Identification of palliative care needs and prognostic factors of survival in tailoring appropriate interventions in advanced oncological, renal and pulmonary diseases: a prospective observational protocol.

INTRODUCTION: It is estimated that of those who die in high-income countries, 69%-82% would benefit from palliative care with a high prevalence of advanced chronic conditions and limited life prognosis. A positive response to these challenges would consist of integrating the palliative approach into all healthcare settings, for patients with all types of advanced medical conditions, although poor clinician awareness and the difficulty of applying criteria to identify patients in need still pose significant barriers. The aim of this project is to investigate whether the combined use of the NECPAL CCOMS-ICO and Palliative Prognostic (PaP) Score tools offers valuable screening methods to identify patients suffering from advanced chronic disease with limited life prognosis and likely to need palliative care, such as cancer, chronic renal or chronic respiratory failure. METHODS AND ANALYSIS: This multicentre prospective observational study includes three patient populations: 100 patients with cancer, 50 patients with chronic renal failure and 50 patients with chronic pulmonary failure. All patients will be treated and monitored according to local clinical practice, with no additional procedures/patient visits compared with routine clinical practice. The following data will be collected for each patient: demographic variables, NECPAL CCOMS-ICO questionnaire, PaP Score evaluation, Palliative Performance Scale, Edmonton Symptom Assessment System, Eastern Cooperative Oncology Group Performance Status and data concerning the underlying disease, in order to verify the correlation of the two tools (PaP and NECPAL CCOMS-ICO) with patient status and statistical analysis. ETHICS AND DISSEMINATION: The study was approved by local ethics committees and written informed consent was obtained from the patient. Findings will be disseminated through typical academic routes including poster/paper presentations at national and international conferences and academic institutes, and through publication in peer-reviewed journals.

Radiotherapy and palliative care outpatient clinic: a new healthcare integrated model in Italy.

BACKGROUND: On the basis of substantial evidence demonstrate that palliative care combined with standard care improves patient, caregiver, and society outcomes, we have developed a new healthcare model called radiotherapy and palliative care (RaP) outpatient clinic were a radiation oncologist and a palliative care physician make a joint evaluation of advanced cancer patients. METHODS: We performed a monocentric observational cohort study on advanced cancer patients referred for evaluation at the RaP outpatient clinic. Measures of quality of care were carried out. RESULTS: Between April 2016 and April 2018, 287 joint evaluations were performed and 260 patients were evaluated. The primary tumor was lung in 31.9% of cases. One hundred fifty (52.3%) evaluations resulted in an indication for palliative radiotherapy treatment. In 57.6% of cases was used a single dose fraction of radiotherapy (8 Gy). All the irradiated cohort completed the palliative radiotherapy treatment. An 8% of irradiated patients received the palliative radiotherapy treatment in the last 30 days of life. A total of 80% of RaP patients received palliative care assistance until the end of life. CONCLUSION: At the first descriptive analysis, the radiotherapy and palliative care model seem to respond to the need of multidisciplinary approach in order to obtain an improvement on quality of care for advanced cancer patients.

Nurse-led telephone follow-up for early palliative care patients with advanced cancer.

AIM AND OBJECTIVES: To present our experience of a nursing telephone consultation service, describing patient and caregiver requests, and outlining ensuing nursing or medical interventions. BACKGROUND: Recently, there has been an increase in the use of telephone consultation for cancer patients. However, there is still limited data on the characteristics of this type of service and on the nature of the interventions carried out. DESIGN AND METHODS: In this observational retrospective study, we evaluated the phone calls made over a 6-month period by patients or caregivers to the early palliative care team of a cancer institute. Information regarding telephone calls (frequency, reason and management) was systematically collected by a nursing case manager. The study complies with the STROBE checklist File S1. RESULTS: 171 patients used the service, for a total of 323 phone calls. The majority (80.8%) were from patients followed at the outpatient clinic and the most common requests were for pain management (38.4%) and for updates on the clinical situation (23.8%). Other frequent requests were for medication management (18.9%) and scheduling (18.3%). 210 of the 323 phone calls were handled by the nurse, while 22 were managed in collaboration with a physician. An 87.6% effectiveness in telephone management was observed. CONCLUSION: The overall use of the phone service was higher for early palliative care patients. The majority of phone calls were effectively handled by the nursing case manager. RELEVANCE TO CLINICAL PRACTICE: An effective and feasible nurse-led telephone follow-up of early palliative care patients with advanced cancer could improve their care experience. Specifically, it could impact on patients and families improving quality of life and symptom control securing access to timely care without travel or additional cost.It can also improve continuity of care, adherence to oncological treatments and minimise acute care visits.

Prognostication in palliative radiotherapy-ProPaRT: Accuracy of prognostic scores.

Background: Prognostication can be used within a tailored decision-making process to achieve a more personalized approach to the care of patients with cancer. This prospective observational study evaluated the accuracy of the Palliative Prognostic score (PaP score) to predict survival in patients identified by oncologists as candidates for palliative radiotherapy (PRT). We also studied interrater variability for the clinical prediction of survival and PaP scores and assessed the accuracy of the Survival Prediction Score (SPS) and TEACHH score. Materials and methods: Consecutive patients were enrolled at first access to our Radiotherapy and Palliative Care Outpatient Clinic. The discriminating ability of the prognostic models was assessed using Harrell's C index, and the corresponding 95% confidence intervals (95% CI) were obtained by bootstrapping. Results: In total, 255 patients with metastatic cancer were evaluated, and 123 (48.2%) were selected for PRT, all of whom completed treatment without interruption. Then, 10.6% of the irradiated patients who died underwent treatment within the last 30 days of life. The PaP score showed an accuracy of 74.8 (95% CI, 69.5-80.1) for radiation oncologist (RO) and 80.7 (95% CI, 75.9-85.5) for palliative care physician (PCP) in predicting 30-day survival. The accuracy of TEACHH was 76.1 (95% CI, 70.9-81.3) and 64.7 (95% CI, 58.8-70.6) for RO and PCP, respectively, and the accuracy of SPS was 70 (95% CI, 64.4-75.6) and 72.8 (95% CI, 67.3-78.3). Conclusion: Accurate prognostication can identify candidates for low-fraction PRT during the last days of life who are more likely to complete the planned treatment without interruption.All the scores showed good discriminating capacity; the PaP had the higher accuracy, especially when used in a multidisciplinary way.

Fentanyl pharmacokinetics in blood of cancer patients by Gas Chromatography - Mass Spectrometry.

In order to find a correlation between Fentanyl action on pain and inter-individual variability in different cancer patients, the pharmacokinetic characterization of the drug becomes essential. Therefore, a gas chromatographic-mass spectrometric (GC-MS) in SIM mode analytical procedure has been developed and validated for the determination of Fentanyl in human blood. The sample preparation consisted of a liquid-liquid extraction (LLE) from whole blood. The analysis were carried out with Agilent 7820 A series gas chromatograph equipped with a 5977E series mass selective single quadrupole detector (MSD) with an electron impact (EI) source (70 eV), under a temperature gradient elution. The limit of detection (LoD) and the limit of quantification (LoQ) values were found to be 5.60E-02 ± 3.50E-02 ng mL-1 and 1.86E-01 ± 1.18E-01 ng mL-1 respectively. The developed method was found selective and sensitive and therefore suitable for a fast determination of Fentanyl in human blood and for its pharmacokinetic characterization. Blood samples from 31 cancer patients treated with transdermal Fentanyl (doses in the range of 12-100 µg h-1) were collected at fixed intervals during an overall exposure time of 72 h. The analysis of data and the pharmacokinetic parameters revealed dissimilar pharmacokinetic profiles in the patients examined. Patients were therefore grouped in three categories representing the different trends observed: high, medium and slow responders. These preliminary data provided significant outcomes for a correlation to clinical response.

Methadone as First-line Opioid for the Management of Cancer Pain.

AIM: The aim of this study was to assess the efficacy and adverse effects of methadone when used as first-line therapy in patients that are either receiving low doses of opioids or none. METHODS: Patients with advanced cancer were prospectively assessed. Opioid-naive patients (L-group) were started with methadone at 6 mg/day. Patients receiving weak or other opioids in doses of <60 mg/day of OME (H-group) were started with methadone at 9 mg/day. Methadone doses were changed according to the clinical needs to obtain the most favorable balance between analgesia and adverse effects. Edmonton Symptom Asssement Score (ESAS), Memorial Delirium Assessment Score (MDAS), doses of methadone, and the use of adjuvant drugs were recorded before starting the study treatment (T0), 1 week after (T7), 2 weeks after (T14), 1 month after (T30), and 2 months after (T60). Methadone escalation index percent (MEI%) and in mg (MEImg) were calculated at T30 and T60. RESULTS: Eighty-two patients were assessed. In both groups H and L, there were significant changes in pain and symptom intensity at the different times during the study. Adverse effects as causes of drop-out were minimal. Mean MEImg was 0.09 (SD 0.28) and 0.02 (SD 0.07) at T30 and T60, respectively. MEI% was 1.01 (SD 3.08) and 0.27 (SD 0.86) at T30 and T60, respectively. CONCLUSION: Methadone used as a first-line opioid therapy provided good analgesia with limited adverse effects and a minimal opioid-induced tolerance.

Patients with multiple myeloma referred for palliative care consultation: from retrospective analysis to future directions to improve clinical outcomes.

INTRODUCTION: New treatments have improved the overall survival of patients with multiple myeloma (MM). At diagnosis and during the course of the disease, patients often report pain and other symptoms. Given the long disease trajectory, psychological and social issues are also frequent. Recently, the potential usefulness of early palliative care (EPC) was hypothesized in the area of hematology. We conducted a retrospective analysis of patients with MM referred to our institute for a palliative care (PC) consultation between January 2017 and June 2020. Our aim was to evaluate the main reasons (pain or other clinical symptoms) for the referral for a first PC consultation. METHODS: We examined the main reasons for the first PC consultation, the number of PC consultations carried out, and the period of time between diagnosis, first and subsequent PC visits, and death. We also recorded information on the type of pain experienced and the treatments administered. RESULTS: Of the 325 patients with MM followed at our hematology unit during the study period, 43 were referred for a PC consultation (39 for pain management and 4 to determine the most appropriate care setting (hospice or palliative homecare service)). Nineteen (44.2%) of the 43 patients reported other symptoms in addition to pain. The median time between MM diagnosis and the first PC consultation was 473 days. Fifteen patients died, with a median 332 days between the first PC visit and death. CONCLUSION: Randomized studies on MM involving larger patient populations with access to EPC are needed to identify an effective clinical model to improve the management of patients with MM.

The Role of Religiosity in Symptom Expression of Advanced Cancer Patients.

AIM: The aim of this study was to assess the religious pattern and its impact on symptom expression in patients with advanced cancer. METHODS: A consecutive sample of advanced cancer patients screened at admission to palliative care. Standard epidemiological data were recorded. Patients were asked about their religious beliefs, the degree of social relationship to existing religions, the role of religion in their life, and the frequency of their prayer. The Edmonton Symptom Assessment Scale (ESAS) and Hospital Anxiety Depression scale (HADS) were assessed. RESULTS: Two-hundred-eighty-three patients were screened. Age and gender were found to be independently correlated with religious belief (p = 0.042 and p = 0.016, respectively). Gender (females, p = 0.026), age (p = 0.003), lower Karnofsky performance status (KPS) (p = 0.022), and higher values of HADS-A (p = 0.003) were independently correlated with the degree of social relationship to existing religions. Gender (females, p = 0.002), lower KPS (p = 0.005), and higher values of HADS-A (p = 0.04) were independently correlated with a more relevant role of religiosity. Gender (females, p < 0.0005), lower KPS (p = 0.001), and drowsiness (p = 0.05) were independently correlated with frequency of prayer. CONCLUSION: The more the patients have demanding religious issues, the greater the state of anxiety, particularly in older and female patients with a lower KPS. The religious pattern did not have relevant role in the expression of other symptoms included in the ESAS.

Multiple myeloma and primary erythrocytosis in a dog.

A 13-year-old spayed female mixed breed dog was referred for impaired ambulation, limb tremors, back pain, hypergammaglobulinemia on cellulose acetate electrophoresis, and mild proteinuria. Conventional radiology and magnetic resonance imaging (MRI) suggested multifocal neoplastic bone lesions. At the referral examination, lameness and bright red mucous membranes were observed. Severe erythrocytosis, a monoclonal peak in the ß-2 globulin detected by capillary zone electrophoresis, severe proteinuria, bone marrow infiltration of plasma cells, and low serum erythropoietin concentrations were reported. The final diagnosis was multiple myeloma associated with severe primary erythrocytosis. This presentation in a dog is interesting because the combination of both disorders is rare in humans and has not been reported in dogs. Key clinical message: Although rare, multiple myeloma and primary erythrocytosis can occur together in dogs.

Myélome multiple et érythrocytose primaire chez un chien. Une chienne de race mixte stérilisée âgée de 13 ans a été référée pour troubles de la marche, tremblements des membres, maux de dos, hypergammaglobulinémie à l'électrophorèse sur acétate de cellulose et protéinurie légère. La radiologie conventionnelle et l'imagerie par résonance magnétique (IRM) suggéraient des lésions osseuses néoplasiques multifocales. Lors de l'examen de référence, une boiterie et des muqueuses rouge vif ont été observées. Une érythrocytose sévère, un pic monoclonal de la globuline ß-2 détecté par électrophorèse capillaire, une protéinurie sévère, une infiltration de la moëlle osseuse par des plasmocytes et de faibles concentrations sériques d'érythropoïétine ont été rapportés. Le diagnostic final était un myélome multiple associé à une érythrocytose primaire sévère. Cette présentation chez un chien est intéressante car l'association des deux conditions est rare chez l'homme et n'a pas été rapportée chez le chien.Message clinique clé :Bien que rares, le myélome multiple et l'érythrocytose primaire peuvent survenir simultanément chez le chien.(Traduit par Dr Serge Messier).

Palliative care: not only for treating symptoms: a case report.

INTRODUCTION: Palliative care (PC) aims to treat symptoms independently of the disease. In many medical disciplines, including oncology, there is an emphasis on personalizing treatment, identifying the most effective therapeutic option by studying the genetic heritage of the patient and the molecular characteristics of the disease. PC, on the other hand, encompasses the overall (physical and spiritual) well-being of the patient and his or her caregivers. The increasing use of early PC and its integration with oncology could represent a fruitful collaboration among specialists. CASE DESCRIPTION: We present the case of a 79-year-old woman with advanced breast cancer attending our institute who was referred to our PC Unit because of continuous ear pain, paresthesia around the mouth, strabismus, and facial dysesthesia. The patient was in good clinical condition (Eastern Cooperative Oncology Group 1) and was undergoing chemotherapy at the time. For these reasons, the PC physician carefully assessed the pain characteristics and differential diagnosis and discussed them with the oncologist, radiologist, and neurologist. Joint consultation led to a specific study of Meckel cave by MRI, revealing an extrameningeal gasserian ganglion metastasis, a very rare localization of breast cancer. CONCLUSION: We present a case that underlines the importance of specialized PC assessment not limited to the control of symptoms. The search for the etiopathogenesis of a patient's symptoms and the evaluation of overall clinical conditions may be necessary to plan appropriate diagnostic evaluations, target palliative therapies, and achieve effective symptom control.

Scrambler therapy: what's new after 15 years? The results from 219 patients treated for chronic pain.

Chronic pain is often difficult to treat, requiring a comprehensive multidisciplinary therapeutic intervention and a high level of management expertise.This is particularly true for patients who are unresponsive to standard treatments for chronic pain, for which Scrambler Therapy (ST) is indicated. The aim of the present study was to evaluate the impact of ST on patient-reported moderate to severe chronic pain.This was a prospective trial on 219 patients affected by chronic pain from April 2010 to March 2016. The study consisted of 2 consecutive weeks of treatment with ST (one 30-min daily session, 5 days a week) (T0, T1, T2) and a 2-week follow-up (T3, T4). Patients were asked to describe the pain using the Numeric Rating Scale (NRS) immediately prior to and after the treatment.Two hundred nineteen patients were treated for chronic pain of different nature with mean values of 6.44 (± 2.11) at T0, 3.22 (± 2.20) at T2, and 3.19 (± 2.34) at T4. A reduction in the symptomatology from T0 to T2 was maintained throughout T4 (P value < .0001). Of the 219 patients treated with ST, 83 (37.9%) had cancer pain and 136 (62.1%) had non-cancer pain. No adverse events were reported.Future research should focus on individual response, retreatment, and maintenance therapy. The data showed a statistically significant impact of ST, which was maintained during follow-up, on patients suffering from chronic pain of different nature.

RANKL: A promising circulating marker for bone metastasis response.

Bone metastases are a frequent event in patients with solid tumors. Although great advances have been made in the treatment of these patients, the identification of novel, accurate indicators of bone response would greatly facilitate the clinical management of the disease. The receptor activator of nuclear factor-κB (RANK)/RANK ligand (RANKL)/osteoprotegerin (OPG) signaling pathway is significantly involved in bone metastasis formation. The main aim of the present study was to evaluate the role of circulating RANK, RANKL and OPG levels in predicting bone response. Marker accuracy was also compared with that of the conventional tumor marker N-terminal telopeptide of type I collagen (NTX). A prospective study was performed on 49 patients with bone metastases from breast, lung and prostate cancer, who were undergoing treatment with zoledronic acid. Patients were monitored for 1 year with blood tests, clinical evaluation and instrumental exams according to the response evaluation criteria of the University of Texas M. D. Anderson Cancer Center (Houston, TX, USA) and the Positron Emission Tomography Response Criteria in Solid Tumors. Circulating RANK/RANKL/OPG transcripts and NTX levels were evaluated by reverse transcription-quantitative polymerase chain reaction and immune enzymatic assay, respectively. The baseline RANKL levels differed significantly between responders and non-responders, whereas no differences in NTX levels were observed between the two groups. Receiver operating characteristic curve evaluation for all markers revealed that RANKL was the most accurate marker, with an area under the curve of 0.74 (95% confidence interval, 0.54-0.93). In addition, RANKL, which is the target of the novel monoclonal antibody denosumab, was the most accurate predictor of bone response in the present series of patients with bone metastases. Thus, the use of RANKL as a marker could potentially improve clinical practice, as current bone response evaluation is still somewhat problematic.

Long-lasting activity of trabectedin in refractory uterine leiomyosarcoma: a case report.

BACKGROUND: Leiomyosarcoma (LMS) is an aggressive soft tissue sarcoma derived from smooth muscle cells typically of uterine, gastrointestinal or soft tissue origin. The prognosis for this tumor is poor, with survival rates among the lowest of all soft tissue sarcomas. Surgery is the best approach for localized disease. The principal role of chemotherapy is prevalently in the treatment of metastatic disease. Trabectedin, a promising new DNA-damaging agent with a mechanism of action that differs from that of traditional alkylating agents, has been approved in Europe for the treatment of patients with advanced soft tissue sarcoma after failure of anthracyclines and ifosfamide, CASE PRESENTATION: We report the case of a 53-year-old woman with metastatic well differentiated uterine leiomyosarcoma refractory to multiple treatments who underwent 22 cycles of trabectedin over 30 months, obtaining a partial response according to RECIST (Response Evaluation Criteria in Solid Tumors) criteria, with good tolerability, and maintaining the response for 10 months after trebectedin withdrawal. CONCLUSION: This very prolonged response, which persisted after drug discontinuation, suggests that trabectedin exerts an oncostatic effect rather than the cytotoxic one produced by other chemotherapeutic agents. Our experience also raises the question of the best way to evaluate trabectedin efficacy.

First-line chemotherapy in patients with metastatic gastroenteropancreatic neuroendocrine carcinoma.

BACKGROUND AND AIM: To investigate the efficacy of platinum-based chemotherapy in patients with metastatic gastroenteropancreatic neuroendocrine carcinoma (mGEP-NEC) and define predictive and prognostic factors. METHODS: Twenty mGEP-NEC patients were treated with cisplatin or carboplatin/etoposide between April 2010 and October 2014. Both large-cell and small-cell histologies were included. Cisplatin 25 mg/m(2) was administered on days 1-3 followed by etoposide 100 mg/m(2) on days 1-3 every 21 days. Carboplatin 300 mg/m(2) was administered on day 1 followed by etoposide 100 mg/m(2) on days 1-3. RESULTS: Of the 19 evaluable patients, 13 obtained a partial response, four showed stable disease, and two progressed. Median overall survival (mOS) was 13.5 months and median progression-free survival (mPFS) was 10.9 months. Gallium-68 positron emission tomography/computerizsed tomography-positive patients had a higher, albeit not significantly, OS than those with negative results (75% vs 34.3% at 18 months; P=0.06). mPFS was 19.3 and 6.3 months (P<0.01) in mGEP-NEC patients with Ki67 ≤55% or >55%, respectively. mOS was 8.1 months in the latter group but was not reached in the Ki67 ≤55% group (P-value =0.039). Patients with a lower body mass index (BMI) had a better prognosis in terms of both OS and PFS. Patients with BMI ≥25 had a mOS of 11.7 months (P=0.0293) and a mPFS of 6.2 months (P=0.0057). CONCLUSION: Platinum-based chemotherapy showed good efficacy in mGEP-NEC patients. Those with Ki67 ≤55%, positive Gallium-68 positron emission tomography/computerized tomography and BMI <25 had a better prognosis.

Pleural effusion in a patient with metastatic gastrointestinal stromal tumor treated with imatinib: case report.

Gastrointestinal stromal tumors are rare malignancies characterized by c-kit and PDGFR-α mutations targeted by imatinib. Pleural effusion is a very rare side effect of imatinib treatment. A 65-year-old female with metastatic gastrointestinal stromal tumor developed electrolyte imbalance, severe peripheral edema and progressively worsening dyspnea 2 months after starting imatinib. Having excluded cardiovascular and pulmonary disorders, imatinib was discontinued and prednisone 25 mg orally daily was begun. The patient's condition improved substantially over the next 48 h with a progressive decrease in dyspnea and a reduction in pleural effusion and peripheral edema. All side effects had resolved within 1 month. In view of the partial response obtained, the patient re-started imatinib after a 1-week interruption. Prednisone was maintained and there was no further toxicity.

Metronomic capecitabine in gastroenteropancreatic neuroendrocrine tumors: a suitable regimen and review of the literature.

BACKGROUND: We present a retrospective analysis of metronomic capecitabine in metastatic gastroenteropancreatic neuroendrocrine tumors (GEP-NETs). A review of the literature is also presented. METHODS: From January 2007 to December 2013, ten patients with metastatic GEP-NETs (four pancreatic and six ileal) who progressed after treatment with somatostatin analogs and other cytotoxic agents received oral capecitabine 1,500 mg/day continuously. The median patient age was 68 (range 29-82) years. The median treatment duration was 8 months. RESULTS: Five (50%) patients achieved a partial radiographic response, four (40%) showed stable disease, and one (10%) progressed. Median overall survival was 56 months. Three of the four pancreatic patients achieved a partial radiographic response that lasted for a median of 15.5 months; overall survival and progression-free survival in this subgroup was 58 and 6 months, respectively. CONCLUSION: Data in the literature show that capecitabine has only occasionally been used as a single agent, with increased toxicity. Only one study using single-agent capecitabine reported a progression-free survival of 9.9 months and overall survival of 36.5 months, without an objective response or major toxicity. In our experience, metronomic capecitabine was well tolerated, although minor side effects may have been underestimated due to the retrospective nature of our study. This regimen also seems to be feasible in elderly people. Although high response rates and prolonged response duration indicate the potential efficacy of this treatment, our results should be interpreted cautiously because of the small number of patients involved. Capecitabine was most effective in the pancreatic subgroup, which would seem to be more sensitive to chemotherapy.

Single bone metastasis from adenocarcinoma of the lacrimal gland: a case report.

Malignant tumors of the lacrimal gland are rare, and single bone metastases from lacrimal gland carcinoma are an exceptional event. We present the case of a 71-year-old man with a history of lumbar pain and left exophthalmos. Surgical resection of the lacrimal lesion and a bone biopsy gave a final histopathological diagnosis of primary ductal adenocarcinoma of the lacrimal gland with bone metastasis. The pathological tissue from both procedures was positive for androgen receptor expression. The patient underwent embolization and radiotherapy in association with total androgen blockade. After 20 months, the patient is still asymptomatic and has maintained the partial response at L1 with no progression to other sites. Our patient would appear to have a better prognosis and the disease a more indolent clinical course than the other cases of ductal adenocarcinoma of the lacrimal gland reported in the literature.