Italian position paper (SIPMO-SICMF) on medication-related osteonecrosis of the jaw (MRONJ).

OBJECTIVE: This paper aims to describe the 2023 update position paper on MRONJ developed by the Italian Societies of Oral Pathology and Medicine (SIPMO) and of Maxillofacial Surgery (SICMF). METHODS: This is the second update following the 2013 and 2020 Italian position papers by the Expert panel, which is a representation of the two scientific societies (SIPMO and SICMF). The paper is based on an extensive analysis of the available literature from January 2003 to February 2020, and the subsequent review of literature conducted between March 2020 and December 2022 to include all new relevant published papers to confirm or modify the previous set of recommendations. RESULTS: This position paper highlights the main issues of MRONJ on risk estimates, disease definition, diagnostic pathway, individual risk assessment, and the fundamental role of imaging in the diagnosis, classification, and management of MRONJ. CONCLUSION: The Expert Panel confirmed the MRONJ definition, the diagnostic work-up, the clinical-radiological staging system and the prophylactic drug holiday, as recognized by SIPMO-SICMF; while, it presented novel indications regarding the categories at risk of MRONJ, the prevention strategies, and the treatment strategies associated with the therapeutic drug holiday.

Improving the cancer adult patient support network (iCAN): a pilot study on a communication model and modified focus group.

Background: Many consider that cancer has the greatest impact of any disease in the world, and it can drastically limit patients' quality of life. Combating such a life-threatening disease can pose many challenges to daily life, highlighted by demonstrating the need to discuss one's health status within a focus group and encourage treatment compliance. Aim: the purposes of this study were to share the authors' experience of a modified focus group in an Oral Medicine Unit, termed "Improving Cancer Adult Patients Support Network" (iCAN), and to evaluate how effective communication could improve patients' quality of life and empower them by virtue of enhanced knowledge and an awareness of cancer management. Methods: the paper adhered to the COREQ checklist regarding its reporting procedures. The iCAN format was precisely reproduced four times with four groups, consisting of 12 adult male and female patients with solid cancers. They discussed several main topics relating to cancer treatment, as chosen by a majority of the participants. Four specialists were involved in the discussion of the selected topics The iCAN format was faithfully reproduced during each meeting, with the participants in the roles of moderator and health specialists. Finally, a satisfaction questionnaire was administered. Results: the most reliable results demonstrated a marked change in lifestyle and eating habits in more than 50% of participants. More than 80% were unaware of the side effects of cancer treatments in general and the oral mucosa in particular. Each meeting reported a maximum degree of satisfaction experienced by the participants. Conclusion: iCAN focus group meetings appear to have facilitated a process of narrative interviewing, thereby improving the doctor-patient relationship underlying the humanization of the care process.

Doctoral: A smartphone-based decision support tool for the early detection of oral potentially malignant disorders.

Oral potentially malignant disorders can be defined as mucosal lesions and conditions with an increased risk of malignant transformation. Oral potentially malignant disorders are a significant health burden, and they are often diagnosed late due to scant attention to routine dental practice and the low number of specialized oral medicine centres. This report summarizes the DoctOral experience, a research initiative, providing a free smartphone-based decision support tool for the general medical/dental practitioner; the tool is based on the clinical appearance of oral lesions. Captured, oral pictures can be immediately examined via interactive decision trees and constructed on the smartphone. Such decision trees are expressed in standard formats, and they are readily accessible for facilitating the completion of a hypothetical diagnostic path. Since October 2017 the DoctOral mobile app has been downloaded by 10K + users, achieving a score of 4.8 out of 5. DoctOral also supports an unfolding joint initiative, called DoctOralAI: this involves selecting reference images, with which to create an open-source model, and perform a Case-Based Reasoning method, both of which are combined with machine learning. The DoctOral mobile app has revolutionized oral pathology by providing dental students and professionals with an interactive platform for recognizing and diagnosing oral lesions.

Impact of medications on salivary flow rate in patients with xerostomia: a retrospective study by the Xeromeds Consortium.

OBJECTIVES: This study evaluates the impact of systemic medications and polypharmacy on unstimulated (UWS) and chewing-stimulated whole saliva (SWS) flow rates in patients with xerostomia. MATERIAL AND METHODS: This cross-sectional multicenter study is based on data of patients referred to five oral medicine outpatient practices in Europe and USA from January 2000 and April 2014. Relevant demographic, social, medical history and current medications were collected. RESULTS: The study included 1144 patients, 972 (85%) females, with a mean (SD) age of 59 (14.1) years. In unmatched patients, the UWS flow rate was lower in patients taking a medication (vs. not taking a medication) from the following drug categories: opioid analgesics, anticonvulsants, antidepressants, antihypertensives, benzodiazepines, corticosteroids, diuretics, disease-modifying antirheumatic drugs (DMARDs) and hormones. There was a greater negative effect on SWS flow rate in patients taking (vs. not taking) anticonvulsants, antidepressants, benzodiazepines, corticosteroids, and DMARDs. In matched patients, both UWS (0.22 vs. 0.19 ml/min; p = 0.03) and SWS (0.97 vs. 0.85 ml/min; p = .017) flow rates were higher in patients on non-opioid analgesics (vs. not taking). The UWS flow rate was lower in patients taking antidepressants (vs. not taking) (0.16 vs. 0.22 ml/min p = .002) and higher (and within normal range) in patients taking sex hormones (vs. not taking) (0.25 vs. 0.16 ml/min; p = .005). On the other hand, SWS was lower in patients taking corticosteroid (vs. not taking) (0.76 vs. 1.07 ml/min; p = .002), and in patients taking DMARDs (vs. not taking) (0.71 vs. 0.98 ml/min; p = .021). Finally, differences in medians of both UWS and SWS were statistically significant in patients taking 1 or more than 1 opioid analgesic (vs. not taking, p ≤ .0001 and p = .031, respectively), 1 or more than 1 anticonvulsants (vs. not taking, p = .008 and p = .007), 1 or more than 1 antidepressants (vs. not taking, p < .0001 for both), 1 or more than 1 DMARDs (vs. not taking, p = .042, and p = .003). CONCLUSIONS: A greater negative impact on UWS and SWS flow rates was seen in patients taking more than one medication from the same drug class. Intake of antidepressants, corticosteroids and DMARDs is associated with lower whole saliva flow rates. CLINICAL RELEVANCE: Salivary flow rate can be modified by some specific medications, mostly by polypharmacy.

Site-Coded Oral Squamous Cell Carcinoma Evaluation by Optical Coherence Tomography (OCT): A Descriptive Pilot Study.

Optical Coherence Tomography (OCT) is an emerging non-invasive method for oral diagnostics, proving to be a practicable device for epithelial and subepithelial evaluation. The potential validity of OCT in oral cancer assessment has been explored but, to date, there are very few investigations conducted with a systematic comparison between clinical/histological and OCT parameters, especially in strict reference to the anatomical site-codification of the oral mucosa. In this regard, our study performed a two-steps evaluation (in vivo OCT and histological investigations) of suspected OSCCs, progressively recruited, using as references the OCT images of the same site-coded healthy mucosa, to provide as much as possible site-specific determinants. Thirty histologically confirmed OSCCs were recruited. Specific OCT mucosal features (SEL-Stratified Epithelial Layer; BM-Basement Membrane; LP-Lamina Propria) were registered and processed using the SRQR (Standards for Reporting Qualitative Research) statement. The systematic dual descriptive OCT analysis revealed that OSCC scans present a complete alteration of epithelial (KL, SEL) and subepithelial (BM, LP) layers with a site-specificity characteristic; moreover, peculiar OCT configurations such as "icicle-like" structures could be strongly suggestive of neoplastic infiltration. This study supports the OCT use for the development of more specific optical structural models applied to oral carcinogenesis.

Salivary Microbiota Composition in Patients with Oral Squamous Cell Carcinoma: A Systematic Review.

BACKGROUND: Oral squamous cell carcinoma (OSCC) is one of the most prevalent cancers worldwide. Despite recent advances in diagnosis and treatment, in recent years, an increase in the incidence of OSCC has been registered, and the mortality rate is still high. This systematic review aims to identify a potential association between the composition of salivary microbiota and OSCC. MATERIALS AND METHODS: The protocol for this study was designed following the PRISMA guidelines. Records were identified using different search engines (e.g., Medline/PubMed). Observational studies, in human subjects with histological diagnosis of OSCC, concerning the analysis of salivary microbiota, were selected. RESULTS: Eleven papers were included. The salivary microbiomes of 1335 patients were analysed (n.687 OSCC and n.648 controls). Due to the great heterogeneity of the studies, it was not possible to profile a specific microbiota associated with OSCC. However, periodontal pathogens were the most common bacteria detected in patients with OSCC (i.e., Fusobacterium, Prevotella). CONCLUSIONS: Although there are evident alterations in the salivary microbiota composition in OSCC patients, it is still a challenge to identify a specific microbiota pattern in OSCC patients. If the associations between specific salivary microorganisms and OSCC are confirmed, microbiome analysis could be a useful tool for the screening and follow-up of patients affected by OSCC.

Ozone Infiltration for Osteonecrosis of the Jaw Therapy: A Case Series.

Medication-related osteonecrosis of the jaw (MRONJ) is a serious adverse reaction, mainly due to bone-modifying agents (BMA), and it is a potentially painful and debilitating condition. To date, the literature has reported a 90% rate of successful outcomes for MRONJ patients undergoing surgical treatment. Particularly for patients with advanced disease stages who are unsuitable for surgery, prolonged medical treatment is required, with a consequent risk of the overuse of antibiotics and antibiotic resistance. The aim of this study is to evaluate the efficiency and safety of ozone, via oral mucosal infiltrations, in seven cancer patients with MRONJ, who are not eligible for surgery. The protocol (OZOPROMAF) consists of intratissue injections of an oxygen ozone (O2O3) mixture, which is applied until formation of a sequestrum and clinical healing. Follow-up was scheduled to confirm the healing of MRONJ and radiological evaluations by CBCT were planned. In order to assess the level of pain, a questionnaire including the Numeric Rating Scale for Pain (NRS Pain) was administered on the first visit, one day after treatment, and one week after treatment. After an application of OZOPROMAF, all patients reported discomfort for some hours, probably due to soft tissue pressure around the infiltration site. Thereafter, the discomfort subsided within 6-8 h. Complete mucosal healing of MRONJ occurred within a number of cycles ranging from 7 to 16. Complete resolution with an improvement in bone condition was observed in all patients. The MRONJ lesions of all patients healed after 18-24 months. The authors of this study contend that these preliminary results suggest the efficiency and safety of the O2O3 mixture. However, further research is required to confirm the efficacy of the O2O3 mixtures in MRONJ treatment, at least for patients who are unsuitable for surgery.

The preventive care of medication-related osteonecrosis of the jaw (MRONJ): a position paper by Italian experts for dental hygienists.

PURPOSE: The prevention and early diagnosis of medication-related osteonecrosis of the jaw (MRONJ) is fundamental to reducing the incidence and progression of MRONJ. Many in the field believe that dental hygienists should play an integral role in primary and secondary MRONJ prevention. However, to date, very few publications in the literature have proposed standardised MRONJ protocols, which are dedicated to dental hygienists. The aim of this study was to provide guidance to the health care providers managing MRONJ. METHODS: The expert opinion in this study was developed by dental hygienists from the main Italian technical-scientific associations (Italian Dental Hygienists Association, AIDI and National Union of Dental Hygienists, UNID) and authors of the latest Italian recommendations regarding MRONJ from the field of dentistry and maxillofacial surgery. RESULTS: The oral care protocol outlined in this position paper is focused on the role of dental hygienist in patients at risk or affected by MRONJ, and it regards 3 main issues: primary prevention, secondary prevention and supporting the treatment of MRONJ. Each issue contains easy-to-apply indications and procedures, as described by the authors, regarding the role of the dental hygienist. CONCLUSION: Referring to the main issues under consideration (primary prevention, secondary prevention and the treatment of MRONJ), a clinical examination of periodontal tissue is critical in preventing MRONJ. It is the opinion of the authors of this study that the application of a periodontal screening score is fundamental in defining personalised strategies for patients at risk of MRONJ. By means of these basic procedures, a protocol for assisting the health care provider and the presentation of a practical approach for patients at risk or affected by MRONJ are described in this study.

Low Frequency of Human Papillomavirus in Strictly Site-Coded Oral Squamous Cell Carcinomas, Using the Latest NHI/SEER-ICD Systems: A Pilot Observational Study and Critical Review.

The aim of this study was to evaluate HPV status in oral squamous cell carcinoma (OSCC), as coded by the latest classifications and applying a combination of detection methods used in clinical practice. Forty-two patients with suspect OSCC were consecutively recruited. Patients underwent an incisional biopsy for histological OSCC diagnosis and HPV identification by PCR DNA and p16 IHC. All lesions were coded by the latest ICD-0-3.2 site/histology classifications, as proposed for OSCC by the National Cancer Institute Surveillance, Epidemiology and End Results Programs. Moreover, a comparative analysis review, critically evaluated by the same site-coded systems and HPV detection methods, was performed. In 40 confirmed cases of OSCC, the frequency of HPV infection was 10% (4/40). Among positive patients, two cases were PCR DNA/p16 IHC positive (high-risk HPV 51, high-risk HPV 67), two cases were PCR DNA positive/p16 IHC negative (high-risk HPV 31 + 68, high-risk HPV 66). Applying the latest site coding systems for OSCC, the frequency of HPV infection in this study and in similar, reviewed investigations was low (from 3.3% to 12.5%). These results suggested no significant HPV role in oral carcinogenesis, particularly where an updated site-coded classification of OSCCs (categorically excluding the base of the tongue) had been performed.

Immune-Mediated Desquamative Gingivitis and Optical Coherence Tomography Diagnostic Patterns: Clinical Implication from a Systematic Review.

Desquamative Gingivitis (DG) comprises heterogeneous clinical manifestations of numerous immune-mediated muco-cutaneous diseases. Optical Coherence Tomography (OCT) has been proposed as a valuable diagnostic support even if, to date, there are no standardized OCT-diagnostic patterns applicable to DGs. A systematic review was performed to detect existing data on in vivo OCT diagnostic patterns of the most common immune-mediated DGs (i.e., pemphigus vulgaris, mucous membrane pemphigoid and oral lichen planus). It has been found that OCT exhibits specific patterns that address the diagnosis of DG by pemphigus vulgaris (i.e., intraepithelial unilocular blister, reduced epithelial thickness, presence of acantholytic cells in the blister) and by mucous membrane pemphigoid (i.e., subepithelial multilocular blister, presence of inflammatory infiltrate), but not by oral lichen planus. These patterns could offer an attractive diagnostic OCT framework to support the clinical preliminary assessment and monitoring of these complex pathological conditions.

The Treatment of Medication-Related Osteonecrosis of the Jaw (MRONJ): A Systematic Review with a Pooled Analysis of Only Surgery versus Combined Protocols.

Medication-related osteonecrosis of the jaw (MRONJ) is a serious adverse reaction of antiresorptive and antiangiogenic agents, and it is also a potentially painful and debilitating condition. To date, no specific studies have prospectively evaluated the efficacy of its treatment and no robust standard of care has been established. Therefore, a systematic review (2007-2020) with a pooled analysis was performed in order to compare MRONJ surgical techniques (conservative or aggressive) versus combined surgical procedures (surgery plus a non-invasive procedure), where 1137 patients were included in the pooled analysis. A statistically significant difference in the 6-month improvement rate, comparing combined conservative surgery versus only aggressive (91% versus 72%, p = 0.05), was observed. No significant difference regarding any group with respect to the 6-month total resolution rate (82% versus 72%) was demonstrated. Of note, conservative surgery combined with various, adjuvant, non-invasive procedures (ozone, LLLT or blood component + Nd:YAG) was found to achieve partial or full healing in all stages, with improved results and the amelioration of many variables. In conclusion, specific adjuvant treatments associated with minimally conservative surgery can be considered effective and safe in the treatment of MRONJ, although well-controlled studies are a requisite in arriving at definitive statements.

The patient-doctor relationship: new insights in light of the current Ministerial recommendations regarding Phase 2 of the COVID-19 pandemic.

Following the publication of the Italian Ministerial recommendations relating to dentistry in Phase 2 of the COVID-19 pandemic (focusing on operational protocols for all dental staff), we believe that the patient/dentist relationship should increasingly take into account the heightened fears and anxious thoughts of patients. This particularly regards patients who are about to undergo dental work. Moreover, dentists should also pay close attention to recent events, which have determined the new recommendations regarding SARS-COV-2 biocontainment. Furthermore, the authors of this paper consider it appropriate to make suggestions and develop interventionist techniques regarding the interface with the patient starting from the initial consultation. The latter is invariably determinant in establishing clear communication of the Ministerial recommendations in encouraging a relaxed atmosphere with the patient. This interface is also a decisive factor in promoting patient empowerment, including specifying the time period envisaged for treatment in the new COVID-19 era in as calm a manner as possible. Such an approach will have a positive impact on the dentistry team.

Medication-Related Osteonecrosis of Jaws (MRONJ) Prevention and Diagnosis: Italian Consensus Update 2020.

The Medication-Related Osteonecrosis of Jaws (MRONJ) diagnosis process and its prevention play a role of great and rising importance, not only on the Quality of Life (QoL) of patients, but also on the decision-making process by the majority of dentists and oral surgeons involved in MRONJ prevention (primary and secondary). The present paper reports the update of the conclusions from the Consensus Conference-held at the Symposium of the Italian Society of Oral Pathology and Medicine (SIPMO) (20 October 2018, Ancona, Italy)-after the newest recommendations (2020) on MRONJ were published by two scientific societies (Italian Societies of Maxillofacial Surgery and Oral Pathology and Medicine, SICMF and SIPMO), written on the inputs of the experts of the Italian Allied Committee on ONJ (IAC-ONJ). The conference focused on the topic of MRONJ, and in particular on the common practices at risk of inappropriateness in MRONJ diagnosis and therapy, as well as on MRONJ prevention and the dental management of patients at risk of MRONJ. It is a matter of cancer and osteometabolic patients that are at risk since being exposed to several drugs with antiresorptive (i.e., bisphosphonates and denosumab) or, more recently, antiangiogenic activities. At the same time, the Conference traced for dentists and oral surgeons some easy applicable indications and procedures to reduce MRONJ onset risk and to diagnose it early. Continuous updating on these issues, so important for the patient community, is recommended.

Salivary Biomarkers for Oral Squamous Cell Carcinoma Diagnosis and Follow-Up: Current Status and Perspectives.

Oral cancer is the sixth most common cancer type in the world, and 90% of it is represented by oral squamous cell carcinoma (OSCC). Despite progress in preventive and therapeutic strategies, delay in OSCC diagnosis remains one of the major causes of high morbidity and mortality; indeed the majority of OSCC has been lately identified in the advanced clinical stage (i.e., III or IV). Moreover, after primary treatment, recurrences and/or metastases are found in more than half of the patients (80% of cases within the first 2 years) and the 5-year survival rate is still lower than 50%, resulting in a serious issue for public health. Currently, histological investigation represents the "gold standard" of OSCC diagnosis; however, recent studies have evaluated the potential use of non-invasive methods, such as "liquid biopsy," for the detection of diagnostic and prognostic biomarkers in body fluids of oral cancer patients. Saliva is a biofluid containing factors such as cytokines, DNA and RNA molecules, circulating and tissue-derived cells, and extracellular vesicles (EVs) that may be used as biomarkers; their analysis may give us useful information to do early diagnosis of OSCC and improve the prognosis. Therefore, the aim of this review is reporting the most recent data on saliva biomarker detection in saliva liquid biopsy from oral cancer patients, with particular attention to circulating tumor DNA (ctDNA), EVs, and microRNAs (miRNAs). Our results highlight that saliva liquid biopsy has several promising clinical uses in OSCC management; it is painless, accessible, and low cost and represents a very helpful source of diagnostic and prognostic biomarker detection. Even if standardized protocols for isolation, characterization, and evaluation are needed, recent data suggest that saliva may be successfully included in future clinical diagnostic processes, with a considerable impact on early treatment strategies and a favorable outcome.

The Dental Management of Patients at Risk of Medication-Related Osteonecrosis of the Jaw: New Paradigm of Primary Prevention.

Medication-related osteonecrosis of the jaw (MRONJ) is a serious adverse reaction of antiresorptive and antiangiogenic agents; it is a potentially painful and debilitating condition that can considerably affect the quality of life of patients. Furthermore, even if its epidemiology and pathogenesis have still not been fully clarified, several risk factors related to MRONJ have been recognized in prevention protocols. Three main risk factors are as follows: (i) the type of ONJ-related medications: antiresorptive (e.g., Bisphosphonates, Denosumab) and antiangiogenic drugs (e.g., Bevacizumab, Sunitinib); (ii) the category of patient at MRONJ risk: cancer versus non-cancer patient; (iii) the typologies and timing of dental treatments (e.g., before, during, or after the drug administration). The aim of this paper is to describe the new paradigm by the Italian Society of Oral Pathology and Medicine (SIPMO) on preventive dental management in patients at risk of MRONJ, prior to and during/after the administration of the aforementioned ONJ-related drugs. In reducing the risk of MRONJ, dentists and oral hygienists are key figures in applying a correct protocol of primary prevention for pre-treatment and in-treatment patients. However, the necessity of a multidisciplinary standardized approach, with a sustained dialogue among specialists involved, should be always adopted in order to improve the efficacy of preventive strategies and to ameliorate the patient's quality of life.

Conservative Surgical Treatment of Bisphosphonate-Related Osteonecrosis of the Jaw with Er,Cr:YSGG Laser and Platelet-Rich Plasma: A Longitudinal Study.

INTRODUCTION: The management of bisphosphonate-related osteonecrosis of the jaw (BRONJ), with no evidence-based guidelines, remains controversial. We aimed to evaluate the efficiency of a conservative surgical treatment combining Er,Cr:YSGG laser and platelet-rich plasma (PRP) for the treatment of BRONJ in cancer patients. METHODS: We performed a longitudinal cohort study. Inclusion criteria were (1) age ≥ 18 years; (2) cancer diagnosis; (3) treatment with NBP because of the underlying cancer. RESULTS: We consecutively recruited ten patients diagnosed with BRONJ in stage I or II. These patients underwent a surgical laser-assisted therapy together with autologous PRP. At the latest follow-up at 12 months, clinical improvement was observed in eight patients. Registration Number is IRCT20180329039159N1. CONCLUSION: We could successfully manage the BRONJ utilizing this combined protocol to heal the 30% of surgically treated sites and to improve the 50% of patients' lesions clinically. Our findings suggest that a surgical approach combined with Er,Cr:YSGG laser and PRP benefit cancer patients with general health issues.

Appropriateness in Dentistry: A Survey Discovers Improper Procedures in Oral Medicine and Surgery.

OBJECTIVES: The aim of this study was to assess appropriateness of diagnostic exams, treatments, and procedures among Italian dental practitioners. MATERIALS AND METHODS: A questionnaire with multiple responses on topics of dentistry and oral medicine was administered to a sample of 198 Italian dental practitioners. Information on characteristics of the respondents was also collected. Descriptive statistics and multiple correspondence analysis (MCA) were applied. Data were analyzed using R software (version 3.3.2). RESULTS: The survey respondents included Doctors of Medicine (MD) (54/198 = 27%) with or without specialty in dentistry (33% versus 67%), Doctors of Dental Surgery (DDS) (144/198 = 73%), DDS with specialty in orthodontics (7%), and DDS with specialty in oral surgery (4%). Mandatory procedures in dental and oral medicine education and training include (a) prescription of antibiotics before/after oral surgery procedures; (b) prevention strategies for oral cancer, and (c) prescription of dental X-ray examinations (41%, 52%, and 48%, resp.). CONCLUSION: On examining the results of the survey, it is evident that information and implementation of the above mentioned procedures are crucially needed. Our results confirm the necessity to reduce inappropriate practices in dentistry, implementing formation and information, leading to correct prescriptions, and optimizing patients' oral health. This coincides with the Italian Slow Medicine program entitled "Fare di più non significa fare meglio-Choosing Wisely Italy," which has also motivated this study.

Could the Combined Administration of Bone Antiresorptive Drug, Taxanes, and Corticosteroids Worsen Medication Related Osteonecrosis of the Jaws in Cancer Patients?

The study presents a report of 58 metastatic cancer patients who developed osteonecrosis of the jaws after being treated with zoledronic acid and taxanes, plus corticosteroids. A retrospective analysis of data registered in the archives of two Italian osteonecrosis of the jaws treatment centers, who are based at the University of Messina and at the University of Palermo, was performed in order to study, in these patients, demographic data and characteristics such as frequency of cancer location, lines of therapy, frequency of cancer drugs, presence/absence of oral trigger, number, location, and stage of jaw osteonecrosis. It was found that the majority of patients developed advanced stages of osteonecrosis, frequently complicated with infection. It was hypothesized that the concurrent administration of chemotherapeutic agents could be eventually considered as a factor able to allow a faster worsening of the clinical manifestation through the exacerbation of soft tissue defects, due to chemotherapy drugs.