Depressive symptoms and oral mucositis in children with oncological diseases: a cross-sectional study.

The aim of this study was to investigate the correlation between depressive symptoms and the occurrence of oral mucositis in children with oncological diseases treated at a reference hospital. This was a cross-sectional study conducted with individuals aged 4 to 18 years, diagnosed with primary neoplasms. Data was collected by using a questionnaire that assessed the degree of oral mucositis according to the World Health Organization index, the risk of oral mucositis according to the Child's International Mucositis Evaluation Scale, and depressive symptoms using the Children's Depression Inventory. The data were analyzed and subjected to Spearman's correlation, chi-square test, and Fisher's exact test, considering p<0.05. A statistically significant correlation was observed between depressive symptoms and the degree of oral mucositis (p = 0.044), and also between the "pain" variable within the risk of oral mucositis and depressive symptoms (p = 0.021). Based on the findings, it can be inferred that oral mucositis may be associated with the development of depressive symptoms and may be influenced by the individual's hospitalization, thereby affecting the quality of life of pediatric patients.

Patient-, implant- and prosthetic-related factors on peri-implant mucositis and bone loss.

Peri-implant diseases, including peri-implant mucositis (PIM) and peri-implantitis, are a chronic inflammatory disorder triggered by bacterial biofilm in susceptible hosts. Potential risk factors for peri-implant diseases include smoking, dental plaque accumulation, poor oral hygiene, genetics, and absence of peri-implant keratinized mucosa. This cohort study aimed to evaluate the influence of patient-, implant-, and prosthetic-related factors on PIM and peri-implant bone loss (PBL) around dental implants after 1 year of loading. A total of 54 subjects (22 males and 32 females) were included in the study. Peri-implant clinical parameters were assessed and standardized periapical radiographs of each dental implant were obtained 15 days after the definitive prosthesis installation (baseline) and at 3, 6, and 12 months of follow-up. A total of 173 implants were evaluated. PIM affected 44.8% of the implants and no significant association was found between the investigated parameters and PIM incidence, except for type of implant connection. A significantly higher incidence of PIM (80.0%) was observed for implants with internal hexagon connection type after 1 year of follow-up (p = 0.015). Moreover, a mean PBL of 0.35 ± 1.89 mm was observed and no dental implant was affected by peri-implantitis after 1 year of function. No specific influence of patient, implant, or prosthetic factors on PBL was observed. No association was found between the occurrence of PIM/PBL and the patient-, implant-, and prosthetic-related factors investigated in this cohort study, except for the type of dental-implant connection.

In Response to "Acute Oral Mucositis During Hypo-Fractionated Radiation in Squamous Cell Carcinoma of Oral Cavity".

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Efficacy of Episil® in patients with hematologic malignancies: a comparative study.

BACKGROUND: Episil® is a nonabsorbable liquid medical material used to coat and protect the mucosa in patients with oral mucositis. A few studies have reported its efficacy in patients with head and neck cancer. However, reports on its use in patients with hematologic malignancies are scarce. Thus, we aimed to evaluate the efficacy of Episil for the treatment of oral mucositis in patients with acute myelogenous leukemia, malignant lymphoma, acute lymphocytic leukemia, multiple myeloma, and myelodysplastic syndrome. METHODS: Between May 2018 and March 2019, a total of thirty-seven patients with acute myelogenous leukemia, malignant lymphoma, acute lymphocytic leukemia, multiple myeloma, and myelodysplastic syndrome who received Episil® for the treatment of oral mucositis were included in this study. All patients were treated at the Hiroshima Red Cross and Atomic-bomb Surgery Hospital. To determine the severity of oral mucositis, 22 out of the 37 patients were interviewed and compared objectively using the Common Terminology Criteria for Adverse Events, version 3.0. In addition, subjective measures of the effects of oral mucositis were assessed using an original evaluation protocol (a unique evaluation chart specific to the Department of Oral Surgery, Hiroshima Red Cross & Atomic-bomb Survivors Hospital). RESULTS: Out of 37 participants recruited in the study, 31 (84%) described the sensation of Episil® as very good or good. Moreover, the severity of mucositis was found to decrease after the use of Episil® in seven patients out of 22 (19%), particularly in those with mucositis at multiple sites. Participants' evaluations revealed pain relief and improvement in speech and feeding functions. Participants with grade 3 mucositis reported a greater improvement in pain relief, speech, and feeding functions than those with grade 2 mucositis. CONCLUSIONS: This study suggests the efficacy of Episil® in treating oral mucositis in patients with hematologic malignancies, particularly in those with oral mucositis at multiple sites. In addition to pain relief, Episil® may improve speech and feeding functions.

Comparisons of successful and failed Phase III trials of drugs and biologicals tested for mitigation of oral mucositis in patients being treated with radiotherapy with or without concomitant chemotherapy for cancers of the head and neck.

Oral mucositis (OM) remains a significant toxicity among patients being treated with radiotherapy (RT) alone or with concomitant chemotherapy (CRT) for cancers of the head and neck (HNC). Given its clinical significance as an unmet need and its potential commercial viability, the pharmaceutical industry has been actively pursuing an effective intervention. Despite this interest and activity, only a few agents have been studied in Phase III trials (n = 6). The objective of this study was to identify common features that differentiate successful and failed Phase III OM trials. We used the United States Patent and Trademark Office Patent Public Search database to search patents with "oral mucositis" in the claims. We then searched ClinicalTrials.gov and PubMed to determine if Phase III or Phase II trial data for identified biologics/drugs had been published. We assessed each Phase III and Phase II trial for characteristics that may be associated with trial success or failure. We considered a study as a "success" if the primary endpoint reached statistical significance, and we considered a study as "failure" if the primary endpoint did not reach statistical significance. Of the three successful Phase III trials, one investigated avasopasem manganese (Galera Therapeutics) and two examined palifermin (Amgen). The three failed trials included those evaluating dusquetide (Soligenix), iseganan hydrochloride (IntraBiotics Pharmaceuticals), and clonidine (Monopar Therapeutics). We found that differences in the level of sponsor funding, patient inclusion criteria including radiation source and concomitant chemotherapy regimen, and concordance of primary efficacy outcomes between Phase II and Phase III trials influenced outcomes. To properly design clinical trials for OM in HNC patients, it is important that researchers and sponsors take note of specific study characteristics associated with success or failure, particularly with Phase III trials where the risks and costs are the highest.

Implementation of a light therapy team to administer photobiomodulation therapy: A standardized protocol to prevent and treat oral mucositis in the pediatric hematopoietic stem cell transplant population.

BACKGROUND: Oral mucositis (OM) is a painful and common complication of hematopoietic stem cell transplant (HSCT). The Children's Oncology Group recently published guidelines recommending photobiomodulation (PBM) for preventing and treating OM in pediatric HSCT patients. However, this is a rarely used intervention in pediatric hospitals. PROCEDURE: Patients undergoing allogeneic HSCT, or autologous HSCT for a neuroblastoma diagnosis, had PBM administered from the first day of conditioning to transplant Day +20. We successfully developed a standardized treatment protocol and workflow to ensure consistent and uniform delivery of PBM. In addition, clinical patient data were compared before and after PBM implementation. RESULTS: The administration of PBM at our center was feasible, but required dedicated staff. A registered nurse (RN) was determined to be the best fit to deliver PBM. Sixty-two patients received PBM from October 2022 to September 2023; patients from 2021 before PBM implementation were used for comparison. Patients receiving PBM were more likely (p = .03) to engage in teeth brushing (56/62 = 90%) compared to baseline (61/81 = 75%). Mean days of OM decreased from 11.3 to 9 days; patients who received PBM were less likely (p < .001) to be discharged on total parental nutrition (TPN) (11/62 = 18%) compared to baseline (50/82 = 61%). OM-related supportive care costs (TPN and patient-controlled anesthesia [PCA]) were lower (p = .02) for those who received PBM (median cost = $31,229.87 vs. $37,370.66). CONCLUSION: PBM, as the standard of care in the pediatric HSCT population, is safe, feasible, and well-tolerated. At our center, a dedicated RN was critical to providing standardized treatment and ensuring sustainability.

The role of probiotic therapy on clinical parameters and human immune response in peri-implant diseases: a systematic review and meta-analysis of randomized clinical studies.

Background: Peri-implant diseases (peri-implant mucositis and peri-implantitis) are pathologies of an infectious-inflammatory nature of the mucosa around dental implants. Probiotics are microorganisms that regulate host immunomodulation and have shown positive results in the treatment of peri-implant diseases. The objective of the systematic review and meta-analysis was to evaluate the efficacy of probiotics in the treatment of peri-implant oral diseases. Methods: According to the PRISMA guidelines, the research question was established: Are probiotics able to favorably modify clinical and immunological biomarkers determinants of peri-implant pathologies? and an electronic search of the databases MEDLINE/PubMed, Embase, Cochrane Central, Web of Science, (until December 2023) was performed. Inclusion criteria were established for intervention studies (RCTs), according to the PICOs strategy in subjects with peri-implant pathology (participants), treated with probiotics (intervention) compared to patients with conventional treatment or placebo (control) and evaluating the response to treatment (outcomes). Results- 1723 studies were obtained and 10 were selected. Risk of bias was assessed using the Cochrane Risk of Bias Tool and methodological quality using the Joanna Briggs Institute for RCTs. Two meta-analyses were performed, one to evaluate probiotics in mucositis and one for peri-implantitis. All subgroups were homogeneous (I2 = 0%), except in the analysis of IL-6 in mucositis (I2 = 65%). The overall effect was favorable to the experimental group in both pathologies. The analysis of the studies grouped in peri-implantitis showed a tendency to significance (p=0.09). Conclusion: The use of probiotics, as basic or complementary treatment of peri-implant diseases, showed a statistically significant trend, but well-designed studies are warranted to validate the efficacy of these products in peri-implant pathologies.

Honey in Alleviating Severe Oral Mucositis Among Head and Neck Cancer Patients Undergoing Radiation Therapy.

BACKGROUND/AIM: Aiming to resolve debates on honey's efficacy for radiotherapy-induced severe oral mucositis in head and neck cancer, we conducted a meta-analysis focused on randomized trials, primarily assessing severe mucositis incidence. Secondary outcomes included weight loss, pain management, and honey types. MATERIALS AND METHODS: A comprehensive literature search was conducted in PubMed, Embase, WOS, and the Cochrane Library up to December 2023. The analysis concentrated on randomized controlled trials that assessed the efficacy of honey, targeting the incidence of mucositis as the main outcome. Additional outcomes explored were weight loss, intolerable pain, and the specific types of honey used in interventions. Data analysis was performed using CMA software, and a funnel plot was employed to identify publication bias. RESULTS: The analysis of 176 records resulted in the inclusion of 10 studies with 599 patients receiving radiotherapy. The research showed that honey significantly reduced the occurrence of grade 3-4 mucositis (severe mucositis), provided significant pain relief, and had a positive effect on reducing weight loss. Regarding the type of honey used, no significant differences were found in their effectiveness in alleviating severe mucositis. CONCLUSION: Honey serves as an effective intervention for individuals with oral mucositis. It can be considered as an adjuvant in the management of clinical radiotherapy-associated oral mucositis, particularly for patients requiring prolonged use of anti-analgesic or antifungal medications.

Prevention and Treatment of Oral Mucositis in Pediatric Patients: Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND/AIM: Oral mucositis (OM) is a common and serious side effect of cancer treatment. The incidence of chemotherapy-induced OM in pediatric patients can reach up to 91.5% and has a major impact on patients' quality of life. The aim of the study was to assess the efficacy of current interventions and agents for the management of OM in children undergoing chemo/radiotherapy or hematopoietic stem cell transplantation (HSCT). MATERIALS AND METHODS: A systematic search of randomized controlled trials (RCTs) was conducted in the MEDLINE and Scopus databases from January 2000 until March 2023. Thirty-four randomized studies meeting the inclusion criteria were identified and five RCTs investigating the efficacy of Low Level Laser Therapy (LLLT) intervention or the agent honey were included in the meta-analysis. RESULTS: The meta-analysis of two RCTs indicated that topical application of honey on oral mucosa was effective in shortening the mean duration of hospital stay in children with severe OM (MD=-4.33, p=0.002). However, LLLT was not found to be effective for the prevention or treatment of OM grade ≥II (RR=0.99, p=0.99). Moreover, the therapeutic application of LLLT did not show significant benefit for lower risk of OM grade ≥II (RR=0.48, p=0.58). CONCLUSION: Various interventions and agents were examined in the present study for the management of OM. Honey could be a promising candidate for the treatment of OM in pediatric patients. Further high-quality RCTs are required to enhance our findings.

Prediction of severe radiation-induced oral mucositis in locally advanced nasopharyngeal carcinoma using the combined systemic immune-inflammatory index and prognostic nutritional index.

OBJECTIVE: Severe radiation-induced oral mucositis (sRIOM) can seriously affect patients' quality of life and treatment compliance. This study was to investigate the utility of the systemic immune-inflammatory index (SII) and prognostic nutritional index (PNI) in predicting sRIOM in patients with locally advanced nasopharyngeal carcinoma (LANPC). METHODS: 295 patients with LANPC were retrospectively screened. The pre-radiotherapy SII and PNI were calculated based on peripheral blood samples. A receiver operating characteristic (ROC) curve was used to determine the cut-off value. Logistic regression was used for univariate and multivariate analyses. Patients were classified into three groups based on the SII-PNI score: score of 2, high SII (> cut-off value) and low PNI (≤ cut-off value); score of 1, either high SII or low PNI; score of 0, neither high SII nor low PNI. RESULTS: The SII-PNI demonstrated significant predictive ability for sRIOM occurrence, as evidenced by an area under the curve (AUC) of 0.738. The incidence rates of sRIOM with SII-PNI score of 2, 1, and 0 were 73.86%, 44.35%, and 18.07%, respectively. Multivariate analysis confirmed that the SII-PNI score was an independent risk factor for sRIOM. CONCLUSION: The SII-PNI score is a reliable and convenient indicator for predicting sRIOM in patients with LANPC.

Local Oxygen-Based Therapy (blue®m) for Treatment of Peri-Implant Disease: Clinical Case Presentation and Review of Literature about Conventional Local Adjunct Therapies.

Peri-implant diseases including peri-implant mucositis and peri-implantitis are among the major causes of failure of implant-supported dental restorations. They are characterized by progressive inflammation of the peri-implant mucosa, extending to the surrounding connective tissues and leading to bone loss and implant failure. Although strict oral hygiene practices help in preventing peri-implant diseases, plaque buildup around the implant restoration leads to chronic inflammation, due to the adherent bacterial biofilm. While mechanical debridement and non-surgical therapy to remove inflamed connective tissue (ICT) form the mainstay of treatment, additional local adjunctive therapies enhance clinical outcomes. Topical oxygen therapy is known to reduce inflammation, increase vascularity, and act as a bacteriostatic measure. The use of oxygen-based therapy (blue®m) products as a local adjunctive therapy for peri-implant mucositis and peri-implantitis can result in clinical outcomes similar to that of conventional local adjuncts such as chlorhexidine, antibiotics, and antibacterial agents. This report aims to present the clinical findings of patients with peri-implant mucositis and peri-implantitis, who were managed using local oxygen-based therapy as an adjunct to non-surgical therapy. In addition, a review of the literature about commonly used local adjuncts for peri-implant diseases has been included in the report to provide a means of comparison between conventional local adjunct therapy and topical oxygen-based therapy. Based on the reported findings and reviewed literature, local oxygen-based adjunct therapy was equally effective as conventionally used local adjuncts such as antibiotics, antibacterials, and probiotics, in treating patients with peri-implant diseases.

[Questionnaire Survey on Oral Care and Oral Troubles for Patients with Gastric Cancer Received Chemotherapy].

BACKGROUND: The actual situation of oral care and oral troubles for patients with gastric cancer received chemotherapy is not clear. METHODS: Questionnaire survey in the form of oral questions was performed for patients with gastric cancer who received chemotherapy from December 2021 to February 2022. The relevance between the survey results and background factors was examined using the χ2 test. RESULTS: We performed the questionnaire survey for 36 patients. Of the 36 patients, 29 patients received dental check-up before starting chemotherapy. Fourteen of the 29 patients(48%)continued the dental check-up. Of 14 patients who continued the dental check-up, 9 patients were 65 years or older, while 14 of 15 patients who discontinued the dental check-up were 65 years or older. Continuity of dental check-up was low among the elderly patients. The rate of dysgeusia were 78 vs 30% in the patients who adopted and who did not adopt oral care other than toothbrushing(p=0.01). The frequency of oral troubles was dysgeusia(47%), stomatitis(42%), and dry mouth(36%). The severity of the oral troubles was, in order, dysgeusia, dry mouth, and pain. The most common side effect due to chemotherapy causing decreased food intake was dysgeusia. CONCLUSIONS: Dysgeusia was the most frequent and severe oral trouble.

Preventive versus curative photobiomodulation for oral mucositis in patients with multiple myeloma undergoing hematopoietic stem cell transplantation: which approach is more effective?

PURPOSE: There is increasing evidence that photobiomodulation (PBM) therapy is both an effective and safe approach in hematopoietic stem cell transplantation (HSCT) for both prevention and management of oral mucositis (OM), but its use in clinical practice is still limited and the timing of application is under discussion. The aim of this retrospective study was to evaluate possible differences between patients treated either with preventive or curative PBM therapy. METHODS: The retrospective case series included 24 patients suffering from multiple myeloma who underwent the same conditioning and transplantation protocol. Patients were treated either with preventive PBM starting from the first day of conditioning up to two days post-HSCT or with curative PBM (starting at OM onset for four consecutive days). OM score, pain, and functional parameters were recorded. RESULTS: All patients developed OM. Preventive PBM was significantly more effective in reducing OM severity (p < 0.0001) and pain (p < 0.0001) post-HSCT than curative PBM. Furthermore, we found a lower number of patients reporting discomfort in all subjective parameters (pain during swallowing, chewing, and speaking) in the preventive PBM group. No adverse events related to PBM therapy were recorded in both groups. CONCLUSION: The timing for PBM therapy in patients undergoing HSCT is crucial: when started on the first day of conditioning, it significantly reduces both pain and OM severity, providing an important benefit also in subjective oral functions such as speaking, swallowing, and chewing, thus increasing the overall adherence to the oncological therapies.

Oral Complications and Management Strategies for Cancer Patients: Principles of Supportive Oncology in Dentistry.

PURPOSE OF REVIEW: It is recognized that patients undergoing cancer treatment experience different adverse effects depending on the type of therapy they received. The objective of this work is to provide a scientific evidence-based protocol for oral care in cancer patients. Cancer resection surgery, chemotherapy, and radiotherapy can cause important complications that impact patients' quality of life. RECENT FINDINGS: Cancer patients, from the moment of diagnosis to the end of treatment and subsequent follow-up, have diverse care needs, both from a systemic and local point of view. The implementation of oral care protocols before, during, and after cancer therapy is essential because it helps to identify risk factors for the development of predictable oral complications. It is essential to establish that all cancer patients, before starting treatment, undergo a systematic dental check-up to avoid limitations during treatment and also alter their quality of life. Regular professional oral care maintenance and follow-up programs are essential to maintaining a patient's long-term oral health.

Efficacy of nonpharmacological interventions for severe radiation-induced oral mucositis among head and neck cancer patients: A network meta-analysis of randomised controlled trials.

AIMS AND OBJECTIVES: To assess the effectiveness of different nonpharmacological treatments for severe radiation-induced oral mucositis in patients with head and neck cancer. BACKGROUND: Radiation-induced oral mucositis is highly prevalent in patients with head and neck cancer. Current medications for radiation-induced oral mucositis are limited in effectiveness and susceptible to side effects, and while there is an increasing adoption of nonpharmacological interventions, the optimal one remains unclear. DESIGN: Systematic review and network meta-analysis based on the PRISMA-NMA guidelines. METHODS: Six databases were searched. Two authors independently performed the literature screening, data extraction and methodological quality assessment of the included studies. Traditional pairwise meta-analysis was performed by R Studio. A network meta-analysis was then conducted to assess the effects of nonpharmacological interventions for severe radiation-induced oral mucositis in patients with head and neck cancer. RESULTS: Fifty-two studies involving seven types of nonpharmacological interventions were enrolled. The network meta-analysis indicated that natural plant-based therapies might be the most effective, health education interventions might be the second most effective, and honey might be the third most effective interventions for reducing the incidence of severe radiation-induced oral mucositis. For reducing the incidence of severe oral mucositis-related pain, the pairwise meta-analysis showed that only natural plant-based therapies and health education interventions were effective. CONCLUSIONS: Nonpharmacological interventions are effective in the management of severe radiation-induced oral mucositis among patients with head and neck cancer. RELEVANCE TO CLINICAL PRACTICE: Nonpharmacological interventions are a category of safe and effective adjunctive therapies that should be encouraged in clinical practice. TRIAL REGISTRATION DETAILS: CRD42023400745.

TGF-ß3 increases the severity of radiation-induced oral mucositis and salivary gland fibrosis in a mouse model.

PURPOSE: Toxicities from head and neck (H&N) radiotherapy (RT) may affect patient quality of life and can be dose-limiting. Proteins from the transforming growth factor beta (TGF-ß) family are key players in the fibrotic response. While TGF-ß1 is known to be pro-fibrotic, TGF-ß3 has mainly been considered anti-fibrotic. Moreover, TGF-ß3 has been shown to act protective against acute toxicities after radio- and chemotherapy. In the present study, we investigated the effect of TGF-ß3 treatment during fractionated H&N RT in a mouse model. MATERIALS AND METHODS: 30 C57BL/6J mice were assigned to three treatment groups. The RT + TGF-ß3 group received local fractionated H&N RT with 66 Gy over five days, combined with TGF-ß3-injections at 24-hour intervals. Animals in the RT reference group received identical RT without TGF-ß3 treatment. The non-irradiated control group was sham-irradiated according to the same RT schedule. In the follow-up period, body weight and symptoms of oral mucositis and lip dermatitis were monitored. Saliva was sampled at five time points. The experiment was terminated 105 d after the first RT fraction. Submandibular and sublingual glands were preserved, sectioned, and stained with Masson's trichrome to visualize collagen. RESULTS: A subset of mice in the RT + TGF-ß3 group displayed increased severity of oral mucositis and increased weight loss, resulting in a significant increase in mortality. Collagen content was significantly increased in the submandibular and sublingual glands for the surviving RT + TGF-ß3 mice, compared with non-irradiated controls. In the RT reference group, collagen content was significantly increased in the submandibular gland only. Both RT groups displayed lower saliva production after treatment compared to controls. TGF-ß3 treatment did not impact saliva production. CONCLUSIONS: When repeatedly administered during fractionated RT at the current dose, TGF-ß3 treatment increased acute H&N radiation toxicities and increased mortality. Furthermore, TGF-ß3 treatment may increase the severity of radiation-induced salivary gland fibrosis.

Increased frequency of oral plasma cell mucositis/plasma cell gingivitis after the COVID-19 pandemic: a 23-year retrospective analysis and review of diagnostic challenges relating to this condition.

OBJECTIVE: Oral plasma cell mucositis (PCM) or localized plasma cell gingivitis (PCG) is an idiopathic inflammatory condition often associated with hypersensitivity reactions. This study aimed to evaluate the frequency and features of PCM/PCG in a large biopsy service over a time period of more than 20 years. STUDY DESIGN: The biopsy archives at University of Florida College of Dentistry were searched from 2000 through the first quarter of 2023 for cases of oral PCM or PCG. Case data were aggregated and analyzed. RESULTS: A total of 107 cases were included. Between 2000 and 2019, PCM/PCG was diagnosed in 0.03% of all biopsy cases. Starting in 2020 through 2023, the percentage of biopsies diagnosed as PCM/PCG increased threefold to 0.10% of all biopsy cases, and the mean patient age increased by 3 years. There were no statistically significant differences between cases diagnosed from 2000 to 2019 and those from 2020 to 2023 regarding age, sex, location, or histology. CONCLUSIONS: A significant increase in PCM/PCG was identified in this study at one institution coinciding with the start of the COVID-19 pandemic. Further investigation is recommended to determine if this is a widespread phenomenon and identify possible etiologic mechanisms.

Effectiveness of intraoral stents in reducing oral adverse events during radiotherapy for maxillary or nasal cavity malignant tumors.

PURPOSE: Many patients experience oral adverse events during head and neck cancer radiotherapy (RT). The methods of management of such events are under debate. One such technique is the intraoral stent (IOS) technique, which removes normal tissue from the irradiation field. This retrospective study examined the factors associated with the occurrence of oral mucositis (OM) and dysgeusia and the efficacy of IOSs in preventing them. METHODS: Twenty-nine patients who underwent RT in the maxilla or nasal cavity between 2016 and 2022 were included. They were investigated for background characteristics, treatment factors (IOS and dose-volume histogram), and oral adverse events (OM and dysgeusia). RESULTS: Significant risk factors for the incidence of grade ≥ 2 (Common Terminology Criteria for Adverse Events v5.0) OM were the non-use of IOSs (p = 0.004) and diabetes (p = 0.025). A significant risk factor for the incidence of grade ≥ 1 dysgeusia was concomitant chemotherapy (p = 0.019). The radiation dose to the tongue was significantly lower in the IOS group than in the non-IOS group. CONCLUSION: Our findings suggest that the use of an IOS during RT reduces the severity of OM by reducing irradiation to the tongue. Therefore, the use of an IOS is recommended during RT performed in the maxilla or nasal cavity.

Utilization of Photobiomodulation for the Prevention and Treatment of Oral Mucositis.

Background: Oral mucositis is a significant and common toxicity experienced by patients who receive high-dose chemotherapy as a preparatory regimen for a hematopoietic cell transplant (HCT). Photobiomodulation (PBM) has been found to be feasible with significant efficacy in preventing the progression of oral mucositis in adult patients undergoing HCT. The purpose of this study was to determine the feasibility and efficacy of PBM in pediatric oncology patients undergoing HCT. Method: Forty children and adolescents admitted to the transplant unit for an allogeneic HCT for acute lymphoblastic leukemia or acute myeloid leukemia were treated daily at six sites until day + 20 or engraftment. Results: There were 1,035 patient encounters, with successful treatment of four or more sites during 979 patient encounters for a feasibility 93.3% CI [0.926, 0.039]. We had estimated a meaningful effect size of 20% for PBM and estimated 51% of patients treated with PBM would have at least one day or more of Grade 3 mucositis. The rate of patients who received PBM and developed Grade 3 mucositis was 20% CI [0.091, 0.356]. Patients treated with PBM had fewer days of hospitalization (p = .009) and less severe mucositis in comparison to the matched control group (p = .03). Conclusion: PBM is feasible and effective in preventing and treating oral mucositis and is now supported by the Children's Oncology Group for prevention and treatment of oral mucositis in patients undergoing an allogeneic HCT or receiving head/neck radiation.

TLD-1, a novel liposomal doxorubicin, in patients with advanced solid tumors: Dose escalation and expansion part of a multicenter open-label phase I trial (SAKK 65/16).

BACKGROUND: TLD-1 is a novel liposomal doxorubicin that compared favorably to conventional doxorubicin liposomal formulations in preclinical models. This phase I first-in-human study aimed to define the maximum tolerated dose (MTD), recommended phase 2 dose (RP2D), safety and preliminary activity of TLD-1 in patients with advanced solid tumors. PATIENTS AND METHODS: We recruited patients with advanced solid tumors who failed standard therapy and received up to 3 prior lines of palliative systemic chemotherapy. TLD-1 was administered intravenously every 3 weeks up to a maximum of 9 cycles (6 for patients with prior anthracyclines) from a starting dose of 10 mg/m2, according to an accelerated titration design followed by a modified continual reassessment method. RESULTS: 30 patients were enrolled between November 2018 and May 2021. No dose-limiting toxicities (DLT) were observed. Maximum administered dose of TLD-1 was 45 mg/m2, RP2D was defined at 40 mg/m2. Most frequent treatment-related adverse events (TRAE) of any grade included palmar-plantar erythrodysesthesia (PPE) (50% of patients), oral mucositis (50%), fatigue (30%) and skin rash (26.7%). Most common G3 TRAE included PPE in 4 patients (13.3%) and oral mucositis in 2 (6.7%). Overall objective response rate was 10% in the whole population and 23.1% among 13 patients with breast cancer; median time-to-treatment failure was 2.7 months. TLD-1 exhibit linear pharmacokinetics, with a median terminal half-life of 95 h. CONCLUSIONS: The new liposomal doxorubicin formulation TLD-1 showed a favourable safety profile and antitumor activity, particularly in breast cancer. RP2D was defined at 40 mg/m2 administered every 3 weeks. (NCT03387917).