Application and accuracy of the EAPC/IASP diagnostic algorithm for neuropathic cancer pain and quantitative sensory testing profile in patients with pain due to cancer.

Introduction: Better diagnosis and treatment of neuropathic cancer pain (NcP) remains an unmet clinical need. The EAPC/IASP algorithm was specifically designed for NcP diagnosis; yet, to date, there is no information on its application and accuracy. Objectives: Our aim was to determine the accuracy of the EAPC/IASP algorithm compared with the Neuropathic Special Interest Group grading system (gold standard) and to describe patients' sensory profile with quantitative sensory testing (QST). Methods: This is a cross-sectional observational study conducted in a palliative care and pain outpatient clinic. Patients with cancer pain intensity ≥3 (numerical rating scale 0-10) were eligible. The palliative care physician applied the EAPC/IASP algorithm as a grading system to diagnose probable or definite NcP, and an independent investigator applied the gold standard and performed the QST. Sensitivity and specificity of the EAPC/IASP algorithm were measured in comparison with the gold standard results. Kruskal-Wallis and unequal variance independent-samples t tests were used to compare the QST parameters in patients with and without NcP. Results: Ninety-eight patients were enrolled from August 2020 to March 2023. Sensitivity and specificity for the EAPC/IASP algorithm were 85% (95% CI 70.2-94.3) and 98.3% (95% CI 90.8-100), respectively. Patients with NcP in contrast to patients without NcP showed cold hypoesthesia (P = 0.0032), warm hypoesthesia (P = 0.0018), pressure hyperalgesia (P = 0.02), and the presence of allodynia (P = 0.0001). Conclusion: The results indicate a good performance of the EAPC/IASP algorithm in diagnosing NcP and the QST discriminated well between patients with and without NcP.

A real-world study on the prevalence and risk factors of medication related osteonecrosis of the jaw in cancer patients with bone metastases treated with Denosumab.

AIM: Assessing the incidence of Medication Related Osteonecrosis of the Jaw (MRONJ) in cancer patients with bone metastases receiving Denosumab (Dmab) and identifying potential risk factors. METHODS: A retrospective observational study on consecutive cancer patients with bone metastases, who received at least one dose of Dmab and one follow-up visit. MRONJ crude cumulative incidence (CCI) was estimated considering death without MRONJ as competing event. Multiple regression models were used to study the association between MRONJ incidence and potential risk factors: age, cancer diagnosis, previous bisphosphonates, dental treatments before starting Dmab, extraction or other dental treatment during Dmab, chemotherapy, hormone therapy, and antiangiogenic (AA) agents concurrent use. RESULTS: On 780 patients included (median follow-up 17 months), 54% and 18% had, respectively, breast and prostate cancer. The mean number of Dmab administration was 12. Fifty-six patients developed MRONJ with a 24- and a 48-month crude cumulative incidence of 5.7% (95% Cl: 4.2%-7.8%) and 9.8% (95% CI: 7.6%-12.7%), respectively. Higher MRONJ incidence was significantly associated with middle aged group (>56 and ≤73), both at univariate and multivariate analysis (p = 0.029 and 0.0106). Dental treatments (Hazard Ratio [HR] = 3.67; p = 0.0001), dental extractions (HR = 23.40; p < 0.0001), and previous BP administration (HR = 2.62; p = 0.0024) were significantly associated with higher MRONJ incidence at multivariate Cox analysis. Although not statistically significant, MRONJ incidence was lower for patients receiving chemotherapy or hormone therapy and higher for those receiving AAs. CONCLUSIONS: The results confirm a clinically relevant incidence of Dmab-induced MRONJ. Dental treatments, especially extraction, during and before Dmab, constitute a serious risk factor. The role of AA concurrent administration deserves further investigations.

Outpatient palliative care referral system (PCRS) for patients with advanced cancer: an impact evaluation protocol.

INTRODUCTION: Early palliative care (PC) in the clinical pathway of advanced cancer patients improves symptom control, quality of life and has a positive impact on overall quality of care. At present, standardised criteria for appropriate referral for early PC in oncology care are lacking. The aim of this project is to develop a set of standardised referral criteria and procedures to implement appropriate early PC for advanced cancer patients (the palliative care referral system, PCRS) and test its impact on user perception of quality of care received, on patient quality of life and on the use of healthcare resources. SETTING: Selected oncology clinics and PC outpatient clinic. METHODS AND ANALYSIS: A scoping literature review and an expert consultation through a nominal group technique will be used to revise existing referral tools and to develop a new one, the PCRS. 25 patients will be enrolled in a pilot study to assess feasibility of the implementation of PCRS; 10 interviews with patients and healthcare professionals will be carried out to evaluate applicability.A pretest-post-test quasiexperimental study involving 150 patients before implementation of the PCRS and 150 patients after implementation will be carried out.Patient satisfaction with care received, quality of life and use of resources, and caregiver satisfaction with care will also be assessed to explore the impact of the intervention. ETHICS AND DISSEMINATION: Ethical approval for the study has been granted by the Institutional Review board of the Fondazione IRCCS Istituto Nazionale Tumori; approval reference INT201/19.Results will be disseminated through open access publications and through scientific communication presented at national and international conferences. TRIAL REGISTRATION NUMBER: NCT04936568.

Cancer pain: Results of a prospective study on prognostic indicators of pain intensity including pain syndromes assessment.

BACKGROUND: Pain is a prevalent symptom in patients with advanced cancer. Recognition of prognostic factors associated with pain intensity, could help provide better assessment, leading to better pain management. AIM: identifying prognostic factors which could guide improvements on cancer pain classification. DESIGN: a prospective observational study on chronic cancer pain, exploring the association between average mean pain intensity during a 28 days study follow-up and patients' clinical and pain-related characteristics, including pain syndromes. To evaluate these associations, a mixed model was built. SETTING/PARTICIPANTS: Patients attending a Palliative Care and Pain Outpatient Clinic from May 2015 to June 2019 were screened. Patients with moderate to severe cancer pain who were already receiving or needed treatment with third step WHO ladder opioids were enrolled in the study. Data from 342 patients with at least one follow-up visit were analyzed. RESULTS: Pain intensity decreased significantly for all patients during time (p < 0.001). Age, sex, emotional distress, pain duration and neuropathic pain presence evaluated by the Douleur Neuropathique 4 Questions (DN4) questionnaire were not significantly associated to pain intensity. Breakthrough/episodic pain was associated with higher pain intensity during follow-up (p < 0.001). The diagnosis of pain syndrome was overall significantly associated with mean pain intensity during follow-up (p = 0.016). Particularly, the concurrent presence of visceral and soft (p = 0.026) or soft and nervous tissue pain (p = 0.043) were significantly related to worse outcome, whereas pain due to only soft tissue damage with better outcome (p = 0.032). CONCLUSIONS: The recognition of specific pain syndromes may help to better classify cancer pain.

Telemedicine for outpatient palliative care during COVID-19 pandemics: a longitudinal study.

OBJECTIVES: During the COVID-19 pandemic, telemedicine (TM) emerged as an important mean to reduce risks of transmission, yet delivering the necessary care to patients. Our aim was to evaluate feasibility, characteristics and satisfaction for a TM service based on phone/video consultations for patients with cancer attending an outpatient palliative care clinic during COVID-19 pandemics. METHODS: A longitudinal observational study was conducted from April to December 2020. Consecutive patients were screened for video consultations feasibility. Either patients or their caregivers received video/phone consultations registering reason and intervention performed. Those contacted at least twice were eligible for experience of care assessment. RESULTS: Video consultations were feasible in 282 of 572 screened patients (49%, 95% CI 45% to 52%); 112 patients among the 572 had at least two phone/video consultations and 12 of them had one or more video consultations. Consultations were carried out with patients (56%), caregivers (30%) or both (14%). 63% of the consultations were requested by the patients/caregivers. Reasons for consultation included uncontrolled (66%) or new symptom onset (20%), therapy clarifications (37%) and updates on diagnostic tests (28%). Most interventions were therapy modifications (70%) and appointments' rescheduling (51%). 49 patients and 19 caregivers were interviewed, reporting good care experience (average of 1-5 satisfaction score of 3.9 and 4.2, respectively). The majority (83% and 84%) declared they would use TM after the pandemics. CONCLUSIONS: Although feasibility is still limited for some patients, TM can be a satisfactory alternative to in-person visits for palliative care patients in need of limiting access to the hospital.

Neuropathic pain: clinical classification and assessment in patients with pain due to cancer.

ABSTRACT: Neuropathic cancer pain (NcP) is associated with worse treatment responses and specific therapy indications, but a standardized clinical diagnosis of NcP is still lacking. This is a prospective observational study on outpatients with cancer, comparing different clinical approaches with NcP evaluation. A three-step assessment of NcP was performed using DN4 (cutoff of 4), palliative care physician Clinical Impression, including etiology and pain syndrome identification, and Retrospective Clinical Classification by a board of specialists with the IASP Neuropathic Pain Special Interest Group criteria. Neuropathic cancer pain classification was specifically referred to pain directly due to cancer. Three hundred fifty patients were assessed, and NcP prevalence was 20% (95% confidence interval [CI] 15.9%-24.6%), 36.9%, (95% CI 31.6%-42.1%), and 28.6% (95% CI 23.8%-33.9%) according to DN4, Clinical Impression, and Retrospective Clinical Classification, respectively. Cohen's kappa concordance coefficient between DN4 and Retrospective Clinical Classification was 0.57 (95% CI 0.47-0.67), indicating moderate concordance. Higher percentages of discordance were found for specific pain syndromes such as pain due to deep soft tissue infiltration and pain associated with tenesmus. Disagreement among clinicians accounted also for different NcP diagnoses and highlighted lack of homogeneous clinical criteria. Rigorous application of etiological and syndrome diagnosis to explain pain cause, associated with standardized diagnostic criteria and assessment of pain characteristics, that is also specific for the cancer pain condition could improve clinical classification of NcP.

Outpatient palliative care and thoracic medical oncology: Referral criteria and clinical care pathways.

OBJECTIVES: Recent evidences show that early integration of palliative care (PC) with oncology has a positive impact on patients' quality of life, quality of care and costs. However, there is no consensus on outpatient referral criteria. Based on real world data, the aim of this study was to identify timing and factors associated to PC referral in patients with thoracic malignancies, and to describe their clinical care pathway. MATERIAL AND METHODS: This observational retrospective study included consecutive patients with thoracic cancer, seen for the first time at the Thoracic Medical Oncology outpatient Clinic (TMOC) of our institution, between Jan.01-Dec.31 2014. Patients were followed-up till death or Dec.31 2015. Clinical and demographic data were collected from the electronic patient records. Cox regression models were used to evaluate the association between time to Palliative care Outpatient Clinic (POC) referral and performance status (PS), disease stage and symptoms at inclusion. RESULTS: 229 patients were eligible. 98 of them (43%; 95%IC 36%-49%) were referred to the POC within a median of 30 days (IQR 4-188). 80/98 patients received simultaneous anticancer therapy and PC. Univariable analysis showed that the hazard ratio (HR) of being referred to POC was significantly higher for patients with worse PS (HR = 4.5), more advanced disease stage (HR = 3.1), pain (HR = 4.9), dyspnea (HR = 2.5) and cough (HR = 2.2). The multivariable model confirmed independent prognostic value for PS, disease stage and pain. On Dec.31, 2015, 25/98 patients were still alive, 8 were lost at follow up and 65 had died. Among the latter, 61% died with hospice or home care, and, in the last 30 days of life, 16% received chemotherapy and 29% were admitted to hospital. CONCLUSIONS: Our results suggest considering symptom burden, PS and disease stage as screening criteria for referral to PC in patients with thoracic malignancies.

Comparison of the Tolerability Profile of Controlled-Release Oral Morphine and Oxycodone for Cancer Pain Treatment. An Open-Label Randomized Controlled Trial.

CONTEXT: Oxycodone and morphine are recommended as first-choice opioids for moderate/severe cancer pain, but evidence about their relative tolerability has significant methodological limitations. OBJECTIVES: This study was mainly aimed at comparing the risk of developing adverse events (AEs) with controlled-release oral morphine vs. oxycodone; secondary aims were comparing their analgesic efficacy and testing heterogeneity in tolerability across different age and renal function subgroups. METHODS: An open-label multicenter RCT (EudraCT number: 2006-003151-21) was carried out in patients with moderate/severe cancer pain. At baseline, 7 and 14 days, patients scored on 0-10 rating scales (0-10 numerical rating scale) the intensity of pain and of a list of common opioid side effects. The primary end point was the percentage of patients reporting an AE (a worsening ≥ 2 points on any of the listed side effects); tolerability by subgroups and average follow-up pain intensity were compared through regression models. RESULTS: One hundred eighty-seven patients were enrolled (47% of originally planned). Intention to treat (ITT) analysis (N = 185, morphine 94, oxycodone 91) did not show any difference in the risk of developing AEs (risk difference -0.6%, 95% CI -11.0% to 9.9%) nor in analgesia (0-10 numerical rating scale pain intensity difference -0.28, 95% CI -0.83 to 0.27). No evidence of heterogeneity of tolerability across age and renal function patient subgroups emerged. CONCLUSION: This trial failed to show any difference in tolerability and analgesic efficacy of morphine and oxycodone as first-line treatment for moderate/severe cancer pain but results interpretation is difficult due to lack of power, potential bias from open-label design, and concerns about assay sensitivity. These data, however, can significantly contribute to future meta-analyses comparing WHO Step-III opioids and are relevant in designing future randomized studies.