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.

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.

Can malignant bowel obstruction in advanced cancer patients be treated at home?

Eleven advanced cancer patients affected by malignant bowel obstruction (MBO) were treated at home with a combination of octreotide, metoclopramide, morphine, and dexamethasone. In all patients, we observed a prompt control of gastrointestinal symptoms and recovery of bowel movements within 1-5 days. Based on our results, a combination of drugs with different mechanisms of action allows an effective and safe treatment for MBO at home. Further studies with larger number of patients are warranted to confirm these preliminary data.

Bone recurrence in early breast cancer patients: The paradox of aromatase inhibitors induced bone resorption.

BACKGROUND: Despite the increase in chances of cure for early breast cancer (EBC) patients, approximately 20-45% of them will experience a disease recurrence, particularly bone metastases in 60-80% of cases, which occur more frequently in luminal subtypes. Endocrine therapy (ET) has always been the milestone of adjuvant treatment for hormone receptor-positive EBC patients, leading to indubitable reduction of disease recurrence risk. However, adjuvant aromatase inhibitors (AIs) therapy may promote a progressive decrease in bone mineral density (BMD), which can lead to osteoporosis. The increased bone resorption associated with osteoporosis may provide fertile soil for cancer growth and accelerate the development of bone metastases. PATIENTS AND METHODS: In this single-institution cohort study, we performed a retrospective analysis of "luminal-like" EBC patients who experienced bone recurrence after a subsequent disease free interval. The aim of the study was to evaluate the median time to skeletal recurrence (TSkR). RESULTS: 143 patients experienced bone recurrence. Median TSkR was 54 months (95%CI: 45-65). Among patients who received adjuvant AIs median TSkR was 35 months (95%CI: 25-54), while among patients who did not was 61 months (95%CI: 50-80) (HR = 1.45 [95%CI: 0.97-2.17], p = 0.0644). After adjusting for TNM stage (AJCC 8th edition), adjuvant AIs treatment was significantly related to a shorter TSkR (HR = 1.60 [95%CI: 1.06-2.42], p = 0.0244). Adjuvant Tamoxifen, adjuvant AIs/Tamoxifen and no-treatment did not revealed to be associated to TSkR. CONCLUSIONS: In this cohort of EBC patients with bone recurrence, AIs treatment seems to be related to a shorter TSkR. AIs-induced bone resorption might represent the underlying mechanism.

Efficacy and safety of deep, continuous palliative sedation at home: a retrospective, single-institution study.

GOALS: The goal of this study is to evaluate the feasibility and efficacy of palliative sedation at home (PSH) to approach refractory symptoms in dying cancer patients. MATERIALS AND METHODS: Charts of 121 patients, observed by "L'Aquila per la Vita" Home Care Unit, from August 2006 to May 2008, were reviewed. Sixteen patients out of 44 who died at home (36.4%) were sedated. Indication for sedation was agitated delirium in 13 patients and dyspnea in three patients. A multistep midazolam-based protocol was administered. RESULTS: In all patients, a deep, prolonged, continuous sedation was obtained. No treatment-related complications were registered. CONCLUSION: A midazolam-based protocol for PSH is feasible and effective. Our results need to be confirmed by prospective, multicentric, controlled studies.

Home Care for Cancer Patients During COVID-19 Pandemic: The Double Triage Protocol.

Patients with cancer have an increased risk of developing severe forms of coronavirus disease 2019, and patients with advanced cancer who are followed at home represent a particularly frail population. Although with substantial differences, the challenges that cancer care professionals have to face during a pandemic are quite similar to those posed by natural disasters. We have already managed the oncological home care service in L'Aquila (middle Italy) after the 2009 earthquake. With this letter, we want to share the procedures and tools that we have started using at the home care service of the Tuscany Tumor Association during the coronavirus disease 2019 pandemic.

Haloperidol for the treatment of opioid addiction in advanced cancer patients: a case series.

Opioid addiction, if not well diagnosed and treated, can be a significant challenge for optimal pain management even in cancer patients. To date there is no definitive pharmacological standard of care for treating addiction, especially in this setting of patients. We present a clinical case series of three opioid-addicted advanced cancer patients, effectively treated with haloperidol, a well-known first-generation typical antipsychotic.

Predictive Ability for Disease-Free Survival of the GRade, Age, Nodes, and Tumor (GRANT) Score in Patients with Resected Renal Cell Carcinoma.

BACKGROUND: Recently, the GRANT (GRade, Age, Nodes, and Tumor) score was validated through an adjuvant trial population. METHODS: This retrospective study evaluated the performance of the GRANT score as a prognostic model for disease-free survival (DFS), compared to the University of California Los Angeles Integrated Staging System (UISS) score, in a "real-life" population of early renal cell carcinoma patients. A uni-/multivariate analysis of DFS was also performed, to weigh the roles of baseline clinical factors. RESULTS: From February 1998 to January 2018, 134 consecutive patients were enrolled, of which 85 patients (63.4%) had a favorable GRANT score, 49 (36.6%) an unfavorable GRANT score, and 21 (15.7%), 84 (62.6%), and 29 (21.6%) patients had a low, intermediate, or high risk of recurrence according to the UISS score, respectively. The median follow-up was 96 months. The median DFS of the overall study population was 53.7 months (95% CI: 38.4-87.8). Only bilateral renal cell carcinoma (p = 0.0041), Fuhrman grade 3/4 (p = 0.0008), pT3b- 4 (p = 0.0324), and pN1-2 (p = 0.0303) pathological status were confirmed as independent predictors of a shorter DFS by the multivariate analysis. The median DFS of patients with favorable and unfavorable GRANT scores were 84.9 (95% CI: 49.8-129) and 38.4 months (95% CI: 24.4-87.8), respectively, with a statistically significant difference (p = 0.0147). The median DFS of patients with low, intermediate, and high risk of recurrence according to the UISS score were 92.3 (95% CI: 18.1-153.9), 51.7 (95% CI: 36.2-87.8), and 49.8 months (95% CI: 31.3-129), respectively, without statistically significant differences (p = 0.4728). DFS c-statistic values were 0.59 (95% CI: 0.51-0.67) and 0.51 (95% CI: 0.42-0.60) for the GRANT and the UISS scores, respectively. CONCLUSION: The GRANT score might be a useful tool that is user-friendly and easy to perform in clinical practice.

Weighing the role of skeletal muscle mass and muscle density in cancer patients receiving PD-1/PD-L1 checkpoint inhibitors: a multicenter real-life study.

Sarcopenia represents one of the hallmarks of all chronic diseases, including cancer, and was already investigated as a prognostic marker in the pre-immunotherapy era. Sarcopenia can be evaluated using cross-sectional image analysis of CT-scans, at the level of the third lumbar vertebra (L3), to estimate the skeletal muscle index (SMI), a surrogate of skeletal muscle mass, and to evaluate the skeletal muscle density (SMD). We performed a retrospective analysis of consecutive advanced cancer patient treated with PD-1/PD-L1 checkpoint inhibitors. Baseline SMI and SMD were evaluated and optimal cut-offs for survival, according to sex and BMI (+/-25) were computed. The evaluated clinical outcomes were: objective response rate (ORR), immune-related adverse events (irAEs), progression free survival (PFS) and overall survival (OS). From April 2015 to April 2019, 100 consecutive advanced cancer patients were evaluated. 50 (50%) patients had a baseline low SMI, while 51 (51%) had a baseline low SMD according to the established cut offs. We found a significant association between SMI and ECOG-PS (p = 0.0324), while no correlations were found regarding SMD and baseline clinical factors. The median follow-up was 20.3 months. Patients with low SMI had a significantly shorter PFS (HR = 1.66 [95% CI: 1.05-2.61]; p = 0.0291) at univariate analysis, but not at the multivariate analysis. They also had a significantly shorter OS (HR = 2.19 [95% CI: 1.31-3.64]; p = 0.0026). The multivariate analysis confirmed baseline SMI as an independent predictor for OS (HR = 2.19 [1.31-3.67]; p = 0.0027). We did not find significant relationships between baseline SMD and clinical outcomes, nor between ORR, irAEs and baseline SMI (data not shown). Low SMI is associated with shortened survival in advanced cancer patients treated with PD1/PDL1 checkpoint inhibitors. However, the lack of an association between SMI and clinical response suggests that sarcopenia may be generally prognostic in this setting rather than specifically predictive of response to immunotherapy.

[Symptom assessment and chemical coping detection: the assessment of the cancer patient's symptoms between consumption, use and abuse.] / Symptom assessment and chemical coping detection: la valutazione dei sintomi del paziente oncologico tra il consumo, l'uso e l'abuso.

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. 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. 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. The influence of alcoholism and of substance abuse in oncology, due to the multiple interconnections with metabolic pathways and drug-drug interactions, represents certainly an important aspect in the era of personalization of care, from palliative care to active cancer treatments.

Predictive value of skeletal muscle mass for immunotherapy with nivolumab in non-small cell lung cancer patients: A "hypothesis-generator" preliminary report.

Sarcopenia represents one of the hallmarks of all chronic disease, including non-small cell lung cancer (NSCLC). A computed tomography scan is an easy modality to estimate the skeletal muscle mass through cross-sectional image analysis at the level of the third lumbar vertebra (L3). Baseline skeletal muscle mass (SMM) was evaluated using gender-specific cutoffs for skeletal muscle index in NSCLC patients administered immunotherapy with nivolumab to evaluate its possible correlations with clinical outcomes. From April 2015 to August 2018, 23 stage IV NSCLC patients were eligible for image analysis. Nine patients (39.1%) had low SMM. Among patients with baseline low and non-low SMM, median progression free survival was 3.1 and 3.8 months, respectively (P = 0.0560), while median overall survival was 4.1 and 13 months, respectively (P = 0.2866). This hypothesis-generating preliminary report offers the opportunity to speculate about the negative influence of sarcopenia on immune response. In our opinion, nutritional status could affect the clinical outcomes of immunotherapy, even if we cannot make definitive conclusions here. Further studies on the topic are required.

Physical exercise and quality of life in breast cancer survivors.

An important goal for cancer patients is to improve the quality of life (QOL) by maximising functions affected by the disease and its therapy. Preliminary research suggests that exercise may be an effective intervention for enhancing QOL in cancer survivors. Research has provided preliminary evidence for the safety, feasibility, and efficacy of exercise training in breast cancer survivors. The aim of this study was to assess the association between physical exercise and quality of life in a population of female breast cancer survivors, followed up from diagnosis to the off-treatment time period, and investigated about their exercise habits in pre-diagnosis.A total of 212 female breast cancer survivors consecutively registered from January 2002 to December 2006 at a Supportive Care Unit in an Italian Oncology Department were enrolled. Exercise behaviour was assessed by the Leisure Score Index (LSI) of the Godin Leisure-Time Exercise Questionnaire. Patients were asked to report their average weekly exercise for three cancer-related time periods, i.e. pre-diagnosis, during active treatment and off-treatment. Quality of life was assessed by the Italian version of the WHOQOL-BREF standardised instrument. Statistical analysis indicated significant differences across the cancer-relevant time-periods for all exercise behaviour outcomes: the exercise behaviour was significantly lower during both on- and off- treatment than during prediagnosis; exercise during active treatment was significantly lower than during off-treatment. QOL strongly decreases during active treatment. Significant correlations were found between total exercise on- and off-treatment and all QOL indicators. Strenuous exercise is strongly correlated with QOL. Absent/mild exercise seems to be inversely correlated with a positive perception of disease severity and with quality of life on all axes. Need clearly results for inclusion of physical activity programs in comprehensive, complementary treatment regimes for breast cancer patients in Italian oncology departments.