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e22530
Background: Chemotherapy induced cardio-toxicity has been recognized as a serious side effect since the first introduction to anthracycline (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 therapeutic related cardiac dysfunction (CTRCD), defined as a left ventricular ejection fraction (EF) reduction of > 10%, to a value below 53%. Our objective was to estimate the prevalence of CTRCD among patients with sarcoma, to evaluate echocardiography parameters associated with its development and whether CTRCD is associated with mortality. Methods: Data were collected as part of the International Cardio-Oncology Registry (ICOR), enrolling all patients who were evaluated in the cardio-oncology clinic at our institution. All sarcoma patients were enrolled and divided into two groups - CTRCD group vs. "Preserved EF" group. Results: Among 43 consecutive patients, 6 (14%) developed CTRCD. Elevated left ventricular end systolic diameter (p = 0.007) and a trend of reduced Global Longitudinal Strain (p = 0.092) were observed among the CTRCD group. During follow-up, 2 (33%) patients died in the CTRCD group vs. 3 (8.1%) patients in the "Preserved EF" group. In a multivariate analysis, adjusted to age and EF, CTRCD remained a significant predictor for mortality (p = 0.039). Conclusions: CTRCD is an important concern among patients with sarcoma, regardless of baseline risk factors, and is associated with mortality. Echocardiography parameters may provide an early diagnosis of cardio-toxicity.
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).
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.
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.
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.
•Cannabis might alter tumour's microenvironment and, hence, reduce the immune checkpoint inhibitors efficacy.•We investigate this theory in murine models and real-world data.•We found no determinantal effect of this combination in clinic or laboratory.•This conclusion has a great reassuring impact on our patients having non-small cell lung cancer.
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.
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Background:
AL amyloidosis is a rare disorder characterized by organ infiltration of unstable misfolded light chain proteins. Diagnosis requires a high degree of suspicion, and cardiac ...involvement has poor outcomes. Anthracycline-based regimens are preferred for treating abdominal leiomyosarcoma (LMS) but pose a challenge in the presence of cardiac AL amyloidosis.
Case:
A 66-year-old male presented with bilateral leg edema and underwent evaluation for new heart failure. Echocardiography revealed preserved left ventricle ejection fraction (LVEF) with mild hypertrophy, increased interventricular septum thickness, and diastolic dysfunction. Due to concern for cardiac amyloidosis, the patient underwent nuclear scintigraphy scan, which was negative. Ongoing clinical suspicion prompted endomyocardial biopsy, which was positive for Congo Red staining, and serum studies revealed monoclonal lambda spike with increased free light chains. PET-CT was done to assess the lung nodule, revealing abdominal LMS. While Anthracycline is the drug of choice for LMS, its potential cardio-toxic effect in the presence of heart failure need be addressed. Treatment decisions involved a multidisciplinary team, resulting in bortezomib for AL amyloidosis, gemcitabine/paclitaxel for LMS, and symptomatic heart failure management.
Decision-making:
Anthracycline therapy was avoided due to potential cardiotoxicity. Daratumumab was added to expedite light chain reduction and minimize cardiotoxic effects. Individualized treatment considered the patient's clinical presentation and comorbidities.
Conclusion:
Diagnosing cardiac amyloidosis requires a high index of suspicion. Concurrent AL amyloidosis and LMS is extremely rare and presents a therapeutic dilemma, necessitating personalized management. Further research is needed to assess the potential cardio-toxic effect of anthracycline in the presence of cardiac AL amyloidosis.
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.
One in four non–small cell lung cancer patients treated with pembrolizumab in our cohorts had diabetes mellitus. Patients with diabetes mellitus had a decreased progression‐free survival and overall survival compared to nondiabetic patients.
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.
TPS8121 Background: Management of resectable NSCLC involves surgery with perioperative systemic therapy. Immune checkpoint inhibitors (CPIs) and targeted therapies are now used in the perioperative ...setting, leading to improved survival outcomes. The combination of dom (anti–T-cell immunoglobulin and ITIM domain TIGIT) and zim (anti–programmed death protein 1 PD-1) has shown promising antitumor activity with a manageable safety profile in metastatic NSCLC and may provide an opportunity to improve clinical outcomes in the perioperative setting in early-stage, resectable NSCLC. Substudy-03 of the VELOCITY-Lung platform study is evaluating novel perioperative treatment combinations in patients with newly diagnosed, resectable, stage II-III NSCLC. Methods: VELOCITY-Lung (NCT05633667) is an open-label, multicenter, phase 2 platform study with 3 ongoing substudies targeting the different NSCLC patient populations. Key eligibility criteria for Substudy-03 include age ≥ 18 years, histologically/cytologically confirmed stage II, IIIA, IIIB (T3-4N2) (per AJCC 8th ed.) squamous or nonsquamous NSCLC considered resectable with curative intent, no prior systemic or CPI therapy or radiotherapy, ECOG PS 0-1, any PD-1 ligand (PD-L1) status, and no actionable EGFR or ALK genomic alterations in patients with nonsquamous NSCLC. Randomization in Substudy-03 will be stratified by disease stage (II vs III) and baseline PD-L1 expression status (≥ 50% vs < 50%). Current treatment groups in the neoadjuvant phase of the preliminary stage are: (A) dom+zim+platinum (Pt)-based chemo or (B) zim+Pt-based chemo for a maximum of 3 cycles; this will be followed by definitive surgery within 6 weeks of completing neoadjuvant treatment. Adjuvant treatment will include: (A) dom+zim or (B) zim and will begin within 12 weeks of surgery. Patients will continue to receive adjuvant treatment until disease recurrence, death, or unacceptable toxicity or to a maximum of 14 cycles. Dosing will be as follows: zim 360 mg intravenously (IV) once every 3 weeks (Q3W) and dom 1200 mg IV once Q3W (up to 3 cycles in the neoadjuvant phase and up to 14 cycles in the adjuvant phase). Pt-based chemo will be based on patient tumor histology (squamous vs nonsquamous). The primary endpoint is pathological complete response rate, defined as the percentage of patients with no residual invasive cancer in resected lung specimens and lymph nodes, assessed by local pathology review. Secondary endpoints include major pathological response rate (percentage of patients with ≤ 10% residual tumor in lung and lymph nodes at surgery), event-free survival, overall survival, and safety. Approximately 31 patients will be enrolled into each treatment group of the preliminary phase. The study is currently recruiting. Clinical trial information: NCT05633667 .
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.
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