Purpose
To discuss
the role of benzydamine
in the prevention and treatment of radiation-induced oral mucositis (OM) in head and neck (H&N) cancer patients. This document represents an
expert opinion ...paper
on indications and key-role aspects in
OM pathogenesis
,
prevention and treatment
.
Oral mucositis
OM represents a common side effect of chemotherapy (CHT) and radiotherapy (RT). It consists in a painful erythema involving the oral cavity mucosa, which may progress to ulceration. Five biologically dynamic phases are considered crucial in mucositis: “initiation, signalling, amplification, ulceration and healing”. Oral environment and microbiota are fundamental in mucositis development being involved in susceptibility to infections and in ulceration consequences. Different agents against mucositis have been studied and the use of benzydamine is strongly supported in literature. The Multinational Association of Supportive Care in Cancer and International Society for Oral Oncology (MASCC/ISOO) guidelines recommend its use for the prevention of OM in H&N patients undergoing RT and RT/CHT.
Benzydamine
Benzydamine is a local anti-inflammatory drug with analgesic properties. It can decrease TNF-α, IL-1β and prostaglandin synthesis, also inhibiting leukocyte-endothelial interactions, neutrophil degranulation, vasodilation and vascular permeability. Literature agrees on the beneficial effects of benzydamine in preventing and reducing oral mucositis severity in H&N cancer patients undergoing RT/CHT.
Conclusions
Mucositis represents a major concern in H&N cancer patients and a clinical and economical issue. A multimodal and multidisciplinary approach is needed for its management. International guidelines recommend benzydamine for OM prevention and treatment in H&N cancer patients, but further “real world” trials should be designed.
The skull base is an anatomically and functionally critical area surrounded by vital structures such as the brainstem, the spinal cord, blood vessels, and cranial nerves. Due to this complexity, ...management of skull base tumors requires a multidisciplinary approach involving a team of specialists such as neurosurgeons, otorhinolaryngologists, radiation oncologists, endocrinologists, and medical oncologists. In the case of pediatric patients, cancer management should be performed by a team of pediatric-trained specialists. Radiation therapy may be used alone or in combination with surgery to treat skull base tumors. There are two main types of radiation therapy: photon therapy and particle therapy. Particle radiotherapy uses charged particles (protons or carbon ions) that, due to their peculiar physical properties, permit precise targeting of the tumor with minimal healthy tissue exposure. These characteristics allow for minimizing the potential long-term effects of radiation exposure in terms of neurocognitive impairments, preserving quality of life, and reducing the risk of radio-induced cancer. For these reasons, in children, adolescents, and young adults, proton therapy should be an elective option when available. In radioresistant tumors such as chordomas and sarcomas and previously irradiated recurrent tumors, particle therapy permits the delivery of high biologically effective doses with low, or however acceptable, toxicity. Carbon ion therapy has peculiar and favorable radiobiological characteristics to overcome radioresistance features. In low-grade tumors, proton therapy should be considered in challenging cases due to tumor volume and involvement of critical neural structures. However, particle radiotherapy is still relatively new, and more research is needed to fully understand its effects. Additionally, the availability of particle therapy is limited as it requires specialized equipment and expertise. The purpose of this manuscript is to review the available literature regarding the role of particle radiotherapy in the treatment of skull base tumors.
A study has shown that MYD88 (L265P) is a recurring somatic mutation in Waldenström's macroglobulinemia (WM). We developed an allele-specific polymerase chain reaction (PCR) for this mutation, and ...analyzed bone marrow or peripheral blood samples from 58 patients with WM, 77 with IgM monoclonal gammopathy of undetermined significance (IgM-MGUS), 84 with splenic marginal zone lymphoma (SMZL), and 52 with B-cell chronic lymphoproliferative disorders (B-CLPD). MYD88 (L265P) was detected in 58/58 (100%) patients with WM, 36/77 (47%) with IgM-MGUS, 5/84 (6%) with SMZL, and 3/52 (4%) with B-CLPD. Compared to IgM-MGUS patients with wild-type MYD88, those carrying MYD88 (L265P) showed significantly higher levels of IgM (P < .0001) and presented Bence-Jones proteinuria more frequently at diagnosis (P = .002). During follow-up, 9 patients with IgM-MGUS progressed to WM or to marginal zone lymphoma. Using a case-control approach, the risk of evolution of patients carrying MYD88 (L265P) was significantly higher than that of patients with wild-type MYD88 (odds ratio 4.7, 95% confidence interval 0.8 to 48.7, P = .047). These findings indicate that the allele-specific PCR we developed is a useful diagnostic tool for patients with WM or IgM-MGUS. In this latter condition, MYD88 (L265P) is associated with greater disease burden and higher risk of disease progression, and the mutation may therefore also represent a useful prognostic marker.
•Using a sensitive method, the MYD88 (L265P) mutation is detectable in all patients with Waldenström's macroglobulinemia, therefore representing a hallmark of the disease.•MYD88 (L265P) is also found in a substantial proportion of patients with IgM-MGUS.
Summary
MicroRNAs (miRNAs) are a large class of small regulatory molecules able to control translation of target mRNAs and consequently to regulate various biological processes at a ...posttranscriptional level. Their importance is highlighted by the fact that altered miRNA expression is linked to a variety of human diseases, particularly cancer. Accordingly, miRNA biogenesis itself must be carefully regulated, both transcriptionally and posttranscriptionally. Here, we focus on the role of miRNAs in three lineages of myeloid cells important in both innate and acquired immunity: mast cells, macrophages, and dendritic cells. These three cell types are strategically located throughout the body tissues, where they can respond to foreign material, danger, and inflammatory signals. We discuss the role of miRNAs in these cell types, with a special focus on three of the most extensively studied miRNAs, namely miR‐221, miR‐146a, and miR‐155. We also discuss the role of cell‐to‐cell transfer of miRNAs in dendritic cells, mast cells, and macrophages, and we speculate about possible future directions in the field.
•Planning on multiple anatomic scenarios could improve CIRT robustness for pancreatic cancer.•The PRV approach fails in predicting duodenum position along the RT course.•Efficient online adaptation ...is needed to guarantee CIRT quality for pancreatic cancer.
To quantify benefits of robust optimization on multiple 4DCT acquisitions combined with off-line treatment adaptation for neoadjuvant carbon ion therapy (CIRT) of pancreatic cancer.
For 10 previously treated patients, 4DCTs were acquired around −15 (CTPlan), −5 (RE1), −1 (RE2) and +6 (RE3) days from RT start. Treatment plans were newly optimized to a dose prescription of 38.4 Gy(RBE) (8 fractions) with a constraint of 38 Gy(RBE) to 1% of the gastrointestinal organs at risk volume (D1%). Three strategies were tested: (A) robust optimization on CTPlan maximum exhale (0Ex) with 3 mm set-up, 3% range uncertainty, including 30%-inhale; (B) addition of the RE1-0Ex scenario; (C) plan recalculation at each REi and adaptation (RPi) according to deviation thresholds from clinical goals. The cumulative variation of target coverage and GI-OARs doses was evaluated. Duodenum contours of all 4DCTs of each patient were registered on CTPlan-0Ex. The capacity of pre-RT acquisitions to predict duodenum position was investigated by computing the intersection of contours at CTplan, RE1, or their union, with respect to subsequent 4DCTs and the CTV, coupled with increasing margin.
(A) No recalculation exceeded the D1% constraint. (B) The inclusion of RE1-0Ex in the optimization problem improved inter-fraction robustness on a patient-specific basis, but was non-significant on average. (C) Half of the plans would be re-optimized to recover target coverage and/or minimize duodenum dose, at least once. A significant difference was observed between pre-RT duodenum contours when intersecting subsequent contours, either with a margin expansion.
Anatomical variations highlighted at multiple REi proved that a fast and efficient online adaptation is essential to optimize treatment quality of CIRT for pancreatic cancer.
Highlights • Advanced RT technique are promising in SGCs treatment. • Based on retrospective data PORT is recommended in high risk SGCs patients. • Particle therapy should be the first option for ...inoperable or R2-resected SGCs.
Background: Despite the large use of inhibitors of Poly-ADP ribose polymerase (PARP-I), the feasibility and safety of their combination with radiotherapy (RT) is unclear. Aim: We conducted a ...literature analysis with the aim to evaluate the efficacy and safety profile of a combination with RT and PARP-I. Method: The key issues for the current review were expressed in two questions according to the Population, Intervention, Control, Outcome (PICO) criteria: 1. What is the outcome and 2. What is the toxicity in patients treated with a combination of PARP-I and RT for a newly diagnosed or recurrent tumors? Results: A total of 12 clinical studies met the inclusion criteria including seven single-arm dose-escalation phase I studies, two phase II (two- and three-arms controlled trials) trials, one parallel-arm phase I study, and two phase I/II studies published between 2015 and 2021. RT was performed with photon beams and several schedules according to the clinical situation. The acute toxicity ≥ grade 3 ranged between 25% and >96%, which was divided into hematological or non-hematological adverse events. Conclusions: despite the heterogeneity of the evaluated patient populations and tumor types, and the limited number of the studies, this review suggests that a combination approach is feasible even though the efficacy profile remains unclear.
•In total, more than 4000 adult patients are currently treated with PT across Europe annually.•CNS and HNC tumours are the most frequently treated tumour sites.•Most centres use national or ...institutional guidelines for selecting patients for PT.•Treatments are usually reimbursed by national health care systems.•Most patients are included in prospective data registries and clinical trials.
Major differences exist among proton therapy (PT) centres regarding PT delivery in adult cancer patient. To obtain insight into current practice in Europe, we performed a survey among European PT centres.
We designed electronic questionnaires for eight tumour sites, focusing on four main topics: 1) indications and patient selection methods; 2) reimbursement; 3) on-going or planned studies, 4) annual number of patients treated with PT.
Of 22 centres, 19 (86%) responded. In total, 4233 adult patients are currently treated across Europe annually, of which 46% consists of patients with central nervous system tumours (CNS), 15% head and neck cancer (HNC), 15% prostate, 9% breast, 5% lung, 5% gastrointestinal, 4% lymphoma, 0.3% gynaecological cancers. CNS are treated in all participating centres (n = 19) using PT, HNC in 16 centres, lymphoma in 10 centres, gastrointestinal in 10 centres, breast in 7 centres, prostate in 6 centres, lung in 6 centres, and gynaecological cancers in 3 centres. Reimbursement is provided by national health care systems for the majority of commonly treated tumour sites. Approximately 74% of centres enrol patients for prospective data registration programs. Phase II-III trials are less frequent, due to reimbursement and funding problems. Reasons for not treating certain tumour types with PT are lack of evidence (30%), reimbursement issues (29%) and/or technical limitations (20%).
Across European PT centres, CNS tumours and HNC are the most frequently treated tumour types. Most centres use indication protocols. Lack of evidence for PT and reimbursement issues are the most reported reasons for not treating specific tumour types with PT.
Purpose
Fatigue is a distressing symptom in head & neck cancer patients before during and at the end of curative therapy. Pharmacologic and not pharmacologic treatments have been proposed with scarce ...or no evidence of efficacy. The aim of the study is to evaluate the efficacy of American ginseng in respect to placebo in reducing fatigue in patients treated for head and neck cancer with curative intent.
Methods
Thirty-two patients who had completed oncological treatment for a primary Head & neck tumor for at least 1 year and had a global fatigue score > 4 by means of Brief Fatigue Inventory (BFI) were randomized to receive 1000 mg of American ginseng or placebo per day for 8 weeks with the aim to assess their efficacy. Changes in fatigue scores in the 2 subgroups of patients before and after the treatment with American ginseng or placebo, were assessed by the BFI at baseline and at the end of week 8.
Results
The mean of the mean values of the BFI measured at 8 weeks (end of treatment) was 4.6 in the Ginseng arm and 3.4 in the Placebo arm (
p
= ns). Mean comparison showed a tendency to statistical significance only for the single item on interference with general activity (
p
= 0.06), with better performance for placebo. The mean of the differences between baseline values and 8 weeks values was not significantly different between treatment arms considering the entire questionnaire.
Conclusion
The present data shows that American ginseng has insufficient evidence to be recommended for Cancer Related Fatigue (CRF) in post treatment HNC survivors.
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