Immune-related toxicities of immune checkpoint inhibitors (CPIs) require prompt diagnosis and treatment. Atherosclerosis has an inflammatory component; we speculated this inflammation could be ...enhanced by CPIs. We aimed to evaluate the risk of acute vascular events (AVEs) on CPIs.
Patients treated by CPIs in Sheba Medical Center (Israel) between January 2015 and May 2018 were retrospectively identified from electronic medical records. AVEs were identified and verified by chart review. Age, sex, diabetes, hypertension, smoking, dyslipidemia, previous AVE, renal failure, cancer type and specific treatments were evaluated as potential risk factors. AVE rate on CPIs was compared with that on chemotherapy or on combined chemo-immunotherapy in patients with lung adenocarcinoma. Survival of patients with AVEs was compared with that of patients without AVEs.
CPI was administered to 1215 patients. AVEs within six months after CPI initiation occurred in 2.6% (95% confidence interval CI: 1.8–3.6) of patients, more common than in later time periods. In lung adenocarcinoma, event rate was 5.2% (95% CI: 2.8–9.2). Lung adenocarcinoma, prior AVE, hypertension and dyslipidemia were correlated with AVEs. AVE rate in patients with non-small cell lung cancer adenocarcinoma was similar whether on chemotherapy or on CPI. Survival of patients with AVEs was worse than that of those without AVEs.
The similarly increased rates of AVEs for patients on CPI, on chemotherapy or on both suggest that although CPI may not augment the risk of AVE over that of chemotherapy, it carries a similar and significant risk of such adverse event. Caution should be exercised for patients with risk factors for AVEs.
•Event rate on checkpoint inhibitors (CPIs) (2.6%) was in the same range as for patients on chemotherapy.•CPIs were more common during 1–6 months from initiation vs. during 7–12 months.•Of all patients with lung adenocarcinoma, 5.2% had an acute vascular event (AVE) within 6 months of starting CPIs.•Past AVE, hypertension, dyslipidemia and lung adenocarcinoma were correlated with AVEs.•AVE development on CPI conveys a significantly worth outcome.
Context and objectives
The present study examined the impact of an integrative oncology treatment program in the relief of pain in patients undergoing chemotherapy and/or palliative care.
Methods
In ...this pragmatic prospective controlled study, patients undergoing chemotherapy and/or palliative care were referred by their oncology healthcare providers to an integrative physician (IP) consultation, followed by weekly integrative treatments. Patients attending ≥ 4 sessions during the first 6 weeks of the study were considered to be highly adherent to integrative care (AIC). Pain was assessed at baseline and at 6 and 12 weeks using the ESAS (Edmonton Symptom Assessment Scale) and EORTC QLQ-C30 (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire) tools.
Results
Of 815 eligible patients, 484 (59.4%) were high-AIC and 331 low-AIC. Mean pain scores decreased significantly from baseline to 6 and 12 weeks in both groups. However, ESAS and EORTC pain scores improved significantly more in the high-AIC group at 6 weeks (
p
= 0.008), though not at 12 weeks. Between-group analysis of participants undergoing adjuvant/neo-adjuvant chemotherapy showed higher pain reduction in the high-AIC group at 6 weeks (ESAS,
p
= 0.006; EORTC,
p
= 0.046), as was the case with patients receiving palliative care (ESAS
p
= 0.04; EORTC
p
= 0.056).
Conclusions
High adherence to integrative care was found to be associated with a greater effect on pain relief at 6 weeks but not at 12 weeks in patients undergoing chemotherapy and/or palliative care.
Breast cancer is a common malignancy and a common cause of cancer-related mortality in women. Pre-treatment workup of breast cancer does not routinely include positron emission tomography scans. We ...aimed to review cases of women with breast cancer and a synchronous second primary malignancy. We present three cases of women with non-metastatic cancer in whom a synchronous second primary malignancy was found. Synchronous, second primary malignancies which were identified included rectal cancer, gastrointestinal stromal tumor, and non-small cell lung cancer. All second primary malignancies were identified by a PET-CT scan. In conclusion, PET-CT may be used for detection of secondary primary malignancies in select breast cancer patients.
ObjectivesUS FDA and EMA allow facilitated regulatory pathways to expedite access to new treatments. Limited supportive data may result in major postapproval variations. In Israel, partly relying on ...Food and Drug Administration (FDA) and European Medicines Agency (EMA), clinical data are reviewed independently by the Advisory Committee of Drug Registration (ACDR). In this study, the correlation between the number of discussions at the ACDR and major postapproval variations is examined.DesignThis is an observational retrospective comparative cohort study.SettingApplications with FDA and/or EMA approval at time of assessment in Israel were included. The timeframe was chosen to allow a minimum of 3 years of postmarketing approval experience for potential major label variations. Data regarding the number of discussions at ACDR were extracted from protocols. Data on postapproval major variations were extracted from the FDA and EMA websites.ResultsBetween 2014 and 2016, 226 (176 drugs) applications, met the study criteria. 198 (87.6%) and 28 (12.4%) were approved following single and multiple discussions, respectively. A major postapproval variation was recorded in 129 (65.2%) compared with 23 (82.1%) applications approved following single and multiple discussions, respectively (p=0.002). Increased risk for major variation was found for medicines approved following multiple discussions (HR=1.98, 95% CI: 1.26 to 3.09) with a median time of 1.2 years, applications approved based on phase II trials (HR=2.58, 95% CI: 1.72 to 3.87), surrogate endpoints (HR=1.99, 95% CI: 1.44 to 2.74) and oncologic indications (HR=2.48, 95% CI: 1.78 to 3.45).ConclusionsMultiple ACDR discussions associated with limited supportive data are predictive for major postapproval variations. Moreover, our findings demonstrate that approval by the FDA and/or EMA does not pave the way to automatic approval in Israel. In a substantial per cent of the cases, submission of the same clinical data resulted in different safety and efficacy considerations, requiring additional supporting data in some cases or even rejection of the application in others.
Substantial evidence has accumulated showing that psychological distress affects immune regulation, the response to cancer treatment, and survival. The effect of psychological parameters on the ...effectiveness of immune checkpoint inhibitor (ICI) treatment has not yet been studied. This preliminary study aimed to (a) examine the associations between psychological factors and responses to ICI treatment and (b) assess the associations between psychological factors and blood measures of sPD-1, sCTLA-4, and cytokines that may alter the effect of ICI treatment. The participants were 62 individuals with advanced cancer, aged 18 years or older, who were candidates for ICI treatment as a new line of treatment. The participants answered questionnaires and provided blood samples and medical data prior to the start of ICI treatment and 3 months after. Perceived health status was positively associated with better responses to ICI treatment. In the subsample of participants with biomarkers, worse health-related quality of life was associated with higher IL-6 and sCTLA-4; emotional distress and sleep difficulties were associated with higher sCTLA-4; and better perceived health was associated with lower IL-6 and TNFα. sPD-1 was not associated with psychological measures. This preliminary study found for the first time that some psychological measures could be linked to responses to cancer treatment, possibly via pro-inflammatory cytokines and sCTLA-4.
Abstract Objectives To evaluate the impact of the 12-gene Colon Cancer Recurrence Score Assay—a clinically validated prognosticator in stage II colon cancer after surgical resection—on adjuvant ...treatment decisions in T3 mismatch repair proficient (MMR-P) stage II colon cancer in clinical practice. Methods This retrospective analysis included all patients with T3 MMR-P stage II colon cancer (Clalit Health Services members) with Recurrence Score results (time frame January 2011 to May 2012). Treatment recommendations pretesting were compared with the treatments received. Changes were categorized as decreased (to observation alone/removing oxaliplatin from the therapy) or increased (from observation alone/adding oxaliplatin to the therapy) intensity. Results The analysis included 269 patients; 58%, 32%, and 10% of the values were in the low (<30), intermediate (30–40), and high (≥41) score groups, respectively. In 102 patients (38%), treatment changed post-testing (decreased/increased intensity 76/26 patients). The overall impact was decreased chemotherapy use (45.0% to 27.9%; P < 0.001). Treatment changes occurred in all score groups, but more frequently in the high (change rate 63.0%; 95% confidence interval CI 42.3%–80.6%) than in the intermediate (30.6%; 95% CI 21.0%–41.5%) and low (37.6%; 95% CI 30.0%–45.7%) score groups. The direction of the change was consistent with the assay result, with increased intensity more common in higher score values and decreased intensity more common in lower score values. Conclusions Testing significantly affected adjuvant treatment in T3 MMR-P stage II colon cancer in clinical practice. The study is limited by its design, which compared treatment recommendations pretesting to actual treatments received post-testing, lack of a control group, and nonassessment of confounding factors that may have affected treatment decisions.
Pancreatic cancer is one of the most lethal types of malignant tumours, commonly diagnosed at an advanced stage. The only curative treatment for this fatal disease is surgery and early diagnosis is ...the key to a better outcome and prognosis. In this case report we present a 57-year-old woman presenting to the emergency room with abdominal pain and weight loss. Computer Tomography (CT) imaging showed a rupture of the main pancreatic duct and a peri-pancreatic fluid collection with no evidence of a pancreatic mass. An Endoscopic Ultrasound (EUS) guided Fine Needle Aspiration (FNA) did not show any malignant cells and Carcinoembryonic Antigen (CEA) and Carbohydrate Antigen (CA) 19-9 markers were in the normal range. The patient then underwent pancreatectomy that revealed multiple microscopic foci of pancreatic adenocarcinoma with evidence of massive perineural and vascular invasion.
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