatment delays or changes. This prospective exploratory study was conducted to evaluate the efficacy of Episil® oral liquid, which is an approved protective formulation for the oral mucosa in patients with OM. The extent of the pain-relieving effect, feeling during use, and adverse events or problems were evaluated. METHODS: In total, 10 Japanese cancer patients with OM receiving chemotherapy, pretreatment therapy for hematopoietic stem cell transplantation, or radiation therapy for head and neck cancer were enrolled. RESULTS: A numerical rating scale (NRS) was used to assess oral pain intensity due to OM. Compared to baseline, the mean NRS began to decrease at 5 min after using Episil® (7.1 ± 1.4 to 4.6 ± 2.87; p = 0.264). A significant decrease was observed in the pain score after using Episil® compared with that before using Episil®, and this effect lasted up to 120 min. The protective effects of Episil® were observed 3-5 min after application. Some patients felt slight soreness or discomfort when applying Episil®. However, this discomfort due to Episil®'s stimulation was within the allowable range and transient. No adverse events were observed in any of the cases. CONCLUSIONS: The results of this prospective study showed that Episil® could be an effective treatment to relieve oral pain in Japanese patients with moderate to severe OM, and this newly approved product might adequately support patients' oral intake. TRIAL REGISTRATION: University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR) ( UMIN000031921 ).

Feasibility and usefulness of recommended screenings at long-term follow-up clinics for hematopoietic cell transplant survivors.

PURPOSE: Advances in allogeneic hematopoietic cell transplantation (allo-HCT) have resulted in a growing number of transplant survivors; however, long-term survivors are at risk of developing late complications, and published guidelines recommend screening of this population. We conducted a single-center prospective study to evaluate the adherence to and usefulness of recommended screenings at a long-term follow-up (LTFU) clinic. METHODS: We included consecutive patients who received allo-HCT at our center from 2014, as well as post-HCT patients visiting our outpatient clinic. Visits and screenings were planned at 3 months, 6 months, and 1 year after allo-HCT, and annually thereafter. Outcomes were reported by physicians including the incidence of findings at each screening that led to interventions. RESULTS: Among the 216 participants, 95% visited the LTFU clinic, and 94% completed planned screenings. However, the rate of secondary cancer screenings targeting high-risk subjects was lower (38% to 68%). The overall percentage of screening results leading to interventions was 4.5%, with higher percentages (> 10%) for bone density testing, ophthalmological examinations, dental assessment, upper gastrointestinal endoscopy, and colonoscopy, with two patients diagnosed with secondary cancers. CONCLUSIONS: Although the overall screening rate was high, it should be possible to improve the detection rate of late complications by decreasing screening failures, especially the screening for secondary cancers limited for high-risk survivors. A nationwide effort to educate HCT survivors and health practitioners using standardized nationwide LTFU tools may be effective, along with the development of institutional, local, and nationwide networks to maintain effective follow-up systems.

Time-Course of Salivary Metabolomic Profiles during Radiation Therapy for Head and Neck Cancer.

Oral mucositis (OM) is one of the most frequently observed adverse oral events in radiation therapy for patients with head and neck cancer. Thus, objective evaluation of OM severity is needed for early and timely intervention. Here, we analyzed the time-course of salivary metabolomic profiles during the radiation therapy. The severity of OM (National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events v3.0) of nine patients with head and neck cancer was evaluated. Partial least squares regression-discriminant analysis, using samples collected before radiation therapy, showed that histidine and tyrosine highly discriminated high-grade OM from low-grade OM before the start of radiation therapy (significant difference, p = 0.048 for both metabolites). Further, the pretreatment concentrations of gamma-aminobutyric acid and 2-aminobutyric acids were higher in the high-grade OM group. Although further validations are still necessary, this study showed potentially associated metabolites with worse radiotherapy-related OM among patients with head and neck cancer.

A cost-minimization analysis of measures against metallic dental restorations for head and neck radiotherapy.

The aim of this study was to compare the estimated public medical care cost of measures to address metallic dental restorations (MDRs) for head and neck radiotherapy using high-energy mega-voltage X-rays. This was considered a first step to clarify which MDR measure was more cost-effective. We estimated the medical care cost of radiotherapy for two representative MDR measures: (i) with MDR removal or (ii) without MDR removal (non-MDR removal) using magnetic resonance imaging and a spacer. A total of 5520 patients received head and neck radiation therapy in 2018. The mean number of MDRs per person was 4.1 dental crowns and 1.3 dental bridges. The mean cost per person was estimated to be 121 720 yen for MDR removal and 54 940 yen for non-MDR removal. Therefore, the difference in total public medical care cost between MDR removal and non-MDR removal was estimated to be 303 268 800 yen. Our results suggested that non-MDR removal would be more cost-effective than MDR removal for head and neck radiotherapy. In the future, a national survey and cost-effectiveness analysis via a multicenter study are necessary; these investigations should include various outcomes such as the rate of local control, status of oral mucositis, frequency of hospital visits and efforts of the medical professionals.

Effects of oral moisturizing gel containing propolis following head and neck radiotherapy: randomized controlled pilot trial.

AIM: Topical administration of oral gel may reduce radiotherapy-related oral complications. The aim of this study was to examine clinical and microbiological effects of self-administration of different gel formulations to oral mucosa in head and neck cancer patients. MATERIALS AND METHODS: Twenty-seven subjects were recruited from outpatients who underwent radiotherapy of at least 50 Gy to the head and neck area. They were randomly assigned to oral gel with the following different ingredients: placebo, chlorhexidine, curry leaf, propolis, and turmeric. Before and after intervention, oral symptoms were evaluated, and nine oral pathogens in saliva were also quantified using real-time PCR. RESULTS: Twenty-five subjects completed the study and their data were analyzed. The number of Porphyromonas gingivalis in saliva significantly decreased after treatment with propolis gel, but not after any other treatments. Propolis gel treatment also relieved oral pain in all subjects who had oral pain at the baseline. CONCLUSIONS: Topical administration with propolis gel may not only reduce P. gingivalis carriage in saliva, but also relieve oral pain. DISCUSSION: A future larger-scale clinical trial of oral propolis gel is needed to determine its clinical efficacy in radiotherapy-related oral complications of head and neck cancer patients.

Hybrid Intracavitary-Interstitial brachytherapy in a case of nasal vestibule cancer penetrating the hard palate.

Because of its rarity, no standard therapy exists for localized squamous cell carcinoma of the nasal vestibule. Interstitial brachytherapy (ISBT) is reported to be a preferable treatment modality of choice for early-stage localized nasal vestibule cancer. In this report, a nasal vestibule cancer with hard palate invasion (T3) was treated by definitive radiation therapy. Because it was considered to be difficult to cover the entire target volume only by ISBT, a hybrid of intracavitary (dental mold-based) and ISBT was applied to the patient following external beam radiation therapy.

The Japanese Herbal Medicine Hangeshashinto Induces Oral Keratinocyte Migration by Mediating the Expression of CXCL12 Through the Activation of Extracellular Signal-Regulated Kinase.

Several clinical studies have reported that Japanese herbal medicine Hangeshashinto (HST) has beneficial effects on chemotherapy-induced oral ulcerative mucositis (OUM). Our previous research demonstrated that HST improves chemotherapy-induced OUM through human oral keratinocyte (HOK) migration, which was suppressed by mitogen-activated protein kinase (MAPK) and C-X-C chemokine receptor 4 (CXCR4) inhibitors. However, the association between these molecules and HOK migration was unclear. Here, we examined the effects of HST on the expression of CXCR4/CXCR7 and C-X-C motif chemokine ligands 11 and 12 (CXCL11/CXCL12) in HOKs. Our results indicated that HST upregulated CXCL12, but not CXCR4, CXCR7, nor CXCL11 in HOKs. HST-induced expression of CXCL12 was significantly suppressed by an inhibitor of extracellular signal-regulated kinase (ERK), but not of p38 and c-Jun N-terminal kinase (JNK). In addition, HST induced phosphorylation of ERK in HOKs. These findings suggest that HST enhances HOK migration by upregulating CXCL12 via ERK.

Prognostic impact of immunohistopathologic features in definitive radiation therapy for nasopharyngeal cancer patients.

Our previous study by Murakami N, Mori T, Nakamura S, Yoshimoto S, Honma Y, Ueno T, Kobayashi K, Kashihara T, Takahashi K, Inaba K, Okuma K, Igaki H, Nakayama Y, Itami J. (J Radiat Res. 2019 Jul 30. pii: rrz053. doi: 10.1093/jrr/rrz053. [Epub ahead of print]) showed that strong expression of epithelial cell adhesion molecule (EpCAM) was associated with radiation resistance in head and neck squamous cell cancer patients (SCC). In this study, the prognostic impact of histopathologic features including EpCAM for nasopharyngeal cancer (NPC) patients was investigated. Since 2009, our institution has performed chemoradiation for locally advanced NPC patients with intensity modulated radiation therapy (IMRT). Tri-weekly adjuvant cisplatin (CDDP, 80 mg/m2) was administered concurrently with definitive radiation therapy 70 Gy in 35 fractions. One month after radiation therapy, adjuvant chemotherapy of three cycles of CDDP/5 fluorouracil (5-FU) was administered. Using a pretreatment biopsy specimen, EBV-encoded small RNA in situ hybridization (EBER-ISH), EpCAM, p16 and p53 were assessed by immunohistochemical analysis. Between May 2009 and September 2017, 51 NPC patients received definitive radiation therapy. Five, 13, 17 and 16 patients were staged as I, II, III and IV, respectively. The median follow-up period for alive patients was 31.1 months (12.4-109.7 months). Three-year overall survival (OS), progression-free survival (PFS) and locoregional control (LRC) were 87.1, 57.1 and 85.7%, respectively. EpCAM, p16 and p53 were not associated with PFS, OS nor LRC. Three-year PFS for patients with keratinizing and non-keratinizing SCC were 25 and 60.5%, respectively (P = 0.033, hazard ratio 4.851 (95% confidence interval 1.321-17.814)).Prognosis of NPC patients with keratinizing SCC was worse than non-keratinizing SCC patients, suggesting a biological difference between the two types of tumor.

Metabolomic profiling reveals salivary hypotaurine as a potential early detection marker for medication-related osteonecrosis of the jaw.

Medication-related osteonecrosis of the jaw (MRONJ) is a rare but serious adverse event of bone-modifying agents used to prevent bone complications in cancer patients with bone metastasis. Currently, early treatment is the only way to prevent further progression, as the pathogenesis of MRONJ has not yet been elucidated, and a standard treatment has not been established. The aim of this study was to identify a marker for early detection marker of MRONJ by exploring substances in saliva specific to MRONJ at an early stage. We collected salivary samples from 17 patients with MRONJ and conducted metabolomic analyses using capillary electrophoresis mass spectrometry for non-targeted analysis of hydrophilic metabolites. In the screening cohort, we compared the saliva of patients with stage ≥1 advanced MRONJ (n = 9) with that of controls without MRONJ before chemotherapy (n = 9). The top 5 most elevated salivary metabolites were histamine, 3-(4-hydroxyphenyl)propionate, malonate, carnosine, and hypotaurine. In the validation cohort, we analyzed additional patients with stage ≥1 advanced MRONJ (n = 8) and controls without MRONJ after chemotherapy (n = 9), confirming a significant 2.28-fold elevation in the salivary concentration of hypotaurine. These results revealed elevated salivary hypotaurine concentration as a potential marker for the early detection of MRONJ.

Is Oral Mucositis Occurring During Chemotherapy for Esophageal Cancer Patients Correctly Judged? EPOC Observational Cohort Study.

BACKGROUND/AIM: Oral mucositis (OM) is one of the frequent adverse events experienced by patients receiving chemotherapy. Most diagnoses of OM are based on complaints from patients. The aim of this study was to develop a tool to diagnose OM accurately. MATERIALS AND METHODS: A central review system (CRS) was created to allow judgment when the patient background is completely unknown. The primary endpoint was the rate of grade 2 or higher OM, and the secondary endpoint was the difference in grade between each institution's clinician judgement and that of the CRS. RESULTS: In total, 53 patients were registered from four institutions. CRS successfully detected grade 2 or higher OM in 16 (30.2%) of the 53 patients. The detection rate of all grades of OM was 41.5% (22 of 53 patients) by each institution's clinician judgement and 84.9% (45 of 53 patients) by CRS judgement (p<0.0001). CONCLUSION: OM during chemotherapy may be underestimated.

Prognostic value of the expression of epithelial cell adhesion molecules in head and neck squamous cell carcinoma treated by definitive radiotherapy.

A reliable biomarker can contribute to appropriate treatment selection in the management of head and neck squamous cell carcinoma (HNSCC). Recently, epithelial cell adhesion molecule (EpCAM) was shown to have prognostic features in several malignancies. However, it remains to be elucidated whether EpCAM predicts prognosis of HNSCC after radiotherapy. Therefore, the prognostic potential of EpCAM in HNSCC patients treated by radiotherapy was investigated in this study. All HNSCCs patients examined between January 2013 and December 2015 were analyzed for the expression of EpCAM. One hundred HNSCC patients were identified who were treated by primary radiotherapy. Intense expression of EpCAM was found in 29 HNSCC patients. Two-year overall survival (OS) for patients with intense EpCAM expression was 62.2%, whereas it was 87.9% for those without (P = 0.011). In multivariate analysis, intense EpCAM expression was found to be an independent prognostic factors for OS (P = 0.036). Overall, EpCAM was found to be an independent prognostic factor for HNSCC.

The post hoc analysis comparing the severity grades of chemoradiotherapy-induced oral mucositis scored between the central and local assessors in a multicenter, randomized controlled trial of rebamipide for head and neck cancer.

BACKGROUND: In the treatment of head and neck cancer, severity of chemoradiotherapy-induced oral mucositis has been recognized as one of the key factors affecting the outcomes of the anticancer therapies. Therefore, the development of treatments mitigating oral mucositis would be of clinical significance, although the adequate assessment procedure for efficacy evaluation remains to be established. We conducted this post hoc study to assess the effect of objective evaluation of the severity grade on the outcomes of the clinical trial. METHODS: In the original trial with rebamipide liquids (0, 2, and 4%) for chemoradiotherapy-induced oral mucositis, the investigators in local sites and independent central review separately determined the severity grades in accordance with Common Terminology Criteria of Adverse Events version 3.0 based on the Assessment Sheet scored by the investigators. The discordance in severity grades between the investigators and central review was analyzed on cross table. RESULTS: The analysis revealed the discordance rate over the trial was 34%. While the incidences of severe oral mucositis in the placebo, rebamipide 2%, and 4% groups evaluated by the central review were 39%, 29%, and 25%, respectively, the respective values in the investigator's evaluation were 32%, 39%, and 44%. CONCLUSION: In the clinical trial for the treatment of oral mucositis, it was strongly suggested that objective evaluation with a consistent scale would be required.

Dose coverage comparison between "interstitial catheter-only" and "hybrid intracavitary-interstitial brachytherapy" for early stage squamous cell carcinoma of the buccal mucosa.

PURPOSE: When squamous cell carcinoma of the buccal mucosa (BSCC) extends surrounding anatomical sites such as gingiva, retromolar triangle, or hard palate, it might be challenging to ensure adequate tumor coverage by sole interstitial brachytherapy due to the complexity of catheter implantation. By combining interstitial catheters with an enoral placed, individually assembled "oral spacer plus embedded catheters" device (hybrid of intracavitary-interstitial brachytherapy), it should be easier to deliver the necessary tumoricidal dose to irregular-shaped tumor volumes (clinical target volume - CTV) with improved conformity. The purpose of this analysis was to compare the dose distribution created by the hybrid of intracavitary-interstitial brachytherapy (HBT) with the dose distribution of an interstitial catheter only-approach, based on the interstitial catheters used for HBT (ISBT-only) by evaluating respective treatment plans (HBT plan vs. ISBT-only plan) for the treatment of early stage BSCC. MATERIAL AND METHODS: A retrospective analysis was performed for patients with localized BSCC treated between April 2013 and October 2017. All patients received sole HBT without additional external beam radiation therapy or planned neck dissection. Dosimetric parameters taken into account for comparison between actual HBT and virtual ISBT-only were CTV D90, CTV V100, CTV V150, CTV V200, mandible D2cc, and mucosal surface D2cc. RESULTS: Dosimetrically, HBT showed a trend toward better CTV D90 compared to ISBT-only. In addition, HBT demonstrated statistically better CTV V100 coverage compared to ISBT-only. There was no statistically significant difference with respect to CTV V150, CTV V200, and mucosal surface D2cc, while a trend was seen in better mandible D0.1cc between HBT and ISBT-only. CONCLUSIONS: The HBT approach appears to enable improved dose coverage of irregular-shaped enoral tumor volumes compared to ISBT-only for patients with early stage BSCC.

The effect of an elemental diet on oral mucositis of esophageal cancer patients treated with DCF chemotherapy: a multi-center prospective feasibility study (EPOC study).

PURPOSE: Oral mucositis (OM) is one of the most uncomfortable adverse events experienced by cancer patients undergoing chemotherapy. Previous reports have revealed that the oral administration of an elemental diet (ED) may prevent OM. However, the incidence of OM has not been accurately determined by specialized diagnostic methods and the effects of an ED on OM remain unclear. We investigated the dose that could feasibly be administered and its effects with regard to the suppression of OM in esophageal cancer patients undergoing chemotherapy. METHODS: We performed a prospective multi-center feasibility study of the administration of an ED (160 g/day) with 2 cycles of docetaxel/cisplatin/5-FU (DCF) chemotherapy. We assessed compliance to the ED for 49 days and the incidence of OM according to the amount of the ED that was orally administered. The incidence of OM was graded by a dental specialist who was experienced in dental oncology using a central OM review system. RESULTS: Fourteen of 20 patients (70%) were able to complete the orally administered ED (160 g/day) during the course of chemotherapy. Three patients (15%) could not take the ED orally for 9, 14, and 21 days, respectively, while 1 patient (5%) took the ED orally at an average dose of 80 g/day for 35 days. The remaining 2 patients (10%) could not take the 80 g/day dose for 11 and 12 days, respectively. The incidence of grade ≥ 2 OM in the ED completion group (15.4%, 2 of 13 patients) was significantly lower than that in the non-completion group (66.7%, 4 of 6 patients) (p = 0.046). CONCLUSIONS: An ED might be a one of the test treatment to reduce the incidence of OM in esophageal cancer patients treated with DCF and should be evaluated in further randomized study. CLINICAL TRIAL: The date of submission: Dec 08th, 2017.

Patterns of recurrence after selective postoperative radiation therapy for patients with head and neck squamous cell carcinoma.

BACKGROUND: The radiation field for patients with postoperative head and neck squamous cell carcinoma is narrower in our institution than in Western countries to reduce late radiation related toxicities. This strategy is at a risk of loco-regional or distant metastasis. However, because patients are more closely checked than in Western countries by every 1 to 2 months intervals and it is supposed that regional recurrences are identified and salvage surgeries are performed more quickly. Therefore, it is considered that patient survival would not be compromised with this strategy. The aim of this study was to investigate the feasibility of this strategy retrospectively. METHODS: Patients who underwent neck dissection with close or positive margin, extra-capsular spread (ECS), multiple regional lymph node metastasis, pT4, with or without primary tumor resection were treated with postoperative radiation therapy. The volume of radiation field, especially the coverage of prophylactic regional lymph node area, was discussed among head and neck surgeons and radiation oncologists taking into account the clinical factors including patient's age, performance status, number of positive lymph nodes, size of metastatic lymph nodes, extension of primary tumor beyond the midline, and existence of ECS. RESULTS: Seventy-two patients were identified who were treated with postoperative radiation therapy for head and neck squamous cell carcinoma between November 2005 and December 2014. There were 20 patients with oropharynx, 19 with hypopharynx, 7 with larynx, 23 with oral cavity, and 3 with other sites. Thirty eight patients had their neck irradiated bilaterally and 34 unilaterally. Median follow-up period for patients without relapse was 20.7 months (5.1-100.7). Thirty two patients had disease relapse after treatment including 22 loco-regional recurrence and 14 distant metastases. Among 22 loco-regional recurrence, seven patients underwent salvage surgery and one of them was no relapse at the time of the analysis. Among patients without bilateral neck lymph node metastasis who were treated with unilateral neck irradiation, patients with oral cavity or recurrent disease had significantly lower DFS compared with those without (2-y DFS 41.7 % vs 88.2 %, p = 0.017). CONCLUSIONS: In patients without bilateral neck lymph node involvement, the postoperative unilateral neck irradiation is a reasonable treatment strategy for patients with the exception of oral cavity or recurrent disease.

Treatment for Cancer Patients with Oral Mucositis: Assessment Based on the Mucositis Study Group of the Multinational Association of Supportive Care in Cancer in International Society of Oral Oncology (MASCC/ISOO) in 2013 and Proposal of Possible Novel Treatment with a Japanese Herbal Medicine.

The cancer patients who received chemotherapy, radiotherapy, hematopoietic stem cell transplant and terminal care often have a wide range of stomatitis, which induces severe pain and limits fundamental life behaviors such as "eating, drinking and talking". In addition, oral mucositis frequently leads to systemic infection through opportunistic microorganisms, which causes extension of hospitalization. Severe oral mucositis often causes cancer patients to partially or completely discontinue/modify cancer therapy regimen, which adversely affects the curative effects of cancer. Therefore, the control of oral mucositis is important and indispensable for improvement of quality of life and prognosis. In this review, we introduce recent trends of the oral mucositis management in cancer patients, according to the following sentences; 1) pathophysiological mechanisms of oral mucositis, 2) assessment, 3) risk factors, 4) prevention and treatment, and 5) development of novel therapy for oral mucositis.