Mucositis Grade Research Articles

Fungal flora changes in head-and-neck cancer patients receiving radiotherapy

Background: Oral mucositis is one of the primary toxicities of radiation in head-and-neck radiotherapy (RT). Oral fungal microflora changes have been studied to aggravate the inflammatory process leading to mucositis. The study evaluated the changes in oral fungal microflora during RT in head-and-neck cancer (HNC) using a single-institutional, prospective research and its correlation with oral mucositis. Subjects and Methods: A prospective single-institutional study was conducted on 68 biopsy-proven HNC patients on RT with or without chemotherapy treated in the Department of Radiation Oncology at Father Muller Medical College, Mangalore, between 2015 and 2017. Three samples of saliva were collected before RT, the end of the 3rd week of RT, and 4 weeks after the completion of RT and assessed for developing fungal flora changes by Sabouraud's dextrose agar growth media and CHROMagar in the number of patients. Mucositis grades are correlated with fungal pathogens. Statistical analysis was on fungal changes and mucositis using mean, percentage, standard deviation, and Chi-square test. Results: An increase in fungal microflora was found in patients receiving radiation or chemoradiation in head-and-neck malignancy. Among them, a significant increase was there in Candida albicans (1.5% of patients before RT to 44.1% of patients during RT) and Candida krusei (1.5% of patients before RT to 10.5% of patients during RT) during RT (P

Nursing Procedures for the Prevention and Treatment of Mucositis Induced by Cancer Therapies: Clinical Practice Guideline Based on an Interdisciplinary Consensus Process and a Systematic Literature Search.

Background:Patients with cancer receiving tumor therapy often suffer from oral mucositis.Objectives:The aim of this project was to summarize experiences with nursing procedures by experts in integrative oncology and to establish recommendations for nursing interventions that can prevent or cure mucositis.Methods:The study design was an interdisciplinary consensus process based on a systematic literature search.Results:The panel discussed and agreed on 19 nursing procedures, which included mouthwashes, such as teas, supplements, oil applications, and different kinds of ice cubes to suck, as well as flaxseed solution, propolis, and mare milk. Twelve interventions were classified as effective, with effectiveness for OraLife, propolis, sea buckthorn pulp oil, marshmallow root tea also for xerostomia, Helago chamomile oil, mare milk, and Saliva Natura rated as highly effective in clinical experience. In the systematic literature search, a total of 12 out of 329 randomized controlled trials and meta-analyses on chamomile (n = 3), Calendula (n = 1) and sage (n = 1), propolis (n = 2), and sucking ice cubes (cryotherapy; n = 5) met all inclusion criteria. Trial evidence for effectiveness in oral mucositis was revealed for propolis and cryotherapy.Conclusions:The current evidence supports the use of some nursing procedures (f.e. propolis for 2 and 3 grade mucositis) for improving oral mucositis during cancer therapies. There is still a need to define general clinical practice guidelines for the supportive treatment of mucositis, as well as for more interdisciplinary research in this area.

Altered oral intake during hematopoietic stem cell transplantation: Patterns and countermeasures

Introduction: Hospitalization for stem cell transplantation leads to reduced oral intake, often requiring parenteral nutrition (PN). Preserving enteral nutrition sustains gut mucosa and microbiota and potentially reduces long-term complications. We provide a short report on patterns of altered dietary intake in stem cell transplant recipients and simple measures that can be taken to mitigate the same. Methods: Patients undergoing autologous and allogeneic stem cell transplantation over an 11 month period were included. Baseline calorie and protein intake was calculated according to the National Institute of Nutrition (India) guidelines. Steps to maintain oral intake included: patient education pretransplant, allowance of home food and packaged food (cookies/chocolates), shift to semisolid or liquid diet, and symptomatic local analgesia for all patients with mucositis. Results: A total of 16 patients were included in the analysis, (male:female = 10:6), with a median age of 43 years (range, 6–67). Median body mass index at baseline was 22.5 kg/m2 (range, 11.9–31.8 kg/m2). Median calorie intake at baseline was 26.8 kcal/kg/day (range, 18–51) and protein intake was 0.47 g/kg/day (range 0.19–0.87). During the course of treatment, maximum grade of mucositis was grade III in 9 and grade II in seven patients. The median caloric deficit from baseline at lowest intake was -79% (range, +11 to − 96%), with the nadir occurring by median day 6.5 (range,-1–12). At the time of discharge, the median oral intake was 70% of baseline (range, −1.2% to + 175%). Most patients had a median of − 4.3% (range, −15% to + 0.4%) of weight loss at discharge. No patient required PN during admission. One patient died as a result of regimen-related toxicity. Conclusions: Patients undergoing stem cell transplantation demonstrated significantly low oral intake at admission which further significantly reduced over the course of hospitalization. Pretransplant optimization of calorie intake, patient education, dietary modification, and in-hospital symptomatic control along with daily monitoring of calorie intake is essential so that reduction can be picked up early and corrective actions are taken.

The impact of the methotrexate administration schedule and dose in the treatment of children and adolescents with B-cell neoplasms: a report of the BFM Group Study NHL-BFM95

AbstractIn the Non-Hodgkin Lymphoma–Berlin-Frankfurt-Münster 95 (NHL-BFM95) study, we tested by randomization whether for patients with B-cell neoplasms methotrexate as intravenous infusion over 4 hours (MTX-4h) is not inferior to, but less toxic than, a 24-hour intravenous infusion (MTX-24h). Second, we investigated against the historical control of study NHL-BFM90, whether for patients with moderate tumor mass MTX can be reduced from 5 g/m2 to 1 g/m2. Patients received 2 5-day therapy courses in risk group R1 (resected), 4 in R2 (lactate dehydrogenase [LDH] < 500 U/L), 5 in R3 (LDH > 500 to < 1000 U/L) and 6 in R4 (LDH > 1000 U/L and/or central nervous system [CNS] disease). Courses contained MTX 1 g/m2 in R1 + R2 and 5 g/m2 in R3 + R4. Of 505 patients (April 1996 to March 2001), 364 were randomized to receive MTX-4h or MTX-24h. Failure-free survival (pFFS, 1 year) for arm MTX-4h versus MTX-24h, respectively, was 95% ± 5% (n = 20) versus 100% (n = 19) in R1, 94% ± 2% (n = 88) versus 96% ± 2% (n = 95) in R2, and 77% ± 5% (n = 62) versus 93% ± 3% (n = 69) in R3 ± R4 (per-protocol analysis). Incidence of mucositis grade III/IV was significantly lower with MTX-4h in all risk groups. For patients in R2, event-free survival (pEFS) was 95% ± 2% (n = 222) in NHL-BFM95 (MTX 1 g/m2) and 97% ± 1% (n = 154) in NHL-BFM90 (MTX 5 g/m2). In conclusion, MTX-4h was less toxic than MTX-24h. MTX-4h was noninferior to MTX-24h for limited stage B-cell non-Hodgkin lymphoma (B-NHL) but not for advanced disease. For limited disease, MTX 1 g/m2 is noninferior to 5 g/m2.

Pain management in patients undergoing radiation therapy for head and neck cancer- a descriptive study.

Patients with head and neck cancer (HNC) experience serious pain related to tumour, surgery, chemotherapy, and radiotherapy treatment (RT). Oral mucositis, a painful complication of RT, may require opioid analgesics to control pain.This longitudinal study, during RT but also four weeks post-RT, examines the relationships between oral mucositis, pain, and opioid doses in in HNC patients. The aim was to evaluate the clinical effectiveness of an opioid treatment strategy. Sixty-three patients with HNC undergoing radiotherapy answered self-reported questionnaires on pain intensity on a 0-10 numerical rating scale (NRS) three times a week. Oral mucositis signs were evaluated using the WHO mucositis index score, ranging from 0 (normal) to 4 (severe), and pharmacological treatment with opioids was registered prospectively once a week. All data were related to given radiation dose, and all outcome measures at each time point therefore relate to the same radiation dose (i.e.,not to when the patient was included in the study). Opioids were used by 78% of the patients. Most of the patients experienced only mild pain (NRS 0-4), although the majority developed mucositis grade 2-4 according to WHO mucositis index. Function-related pain intensity and opioid doses were highest during the sixth week of RT, with 3.67 (0-9) in NRS and 84 (0-430)mg oral morphine equivalents per day (median, range). At that same time point, significant positive correlations were found between the grade of mucositis and pain intensities. Patients with mucositis grade 2-4 were investigated further; in this subgroup, we found that opioid doses did not differ between patients with mild pain and patients with moderate to severe pain. Our multivariate data analysis defined a cluster of patients characterized by the presence of mucositis, cancer site in pharynx, concomitant chemotherapy, and the absence of surgery. In HNC patients who were followed closely by pain care personnel during and after RT, pain was often satisfactorily alleviated with a structured use of opioids, including stepwise increases of fentanyl patches and oral morphine as needed. However, some patients with oral mucositis grade 2-4 experienced severe pain. Strong opioids, i.e. the third step of the WHO pain ladder, remain the mainstay of analgesic therapy in treating moderate to severe cancer-related pain, including patients with HNC. This real-life study indicates that RT-related pain is not a fatality. A proactive stance, monitoring these patients closely and regularly, is probably crucial in order to achieve good treatment results. Further studies are needed to develop better pain treatment strategies for those patients who develop severe oral mucositis-related pain despite intensive opioid treatment.

The Effect of Oral-care Program and Mouthwash Useas a Prophylaxis in Minimizing the Incidence of Chemotherapy-Induced Oral Mucositis of Pediatric and Adolescent Cancer Patients

Objective: The aim was to assess the effect of the oral-care program and Kin Care mouthwash on the rate and severity of chemotherapy-induced oral mucositis (OM) in pediatric and adolescent cancer patients. &#x0D; Methods: A randomized clinical trial study was conducted from May 2018 through May 2019. It was held in the Children Cancer Center of Hiwa Oncology and Hematology Hospital and included 48 participants aged 5-17 years who received chemotherapy. They were randomly allocated into either intervention or control groups; 24 patients each. The control group did not receive oral-care protocol intervention except for symptomatic measures. In contrast, the intervention group was provided with oral-care instructions and Kin Care mouthwash. Clinical evaluations were performed before commencing chemotherapy and then, twice per week, for three consecutive weeks. The World Health Organization Mucositis grading, the visual analog scale, oral hygiene status, and drinking and eating abilities were assessed.&#x0D; Results: There were no statistically significant differences between the two groups concerning age, gender, and tumor type. The most severe grades of OM (Grade III-IV) among the intervention group were significantly less than the control group (2.1% versus 22.9%). Besides, the use of Kin Care mouthwash decreased the occurrence of OM into half. The risk ratio of developing OM (Grades II-IV) was 0.51. &#x0D; Conclusions: Regular oral-care program and Kin Care solution for children receiving chemotherapy effectively decreases the rate and severity of OM.

The Effect of Vitamin E on Oral Mucositis Induced by Chemotherapy in Non-Hodgkin Lymphoma Patients Receiving Chemotherapy

Chemotherapy-induced mucositis is a side effect of chemotherapy that often occurs in patients with solid tumors and lymphoma. Oral mucositis can affect nutritional status and the risk of infection, both local and systemic. Antioxidant Vitamin E is beneficial for the prevention and therapy of both oral and gastrointestinal mucositis. Aim: To determine the effect of vitamin E therapy on the incidence of oral mucositis in non-Hodgkin lymphoma (NHL) patients receiving chemotherapy. Methods: This is a single-blind experimental study in 62 NHL patients undergoing chemotherapy who meet the inclusion criteria. Patients who met the inclusion criteria were randomly divided into 2 groups, namely 31 patients (treatment group) received vitamin E 400 mg / IU per day for 7 days and 31 patients in the placebo group. The incidence and grade of oral mucositis were observed on day 7. Statistical analysis used Chi-Square and Mann Whitney test according to the data type. Results: a total of 67% NHL patients were male, most of whom were over 46 years of age and as many as 50% of patients used chemotherapy regimens RCHOP and CHOP. There was an incidence of oral mucositis in 35% in the placebo group and 12.9% in the treated group (p = 0.038). In the placebo group, there were 4.8% of patients with grade 2 and 3 oral mucositis, which was not found in the therapy group. Conclusion: Â treatment with vitamin E in NHL patients undergoing chemotherapy can prevent chemotherapy-induced oral mucositis and prevent its severity.

Total Marrow Irradiation for Second Allogeneic Haematopoietic Stem Cell Transplantation in Patients with Advanced Acute Leukemia

Background. Relapse after allogeneic haematopoietic stem cell transplantation (HSCT) is associated with very poor outcomes. A myeloablative conditioning regimen for patients with advanced acute leukemia before second allogeneic HSCT is crucial to better control the disease, but the risk of transplant mortality due to toxic complications is very high. Total Marrow Irradiation (TMI) is a novel high precision radiation treatment, alternative to standard Total Body Irradiation (TBI) conditioning regimen, allows to deliver therapeutic radiation doses over extensive selected targets while substantially reducing radiation to vital organs to preserve their functions. Aim of the pilot study. To evaluate the efficacy of high dose per fraction TMI in combination with thiotepa, fludarabine and alkeran as conditioning regimen in 9 patients with acute leukemia relapsed after a first allogeneic HSCT. Patients and Methods. Nine patients relapsed after first allogeneic HSCT received a second allogeneic HSCT, 7 from haploidentical, 1 from unrelated (UD) 10/10 and 1 from HLA-identical sibling (SIB) donor. The conditioning regimen consisted of: TMI 8 Gy in 5 patients on day -8 -7 or TMI 12 Gy in 4 patients on day -9 -8 -7, plus Thiotepa 5 mg/Kg on day -6, Fludarabine 50 mg/mq on day -5 -4 -3, alkeran 140 mg/mq on day -2. TMI was delivered in daily single fraction dose of 4 Gy, instead of the conventional 2 Gy in order to potentially enhance the biological effective dose approximately 20% to 60% (for a total dose of 12 Gy), considering alpha/beta ratio between 10-1.49, while total dose of 8 Gy in 2 fractions schedule is potentially equivalent to six fractions of conventional TBI for low alpha/beta ratio. Graft versus host disease (GvHD) prophylaxis for SIB and UD consisted of cyclosporine methotrexate and ATG, whereas for HAPLO it was high dose post-transplant cyclophosphamide (PT-CY), cyclosporine and mycophenolate. The median age was 45 years (range, 19-70 years); 3 patients were in remission, 6 had active disease at the time of the second allogeneic HSCT. The median number of nucleated cells infused was 4.3 x 10e8/Kg (range 2.6-7.7). Four patients received peripheral blood and 5 patients received unmanipulated bone marrow cells. Results. The median time to neutrophil counts of &amp;gt; 0.5 x 10e9/L was 16 days (range 13-22) and to platelet counts of &amp;gt; 20 x 10e9/L was 19 days (range 11-27) respectively. All the patients showed a full donor chimerism on day 30 after transplant; none of the patients had rejection. Three patients developed acute graft versus-host disease (aGvHD) grade I-II and 1 patient had moderate chronic GvHD. During the neutropenic phase of the transplant one patient developed a sepsis from Pseudomonas Aeruginosa; one patient had pericardial effusion and one patient had mucositis grade II. The median follow up was 528 days (range 227-858). Day +30 and day +100 transplant related mortality were 0. Two patients died of transplant related complications; both died of interstitial pneumonia and received TMI 12 Gy. Two patients died of leukemia and they were not in remission at the time of the transplant. The actuarial 17 months disease free-survival (DFS) is 53%. Conclusions. This is the first report demonstrating the safety and the efficacy of the TMI conditioning regimen in patients with advanced acute leukemia receiving second allogeneic transplantation with encouraging outcome in terms of engraftment, early toxocity, GvHD and relapse. Disclosures No relevant conflicts of interest to declare.

Preliminary Experience of Treating Children and Young Adults With Image-Guided Proton Beam Therapy in India.

PURPOSEProton beam therapy (PBT) has been a preferred modality in pediatric malignancies requiring radiotherapy. We report our preliminary experience of treating consecutive patients younger than 25 years with image-guided pencil beam scanning PBT from the first and only center on the Indian subcontinent.METHODSPatients were selected for PBT on the basis of a multidisciplinary tumor board decision. Patient demographic data, as well as tumor and treatment-related characteristics of the cohort, were captured. Patient and treatment-related factors and their association with acute toxicities were analyzed using univariable and multivariable analyses.RESULTSForty-seven patients (27 with CNS and 20 with non-CNS tumors) with a median age of 9 years (range, 2-25 years) were evaluated. Most common diagnoses were ependymoma, rhabdomyosarcoma, and glioma. Seventy-seven percent of patients traveled more than 500 km, and 70% of them lived in metropolitan cities. Forty-nine percent of patients had recurrent disease at presentation, and 15% had received a previous course of radiation. The median dose delivered was 54.8 cobalt gray equivalents (range, 40.0-70.4 cobalt gray equivalents) to a median clinical target volume of 175 mL (range, 18.7-3,083.0 mL), with 34% of patients requiring concurrent chemotherapy (CCT). Acute grade 2 and grade 3 dermatitis, mucositis, and hematologic toxicity was noted in 45% and 2%, 34% and 0%, and 38% and 30% of patients, respectively. Grade 2 fatigue was noted in 26% of patients. On multivariable analysis, for CNS tumors, both CCT and craniospinal irradiation were independently associated with ≥ 2 grade hematologic toxicity, whereas among non-CNS tumors, a clinical target volume > 150 mL was associated with ≥ 2 grade fatigue, head and neck irradiation was associated with ≥ 2 grade mucositis, and CCT was associated with grade ≥ 2 hematologic toxicity.CONCLUSIONThis study demonstrates safe implementation of a PBT program for children and young adults on the Indian subcontinent. Image-guided pencil beam scanning PBT in judiciously selected patients is feasible and can be delivered with acceptable acute toxicities.

EFFECTIVENESS OF TOPICAL APPLICATION OF MIXTURE OF HONEY AND COFFEE IN RADIATION INDUCED ORAL MUCOSITIS AMONG PATIENTS WITH HEAD &amp; NECK CANCER UNDERGOING RADIOTHERAPY AT RADIOTHERAPY DEPARTMENT OF KGMU, LUCKNOW, U.P

Background: Cancers commonly known as head and neck cancers typically begin in the squamous cells that line the moist, mucosal surfaces within the head and neck. Oral mucositis is erythematous and ulcerative lesion of the oral mucosa in patients with cancer being treated with chemotherapy/ radiation therapy in the areas of oral cavity. Objectives: To assess the grade of the oral mucositis among head &amp; neck cancer patients receiving radiotherapy. 2. To evaluate the effectiveness of mixture of honey and coffee application on radiation induced oral mucositis among the study group. 3. To find the association between the radiation induced oral mucositis with selected demographic variables. Method: quasi experimental non randomized control group design was applied and 60 samples (30 in each group) were selected by convenience sampling technique. The mixture of honey and coffee was applied to the study group before and after 15 minutes of radiotherapy till the continuation of radiotherapy and no intervention was given in the control group. Result: The result revealed that the application of honey and coffee mixture was significantly effective on oral mucositis (p&lt;0.001) in the study group. Conclusion: The study concluded that, application of mixture of honey and coffee is an effective method of reducing the onset and severity of oral mucositis in comparison with no intervention.

Impact of Palifermin on Transplant Outcomes in Children and Adolescents Undergoing Allogeneic Hematopoietic Cell Transplantation.

Oral mucositis (OM) is considered to be one of the worst and most debilitating complications of conditioning for hematopoietic cell transplantation (HCT). Prevention and treatment of this complication is one of the utmost priorities of supportive therapy during transplant procedure. The objective of this study was the analysis of the influence of palifermin, keratinocyte growth factor (KGF), on transplant outcomes in patients undergoing allo-HCT. A total of 253 allo-HCTs performed between 2003-2018 in patients aged 0-19 years at a single center were analyzed. KGF was administered in 161 HCTs. Uni- and multivariate risk factor analyses were performed. In spite of reducing the duration and grade of mucositis, no prognostic impact of KGF was shown for overall survival, event-free survival, relapse incidence, acute and chronic graft-versus-host disease (GVHD), nor GVHD-free relapse-free survival. Palifermin had no impact on transplant outcomes in children and adolescents undergoing allo-HCT.

Treatment of canine oral papillary squamous cell carcinoma using definitive-intent radiation as a monotherapy-a case series.

Canine oral papillary squamous cell carcinoma (COPSCC) is a rare neoplasm and although locally invasive it carries a favourable prognosis following wide surgical excision. Radiotherapy has been reported to be effective as an adjunct treatment to surgery. However, limited information is available on the role of radiotherapy as single treatment. This single‐institution retrospective study describes a series of 10 dogs diagnosed with macroscopic COPSCC that were treated with definitive‐intent radiotherapy (DRT) as a monotherapy. These dogs had a median age of 4 years (range: 0.4‐9.6 years). The tumour was located in the rostral oral cavity in all cases with a median tumour size of 2.5 cm (range: 0.8‐6.8 cm). No local or distant metastases were identified. All dogs were treated with electron beam DRT (>32Gy, 10‐16 daily fractions of 3.2Gy). The median follow‐up time was 961 days (range: 333‐3.498 days) with nine dogs achieving a complete response and one dog a partial response. The dog with the partial response developed disease progression at 228 days after initiation of radiotherapy. Two dogs died from non‐tumour‐related causes. The remaining seven dogs were still alive and in complete remission at the time of last follow‐up. Median progression‐free survival time and median survival time were not reached. DRT was generally well tolerated, but all dogs experienced self‐limiting acute radiation mucositis (grade 2‐3) and/or dermatitis (grade 1). No late radiation toxicity was observed. Macroscopic COPSCC appears to be a radiosensitive tumour that can be successfully treated with DRT eliminating the need for aggressive surgery in advanced cases.

Alteration in Oral Flora and Effect of Mucositis in Head and Neck Cancer Patients Undergoing Chemo-radiotherapy

The main aim of this study is to determine the various types of oral bacteria and yeast. Present in oral flora of head and neck cancer patients at different stages of chemo-radiotherapy, and compare it with the control group (patients with contralateral healthy mucosa). Seventy seven patients with proven history of squamous cell carcinoma were included in the study. The oral mucosa profile was assessed for bacterial manifestations in swab samples from both the sites of the patients. The grade of mucositis was charted out for all patients during the second and third week of radiotherapy. The study revealed that all isolated oral flora showed a non-significant increase during radiotherapy, while there was a decrease in oral flora in post RT. However, E. faecalis showed a non- significant decrease during RT, while Citrobacter showed an increase. Candida albicans showed 83% non- significant decrease post- radiotherapy. When these floras were correlated with grade of mucositis, an insignificant increase in flora was found in G2 and G3 stage of mucositis. In this study, the effect of radiation was evaluated on oral flora of head and neck cancer patients and compared with contralateral healthy mucosa of the patients. Various changes were observed during and after radiation therapy. In patients with head and neck cancer the normal oral flora are replaced by pathogenic flora during radiotherapy, and the latter is responsible for infections in post- radiation phase.

Efficacy of keratinocyte growth factor in prevention of oral mucositis in children undergoing allogeneic hematopoietic cell transplantation

AbstractIntroductionOral mucositis is regarded by patients as one of the worst and debilitating complications of conditioning and hematopoietic cell transplantation (HCT). Prevention of mucositis is one of the priorities of supportive therapy during and after conditioning.ObjectivesThe primary objective of the study was the analysis of efficacy of keratinocyte growth factor (KGF, palifermin) used in prophylaxis of oral mucositis in patients undergoing allo-HCT. The secondary objectives of the study included the analysis of the influence of palifermin on clinical course of oral mucositis and early transplant outcomes, as well as analysis of the contraindications of palifermin in patients undergoing allo-HCT.Patients and methodsA total number of 253 allo-HCT performed between 2003 and 2018 in patients aged 0–19 years in a single center were analyzed. Overall, in 161 HCTs, palifermin was administered.ResultsPatients receiving KGF were transplanted earlier in the context of calendar year, and more often received ATG, mainly due to the higher rate of unrelated donor transplants. Allo-HCT patients who were administered palifermin had shorter time of mucositis (median: 9 vs. 13 days, p &lt; 0.001), lower mucositis grade (median: 2° vs. 3°; p &lt; 0.001), shorter period of total parenteral nutrition (median: 19 vs. 22 days; p = 0.018), and lower incidence of episodes of febrile neutropenia (median: 39.1% vs. 83.1%; p &lt; 0.001).ConclusionsThe use of palifermin has decreased duration and severity of oral mucositis in children after allo-HCT. Palifermin is a safe and well-tolerated compound in children undergoing allo-HCT.

Novel Approach for Bone Marrow Transplantation Conditioning in Acute Myelogenous Leukemia not Responding to the Induction Therapy Using Etoposide Carried in Lipid Core Nanoparticles: A Pilot Clinical Study

Allogeneic hematopoietic cell transplantation (HCT) is the treatment of choice for acute myelogenous leukemia (AML) not responding to induction therapy. It is a therapeutic choice for the blast phase of chronic myelogenous leukemia (CML-BP) in patients failing to respond to tyrosine kinase inhibitors (TKIs). Lipid core nanoparticles (LDEs) concentrate severalfold more in blast cells than in corresponding normal cells. Incorporation of anticancer drugs to LDE formulations increases the pharmacologic action and decreases the toxicity. We tested a drug-targeting system, LDE-etoposide plus total body irradiation (TBI; 1200 cGy dose), in 13 patients with AML not responding to the induction therapy and in 2 patients with CML-BP refractory to second-generation TKIs. The mean patient age was 46.7 years (range, 22 to 66 years). The LDE-etoposide dose was escalated at 20, 30, 40, 50, and 60 mg/kg. No patients developed grade 4 or 5 toxicity; however, mucositis grade 3 occurred in 6 patients, 3 patients experienced diarrhea, and 1 patient had an elevated total bilirubin level. No deaths were related to conditioning. All patients were successfully engrafted. The median times to neutrophil and platelet engraftment were 20 ± 5 days and 16 ± 4 days, respectively. Five patients (33.4%) had acute graft-versus-host-disease (GVHD), including 4 grade I, and 1 with grade II, and 8 patients (57.1%) had moderate-to-severe chronic GVHD. This pilot study shows the potential of LDE-etoposide plus TBI as an HCT conditioning regimen in AML patients not responding to the induction and refractory therapies for CML-BP patient. These findings pave the way for subsequent larger clinical trials.

Frequency of Mucositis Among Head and Neck Cancer Patients Receiving Three-Dimensional (3D) Radiotherapy.

Background and objectiveHead and neck cancer can arise from any site like hypo-pharynx, oro-pharynx, lip, oral cavity, or larynx. Almost 90% of them are head and neck squamous cell carcinomas (HNSCC). In the current project, the goal was to determine the frequency of acute side effects in terms of mucositis during and immediately post-irradiation period in patients receiving concurrent three-dimensional (3D) radiotherapy in a tertiary care hospital. MethodologyThis descriptive case series with 106 enrolled patients was carried out from December 2019 to May 2020 at the Department of Radiation Oncology following approval. All patients were given radiotherapy or chemo-radio-therapy as per the clinician's advice and hospital protocol. All patients were evaluated at pre radiation time, at weekly intervals during treatment and at 11 weeks from 1st radiation fraction. Data was entered and analyzed by Statistical Package for Social Sciences, version 20 (SPSS Inc., Chicago, IL). Chi-square and Fisher's exact test was applied as p-value ≤ 0.05 was considered significant. ResultsIn the present study, all patients (n=106) showed a mean age of 57.8 ± 8.3 years. There was a gradual increase in grades of mucositis in all patients after treatments until seven weeks. After one month of post-treatment, a decrease in grades of mucositis was observed in all patients. ConclusionAcute side effects appeared in all patients receiving 3D radiation therapy (RT) although the treatment response was good. Hence, we concluded it has a high incidence of treatment-related toxicities but it is safe.

The efficacy of the regimens of “graft versus host” disease prophylaxis after hematopoietic stem cell transplantation from unrelated donors in children: single center experience

Graft versus host” disease (GvHD) is one of the most frequent and severe complications of allogeneic hematopoietic stem cell transplantation (allo-HSCT). The optimal model of GvHD prophylaxis in allo-HSCT from alternative donors in children currently remains actual question. Materials and methods. The study was approved by the Independent Ethics Committee and the Scientific Council of the N.N. Blokhin National Medical Research Center of Oncology, Ministry of Healthcare of Russian Federation. Two hundred fifty six allo-HSCT were made during the period 2003–2019 from matched unrelated donors (MUD). Age median was 7.1 years old. The source of hematopoietic stem cells (HSCs) bone marrow – 76% (n = 194), peripheral blood stem cells – 24% (n = 62). GvHD prophylaxis included: tacrolimus (Tacro), cyclosporin A (CsA), methotrexate (Mtx), mycophenolate mofetil (MMF), in following combinations Tacro/Mtx (n = 98), Tacro/MMF (n = 102), tacro/Mtx + MMF (n = 3), CsA/Mtx (n = 24), CsA/Mtx + MMF (n = 12), CsA + MMF (n = 14). Median follow-up 8.9 years. GvHD prophylaxis regimen did not affect significantly the toxicity of therapy (toxicity: severe mucositis grade III–IV, nephrotoxicity, hepatotoxicity) (p = 0.4; p = 0.24; p = 0.62 respectively). In our study the rate of the overall survival (ОS) has significant differences in depending of the source of prevention GvHD. The using a combination of tacrolimus and cyclosporine with low doses of methotrexate had a positive effect on OS (p = 0.035) in patients of common non-malignant and malignant groups, as well as on the level of 2-year relapse-free survival in the group of children with malignant disorders (p = 0.671). In the general group the OS the worst results were achieved when MMF was included in the prophylaxis model. In this experience of treating of a large cohort of patients the choice of calcineurin inhibitors and methotrexate as the agent GvHD prophylaxis showed the efficacy and safety for non-manipulated MUD for both malignant and non-malignant diseases in children.

Simultaneous evaluation of symptoms, swallowing functions, and patient-reported swallowing difficulties and their correlations with ingestion status during definitive chemoradiotherapy for oropharyngeal and hypopharyngeal cancer.

To clarify the correlations among symptoms, swallowing functions, and ingestion status and to validate a method of swallowing evaluation during chemoradiotherapy (CRT) for head and neck cancer. Oropharyngeal and hypopharyngeal cancer patients who were to receive definitive CRT as initial treatment were included in this prospective, single-center, observational study. The Functional Oral Intake Scale (FOIS) for ingestion status and grades of symptoms (dryness, dysgeusia, mucositis, and the analgesic ladder); the Yale Pharyngeal Residue Severity Rating Scale on fiberoptic endoscopic evaluation of swallowing (FEES) and the Penetration-Aspiration Scale (PAS) on videofluoroscopic (VF) evaluation for swallowing functions; and the 10-item Eating Assessment Tool (EAT-10) questionnaire were assessed at 5 time points unless the participant refused. The FEES and VF evaluation findings at each point were also compared. There were 38 participants. Dysgeusia, mucositis, and pain grade, as well as the FOIS score, were the worst at 70Gy and then improved after treatment. The improvements of pharyngeal residue and the PAS after treatment were limited. The EAT-10 and the pain ladder were highly correlated with the FOIS changes at many time points. The VF evaluation rate dropped after 40Gy, whereas the FEES rate remained high. There were good correlations between pharyngeal residue and the PAS at 0Gy, 70Gy, and 3months. The EAT-10 and pain reflected the FOIS score changes well, while two swallowing evaluations did not. To avoid aspiration, VF evaluation may not be necessary during CRT because of high correlations with pharyngeal residue on FEES.

Radiotherapy-related skin toxicity (RAREST-02): A randomized trial testing the effect of a mobile application reminding head-and-neck cancer patients to perform skin care (reminder app) on radiation dermatitis

BackgroundRadiotherapy of head-and-neck cancer can be associated with significant toxicities including dermatitis and oral mucositis. Severe toxicities may require interruptions of the radiation treatment associated with impairment of the patients’ prognoses. This study will investigate whether the addition of a reminder app to standard care can reduce dermatitis and oral mucositis rates during radiotherapy in these patients.MethodsThis randomized trial compares standard care supported by a reminder app (Arm A) to standard care alone (Arm B) with respect to grade ≥ 2 radiation dermatitis and oral mucositis at 60 Gy of radiotherapy, the minimum planned dose for patients receiving definitive or adjuvant radiotherapy for locally advanced head- and-neck cancer. Moreover, radiation-induced dermatitis and oral mucositis grade ≥ 3 at 60 Gy and both grade ≥ 2 and grade ≥ 3 at the end of radiation treatment (EOT) will be evaluated, as well as quality of life and pain. According to sample size calculations, 80 patients are required per arm within the full analysis set. Taking into account that 5% of patients will not qualify for full analysis set, 168 patients should be randomized. The impact of the reminder app will be considered clinically relevant, if the rates of grade ≥ 2 radiation dermatitis (primary endpoint) and oral mucositis (secondary endpoint) can be reduced by 20%.DiscussionIf the addition of a reminder app to standard care will lead to a significant reduction of radiation dermatitis and oral mucositis, it could become a helpful tool for patients with head-and-neck cancer during radiotherapy.Trial registrationclinicaltrials.gov (NCT04110977). Registered on September 27, 2019. First patient is planned to be included in December 2019.

Efficacy of WC03 in treating radiotherapy-induced oral mucositis (RIOM): A multicenter nonrandomized controlled clinical trial.

e24127 Background: RIOM is a common side effect of radiotherapy for head and neck cancer patients, however, no standard and effective treatment existed so far. WC03 is an oily Traditional Chinese Herbal Medicine recipe for external-use in mouth, which had been utilized to treat RIOM in China-Japan Friendship Hospital for more than ten years. This trial aimed to investigate the safety and efficacy of WC03 in treating RIOM. Methods: Between May 2017 and June 2018, we conducted a multicenter, non-randomized controlled trial within 7 hospitals in China. Inclusion criteria included head and neck cancer patients who developed RIOM (≥ grade II) undergoing radiotherapy or after radiotherapy (within 6 months). They were assigned to different groups based on their willingness. Patients in treatment group were treated by WC03, which was daily applied to the oral mucosa for 30 min twice a day. Patients in control group were treated with Kangfuxin (Periplaneta americana) Lotion combined with conventional treatment such as vitamin B12 and rhGM-CSF. The interventions lasted for 2 weeks. The primary outcome was overall effective rate, which was calculated through changes of radio-induced oral mucositis grade before and after interventions (according to National Cancer Institute Common Toxicity Criteria). Secondary outcome was oral pain which was measured by Numeric Pain Rating Scale. Results: 48 eligible participants were enrolled, 24 in treatment group and 24 in control group, respectively. 2 patients in treatment group were withdrawn from the study in the first week because of developing secondary infection and treatment got changed. Thus, 22 were included at the terminal of the study. All the 24 participants in control group were included. After the intervention, the overall effective rate was 95.45%(21/22) in the treatment group, which was significantly higher than that of 70.83% (17/24) in the control group (p = 0.049). Similarly, 86.36%(19/22) of the participants in treatment group got cured, which was significantly higher than that of 45.83%(11/24) in the control group(p = 0.007). There is a trend that oral pain relief rate in the treatment group was higher than that of the control group, but not statistically significant (100.00% vs. 87.50%, p = 0.210). Patients in treatment group used less time to get relieved from RIOM than control group (5 vs. 8 days, p &lt; 0.001). No adverse event had been observed in both two groups. Conclusions: WC03 is safe and effective in treating radiotherapy-induced oral mucositis. RCT is necessary in future studies.