The prognostic value of beta-1 blockers in patients with non-small-cell lung carcinoma treated with pembrolizumab.

BACKGROUND: Immune checkpoint inhibitors (ICIs) such as pembrolizumab have revolutionized the treatment of metastatic non-small cell lung cancer (mNSCLC). Beta-adrenergic activation contributes to cancer initiation and progression. While non-selective beta-blocker were found to improve the efficacy of ICIs therapy, the role of beta-1 (ß1)-selective -blocker (ß1B) in lung cancer patients is unknown. OBJECTIVE: To evaluate the effect of ß1B on overall survival (OS) and progression-free survival (PFS) in patients diagnosed with mNSCLC and treated with pembrolizumab. METHODS: We performed a retrospective analysis of patients diagnosed with mNSCLC and treated with first-line pembrolizumab at our center. RESULTS: Of 200 eligible patients, 53 (27%) were pretreated with ß1B. Patients in the ß1B cohort were older (73 ± 8 vs. 67 ± 10 years, p < 0.001) with a higher prevalence of cardiac risk factors and cardiovascular (CV) diseases including ischemic heart disease (32% vs. 16%, p = 0.010), heart failure (9% vs. 3%, p = 0.043) and atrial fibrillation (23% vs. 3%, p < 0.001). Compared to the non-ß1B group, patient pretreated with ß1B had a significant shorter median OS (12 vs. 24 months, p = 0.004) and PFS (6 vs. 8 months, p < 0.001). In a multivariate analysis, including all CV risk factors and diseases, the use of baseline ß1B was a strong and independent predictor for accelerated disease progression (HR 1.92, 95%CI 1.32-2.79, p < 0.001) and shorter OS (HR 1.8, 95%, CI 1.18-2.75, p = 0.007). CONCLUSIONS: The use of baseline ß1B showed a strong and independent association for shorter OS and PFS in patients diagnosed with mNSCLC and treated with pembrolizumab.

Artificial intelligence (AI) molecular analysis tool assists in rapid treatment decision in lung cancer: a case report.

Leptomeningeal involvement among non-small cell lung cancer (NSCLC) patients is an aggressive form of disease that requires quick and efficient treatment. In this case report, we describe a woman in her 40s with a presenting symptom of headache that ultimately was diagnosed as leptomeningeal spread from NSCLC adenocarcinoma. We identified EGFR mutation in less than 48 hours from the biopsy using imagene-artificial intelligence's real-time algorithmic solution on the pathological diagnostic slide.

Association between diabetes mellitus and reduced efficacy of pembrolizumab in non-small cell lung cancer.

BACKGROUND: Diabetes mellitus (DM) is a highly prevalent chronic metabolic disorder. Although DM has been associated with immune dysfunction, the effect of DM on the efficacy of immunotherapy is unknown. This study aimed to evaluate the impact of DM on the efficacy of pembrolizumab in metastatic non-small cell lung cancer (NSCLC). METHODS: The authors reviewed the medical records of consecutive metastatic NSCLC patients treated with first-line pembrolizumab either alone or in combination with chemotherapy at a single tertiary center. For validation, a computerized data from Maccabi Healthcare Services, a 2.5-million-member state health service was used. RESULTS: Of the 203 eligible patients, 51 (25%) had DM. Patients with DM had a significantly shorter median progression-free survival (PFS) (5.9 vs. 7.1 months, p = .004) and overall survival (OS) (12 vs. 21 months, p = .006). The shorter OS in diabetic patients was more pronounced when pembrolizumab was given alone (12 vs. 27 months, p = .03) than when combined with chemotherapy (14.3 vs. 19.4 months, p = .06). Multivariate analysis confirmed DM as an independent risk factor for shorter PFS (hazard ratio [HR], 1.67; 95% confidence interval [CI], 1.11-2.50, p = .01) and OS (HR, 1.73; 95% CI, 1.09-2.76, p = .02). In a validation cohort of 452 metastatic NSCLC patients, the time on pembrolizumab treatment was shorter in diabetic patients (p = .025), with only 19.6% of patients remaining on treatment at 12 months compared to 31.7% of the nondiabetic patients. CONCLUSIONS: This study suggests immunotherapy is less beneficial in diabetic NSCLC patients. More work is needed to verify our findings and explore similar effects in other cancer entities.

A Lymph Node Ratio Model for Prognosis of Patients with Pancreatic Neuroendocrine Tumors.

The objective of this study was to determine the prognostic value of lymph node (LN) involvement and the LN ratio (LNR) and their effect on recurrence rates and survival in patients with pancreatic neuroendocrine tumors (PNETs) undergoing surgery. This single-center retrospective study reviewed the medical records of 95 consecutive patients diagnosed with PNETs who underwent surgery at our medical center between 1997 and 2017. The retrieved information included patient demographics, pathology reports, treatments, and oncological outcomes. Results: 95 consecutive potentially suitable patients were identified. The 78 patients with PNETs who underwent surgery and for whom there was adequate data were included in the analysis. Their mean ± standard deviation age at diagnosis was 57.4 ± 13.4 years (range 20-82), and there were 50 males (64%) and 28 females (36%). 23 patients (30%) had LN metastases (N1). The 2.5- and 5-year disease-free survival (DFS) rates for the entire cohort were 79.5% and 71.8%, respectively, and their 2- and 5-year overall survival (OS) rates were 85.9% and 82.1%, respectively. The optimal value of the LNR was 0.1603, which correlated with the outcome (2-year OS p = 0.002 HR = 13.4 and 5-year DFS p = 0.016 HR = 7.2, respectively, and 5-year OS and 5-year DFS p = 0.004 HR = 9 and p = 0.001 HR = 10.6, respectively). However, the multivariate analysis failed to show that the LNR was an independent prognostic factor in PNETs. Patients with PNETs grade and stage are known key prognostic factors influencing OS and DFS. According to our results, LNR failed to be an independent prognostic factor.

The use of medical cannabis concomitantly with immune checkpoint inhibitors in non-small cell lung cancer: A sigh of relief?

BACKGROUND: The use of medical cannabis has rapidly increased among cancer patients worldwide. Cannabis is often administered concomitantly with cancer medications, including immune checkpoint inhibitors (ICIs). As the cannabinoid receptors are abundantly expressed and modulate immune cells, it has been hypothesised that cannabis may attenuate the activity of ICIs. We aimed to assess the effect of cannabis on ICIs' efficiency in patients having non-small cell lung cancer (NSCLC). METHOD: The murine model of CT26 tumour-bearing mice treated with an anti-PD-1 antibody and Δ9-tetrahydrocannabinol (THC) was used to evaluate the interaction between THC and ICIs in vivo. Correlation between use of medical cannabis and clinical outcome was evaluated in a cohort of 201 consecutive metastatic NSCLC patients treated with monotherapy pembrolizumab as a first-line treatment. RESULTS: Median overall survival (OS) of the mice receiving a control vehicle, THC, anti-PD-1 antibody or their combination was 21, 24, 31 and 54 days, respectively (p < 0.05 for the combination treatment compared to a control vehicle), indicating that THC did not reduce the efficacy of anti-PD-1 therapy. Of 201 NSCLC patients treated with first-line monotherapy pembrolizumab for metastatic disease, 102 (50.7%) patients received licence for cannabis within the first month of treatment. Cannabis-treated patients were younger compared to the cannabis naïve patients (median age 68 versus 74, p = 0.003), with female predominance (62, 60.8% versus 34, 34.3%, p = 0.002) and with more prevailing brain metastasis (15.7% versus 5%, p = 0.013). Similar distribution of histology, smoking status, ECOG (Eastern Cooperative Oncology Group) and programmed death-ligand 1 expression was noted between the groups. Liver metastases were marginally significant (19.6% versus 10.1%, p = 0.058). The most common indication for cannabis was pain (71%) followed by loss of appetite (34.3%). Time to tumour progression was similar for cannabis-naive and cannabis-treated patients (6.1 versus 5.6 months, respectively, 95% confidence interval, 0.82 to 1.38, p = 0.386), while OS was numerically higher in the cannabis-naive group (54.9 versus 23.6 months) but did not reach statistical significance (95% confidence interval 0.99 to 2.51, p = 0.08). In multivariate analyses, we did not identify cannabis use as an independent predictor factor for mortality. CONCLUSIONS: Preclinical and clinical data suggest no deleterious effect of cannabis on the activity of pembrolizumab as first-line monotherapy for advanced NSCLC. The differences in OS can most likely be attributed to higher disease burden and more symptomatic disease in the cannabis-treated group. These data provide reassurance regarding the absence of a deleterious effect of cannabis in this clinical setting.

The predictive value of high sensitivity troponin measurements in patients treated with immune checkpoint inhibitors.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of cancer; however, at the potential cost of serious adverse events including cardiac injury. OBJECTIVE: To assess the baseline and longitudinal changes in high sensitivity-Troponin (hs-Tn) in patients treated with pembrolizumab as a potential predictor for the development of major adverse cardiac events (MACE) and survival. METHODS: We performed a retrospective analysis of cancer patients treated with pembrolizumab at our center. All participants had baseline measurements of hs-TnI prior to initiation of pembrolizumab (T1), with half of the patients performing follow-up measurements at their second encounter for therapy introduction (T2). We first evaluated the prevalence of abnormally elevated serum hs-TnI (> 50 nanogram per liter) at T1 and T2. We then evaluated the predictive value of abnormal levels at T1 or T2 in relation to the development of MACE (composite outcomes of myocarditis, acute coronary syndrome, heart failure, venous thromboembolism, cardiovascular hospitalization and cardiovascular mortality) and all-cause mortality. RESULTS: Among 135 patients, the mean age was 72 years, predominantly male (61%). Abnormally elevated hs-TnI at T1 was observed in 7 (5%) patients and emerged as a significant independent predictor for MACE (HR 8.1, 95% CI 1.67-37.4, p = 0.009) and all-cause mortality (HR 5.37, 95% CI 2.1-13.57, p < 0.001). Abnormally elevated hs-TnI at T2 was observed in 8 (11%) patients and emerged as a significant independent predictor for MACE (HR 10.49, 95% CI 1.68-65.5, p = 0.009), but not for mortality (p = 0.200). CONCLUSIONS: Abnormally elevated baseline and follow-up hs-TnI served as significant independent predictors for MACE, with an increased risk of development being 8-tenfold. Furthermore, elevated baseline hs-TnI showed a predictive value for all-cause mortality. Central illustration: Novel immune checkpoint inhibitor (ICIs) therapy has been found to revolutionize cancer therapy through increased activation of host immune systems to target and reduce tumor burden, but may come at the cost of serious adverse cardiac events. Identification of early biomarkers for the prediction and detection of these events is necessary.

Selective Intra-Arterial Doxorubicin Eluting Microsphere Embolization for Desmoid Fibromatosis: A Combined Prospective and Retrospective Study.

Desmoid fibromatoses (DFs) are locally aggressive tumors composed of monoclonal fibroblasts within an abundant extracellular matrix. Systemic doxorubicin treatment is effective, but toxic. We investigated arterial doxorubicin eluting embolization (DEE), an approach characterized by high drug concentrations in the tumor alongside limited systemic drug exposure. The primary and secondary endpoints were radiological response using MRI and RECIST 1.1, respectively. The study included 24 patients (median age, 24; interquartile range, 16-34 years). Data were collected prospectively for 9 patients and retrospectively for 15 patients. The most frequent tumor locations were chest/abdomen wall and neck/shoulder/axilla (29% each). Of 24 patients, 7 (24%) were treatment naïve, and 17 (71%) had received one or two prior treatments. Patients underwent a median of two treatments (range, 1-4), with a median of 49 mg (range, 8-75) doxorubicin/treatment. Efficacy outcomes were available for 23 patients. With a median follow-up of 8 months (interquartile range, 3-13), median tumor volumes decreased by 59% (interquartile range, 40-71%) and T2 signal intensity decreased by 36% (interquartile range, 19-55%). Of 23 patients, 9 (39%), 12 (52%), and 2 (9%) had a partial response, stable disease, and progressive disease, respectively. DEE was safe and well tolerated, with one reported grade 3-4 adverse event (cord injury). In conclusion, DEE was safe and achieved rapid clinical/volumetric responses in DFs.

ALK Inhibitors or Chemotherapy for Third Line in ALK-positive NSCLC? Real-world Data.

OBJECTIVES: ALK inhibitors (ALKi) are the standard-of-care treatment for metastatic ALK-rearranged non-small cell lung cancer (NSCLC) in the first- and second-line setting. We conducted a real-world multi-institutional analysis, aiming to compare the efficacy of third-line ALKi versus chemotherapy in these patients. METHODS: Consecutive ALK-positive metastatic NSCLC patients treated with at least one ALKi were identified in the working databases of 7 Israeli oncology centers (the full cohort). Demographic and clinical data were collected. Patients receiving any systemic treatment beyond 2 ALKi comprised the third-line cohort, whether a third ALKi (group A) or chemotherapy (group B). Groups A and B were compared in terms of overall survival (OS) and time-to-next-treatment line (TNT). RESULTS: At a median follow-up of 41 months (95% confidence interval [CI]: 32-55), 80 (47.1%) have died. Median OS (mOS) in the full cohort (n = 170) was 52 months (95% CI: 32-65). Number of ALKi (hazard ratio [HR] 0.765; 95% CI: 0.61-0.95; P = .024) and age (HR 1.02, 95% CI: 1.01-1.04, P = .009) significantly associated with OS in the full cohort. The third-line cohort included 40 patients, of which 27 were treated with third ALKi (group A) and 13 treated with chemotherapy (group B). mOS from third-line initiation was 27 months in group A (95% CI: 13-NR) and 13 months for group B (95% CI: 3-NR); the difference was not significant (NS; P = .12). Chemotherapy as first line (HR 0.17, 95% CI: 0.05-0.52, P = .002) and a higher number of ALKi (HR 0.38, 95% CI: 0.20-0.86, P = .011) associated significantly with longer OS of the third-line cohort. TNT was 10 months for group A (95% CI: 5-19) and 3 months for group B (95% CI: 0-NR); the difference was NS (P = .079). CONCLUSION: We report mature real-world data of more than 4-year mOS in ALK-positive patients. The number of ALKi given was associated with a better outcome. OS and TNT demonstrated a statistically nonsignificant trend for a better outcome in patients receiving a third-line ALKi.

Cancer Therapeutics-related Cardiac Dysfunction in Patients Treated With Immune Checkpoint Inhibitors: An Understudied Manifestation.

The widespread use of immune checkpoint inhibitors (ICI) has become a mainstay of care for a variety of malignancies. However, these therapies portend a range of adverse effects, including a potentially fatal form of cardiotoxicity which to date has not been elucidated. We aimed to evaluate the baseline characteristics of ICI-mediated cardiotoxicity. We performed a retrospective study evaluating patients treated with ICI who performed at least 2 echocardiography examinations, before and after the initiation of ICI. Cardiotoxicity was defined as Cancer Therapeutics-related Cardiac Dysfunction (CTRCD) development, with an absolute left ventricular ejection fraction reduction of >10%, to a value <53%. Fifty-two patients were included with a male preponderance (65%) and a mean age of 66 (±12) years. Twelve (23%) patients developed CTRCD, of which 2 patients were diagnosed with myocarditis. Among the CTRCD group, patients tended to be older and more likely to have baseline diastolic dysfunction: lower e' septal (P=0.026), higher E/e' septal (P=0.035), and a trend of E/e' average (P=0.076). All-cause and cardiovascular hospitalizations were significantly more common among the CTRCD group (P=0.028 and 0.001, respectively). Higher prevalence of cardiovascular mortality was observed among the CTRCD group (25% vs. 2%, P=0.034). We evaluated the development of CTRCD among patients treated with ICI therapies. Our findings suggest that baseline diastolic parameters may be associated with CTRCD development assisting in the early diagnosis of ICI-induced cardiac injury.

COVID-19 Vaccine-Induced Radiation Recall Phenomenon.

Radiation recall phenomenon (RRP) is an uncommon, late occurring, acute inflammatory skin reaction that emerges in localized areas coincident with previously irradiated radiation therapy (RT) treatment fields. RRP has been known to be triggered by a number of chemotherapy agents. To the best of our knowledge, this report is the first description of RRP after administration of the Pfizer-BioNTech vaccine for COVID-19, or any other currently available vaccine against COVID-19. Acute skin reactions were observed in 2 RT patients with differing timelines of RT and vaccinations. In both cases however, the RRP presented within days of the patient receiving the second dose of vaccine. For each RT course, the treatment planning dosimetry of the radiation fields was compared with the area of the observable RRP. RRP developed within the borders of treatment fields where prescription dose constraints were prioritized over skin sparing. Our observation is currently limited to 2 patients. The actual incidence of RRP in conjunction with Pfizer-BioNTech vaccine or any other vaccine against COVID-19 is unknown. For patients with cancer being treated with radiation with significant dose to skin, consideration should be given to the probability of RRP side effects from vaccinations against COVID-19.

Diastolic function as an early marker for systolic dysfunction and all-cause mortality among cancer patients.

BACKGROUND: Increased survival among active cancer patients exposes a wide range of side effects, including cardiotoxicity, manifested by systolic dysfunction and associated with morbidity and mortality. Early diagnosis of subclinical function changes and cardiac damage is essential in the management of these patients. Diastolic dysfunction is considered common among cancer patients; however, its effect on systolic dysfunction or mortality is still unknown. METHODS: Data were collected as part of the Israel Cardio-Oncology Registry, enrolling and prospectively following all patients evaluated in the cardio-oncology clinic in the Tel Aviv Sourasky Medical Center. All patients underwent echocardiographic examinations including evaluation of diastolic parameters and global longitudinal strain (GLS). Systolic dysfunction was defined as either an absolute reduction >10% in left ventricular ejection fraction to a value below 53% or GLS relative reduction >10% between the 1st and 3rd echocardiography examinations. RESULTS: Overall, 190 active cancer patients were included, with a mean age of 58 ± 15 years and a female predominance (78%). During a median follow-up of 243 days (interquartile ranges [IQR]: 164-401 days), 62 (33%) patients developed systolic dysfunction. Over a median follow-up of 789 days (IQR: 521-968 days), 29 (15%) patients died. There were no significant differences in baseline cardiac risk factors between the groups. Using multivariate analysis, E/e' lateral and e' lateral emerged as significantly associated with systolic dysfunction development and all-cause mortality (P = .015). CONCLUSION: Among active cancer patients, evaluation of diastolic function may provide an early marker for the development of systolic dysfunction, as well as all-cause mortality.

Re-introducing immunotherapy in patients surviving immune checkpoint inhibitors-mediated myocarditis.

BACKGROUND: Immune checkpoint inhibitors (ICI) have transformed the standard care of cancer treatment. Recent case reports describe ICI-mediated myocarditis with an atypical presentation and fatal potential which lead to permanent interruption of immunotherapy. OBJECTIVES: To characterize ICI-mediated myocarditis and re-introduction to immunotherapy. METHODS: During 2019, 849 patients were treated with ICI at Tel Aviv Sourasky Medical Center for the diagnosis of lung adenocarcinoma, gastric adenocarcinoma, urothelial carcinoma, and hepatocellular carcinoma. Overall, seven (0.8%) patients were diagnosed with ICI-mediated myocarditis, according to the European Society of Cardiology guidelines of myocarditis 2013. We retrospectively evaluated their presentation, severity, and clinical outcomes. RESULTS: Among the seven patients, only one had a history of cardiac disease. The majority were diagnosed with lung adenocarcinoma and treated with anti-programmed death-1 antibody. All patients were treated with single-agent ICI. Most patients presented with cardiac symptoms, elevated troponin and typical cardiac magnetic resonance; however, only three had reduced ejection fraction. Overall, three patients were chosen for re-introduction with concomitant low dose steroids and weekly troponin follow-up. Two patients diagnosed with grade I and II renewed therapy successfully with no recurrence of symptoms and improvement in disease burden. The one patient diagnosed with grade III developed worsening of cardiac symptoms after the 1st cycle and, therefore, therapy was interrupted permanently. CONCLUSIONS: ICI-mediated myocarditis is potentially fatal and leads to permanent interruption of life-saving cancer therapy. The current data suggest that re-introduction may be considered in low-grade patients; however, a better definition of the diagnosis and grading is needed.

Severe Postoperative Complications are Associated with Impaired Survival in Primary but not in Recurrent Retroperitoneal Sarcoma.

BACKGROUND: Retroperitoneal sarcoma (RPS) surgery entails multivisceral resection, which may cause postoperative complications. We assessed the effects of complications on survival to identify their predisposing factors in primary (PRPS) and recurrent (RRPS) RPS. METHODS: We retrospectively analyzed our institutional database. Severe postoperative complications (SC) were defined as Clavien-Dindo classification ≥ 3. Predisposing factors for complications were investigated, as was their effect on long-term outcomes. RESULTS: In total, 154 RPS resections (78 PRPS and 76 RRPS) performed between January 2008 and December 2018 were included. Neoadjuvant chemotherapy and multifocal tumors were more common in RRPS than PRPS (34.2% vs. 11.3%, P = 0.001 and 42.1% vs. 10.3%, P < 0.001, respectively). Although surgical extent in RRPS was limited compared with PRPS (weighted organ score 1 vs. 2, P = 0.01; transfusion requirement 23.6% vs. 35.8%, P = 0.04), SC and mortality rates were comparable. SC rates were 30.1% and 35.5% for PRPS and RRPS, respectively. NACT rate tended to be higher in PRPS patients with SC (20.8% vs. 7.4%, P = 0.09), whereas weighted organ score and transfusion requirement were increased in RRPS patients with SC (2 vs. 1, P = 0.01; 40.7% vs. 14.3%, P = 0.009, respectively). PRPS patients with SC had decreased overall survival (35 months, 95% confidence interval [CI] 12.2-57.7) compared with those without SC (90 months, 95% CI 71.4-108.5, P = 0.01). CONCLUSIONS: Postoperative complications are associated with impaired outcomes in PRPS but not in RRPS. The negative effects of complications on outcomes should be factored to perioperative management.

Innate inflammatory markers for predicting survival in retroperitoneal sarcoma.

INTRODUCTION: Existing prognostic tools for retroperitoneal sarcomas (RPS) utilize parameters that can be accurately determined only postoperatively. This study evaluated the application of the neutrophil-to-lymphocyte ratio (NLR) and C-reactive protein (CRP) levels for predicting prognosis in primary RPS. MATERIALS AND METHODS: We retrospectively analyzed our database of patients with primary RPS operated between 2008 and 2018. The NLR was calculated from preoperative blood tests and its association with outcomes was determined. RESULTS: The NLR values of 78 suitable patients were analyzed. Patients were classified in the NLR-high group if the NLR was ≥2.1. High-grade tumors were more common in the NLR-high group (71.6% vs 48%, P = .02). NLR-high patients had impaired overall survival (OS) and progression-free survival (PFS) compared to NLR-low patients (median OS not reached vs 74 months 95% confidence interval [CI]: 21.6-126.4, P = .03; median PFS not reached vs 48 months 95% CI: 6.5-98.6, P = .06, respectively). Multivariate analysis showed statistical significance only for PFS but not for OS (hazard ratio [HR] = 4.1, P = .03; HR = 2.3, P = .3). Patients with low CRP levels had improved OS and PFS. CONCLUSIONS: The NLR may serve as a preoperative, easily derived marker for prognosis in RPS. Serum biomarkers may prove useful in these large and spatially heterogeneous tumors.

Cardio-toxicity among patients with sarcoma: a cardio-oncology registry.

BACKGROUND: Chemotherapy induced cardio-toxicity has been recognized as a serious side effect since the first introduction to anthracyclines (ANT). Cardio-toxicity among patients with breast cancer is well studied but the impact on patients with sarcoma is limited, even though they are exposed to higher ANT doses. The commonly used term for cardio-toxicity is cancer therapeutics related cardiac dysfunction (CTRCD), defined as a left ventricular ejection fraction (LVEF) reduction of > 10%, to a value below 53%. The aim of our study was to estimate the prevalence of CTRCD in patients diagnosed with sarcoma and to describe the baseline risk factors and echocardiography parameters among that population. METHODS: Data were collected as part of the Israel Cardio-Oncology Registry (ICOR), enrolling all patients evaluated in the cardio-oncology clinic at our institution. The registry was approved by the local ethics committee and is registered in clinicaltrials.gov (Identifier: NCT02818517). All sarcoma patients were enrolled and divided into two groups - CTRCD group vs. non-CTRCD group. RESULTS: Among 43 consecutive patients, 6 (14%) developed CTRCD. Baseline cardiac risk factors were more frequent among the non-CTRCD group. Elevated left ventricular end systolic diameter and reduced Global Longitudinal Strain were observed among the CTRCD group. During follow-up, 2 (33%) patients died in the CTRCD group vs. 3 (8.1%) patients in the non-CTRCD group. CONCLUSIONS: CTRCD is an important concern among patients with sarcoma, regardless of baseline risk factors. Echocardiography parameters may provide an early diagnosis of cardio-toxicity.

Immune-related Neutropenia Following Treatment With Immune Checkpoint Inhibitors.

The existing data with regard to immune-related neutropenia (irN), a rare (incidence-1%) immune-related adverse event of immune checkpoint inhibitors, are scarce. Eight patients with irN were identified through internal databases of 3 participating Israeli cancer centers. In addition, 11 original articles focusing on the clinical course of 24 patients with irN were selected during the PubMed search. Descriptive analysis of clinical and pathologic factors related to irN was performed (n=32); the effect of these on the irN outcomes was assessed. An algorithm for irN evaluation and treatment was proposed. The median time-to-onset of irN (n=32) was 60 days (range, 10-465 d). Grade 3-5 irN, febrile neutropenia, and irN-related death occurred in 81%, 50%, and 9% of patients, respectively. In all, 56%, 22%, 62%, and 25% of patients received PO corticosteroids, IV corticosteroids, granulocyte colony-stimulating factor (GCSF), and intravenous immunoglobulins (IVIG), respectively, with an improvement/resolution rate of 84%. Odds ratios for irN improvement/resolution were as follows: 1.40 [95% confidence interval (CI), 0.03-68.72], 0.43 (95% CI, 0.04-4.22), 2.60 (95% CI, 0.07-97.24), 0.36 (95% CI, 0.03-4.38), 4.02 (95% CI, 0.16-99.48), 2.01 (95% CI, 0.32-12.70), 1.08 (95% CI, 0.02-49.89), 0.42 (95% CI, 0.06-2.91), and 2.73 (95% CI, 0.42-17.51) for granulocyte hyperplasia, granulocyte/all lineage hypoplasia, granulocyte maturation blockade, lymphocyte infiltration on bone marrow biopsy, IV corticosteroids, PO corticosteroids, cyclosporine, IVIG, and GCSF, respectively (P>0.05 for all factors). IrN recurrence rate following immune checkpoint inhibitors rechallenge was 80%. IrN is a rare, life-threatening, early-onset immune-related adverse event. Differentiating between the central, peripheral, and modified peripheral types allows a better prognosis definition. Corticosteroids and GCSF represent the main treatment approaches; IVIG and cyclosporine should be used as salvage treatment.

Trabectedin for Advanced Soft Tissue Sarcoma: Ten Year Real-Life Perspective.

BACKGROUND: Trabectedin is a marine-derived chemotherapy, which has received U.S. Food and Drug Administration approval for use in anthracycline-resistant advanced soft tissue sarcoma (STS), especially liposarcoma and leiomyosarcoma (L-sarcomas). OBJECTIVES: To describe our 10 year real-life experience with trabectedin regarding safety and efficacy in a cohort of 86 patients. METHODS: In our study cohort, 46.51% were diagnosed with liposarcoma and 43.02% with leiomyosarcoma. A total of 703 cycles of trabectedin were given, with a median of five cycles per patient (range 1-59). Median overall survival was 13.5 months for the whole cohort, 11 months for liposarcoma patients (range 1-63), and 15 months for leiomyosarcoma patients (range 1-35). RESULTS: There was no statistically significant difference in progression free survival when stratified according to previous treatment lines given. Trabectedin exhibited a favorable safety profile, with only 22% requiring dose reductions. Grade 3 and higher toxicity was noted in 25% of the patients, mostly due to myelosuppression. There were no treatment-related deaths. CONCLUSIONS: Trabectedin is a safe and effective drug for treating advanced STS. Our results reflect real-life data with patients receiving the drug as a third and even fourth line of treatment, or with a suboptimal performance status, yet achieving impressive clinical benefit rates and survival.

Efficacy and safety of Nivolumab in non-small cell lung cancer patients in Tel-Aviv tertiary medical center: Facing the reality.

Nivolumab is a human IgG4 programmed death (PD)-1 immune checkpoint inhibitor antibody, which is approved in Israel for the treatment of patients with advanced non-small cell lung cancer (NSCLC). It is also administered to individuals with disease progression during or after platinum-based chemotherapy, without a need to determine the level of PD-L1 expression in the tumor. The present study aimed to evaluate the survival and efficacy of Nivolumab treatment. A retrospective analysis was performed at a thoracic oncology service in a tertiary referral center (Tel-Aviv Sourasky Medical Center), on patients with NSCLC (squamous and non-squamous). All patients were treated with Nivolumab 3 mg/kg, administered intravenously every 2 weeks as part of a compassionate use program. The survival data was analyzed after 22 months. The overall survival (OS) was 34.9%, while the progression free survival (PFS) was 19.3%. The median PFS from the first dose of Nivolumab to treatment discontinuation was 4 months. A response assessment was performed in the 62 patients who received at least four cycles of Nivolumab, out of the 77 patient cohort. There was a complete response in 1 patient, a partial response in 11 patients, stable disease in 25 patients and progressive disease in 25 patients. The observed response rate of Nivolumab as a service treatment in unselected patients with unknown PD-L1 status NSCLC was 19%. The disease control rate was 60%. In the present study Nivolumab was given to a cohort of patients representing those seen in daily clinical practice, as opposed to a clinical trial setting. Survival and efficacy results strongly support the continued use of Nivolumab as a treatment for NSCLC.