Association of opioid use with survival in patients with cancer treated with immune checkpoint inhibitors: it is time for evidence-based behaviors.

Cancer is a leading cause of morbidity and mortality worldwide, with pain experienced by most patients undergoing cancer treatment. Opioids are the recommended treatment for cancer pain management, but recent studies suggest a negative association between opioid use and survival rates among patients undergoing immunotherapy. However, conclusions cannot be drawn regarding causality from these observational data. Immunotherapy, which boosts the body's immune system to fight cancer cells, has emerged as a promising treatment option for all types of cancer. Immune checkpoint inhibitors (ICIs) can activate the anticancer function of exhausted T cells and have shown remarkable survival benefits in patients with multiple malignancies. However, a recent systematic review and meta-analysis suggested that the use of opioids during ICI treatment has an adverse effect on patient prognosis, while the use of NSAIDs is not significantly associated with the prognosis in patients treated with ICIs. These reviews have major limitations due to the retrospective nature of the studies and the multiple factors that can influence the phenomenon. Therefore, caution is required when interpreting results from retrospective data on drug interactions. The findings of this study are alarming and potentially harmful to patients with cancer suffering from pain or other symptoms requiring opioid drugs.

Clinical outcomes of NSCLC patients experiencing early immune-related adverse events to PD-1/PD-L1 checkpoint inhibitors leading to treatment discontinuation.

BACKGROUND: The prognostic relevance of early immune-related adverse events (irAEs) in patients affected by non-small cell lung cancer (NSCLC) upon immunotherapy is not fully understood. METHODS: The Leading to Treatment Discontinuation cohort included 24 patients experiencing severe irAEs after one of two administrations of single anti-PD-1/PD-L1 in any line setting for metastatic NSCLC between November 2015 and June 2019. The control cohort was composed of 526 patients treated with single anti-PD-1/PD-L1 in any line setting with no severe irAE reported. The primary end points were median progression-free survival, overall survival, objective response rate, risk of progression of disease and risk of death. The correlation of clinic pathological features with early severe irAEs represented the secondary end point. RESULTS: Median PFS was 9.3 and 8.4 months, median OS was 12.0 months and 14.2 months at a median follow-up of 18.1 and 22.6 months in the LTD cohort and in the control cohort, respectively. The ORR was 40% (95% CI 17.2-78.8) in the LTD cohort and 32.7% (95% CI 27.8-38.2) in the control cohort. The risk of disease progression was higher in the LTD cohort (HR 2.52 [95% 1.10-5.78], P = .0288). CONCLUSIONS: We found no survival benefit in LTD cohort compared to the control cohort. However, early and severe irAEs might underly an immune anti-tumor activation. We identified a significant association with first-line immune checkpoints inhibitors treatment and good PS. Further studies on risk prediction and management of serious and early irAEs in NSCLC patients are needed.

A multicenter study of skin toxicity management in patients with left-sided, RAS/BRAF wild-type metastatic colorectal cancer treated with first-line anti-EGFR-based doublet regimen: is there room for improvement?

BACKGROUND: Skin toxicity in patients affected by metastatic colorectal cancer (mCRC) treated with epidermal growth factor receptor (EGFR) inhibitors is well known. However, ad hoc ESMO guidelines have only recently been published. AIM AND METHODS: To describe the management (pre-emptive or reactive) of anti-EGFR-related cutaneous adverse events (AEs), in a real-life clinical context, in a selected population of patients with left-sided, metastatic RAS/BRAF wild-type mCRC treated with doublet chemotherapy plus anti-EGFR monoclonal antibody (i.e., panitumumab or cetuximab) as first-line regimen at 22 Institutions. The measured clinical outcomes were treatment-related adverse events, objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). RESULTS: Of 515 patients included in the analysis, 173 (33.6%) received a pre-emptive and 342 (66.4%) a reactive treatment. The median follow-up period for the overall population was 30.0 months. A significantly lower incidence of any grade acneiform rash was found in the pre-emptive compared to the reactive cohort both in the overall population (78.6% vs 94.4%, p < 0.001) and in patients treated with panitumumab (76.1% vs 93.7%, p < 0.001) or cetuximab (83.3% vs 95.4%, p = 0.004), respectively. A lower incidence of any grade (41.6% vs 50.9%, p = 0.047) but a higher incidence of G3-G4 (9.2% vs 4.7%, p = 0.042) paronychia/nail disorders were found in the pre-emptive compared to the reactive cohort. Nevertheless, a lower rate of patients within the reactive compared to the pre-emptive cohort was referred to dermatological counseling (21.4% vs 15.3%, respectively, p = 0.001). A higher rate of anti-EGFR therapy modification was needed in the pre-emptive compared to the reactive cohort (35.9% vs 41.6%, respectively, p < 0.001). The pre-emptive approach did not reduce the efficacy of antineoplastic therapy compared to the reactive in terms of ORR (69.2% vs 72.8%), median PFS (12.3 vs 13.0 months), and median OS (28.8 vs 33.5 months). CONCLUSION: Although recommended by international guidelines, the pre-emptive approach of anti-EGFR-related skin toxicity in mCRC patients still appears less adopted in daily clinical practice, compared to the reactive one. A wider reception and application of this indication is desirable to improve patients' quality of life without compromising the continuity and efficacy of antineoplastic therapy.

PD-1/PD-L1 checkpoint inhibitors during late stages of life: an ad-hoc analysis from a large multicenter cohort.

BACKGROUND: The favourable safety profile and the increasing confidence with immune checkpoint inhibitors (ICIs) might have boosted their prescription in frail patients with short life expectancies, who usually are not treated with standard chemotherapy. METHODS: The present analysis aims to describe clinicians' attitudes towards ICIs administration during late stages of life within a multicenter cohort of advanced cancer patients treated with single agent PD-1/PD-L1 checkpoint inhibitors in Italy. RESULTS: Overall, 1149 patients with advanced cancer who received single agent PD-1/PD-L1 checkpoint inhibitors were screened. The final study population consisted of 567 deceased patients. 166 patients (29.3%) had received ICIs within 30 days of death; among them there was a significantly higher proportion of patients with ECOG-PS ≥ 2 (28.3% vs 11.5%, p < 0.0001) and with a higher burden of disease (69.3% vs 59.4%, p = 0.0266). In total, 35 patients (6.2%) started ICIs within 30 days of death; among them there was a higher proportion of patients with ECOG-PS ≥ 2 (45.7% vs 14.5%, p < 0.0001) and with a higher burden of disease (82.9% vs 60.9%, p = 0.0266). Primary tumors were significantly different across subgroups (p = 0.0172), with a higher prevalence of NSCLC patients (80% vs 60.9%) among those who started ICIs within 30 days of death. Lastly, 123 patients (21.7%) started ICIs within 3 months of death. Similarly, within this subgroup there was a higher proportion of patients with ECOG-PS ≥ 2 (29.3% vs 12.8%, p < 0.0001), with a higher burden of disease (74.0% vs 59.0%, p = 0.0025) and with NSCLC (74.0% vs 58.8%, p = 0.0236). CONCLUSION: Our results confirmed a trend toward an increasing ICIs prescription in frail patients, during the late stages of life. Caution should be exercised when evaluating an ICI treatment for patients with a poor PS and a high burden of disease.

Knowledge and attitudes of Italian medical oncologists and palliative care physicians toward medical use of cannabis in cancer care: a national survey.

PURPOSE: Despite advances in supportive care, cancer-related symptoms tend to be persistent regardless of cancer type, stage of disease, or treatment received. There is an increasing prescription for complementary and alternative medicines, such as medical cannabis (MC). Knowledge and attitudes of Italian medical oncologists and palliative care physicians toward medical cannabis in cancer care remain unknown. METHODS: We conducted a cross-sectional study to investigate the knowledge and attitude toward MC prescription among cancer care professionals in Italy. All invited participants received an email with the electronic questionnaire accessible through a direct link. RESULTS: Among the 2616 members who received the invitation, 475 replied to the questionnaire and were considered for the survey analysis. The most prescribed formulations among those available in Italy were cannabis FM2. The most frequent clinical indications for the use of MC were pain, gastrointestinal, and mood disorders. Only 9 responders reported MC-related side effects like anxiety insomnia and muscle spasms. The question regarding the normative references for MC prescription and use in Italy had conflicting results: only 14% indicated the exact legislative reference. CONCLUSION: Our study highlights a significant discrepancy between personal attitudes, prescription levels, and actual knowledge on MC. This represent a critical issue that should be systemically faced, building educational programs and national guidelines that sublimate personal physicians' beliefs and predispositions, resulting in a robust science-based MC practice. Only through coordinated interventions on science and health policy of MC, there will be success of safety and efficacy, ensuring the best knowledge for the best outcomes.

Clinical and psychometric validation of the BreSAS questionnaire module for symptom assessment among breast cancer survivors.

BACKGROUND: The large number of women surviving many years post breast cancer (BC) diagnosis has heightened interest in studying long-term effects of cancer on quality of life (QoL). Several cancer-specific health-related measures have been developed, but these may not be appropriate for long survivors. This study evaluates the reliability and clinical and psychometric validity of the BreSAS questionnaire (BQ) among BC survivors. METHODS: The BQ is a quick, simple ten-item module for the assessment of long-term physical, psychological, sexual, and cognitive effects that may influence QoL. The total BreSAS score ranks from 0 to 100, with a low score indicating a better QoL. Patients complete the BQ, the FACT-ES questionnaire, and case report forms for clinical and socio-demographic data during follow-up visits. Reliability and clinical and psychometric validity of the questionnaires are assessed by correlation analyses and exploration of known group comparisons. RESULTS: From September 2015 to February 2016, 149 patients from three Italian oncology units were enrolled. Baseline questionnaires were returned from all, and 134 patients (89%) completed the BQ and FACT-ES in less than 15 min. For reliability, Cronbach's alpha coefficients for each scale were greater than 0.70 in all analyzed symptoms. Convergent validity of BQ showed by Pearson's r demonstrated a high correlation between intensity of symptoms and QoL, especially for pain and depression. No data were provided about reproducibility with test-retest study. CONCLUSION: The BQ demonstrates sufficient validity and reliability to support its use to assess patient-reported symptoms during planned follow-up clinical visits among BC survivors. Further full validation studies are needed.

The PERSONS score: A new tool for cancer patients' symptom assessment in simultaneous care and home care settings.

BACKGROUND: Scientific societies recommend early interaction between oncologic and supportive care, but there is still a lack of systematic evaluations regarding symptoms from the perspective of oncologists. PATIENTS AND METHODS: The aim of this prospective study was to evaluate the PERSONS score, in both "simultaneous care" and "supportive care" settings using the Edmonton Symptom Assessment Scale (ESAS) as a comparator. RESULTS: From November 2017 to April 2018, 67 and 110 consecutive patients were enrolled in outpatient and home care cohorts, respectively. The final study population comprised 163 patients. There were no significant changes over time in the total PERSONS scores and total ESAS scale. The intra-interviewer reliability (ICC2,1) and inter-interviewer reliability (ICC2,k) showed good reproducibility (test-retest) in each group of patients: 0.60 (0.49-0.70) and 0.82 (0.75-0.87), respectively, for the home care patients and 0.73 (0.62-0.81) and 0.89 (0.83-0.93), respectively, for the outpatient cohort. There were high correlations between PERSONS and ESAS, both at the baseline and final assessments. The mean PERSONS and ESAS scores between the home care patients and outpatients were not different at the baseline and final assessments. Receiver operating characteristics (ROC) curve for the PERSONS total score revealed good diagnostic ability. Area under the curve (AUC) was 0.825 and 0.805 for improvement and deterioration, respectively. CONCLUSIONS: The PERSONS score is an easy to apply tool for symptom assessment. Importantly, the PERSONS score showed high concordance with the established ESAS scale and, therefore, provides an alternative for everyday use in supportive care assessment.

Clinical Outcomes of Patients with Advanced Cancer and Pre-Existing Autoimmune Diseases Treated with Anti-Programmed Death-1 Immunotherapy: A Real-World Transverse Study.

BACKGROUND: Patients with a history of autoimmune diseases (AIDs) have not usually been included in clinical trials with immune checkpoint inhibitors. MATERIALS AND METHODS: Consecutive patients with advanced cancer, treated with anti-programmed death-1 (PD-1) agents, were evaluated according to the presence of pre-existing AIDs. The incidence of immune-related adverse events (irAEs) and clinical outcomes were compared among subgroups. RESULTS: A total of 751 patients were enrolled; median age was 69 years. Primary tumors were as follows: non-small cell lung cancer, 492 (65.5%); melanoma, 159 (21.2%); kidney cancer, 94 (12.5%); and others, 6 (0.8%). Male/female ratio was 499/252. Eighty-five patients (11.3%) had pre-existing AIDs, further differentiated in clinically active (17.6%) and inactive (82.4%). Among patients with pre-existing AIDs, incidence of irAEs of any grade was significantly higher when compared with patients without AIDs (65.9% vs. 39.9%). At multivariate analysis, both inactive (p = .0005) and active pre-existing AIDs (p = .0162), female sex (p = .0004), and Eastern Cooperative Oncology Group Performance Status <2 (p = .0030) were significantly related to a higher incidence of irAEs of any grade. No significant differences were observed regarding grade 3/4 irAEs and objective response rate among subgroups. Pre-existing AIDs were not significantly related with progression-free survival and overall survival. CONCLUSION: This study quantifies the increased risk of developing irAEs in patients with pre-existing AIDs who had to be treated with anti-PD-1 immunotherapy. Nevertheless, the incidence of grade 3/4 irAEs is not significantly higher when compared with control population. The finding of a greater incidence of irAEs among female patients ranks among the "hot topics" in gender-related differences in immuno-oncology. IMPLICATIONS FOR PRACTICE: Patients with a history of autoimmune diseases (AIDs) have not usually been included in clinical trials with immune checkpoint inhibitors but are frequent in clinical practice. This study quantifies the increased risk of developing immune-related adverse events (irAEs) in patients with pre-existing AIDs who had to be treated with anti-programmed death-1 immunotherapy. Nevertheless, their toxicities are mild and the incidence of grade 3/4 irAEs is not significantly higher compared with those of controls. These results will help clinicians in everyday practice, improving their ability to offer a proper counselling to patients, in order to offer an immunotherapy treatment even to patients with pre-existing autoimmune disease.

Early fatigue in cancer patients receiving PD-1/PD-L1 checkpoint inhibitors: an insight from clinical practice.

BACKGROUND: Fatigue was reported as the most common any-grade adverse event (18.3%), and the most common grade 3 or higher immune-related adverse event (irAE) (0.89%) in patients receiving PD-1/PD-L1 checkpoint inhibitors in clinical trial. METHODS: The aim of this retrospective multicenter study was to evaluate the correlations between "early ir-fatigue", "delayed ir-fatigue", and clinical outcomes in cancer patients receiving PD-1/PD-L1 inhibitors in clinical practice. RESULTS: 517 patients were evaluated. After the 12-weeks landmark selection, 386 (74.7%) patients were eligible for the clinical outcomes analysis. 40.4% were NSCLC, 42.2% were melanoma, 15.3% renal cell carcinoma and 2.1% other malignancies. 76 patients (19.7%) experienced early ir-fatigue (within 1 month from treatment commencement), while 150 patients (38.9%) experienced delayed ir-fatigue. Early ir-fatigue was significantly related to shortened PFS (HR = 2.29 [95% CI 1.62-3.22], p < 0.0001) and OS (HR = 2.32 [95% CI 1.59-3.38], p < 0.0001) at the multivariate analysis. On the other hand, we found a significant association between the occurrence of early ir-fatigue, ECOG-PS ≥ 2 (p < 0.0001), and disease burden (p = 0.0003). Delayed ir-fatigue was not significantly related to PFS nor OS. CONCLUSIONS: Early ir-fatigue seems to be negative prognostic parameter, but to proper weight its role we must to consider the predominant role of performance status, which was related to early ir-fatigue in the study population.

Prophylactic use of antiemetics for prevention of opioid-induced nausea and vomiting: a survey about Italian physicians' practice.

PURPOSE: Antiemetics are being used both for the treatment and prophylaxis of opioid-induced nausea and vomiting (OINV) in clinical practice, despite the lack of evidence for the prophylactic benefit. Studies among Japanese physicians demonstrated over 80% prescribe antiemetics, with neuroleptic antipsychotics as the most commonly prescribed drugs. Our objective was to elucidate the current scenario of the prophylactic use of antiemetics for OINV among Italian physicians. METHODS: We conducted a web-based cross-sectional national survey. All the invited participants received an e-mail with an 11-item electronic questionnaire accessible through a direct link. Anonymity was guaranteed. According to the exploratory intent of the survey, we did not predefine any formal statistical hypothesis. Associations between variables were tested by the Pearson chi-square or the Fisher exact test. RESULTS: From January to March 2017, 112 completed the electronic questionnaire (112/256, overall response rate, 43.7%). Nearly half of the participants were oncologists (54; 48.2%). Sixty-one (54.4%) physicians worked in palliative care units. About 45% of the interviewed prescribed prophylactic antiemetics at the beginning of opioid prescription. The most commonly chosen drugs for this purpose were prokinetics such as metoclopramide and domperidone (84%), followed by 5-HT3 antagonists (8%), neuroleptic antipsychotics (6%), and corticosteroids (2%). Ninety-one physicians (81%) declared to prescribe antiemetics at the occurrence of OINV, mainly prokinetics (N = 70; 77%). CONCLUSION: Italian physicians do not commonly prescribe prophylactic antiemetics for OINV. Unlike previously reported data, dopamine antagonists resulted the most commonly prescribed drugs. Prospective clinical trials are necessary to evaluate the real efficacy of this practice.

The Incidence of Alcoholism in Patients with Advanced Cancer Receiving Active Treatment in Two Tertiary Care Centers in Italy.

INTRODUCTION: Substance abuse is frequently under-diagnosed among cancer patients. Alcoholism is a problem afflicting about 18% of the general population. This percentage is higher in hospitalized patients. Previous studies conducted on advanced cancer patients admitted in palliative care units have highlighted this problem only for a small percentage of cases. The objective of the study was to evaluate the incidence of alcoholism in patients with advanced cancer admitted to two Italian Oncology Units for active cancer treatment, using a recognized and validated assessment tool. SHORT SUMMARY: To evaluate the incidence of alcoholism in cancer patients and its impact on symptoms, the CAGE questionnaire was completed by 117 patients in active anticancer treatment. The percentage of CAGE-positive patients was higher than previously detected in palliative settings and was associated to male sex and lower ESAS score. METHODS: All eligible patients were enrolled consecutively during a 12-month recruitment period. Clinical and demographic data were collected. Each enrolled patient completed the Cut down, Annoyed, Guilty, Eye-opener (CAGE) questionnaire. RESULTS: Hundred and seventeen consecutive patients were surveyed in the 12-month period. The mean age was 63.3 (SD 12.0) years and 66 were males. The mean Karnofsky level was 68.3 (SD 16.0). Twelve patients were CAGE positive (10.3%). Males (P = 0.05) and patients with low Edmonton Symptom Assessment System score (P = 0.03) proved to be CAGE positive. CONCLUSIONS: Alcoholism is widespread and under-diagnosed among patients undergoing active cancer treatment. Compared with other experience in palliative settings among European population, percentage of CAGE-positive patients was double. CAGE-positive patients were more likely to be male, with lower ESAS score. It is possible to hypothesize an effect of alcohol consumption on patients' perception of symptoms. This data has never been reported in the literature and will certainly need confirmation studies.

What cancer patients actually know regarding medical cannabis? A cross-sectional survey with a critical analysis of the current attitudes.

BACKGROUND: In Italy medical cannabis is a prescription drug since 1998. Even though it could not be considered a therapy as such, it is indicated as a symptomatic treatment also in cancer patients, to cure iatrogenic nausea/vomiting and chronic pain. PATIENTS AND METHODS: We conducted a knowledge survey about medical cannabis among cancer patients referred to two outpatient cancer care centers and a home care service. RESULTS: From February to April 2018, 232 patient were enrolled; 210 patients were on active disease-oriented treatment (90.5%), while 22 (9.5%) not. Eighty-one percent of the patients have heard about medical cannabis, but only 2% from healthcare professionals. Thirty-four percent of responders thought about using cannabis to treat one or more of their own health problems, especially pain (55%). Despite that, 18% of the participants believe that medical cannabis could have negative effects on their own symptoms. Patients with high educational level better knew cannabis (odds ratio = 3.52; 95% confidence interval: 1.07-11.53), and medical cannabis (odds ratio = 3.21; 95% confidence interval: 1.48-6.98), when compared to patient with low educational level. Patients who were on active disease-oriented treatment better knew medical cannabis (odds ratio = 3.91; 95% confidence interval: 1.26-12.11) compared to "out of treatment" patients. Metastatic patients were less informed about medical cannabis compared to patients on adjuvant treatment. CONCLUSIONS: Our survey shows that most of Italian cancer patients know medical cannabis and a third of them have considered using cannabis to treat one (or more) of their own health problems. In the same time, they are poorly informed and do not tend to ask for information about medical cannabis to healthcare professionals.

The PERSONS score for symptoms assessment in simultaneous care setting: A pilot study.

One of the first steps to early integrate palliative care into oncology practice is a timely and efficient evaluation of symptoms (Bakitas et al., 2015; Davis et al., 2015; Temel et al., 2010). In a recent position paper, the Italian Association of Medical Oncology tells oncologists that they "must be able to prevent, recognize, measure, and treat all cancer-related symptoms" (Zagonel et al., 2017). Major international scientific societies such as the American Society of Clinical Oncology and the European Society of Medical Oncology have often defined the key role of symptoms evaluation and management to force the integration of palliative care into oncology (Davis et al., 2015; Ferrel et al., 2017). Nevertheless, a recent survey conducted by the Italian Association of Medical Oncology shows that only 20% of oncologists regularly uses valid tools to evaluate symptoms, 45% exclusively use them in the context of clinical trials, 30% use them only occasionally, and 5% never use them (Zagonel et al., 2016).

Topical Menthol for Treatment of Chemotherapy-induced Peripheral Neuropathy.

Chemotherapy-induced peripheral neuropathy is a frequent treatment-limiting factor that significantly impairs patients' everyday life, also because of a lack of valid palliative options. Here, we report a case of a male patient with a history of metastatic colon cancer and previous chemotherapies. He came to our attention with a peripheral neuropathy that impaired his quality of life and could limit the further line of chemotherapy. We treated the neuropathy with menthol aqueous cream with benefit.

Age differences in the last week of life in advanced cancer patients followed at home.

A retrospective analysis of a consecutive sample of patients admitted to a home care program was performed. Data were recorded in the last week through a backward analysis from the day before death as follows: 1 week before dying (-1W), 3 days before death (-3D), and the day before dying (-1D). Data to be collected included the Edmonton Symptom Assessment System (ESAS), background pain intensity, the prevalence of breakthrough pain, the use of opioids in the last week, and the need for palliative sedation, with indications, duration, and drugs used. Patients were distributed according to the following age ranges: adults (<65 years, A) and aged (≥65 years, O). Of the latter group, three subgroups were assessed: old (65-74 years, O1), very old (75-84 years, O2), and the oldest (≥85 years, O3). Four hundred eleven patients were assessed. At -W1, no statistical differences in intensity of ESAS items ≥4 among the age subgroups were found. For ESAS values at -1W, -3D, and -1D, no statistical differences were found unless for anorexia at -1W (p = 0.000) (more likely), depression at -3D (p = 0.000) (less likely), depression (p = 0.000), and dyspnea (p = 0.01) (less likely) at -1D in the oldest group (O3). No differences in pain intensity among the groups were found (p = 0.54). Opioid doses increased in time and were significantly lower in older patients (p = 0.000). The subcutaneous route was more frequently used at -3D and -1D in older patients. No differences in opioid switching were found among the groups (p = 0.56). Adult patients required more often palliative sedation (p = 0.003). Older patients have problems relatively similar to adult patients in the last week of life, unless for some symptoms. Older patients had also a lower opioid consumption, a more frequent use of the subcutaneous route, and a lower need for palliative sedation.

Prevalence of oral mucositis, dry mouth, and dysphagia in advanced cancer patients.

BACKGROUND: Oral symptoms can be a sign of an underlying systemic condition and have a significant impact on quality of life, nutrition, and cost of care, while these lesions are often studied in the context of cancer treatment. However, information regarding oral symptoms in advanced cancer patients is poor. The aim of this multicenter study was to determine the prevalence and the characteristics of oral symptoms in a large population of advanced cancer patients. METHODS: A consecutive sample of patients with advanced cancer for a period of 6 months was prospectively assessed for an observational study. At time of admission, the epidemiological characteristics, surgery-radiotherapy of head and neck, and oncologic treatments in the last month were recorded. The presence of mucositis, dry mouth, and dysphagia was assessed by clinical examination and patients' report and their intensity recorded. Patients were also asked whether they had limitation on nutrition of hydration due to the local condition. RESULTS: Six hundred sixty-nine patients were surveyed in the period taken into consideration. The mean age was 72.1 years (SD 12.3), and 342 patients were males. The primary tumors are listed in Table 1. The prevalence of mucositis was 22.3 %. The symptom relevantly reduced the ingestion of food or fluids and was statistically associated with the Karnofsky level and head and neck cancer. The prevalence of dry mouth was 40.4 %, with a mean intensity of 5.4 (SD 2.1). Several drugs were concomitantly given, particularly opioids (78 %), corticosteroids (75.3 %), and diuretics (70.2 %). Various and nonhomogeneous treatments were given for dry mouth, that was statistically associated with current or recent chemotherapy, and hematological tumors. The prevalence of dysphagia was 15.4 % with a mean intensity of 5.34 (SD 3). Dysphagia for liquids was observed in 52.4 % of cases. A high level of limitation for oral nutrition due to dysphagia was found, and in 53.4 % of patients, alternative routes to the oral one were used. Dysphagia was statistically associated with the Karnofsky level and head and neck cancer. A strong relationship between the three oral symptoms was found. CONCLUSION: In advanced cancer patients, a range of oral problems significantly may impact on the physical, social, and psychological well-being of advanced cancer patients to varying degrees. These symptoms should be carefully assessed early but become imperative in the palliative care setting when they produce relevant consequences that may be life-threatening other than limiting the daily activities, particularly eating and drinking.

Pain intensity as prognostic factor in cancer pain management.

AIM: The aim of this study was to prospectively assess the prognostic value of initial pain intensity and its duration in advanced cancer patients. METHODS: A prospective study was conducted in a sample of patients with cancer requiring pain control. Patients underwent standard analgesic strategies used in our palliative care units. Pain intensity was measured at admission (T0) and after successful dose titration or opioid/route switching within a week (Ts). Patients were also asked about their pain intensity reported 15 days before admission (T-15). Doses of opioids and duration of opioid use were recorded. Patients were also assessed for the presence of incident pain, neuropathic pain, alcoholism, delirium, and symptom intensity, including items representing psychological distress. One week after or at time of stabilization (Ts), the opioid response was clinically graded as follows: (1) good pain control; (2) adequate pain control requiring more aggressive opioid escalation; (3) adequate pain control associated with the occurrence of adverse effects; (4) incapacity to achieve pain control within a week. Opioid escalation indexes and days for dose finding were also recorded. RESULTS: Pain intensity at T0 and at T-15, opioid doses, duration of opioid therapy, and age were associated with more complex analgesic therapies, which were effective in almost all patients within a week. CONCLUSION: High levels of pain intensity, often due to previous undertreatment, are predictive of more complex analgesic treatment. Opioid tolerance, as well as younger age, may also play a role.

Palliative sedation and time to death in home palliative care: retrospective analysis.

OBJECTIVES: We described time to death and rates of palliative sedation during home palliative care leveraging a retrospective cohort of patients with advanced cancer. METHODS: The cohort consists of 143 patients with solid or haematological malignancies admitted to home palliative care in the Tuscany region in central Italy. Only patients for whom a date of death was available were included. The outcome measures were time from admission to home palliative care to death and receipt of palliative sedation. RESULTS: 143 patients were included in this report. Lower Eastern Cooperative Oncology Group (ECOG) performance status (PS) scores were significantly associated with anticancer treatment at admission, as was younger age. Increasing ECOG PS scores were associated with lower survival time. Women and patients on anticancer treatment had longer survival time. Thirty-eight per cent of patients underwent palliative sedation at home; palliative sedation was more frequent among younger patients and among patients with brain or lung cancer. The most common reasons for palliative sedation were delirium and dyspnoea. CONCLUSIONS: ECOG PS, sex and anticancer treatment had a significant impact on survival time. Thirty-eight per cent of patients in our cohort underwent home palliative sedation for refractory symptoms, most often delirium and dyspnoea.

The use of fentanyl buccal tablets for breakthrough pain by using doses proportional to opioid basal regimen in a home care setting.

The dose of rapid onset opioids to be given for breakthrough cancer pain (BTcP) is controversial. Dose proportional to the basal opioid regimen seem to be safe and effective in hospital units. However, data in other less protected settings, like home care, are lacking. The aim of this open-label study was to assess the efficacy and safety in a group of patients with BTcP followed at home, after giving a dose of fentanyl buccal tablets (FBT) proportional to the opioid basal regimen, skipping the steps for dose titration. Consecutive patients admitted to a home care program presenting BTcP episodes and receiving stable doses of opioids for background pain were selected. Data from four consecutive episodes of BTcP were collected. For each episode, patients were instructed to routinely collect changes in pain intensity and severe adverse effects when pain got severe (T0) and to reassess the same items 15 min after FBT, given as a rescue medication in doses proportional to the daily opioid doses used for background pain (T15). One hundred twenty episodes of BTcP were recorded in 30 patients. One hundred eight episodes were defined as successfully treated, while 12 episodes required a further administration of opioids. Pain intensity significantly decreased at T15 (p < 0.001). In 95.5 and 90.8 % of episodes treated, there was a reduction in pain intensity of more than 33 and 50 %, respectively. No relevant adverse effects were recorded, even in older patients. This study suggests that FBT given in doses proportional to the basal opioid regimen for the management of BTcP is very effective and safe in clinical practice in the home care setting.