Pattern and quality of care of cancer pain management. Results from the Cancer Pain Outcome Research Study Group

Most patients with advanced or metastatic cancer experience pain and despite several guidelines, undertreatment is well documented. A multicenter, open-label, prospective, non-randomised study was launched in Italy in 2006 to evaluate the epidemiology, patterns and quality of pain care of cancer patients. To assess the adequacy of analgesic care, we used a standardised measure, the pain management index (PMI), that compares the most potent analgesic prescribed for a patient with the reported level of the worst pain of that patient together with a selected list of clinical indicators. A total of 110 centres recruited 1801 valid cases. 61% of cases were received a WHO-level III opioid; 25.3% were classified as potentially undertreated, with wide variation (9.8–55.3%) according to the variables describing patients, centres and pattern of care. After adjustment with a multivariable logistic regression model, type of recruiting centre, receiving adjuvant therapy or not and type of patient recruited (new or already on follow-up) had a significant association with undertreatment. Non-compliance with the predefined set of clinical indicators was generally high, ranging from 41 to 76%. Despite intrinsic limitations of the PMI that may be considered as an indicator of the poor quality of cancer pain care, results suggest that the recourse to WHO third-level drugs still seems delayed in a substantial percentage of patients. This delay is probably related to several factors affecting practice in participating centres and suggests that the quality of cancer pain management in Italy deserves specific attention and interventions aimed at improving patients' outcomes

Neoadjuvant eribulin mesylate following anthracycline and taxane in triple negative breast cancer: Results from the HOPE study

Background Eribulin mesylate (E) is indicated for metastatic breast cancer patients previously treated with anthracycline and taxane. We argued that E could also benefit patients eligible for neoadjuvant chemotherapy. Methods Patients with primary triple negative breast cancer 2 cm received doxorubicin 60 mg/m2 and paclitaxel 200 mg/m2 x 4 cycles (AT) followed by E 1.4 mg/m2 x 4 cycles. Primary endpoint was pathological complete response (pCR) rate; secondary and explorative endpoints included clinical/metabolic response rates and safety, and biomarker analysis, respectively. Using a two-stage Simon design, 43 patients were to be included provided that 4 of 13 patients had achieved pCR in the first stage of the study. Results In stage I of the study 13 women were enrolled, median age 43 years, tumor size 2–5 cm in 9/13 (69%), positive nodal status in 8/13 (61%). Main grade 3 adverse event was neutropenia (related to AT and E in 4 and 2 cases, respectively). AT followed by E induced clinical complete + partial responses in 11/13 patients (85%), pCR in 3/13 (23%). Median measurements of maximum standardized uptake value (SUVmax) resulted 13, 3, and 1.9 at baseline, after AT and E, respectively. Complete metabolic response (CMR) occurred after AT and after E in 2 and 3 cases, respectively. Notably, 2 of the 5 (40%) patients with CMR achieved pCR at surgery. Immunostaining of paired pre-/post-treatment tumor specimens showed a reduction of β-catenin, CyclinD1, Zeb-1, and c-myc expression, in the absence of N-cadherin modulation. The study was interrupted at stage I due to the lack of the required patients with pCR. Conclusions Despite the early study closure, preoperative E following AT showed clinical and biological activity in triple negative breast cancer patients. Furthermore, the modulation of β-catenin pathway core proteins, supposedly outside the domain of epithelial–mesenchymal transition, claims for further investigation. Trial registration EU Clinical Trial Register, EudraCT number 2012-004956-12

Effetti della somministrazione di buprenorfina transdermica in pazienti oncologici : Risultati di uno studio di outcome

Nonostante il dolore affligga la maggior parte dei pazienti oncologici, soprattutto nelle fasi metastatiche della malattia, spesso il trattamento non \ue8 proporzionato all\u2019intensit\ue0 del dolore. Le preparazioni transdermiche hanno alcuni vantaggi rispetto a quelle orali e parenterali, ma le evidenze fornite da studi comparativi sono ancora scarse. Nel contesto di una iniziativa pi\uf9 ampia, nel 2006 \ue8 stato avviato in Italia uno studio di Outcome Research per studiare gli effetti di diverse terapie analgesiche, in particolare Buprenorfina TDS. Nonostante i limiti legati alla natura osservazionale dello studio, i risultati ottenuti forniscono informazioni ai medici per comprendere meglio gli effetti della somministrazione di Buprenorfina transdermica in una casistica ampia e ben caratterizzata e possono essere utili per disegnare ulteriori studi comparativ

Unexpected detection of SARS-CoV-2 antibodies in the prepandemic period in Italy

There are no robust data on the real onset of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and spread in the prepandemic period worldwide. We investigated the presence of SARS-CoV-2 receptor-binding domain (RBD)–specific antibodies in blood samples of 959 asymptomatic individuals enrolled in a prospective lung cancer screening trial between September 2019 and March 2020 to track the date of onset, frequency, and temporal and geographic variations across the Italian regions. SARS-CoV-2 RBD-specific antibodies were detected in 111 of 959 (11.6%) individuals, starting from September 2019 (14%), with a cluster of positive cases (>30%) in the second week of February 2020 and the highest number (53.2%) in Lombardy. This study shows an unexpected very early circulation of SARS-CoV-2 among asymptomatic individuals in Italy several months before the first patient was identified, and clarifies the onset and spread of the coronavirus disease 2019 (COVID-19) pandemic. Finding SARS-CoV-2 antibodies in asymptomatic people before the COVID-19 outbreak in Italy may reshape the history of pandemic

The FDA guidance for industry on PROs: the point of view of a pharmaceutical company

The importance of the patients point of view on their health status is widely recognised. Patient-reported outcomes is a broad term encompassing a large variety of different health data reported by patients, as symptoms, functional status, Quality of Life and Health-Related Quality of Life. Measurements of Health-Related Quality of Life have been developed during many years of researches, and a lot of validated questionnaires exist. However, few attempts have been made to standardise the evaluation of instruments characteristics, no recommendations are made about interpretation on Health-Related Quality of Life results, especially regarding the clinical significance of a change leading a therapeutic approach. Moreover, the true value of Health-Related Quality of Life evaluations in clinical trials has not yet been completely defined. An important step towards a more structured and frequent use of Patient-Reported Outcomes in drug development is represented by the FDA Guidance, issued on February 2006. In our paper we aim to report some considerations on this Guidance. Our comments focus especially on the characteristics of instruments to use, the Minimal Important Difference, and the methods to calculate it. Furthermore, we present the advantages and opportunities of using the Patient-Reported Outcomes in drug development, as seen by a pharmaceutical company. The Patient-Reported Outcomes can provide additional data to make a drug more competitive than others of the same pharmacological class, and a well demonstrated positive impact on the patient' health status and daily life might allow a higher price and/or the inclusion in a reimbursement list. Applying extensively the FDA Guidance in the next trials could lead to a wider culture of subjective measurement, and to a greater consideration for the patient's opinions on his/her care. Moreover, prescribing doctors and payers could benefit from subjective information to better define the value of drugs

Liquid dynamic medicine and N-of-1 clinical trials: A change of perspective in oncology research

The increasing use of genomics to define the pattern of actionable mutations and to test and validate new therapies for individual cancer patients, and the growing application of liquid biopsy to dynamically track tumor evolution and to adapt molecularly targeted therapy according to the emergence of tumor clonal variants is shaping modern medical oncology., In order to better describe this new therapeutic paradigm we propose the term "Liquid dynamic medicine" in the place of "Personalized or Precision medicine". Clinical validation of the "Liquid dynamic medicine" approach is best captured by N-of-1 trials where each patient acts as tester and control of truly personalized therapies. \ua9 2017 The Author(s)

Pain in cancer. An outcome research project to evaluate the epidemiology, the quality and the effects of pain treatment in cancer patients

BACKGROUND: Management of pain related to advanced or metastatic cancer, although the availability of several pharmacological and non-pharmacological interventions and the existence of well-known guidelines and protocols, is often difficult and inadequate. Evidence of the relative effectiveness of current options for treating cancer pain from comparative randomized studies is scanty. METHODS: In the context of a wider project, a multicenter, open label, prospective Outcome Research study will be launched in Italy in 2006 to investigate the epidemiology of cancer pain and of its treatments, the quality of analgesic-drug therapy and the effectiveness of alternative analgesic strategies in a large, prospective, unselected cohort of cancer patients using the state-of-the art of patient-reported-outcomes. About 100 Italian centers will recruit 2500 patients with advanced/progressive/metastatic cancer with pain (related to the cancer disease) requiring analgesic treatments. Each center is expected to recruit 25 consecutive and eligible patients during the study inception period. Approximately two months will be allowed for subject recruitment and enrollment. Subject evaluation and follow-up will be for 3 months. The effect on outcomes of various therapeutic analgesic options administered by physicians, given the observational approach where patients are not assigned at random to different treatments, will be compared using the propensity score approach, allowing the adjustment for treatment selection bias. Later, after the launch of the observational study and on the basis of results, in specific subsamples of patients and in select centers of the network, a Randomized Controlled Trial will be carried out to formally compare the efficacy of alternative analgesic strategies, with particular emphasis on oral morphine (as comparator) and buprenorphine patch (as experimental arm). Results from the outcome (cohort) and experimental (Randomized Controlled Trial) studies will ensure both the external and internal validity

Community singing, wellbeing and older people: implementing and evaluating an English singing tool for health intervention in Rome

Aim: The aim of this research was to explore the transferability and effectiveness of the English Silver Song Clubs model for older people in a different social and cultural context, i.e. in the capital city of Italy, Rome. Methods: A single condition, pre-test, post-test design was implemented. Participants completed two questionnaires: EQ-5D and York SF-12. Results: After the singing experience, participants showed a decrease in their levels of anxiety and depression. An improvement was also found from baseline to follow up in reported performance of usual activities. The English study showed a difference between the singing and non-singing groups at three and six months on mental health, and after three months on specific anxiety and depression measures. The current (Rome) study shows similar findings with an improvement on specific anxiety and depression items. Conclusions: Policy makers in different national contexts should consider social singing activities to promote the health and wellbeing of older adults as they are inexpensive to run and have been shown to be enjoyable and effective