How early should be "Early Integrated Palliative Care"?

Palliative care, with its focus on comprehensive patient assessment encompassing physical, social, emotional, and spiritual pain, plays a crucial role in modern medicine. Despite its significance, integration with oncology and other healthcare specialties often occurs late in the disease trajectory. Strategies to bridge this gap include considering a "rebranding" of palliative care to "supportive care." Early initiation of palliative care, although challenging to define precisely, aims to improve the quality of life for patients and their families. Studies show some benefits, but the evidence remains limited. An embedded model that encourages interdisciplinary collaboration between oncologists and palliative care practitioners has shown promise. However, it raises questions about training and availability of palliative care specialists. A broader approach involves integrating palliative care principles into medical and nursing education to ensure early recognition of patient needs and empathetic communication. Regular monitoring of patients' physical and non-physical needs, along with appropriate interventions, can alleviate suffering and improve patient outcomes. Ultimately, the integration of palliative care into oncology and other disciplines focuses on addressing the individual's needs and understanding their unique experience of suffering.

Pre-treatment risk factors to predict early cisplatin-related nephrotoxicity in locally advanced head and neck cancer patients treated with chemoradiation: A single Institution experience.

OBJECTIVES: Cisplatin is essential in the curative treatment of locally advanced head and neck squamous cell carcinoma (LA-HNSCC) patients. The assessment of risk factors to predict an early cisplatin-induced nephrotoxicity could help in better managing one of the most relevant cisplatin-related dose-limiting factors. MATERIAL AND METHODS: We retrospectively collected data of LA-HNSCC patients treated at our Institution from 2008 to 2019. Patients received cisplatin in a curative setting concurrently with radiation. Acute Kidney Injury (AKI) was assessed as a dichotomous variable (CreaIncr) based on pre-treatment values, and values recorded at days 6-20 post-first cycle of cisplatin. Univariable logistic regression models were performed to investigate associations between CreaIncr and clinical characteristics. A multivariable logistic model on a priori selected putative covariates was performed. RESULTS: Of the 350 LA-HNSCC treated patients, 204 were analyzed. Ninety (44 %) suffered from any grade AKI (grade I 51.1 %): out of them, 84.4 % received high-dose cisplatin (100 mg/m2 q21). On the univariable logistic regression model, male sex, age, serum uric acid, creatinine, concomitant drugs, and cisplatin schedule were significantly associated with a higher rate of AKI. At multivariable model, age (p = 0.034), baseline creatinine (p = 0.027), concomitant drugs (p = 0.043), and cisplatin schedule (one-day bolus or fractionated high-dose vs. weekly; p = 0.001) maintained their significant association. CONCLUSIONS: Identifying pre-treatment risk factors in LA-HNSCC patients may improve decision-making in a setting where cisplatin has a curative significance. A strict monitoring of AKI could avoid cisplatin dose adjustments, interruptions, and treatment delays, thus limiting a negative impact on outcomes.

Male awareness of prostate cancer risk remains poor in relatives of women with germline variants in DNA-repair genes.

Abstract. Objective: The aim of this study is to evaluate male awareness of developing prostate cancer (PCa) in families with germline DNA-repair genes (DRG) variants. Materials and methods: Data were collected from a prospective, monocentric cohort study. The study was conducted in a university hospital with a multidisciplinary approach to the patient (collaboration of the Departments of Oncology, Urology, Pathology, Radiology, and Medical Genetics Laboratory). We recruited healthy males, relatives of families of women with breast or ovarian cancer who tested positive for pathogenic variants (PVs) or likely pathogenic variants (LPVs) in DRGs. A dedicated PCa screening was designed and offered to men aged 35 to 69 years, based on early visits with digital rectal examination (DRE), prostate health index (PHI) measurement, multiparametric magnetic resonance imaging (mpMRI) and, if necessary, targeted/systematic prostate biopsies. The primary endpoint was to evaluate the willingness of healthy men from families with a DRG variants detected in female relatives affected with breast and/or ovarian cancer to be tested for the presence of familial PVs. The secondary endpoints were the acceptance to participate if resulted positive and compliance with the screening programme. Results: Over 1256 families, of which 139 resulted positive for PVs in DRGs, we identified 378 'healthy' men aged between 35 and 69 years old. Two hundred sixty-one (69.0%) refused to be tested for DRG variants, 66 (17.5%) declared to have been previously tested, and 51 (13.5%) males were interested to be tested. Between those previously tested and those who accepted to be tested, 62 (53.0%) were positive for a DRG variant, and all of them accepted to participate in the subsequent surveillance steps. The main limitation is that is a single-centre study and a short follow-up. Conclusions: All men tested positive for a DRG variants agreed to go under the surveillance scheme. However, only 31% of 'men at risk' (i.e., relative of a DRG variant carrier) expressed their willingness to be tested for the familial DRG variant. This observation strongly supports the urgent need to implement awareness of genetic risk for PCa within the male population.

Assessing suffering of patients on cancer treatment and of those no longer treated using ESAS-Total Care (TC).

AIM: The aim of the study was to assess the suffering of patients on oncologic treatment and of those no longer on treatment. Preliminarily, we aimed to confirm the psychometric properties of Edmonton Symptom Assessment System-Total Care (ESAS-TC) in different stages of the disease. The ESAS-TC screens physical and psychological symptoms, but also spiritual pain, discomfort deriving from financial problems associated with illness, and suffering related to social isolation. METHODS: A sample of consecutive advanced cancer patients on oncologic therapies treated at the Internistic and Geriatric Supportive Care Unit (IGSCU) of Istituto Nazionale dei Tumori, Milano, and of terminal patients no longer on treatment and cared for by the Fondazione ANT palliative home care team were asked to fill the ESAS-TC. In order to strengthen the previous validation study of the ESAS-TC, 3-ULS (to assess social isolation), JSWBS (to assess spiritual well-being), COST-IT (to assess financial distress), and KPS (to assess functional status) were administered too. RESULTS: The questionnaires were self-reported by 108 patients on treatment (52% >60 years old, female 53%, and 61% with KPS 90-100) and by 94 home care patients (71% >60 years old, female 51%, and 68% with KPS 10-50). The sound psychometric characteristics of ESAS-TC were confirmed. Patients on treatment showed lower total ESAS-TC score (19.3 vs 52.7, p<.001) after controlling for age and functional status, and lower financial distress (p.<001). Financial distress, spiritual suffering, and social isolation, after controlling for age, showed a significantly higher score in home care patients. CONCLUSIONS: Only through an adequate routine assessment with validated tools is it possible to detect total suffering, the "Total pain" of patients, and treat it through a multidisciplinary approach. The study confirms the reliability and validity of the Italian version of ESAS-TC and the importance of supportive and early palliative care fully integrated with oncological treatment.

European Society of Breast Cancer Specialists/Advanced Breast Cancer Global Alliance quality indicators for metastatic breast cancer care.

AIMS: Improvement in the care of patients with metastatic breast cancer (MBC) can only occur if the adequate quality of care is implemented and verified, including access to multidisciplinary, specialised care given in accordance with high-quality guidelines. To this purpose, European Society of Breast Cancer Specialists and the Advanced Breast Cancer Global Alliance joined efforts to develop the first set of quality indicators (QI) specifically for MBC that should be routinely measured and evaluated to ensure that breast cancer centres meet the required standards. METHODS: A working group of multidisciplinary European experts in breast cancer met to discuss each identified QI, reporting the definition, the minimum and target standard for breast cancer centres to achieve, and the motivation for selection. The level of evidence was determined according to the short version of the United States Agency for Healthcare Research and Quality classification. RESULTS: QI to measure access to and involvement in multidisciplinary and supportive care, appropriate pathological characterisation of disease, systemic therapies and radiotherapy were developed with the consensus of the working group. CONCLUSIONS: This is the first effort of a multistep project that aims to have QI for MBC routinely measured and evaluated to ensure that breast cancer centres achieve mandated standards in the care of patients with metastatic disease.

How to become a Multinational Association of Supportive Care in Cancer-designated center of excellence in supportive care in cancer.

PURPOSE OF REVIEW: Aim of this review is to encourage and involve more doctors to take care of supportive care in cancer patients and to become centers of excellence. RECENT FINDINGS: In 2019, MASCC initiated a certification program to recognize oncology centers that demonstrate best practices in supportive cancer care but literature on how to become MASCC-designated center of Excellence in Supportive Care in Cancer is scarce and will be bulleted. SUMMARY: Becoming centers of excellence means not only the recognition of the clinical and managerial requirements to provide good supportive care but also the creation of a network of centers to participate in multicenter scientific projects and thus improve knowledge in the field of supportive care in cancer patients.

Evaluation of the CNC® prosthetic system in recurrent breast cancer patients with chemotherapy-induced alopecia: a pilot study.

BACKGROUND: Chemotherapy-induced alopecia (CIA), although generally reversible, is felt as extremely distressing by patients with breast cancer. A certified medical device (Capelli Naturali a Contatto®-CNC®) was produced to provide patients with a personalized scalp prosthesis, reproducing the patient's original hair, resistant to any type of everyday or sporting activity, and hairdressing. AIMS: The present study aimed to evaluate the impact of the CNC® device on the patient's perception of their body image, psychological wellbeing, satisfaction, strengths and weakness of the CNC® device. METHOD: A pilot study was carried out on 21 patients affected by CIA due to recurrent breast cancer. A mixed quantitative/qualitative method was used, including administering a questionnaire and a focus group. RESULTS: Based on the Body Image Scale, body image perception improved after 3 and 6 months using the device in the 20 patients who answered the questionnaire. No significant change over time emerged for the six dimensions investigated by the Italian version of the Psychological Well-Being Scale. The thematic analysis of the focus groups showed six themes: definition of the prosthetic device, acceptance of the proposal, experience with the conventional wig, strengths, weaknesses, economic issues. CONCLUSION: Compared to the previous experience of CIA and the standard wig, the use of the CNC® device improved everyday life and may be proposed to women undergoing chemotherapy and expecting alopecia to prevent discomfort, social embarrassment, and compromised body image.

Effectiveness of a phone-based nurse monitoring assessment and intervention for chemotherapy-related toxicity: A randomized multicenter trial.

Purpose: Anticancer treatment-related toxicities can impact morbidity and mortality, hamper the administration of treatment, worsen the quality of life and increase the burden on the healthcare system. Therefore, their prompt identification is crucial. NICSO (Italian Network for Supportive Care in Cancer) conducted a nationwide randomized trial to evaluate the role of a planned, weekly phone-based nurse monitoring intervention to prevent and treat chemotherapy, targeted therapy- and immunotherapy-related toxicities. Here, we report the results from the chemotherapy arm. Methods: This was a nationwide, randomized, open-label trial conducted among 29 Italian centers (NCT04726020) involving adult patients with breast, colon, or lung cancer and a life expectancy ≥6 months receiving adjuvant chemotherapy. Patients received either a weekly nurse monitoring phone call and an educational leaflet reporting practical advice about prevention and treatment of toxicities (experimental group) or the educational leaflet only (control group). Results: The addition of a nurse monitoring intervention may help reduce time spent with severe toxicities (grade ≥3), particularly those less frequently reported in clinical practice, such as fatigue. When considering grade 1-2 AEs, times with mild/moderate diarrhea, mucositis, fatigue and pain were shorter in the experimental arm. Time spent without AEs was significantly longer in the experimental arms for all the toxicities. The requirement for special medical attention was comparable between groups. Conclusion: This study suggests the need for implementing a better system of toxicity assessment and management for patients treated with adjuvant chemotherapy to promote effective preventive and/or therapeutic intervention against these events.

Italian version of the Edmonton Symptom Assessment System (ESAS)-Total Care (TC): development and psychometric validation in patients undergoing cancer treatment or follow-up.

INTRODUCTION: The routine use of patient-reported outcomes (PROs) in clinical practice improves quality of care, it helps in reducing the access to emergency services and unscheduled visits, and it can improve cancer patients' time survival. The Edmonton Symptom Assessment System (ESAS) is a PRO largely used in different care settings to monitor physical and psychological symptoms. Nonetheless, along with these symptoms, literature also highlighted the presence and effect of spiritual pain, financial distress, and social isolation on quality of care, treatment effectiveness, and survival. AIM: The aims of the current study were (a) to complete the Italian version of the ESAS validation process by adding the missing symptom "insomnia" and (b) to develop and validate the ESAS-Total Care (ESAS-TC) that is intended to evaluate and screen not only physical and psychological symptoms but also spiritual pain, discomfort deriving from financial problems associated with illness, and suffering related to social isolation. METHODS: A sample of Italian native outpatients, who referred to the dedicated Supportive Care Unit of the Fondazione IRCCS, Istituto Nazionale deiTumori (INT), Milano, were asked to fill the ESAS-TC to assess item properties, factorial structure, internal consistency, test-retest reliability (patients were asked to retake the scale after 2-6 weeks), and external validity. Concerning the latter, other self-administered scales were employed to assess perceived stress (Perceived Stress Scale), unmet needs (using theNeed Evaluation Questionnaire that describes informative, assistance/care, relational, needs for psycho-emotional support, material needs), and perceived social support (administering the Multidimensional Scale of Perceived Social Support that evaluates perceived support of family, friends, and significant others in the wider social field). RESULTS: The scales were administered to 243 patients with solid (90%) and hematologic (10%) cancers, mean age 62.6, female 76.5%. Analysis suggested that a single factor better represents the structure of the ESAS scales, their internal consistency and test-retest reliability were good, and evidence of construct and criterion validity were provided. Additionally, incremental validity of the ESAS-TC was proved showing that the added items offer a unique contribution in predicting the patient's stress. Finally, known groups validity was confirmed testing the differences in the ESAS scores due to the Karnofsky Performance Status. CONCLUSIONS: The current study allowed to complete the validation of the Italian version of the ESAS and to develop a psychometrically sound scale, the ESAS-Total Care, that potentially helps in moving cancer research toward personalized total cancer care.

Fears, beliefs, and quality of life of patients with cancer vs the general population during the coronavirus disease 2019 (COVID-19) pandemic in Lombardy.

AIM: To understand how patients with cancer reacted to the coronavirus disease 2019 (COVID-19) pandemic and whether their quality of life (QoL) was affected. METHODS: In June 2020, 111 patients with cancer treated in the supportive care unit of a Comprehensive Cancer Center in Milan and 201 healthy controls from the general population were enrolled and assessed both quantitatively and qualitatively for fears and COVID-19-related beliefs as well as for QoL. RESULTS: Fear of COVID-19 was significantly lower among patients (41% vs 57.6%; p = 0.007), as was fear of cancer (61.5% vs 85.6%; p < 0.001) and other diseases. The perceived risk of getting COVID-19 was lower among patients (25.2% vs 52.7%; p < 0.001), as was the belief of having been exposed to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (18.1% vs 40.8%; p < 0.001). The physical component of QoL was better among the population (54.5 vs 43.8; p < 0.001); the reverse was true for patients' psychological well-being (44.6 vs 39.6; p < 0.001). The qualitative data supported such results, showing a reduced psychological effect on the patients with cancer compared to the controls. Various reasons explain this result, including the awareness of being treated for cancer and nevertheless protected against getting infected in a cancer center of public health reorganized to continue treating patients by protecting them and personnel from the risk of infection. CONCLUSIONS: The experience of a cancer diagnosis, together with proper hospital reorganization, may act as protective factors from fears and psychological consequences of the COVID-19 outbreak.

Medical management of malignant bowel obstruction in patients with advanced cancer: 2021 MASCC guideline update.

BACKGROUND: Malignant bowel obstruction (MBO) is a frequent complication in patients with advanced cancer, particularly colon or gynecological malignancies. MASCC previously published a guideline for symptom management of MBO in 2017. This is a 5-year update. METHOD: A systematic search and review of relevant literature includes a review published in 2010 and 2017. The guideline update used the same literature search process as followed in 2015. The dates of the new search included 2015 up to February 2, 2021. The guidelines involved the pharmacologic management of nausea and vomiting in malignant bowel obstruction (MBO) only. Only randomized trials were included in the updated guideline as evidence. The evidence was reviewed by the panel and the MASCC criteria for establishing a guideline were followed using MASCC level of grading and category of evidence. RESULTS: There was one systematic review and 3 randomized trials accepted as evidence from 257 abstracts. Octreotide is effective in reducing gastrointestinal secretions and colic and thereby reduces nausea and vomiting caused by MBO. Scopolamine butylbromide is inferior to octreotide in the doses used in the comparison study. Olanzapine or metoclopramide may be effective in reducing nausea and vomiting secondary to partial bowel obstructions. The panel suggests using either drug. Additional studies are needed to clarify benefits. Haloperidol has been used by convention as an antiemetic but has not been subjected to a randomized comparison. Ranitidine plus dexamethasone may be effective in reducing nausea and vomiting from MBO but cannot be recommended until there is a comparison with octreotide. DISCUSSION: Octreotide remains the drug of choice in managing MBO. Ranitidine was used in one randomized trial in all participants and so its effectiveness as a single drug is not known until there is a randomized comparison with octreotide. Antiemetics such as metoclopramide and olanzapine may be effective, but we have very few randomized trials of antiemetics in MBO. CONCLUSION: The panel recommends octreotide in non-operable MBO. Randomized trials are needed to clarify ranitidine and antiemetic choices.

MASCC antiemetics in advanced cancer updated guideline.

BACKGROUND: Nausea and vomiting are a common clinical symptom in the advanced cancer patient. Pharmacologic management is important. Evidence for drug choices and guidelines are needed to help clinicians manage nausea and vomiting in this population METHODS: Evidence from a systematic review published in 2010, initial MASCC guidelines developed from a systematic review of literature to 2015, and a new systematic review of randomized trials published between 2015 and February 2, 2021, was combined to establish a new guideline. RESULTS: A search of the literature between 2015 and February 2, 2021, revealed 257 abstracts of which there was one systematic review and 4 randomized trials which were used to modify the guideline. The new guideline is as follows: First Line: Metoclopramide (II) multiple small RCTs including a placebo-controlled trial, haloperidol (II) multiple non-placebo-controlled RCTs, high consensus. Second line: Methotrimeprazine (II) 1 well-powered non-placebo-controlled RCT, olanzapine (II) 1 placebo-controlled pilot RCT, high consensus. Third line: Tropisetron (II) large unblinded lower quality non-placebo-controlled RCT, levosulpiride (II) 1 blinded non-placebo-controlled pilot RCT, high consensus. DISCUSSION: Haloperidol, metoclopramide, methotrimeprazine, olanzapine tropisetron, and levosulpiride have been antiemetics used in randomized trials with antiemetic activity demonstrated. There are only three placebo-controlled randomized trials we could find in our literature review. Placebo responses varied significantly between two randomized trials. More randomized placebo-controlled trials with either metoclopramide or haloperidol rescue are needed to clarify antiemetic choices in advanced cancer. CONCLUSION: First-line antiemetics for nausea and vomiting in advanced cancer are metoclopramide and haloperidol, and second-line medications are methotrimeprazine and olanzapine.

Malignant salivary gland tumours in families with breast cancer susceptibility.

Salivary gland cancers (SGCs) are rare malignancies with highly heterogeneous histological features. Patients affected with SGCs are at increased risk of secondary malignancies, including breast cancer (BC). Previous studies enlightened a possible link between SGCs and hereditary predisposition to BC. Here, we searched for SGC-affected patients in 1796 high-risk BC families recruited at the Genetic Unit of the Istituto Nazionale dei Tumori of Milan, 516 of which carried pathogenic variants in BRCA1 and/or BRCA2, the main genetic risk factors for BC. We detected five families with an individual affected with SGC, including two male patients, one carrying a constitutional mutation in BRCA1 and the other in BRCA2. Loss of heterozygosity of BRCA wild-type alleles was assessed in the patients' tumour DNA. We conclude that our observations support the hypothesis that genetic factors associated with BC susceptibility might play a role also in at least a subset of SGCs.

A randomized, double-blind, placebo controlled, phase II study to evaluate the efficacy of ginseng in reducing fatigue in patients treated for head and neck cancer.

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.

Supportive care in cancer-a MASCC perspective.

The term 'supportive care' arose from the medical oncology literature predominantly in the context of managing the toxicities of cancer treatment but embraces all symptom management through treatment and survivorship. Supportive care should be patient-centred with good communication which includes family and carers and applies across the cancer experience from diagnosis, treatment, survivorship to end of life care. Supportive care encompasses physical and functional, psychological, social and spiritual well-being to improve the quality of life. Supportive care must be evidence-based and thus further research is essential. Supportive care requires screening for some symptoms and tools for patients to report their outcomes. Supportive care has to accommodate new physical toxicities, emotional distress as well as financial toxicity. Supportive care is often delivered by medical oncologists but any organ-related specialist, geriatrician, palliative care clinician, pain specialist, nutritionist, psycho-oncologist, social worker, physiotherapist, nurse or allied health worker who is required to relieve a patient's symptoms or side effects may be involved in a multidisciplinary way. The field is evolving to embrace technology such as eHealth and mHealth capabilities which will enhance integrated care.

Cognitive decline in older long-term survivors from Non-Hodgkin Lymphoma: a multicenter cross-sectional study.

OBJECTIVES: To compare cognition in a group of older long-term survivors from Non-Hodgkin Lymphoma (NHL) and in a corresponding group of non-cancer controls of the same age. Functional status, polypharmacy and multimorbidity were also evaluated. METHODS: A cross-sectional study was performed in a population of 63 outpatient long-term survivors from NHL, aged 65 or more and 61 non-cancer controls. Socio-demographic, clinical and functional data were collected. Cognitive function was assessed through neuropsychological tests. RESULTS: NHL survivors showed a slightly worse functional status than controls, they were affected by more chronic conditions (3.4 vs 2.3; p = .003) and were taking a higher number of medications (3.4 vs 2.3; p = .03). The Mini Mental State Examination (MMSE) was not significantly different between the groups. NHL survivors performed worse than controls in executive functioning (Trail Making Test B-A 47.9 vs 32.1 p = .04, OR for Stroop test time over 75th percentile in survivors: 2.66; CI 95% 1.04-6.61; OR for Multiple Features Target Cancellation time over 75th percentile in survivors: 2.84; CI 95% 1.10-7.31). A small, statistically significant difference was also observed in verbal memory scores between the two groups. . CONCLUSIONS: The findings of this study suggest that, compared with non-cancer controls, older survivors from NHL may have a lower cognitive performance, especially in the executive functioning and attention domains, regardless of multimorbidity and polypharmacy. Further evidence from larger samples is needed to confirm such findings and better characterize cognitive decline in NHL survivors.

Alveolar bone histological necrosis observed prior to extractions in patients, who received bone-targeting agents.

OBJECTIVE: We reported the alveolar bone histology prior to dental extractions in cancer patients, who received bone-targeting agents (BTA). SUBJECTS AND METHODS: Fifty-four patients were included. Patients underwent extractions, and bone biopsies were taken. RESULTS: Extractions were performed due to pain, swelling, purulence, fistula, and numbness, not responding to treatment, in 40 patients (group A); extractions due to asymptomatic, non-restorable teeth, were performed in 14 patients (group B). Complete alveolar jaw bone histological necrosis was observed in 28 of 40 (70%) patients of group A and none of group B (p < .001). The development of clinical osteonecrosis (MRON) was assessed in 44 patients; 10 patients, who were also treated with Low Level Laser Treatments-LLLT, were excluded from this analysis, as the alternative therapies were a confounding factor. Twelve patients, with alveolar bone histological necrosis prior to extraction, developed medication-related osteonecrosis of the jaw (MRONJ) compared with two patients with vital or mixed vital/non-vital bone (p < .0007). BTAs >1 year and concurrent targeted therapy were also significantly associated with MRONJ (p = .016 and p = .050). CONCLUSION: Pain, swelling, purulence, fistula, and numbness were significantly associated with complete bone histological necrosis prior to extractions and increased MRONJ development. Research is justified to explore whether histological necrosis represents an early stage of osteonecrosis.