The association of toxicities and outcomes with circulating endothelial cells (CEC) in non-small cell lung cancer (NSCLC) patients (pts) treated with bevacizumab (Bev).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e19012-e19012
Author(s):  
Nooshin Hashemi Sadraei ◽  
Lingling Du ◽  
Ruchi Yadav ◽  
Ronald Grane ◽  
Barbara Jacobs ◽  
...  
Keyword(s):  
Solid Tumors ◽  
Healthy Subjects ◽  
Proportional Hazards ◽  
Stage Iv ◽  
Stage I ◽  
Circulating Endothelial Cells ◽  
Advanced Solid Tumors ◽  
Chi Square ◽  
Disease Characteristics ◽  
Nsclc Patients

e19012 Background: Bev in combination with chemotherapy (CT) is a standard treatment for pts with stage IV NSCLC. However, there are no established biomarkers to improve benefit-to-risk profile of therapy. CEC are a marker of vascular turnover. We hypothesized CEC may be associated with treatment outcome/toxicity. Methods: Stage IV NSCLC pts were treated with Bev along with CT of choice per clinician. CEC were measured at baseline and after 2 cycles of Bev-containing therapy. CellSearch (Veridex, New Jersey) was used to capture and quantify CEC via immunomagnetic and immunofluorescence techniques. CEC were enumerated as nucleated, CD146+/CD105+/CD45- cells in 4 mL of blood. For comparison, baseline CEC were also collected in 3 other groups; healthy subjects, stage I-III NSCLC, and advanced solid tumor pts. Chi-square tests and non-parametric methods were used to assess associations between CEC and pt/disease characteristics, toxicity, and proportional hazards models were used for comparisons of progression free and overall survival (PFS and OS). Results: Evaluated were 62 individuals: 29 stage IV NSCLC, 10 stage I-III NSCLC, 13 advanced solid tumors (melanoma, sarcoma, renal and adrenal cancers), and 10 healthy subjects. The median of CEC/ml blood in healthy subjects was 6. Based on its distribution, CEC >13/ml was deemed elevated. Elevated CEC was seen in 48% of stage IV NSCLC (median 12/ml), in comparison to 20% of stage I-III NSCLC (8/ml) and 23% of advanced solid tumors (6/ml) Baseline CEC in stage IV NSCLC was independent of patient/ disease characteristics including site of disease and tumor size. CEC increased during treatment in most patients (61%). CEC doubling between baseline and cycle2 was associated with more cytopenia and hemorrhage. (75% vs 20%, p=0.05 and p=0.03 for absolute and relative CEC changes). Baseline CEC and changes during treatment did not correlate with response (p≥ 0.32) and pts with elevated baseline CEC had a trend towards worse PFS (p=0.09) and OS (p=0.10). Conclusions: CEC are commonly elevated in advanced NSCLC. CEC increases may be predictive of adverse events from Bev-CT and when elevated at baseline may suggest worse PFS.

Are the presenting characteristics and prognosis of primary salivary gland-type lung cancers (SG) similar to those of other non-small cell lung cancers (NSCLC)?

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 7054-7054
Author(s):  
John M. Varlotto ◽  
Suhail M. Ali ◽  
Malcolm M. DeCamp ◽  
John Charles Flickinger ◽  
Abram Recht ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Proportional Hazards ◽  
Stage Iv ◽  
Cox Proportional Hazards ◽  
Stage I ◽  
Optimal Care ◽  
Chi Square ◽  
Cancer Specific Survival ◽  
Lung Cancers ◽  
Survival Difference

7054 Background: SG, both adenoid cystic (ACC) and mucoepidermoid (ME) sub-types, are rare lung cancers. We choose to investigate the incidence of these rare sub-types and assess their difference in presentation and prognostic characteristics in comparison to adenocarcinomas (Ad) and squamous cell carcinomas (SCC) during the same time period. Methods: The SEER-17 database was used to collect data during the years 1988-2008. Differences between populations were determined by the chi-square test. Survival curves were generated as Kaplan-Meier techniques. Cox proportional hazards test was used to compare survival differences. Results: During the 20-year study period, ACC (n =100) and ME (n= 178) accounted for 0.03% and 0.06% of NSCLCs. Mean follow-up was 34.5 months for all patients. In comparison to ACC, patients with ME were significantly more likely to be younger (52 yr vs. 60yr), Asian(11.7% vs. 7%), have Stage I disease (62.9% vs 24.0%), and less likely to be in the mainstem bronchi (17.2% vs. 6.3%). In comparison to patients with patients presenting with either SCC or Ad, both ME and ACC were significantly less likely to present with Stage IV disease (26.6% SCC, 41.29% Ad, 16.73% SG), have nodal involvement (35.1% SCC, 27.4% Ad, 23.37% SG), and be older (70 SCC, 68 Ad, 58 years SG). Stratified by stage and treatment, there was no survival (OS) or disease-specific survival difference (DSS) between ACC and ME. The OS of the combined group of ME and ACC was significantly better stage per stage than either Ad (Hazard ratio (HR) range = 0.26- 041), and SCC (HR range = 0.17-0.56). Lung Cancer-Specific survival at 2,3,5 years for surgically-resected Stage I ACC and ME were 83.5%, 80.4%, and 80.4%; and 82.6%, 78.0% and 78%, respectively. Conclusions: Patients with ACC and ME have rare sub-types of lung cancer that present differently and have better survival than patients presenting with either of the more common histologic sub-types (SCC and Ad) of NSCLC. We encourage prospective, multi-institutional studies of these rare sub-types so that care can be optimized. Optimal care may differ for SG because of their stage per stage better prognosis than other NSCLCs.

scholarly journals Gastric Cancer Treatments and Survival Trends in the United States

2020 ◽  
Vol 28 (1) ◽  
pp. 138-151
Author(s):  
Kelly A. Stahl ◽  
Elizabeth J. Olecki ◽  
Matthew E. Dixon ◽  
June S. Peng ◽  
Madeline B. Torres ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Overall Survival ◽  
Stage Iv ◽  
The United States ◽  
Current Treatment ◽  
Stage I ◽  
Stage Ii ◽  
Chi Square ◽  
Specific Guideline ◽  
Kaplan Meier

Gastric cancer is the third most common cause of cancer deaths worldwide. Despite evidence-based recommendation for treatment, the current treatment patterns for all stages of gastric cancer remain largely unexplored. This study investigates trends in the treatments and survival of gastric cancer. The National Cancer Database was used to identify gastric adenocarcinoma patients from 2004–2016. Chi-square tests were used to examine subgroup differences between disease stages: Stage I, II/III and IV. Multivariate analyses identified factors associated with the receipt of guideline concordant care. The Kaplan–Meier method was used to assess three-year overall survival. The final cohort included 108,150 patients: 23,584 Stage I, 40,216 Stage II/III, and 44,350 Stage IV. Stage specific guideline concordant care was received in only 73% of patients with Stage I disease and 51% of patients with Stage II/III disease. Patients who received guideline consistent care had significantly improved survival compared to those who did not. Overall, we found only moderate improvement in guideline adherence and three-year overall survival during the 13-year study time period. This study showed underutilization of stage specific guideline concordant care for stage I and II/III disease.

scholarly journals Liquid Biopsy in Pediatric Renal Cancer: Stage I and Stage IV Cases Compared

Diagnostics ◽  
2020 ◽  
Vol 10 (10) ◽  
pp. 810
Author(s):  
Elisabetta Rossi ◽  
Angelica Zin ◽  
Antonella Facchinetti ◽  
Cristina Poggiana ◽  
Lucia Tombolan ◽  
...  
Keyword(s):  
Renal Cancer ◽  
Cancer Progression ◽  
Liquid Biopsy ◽  
Stage Iv ◽  
Stage I ◽  
Circulating Endothelial Cells ◽  
Response To Treatment ◽  
Late Response ◽  
Metastatic Renal Cancer

Pediatric renal cancer is rare, and robust evidence for treatment recommendations is lacking. In the perspective of personalized medicine, clinicians need new biomarkers to improve risk stratification and patients’ follow-up. Herein, we analyzed some liquid biopsy tools, which have been never tested in pediatric renal cancer: namely, circulating tumor cells (CTCs); the expression of M30, an apoptosis marker, to test CTC metastatic potential; and c-MET expression in CTCs, because of its role in renal cancer progression and drug-resistance. Furthermore, we evaluated the Circulating Endothelial Cells (CECs), whose utility we previously demonstrated in adult metastatic renal cancer treated with anti-angiogenic therapy. We compared two renal cell carcinomas of clear-cell type, stage I and IV, which underwent surgery and surgery plus Sunitinib, respectively. Baseline CTC level and its changes during follow-up were consistent with patients’ outcome. In case 2, stage IV, the analysis of CECs performed during Sunitinib revealed a late response to treatment consistent with poor outcome, as the finding of M30-negative, viable cells. Noteworthily, few CTCs were MET-positive in both cases. Our study highlights the feasibility for a change in the prognostic approach and follow-up of childhood renal cancer, with a view to guide a better treatment design.

scholarly journals Comparative Trends in the Distribution of Lung Cancer Stage at Diagnosis in the Department of Defense Cancer Registry and the Surveillance, Epidemiology, and End Results data, 1989–2012

2020 ◽  
Vol 185 (11-12) ◽  
pp. e2044-e2048
Author(s):  
Joel A Nations ◽  
Derek W Brown ◽  
Stephanie Shao ◽  
Craig D Shriver ◽  
Kangmin Zhu
Keyword(s):  
Lung Cancer ◽  
General Population ◽  
Department Of Defense ◽  
Stage Iv ◽  
Tumor Stage ◽  
Stage I ◽  
Lower Percentage ◽  
Stage At Diagnosis ◽  
Nsclc Patients ◽  
Two Populations

Abstract Introduction We compared the stage at diagnosis for non-small cell lung cancer (NSCLC) patients in the military healthcare system (MHS) and the general public to assess differences between these two groups as well as to assess the trends in stage at diagnosis in the recent past. Method This study was based on the non-identifiable data from the U.S. Department of Defense Automated Central Tumor Registry (ACTUR) and the Surveillance, Epidemiology, and End Results (SEER) program of the National Cancer Institute. Patients diagnosed with NSCLC between 1989 and 2012 were included. The distributions of tumor stage at diagnosis and trends in tumor stage were compared between the two populations. Results The cohorts were predominately male in both ACTUR (65.3%) and SEER (55.1%) and white patients accounted for greater than 80% of patients in both ACTUR and SEER. Among 21,031 patients in ACTUR and 773,356 patients in SEER, stage IV lung cancers predominated (ACTUR 33.6%, SEER 40.5%) followed by stage III (ACTUR 26.1%, SEER 26.4%) and stage I (ACTUR 24.7%, SEER 20.6%). Notable differences between the two populations were the higher percentage of stage I and lower percentage of stage IV, along with a lower rate of unknown stage patients after 2004, in ACTUR than SEER. Between 1989 and 2012, the percentage of stage IV disease increased in ACTUR and SEER coincident with a decrease in unknown stage disease. Conclusions The majority of NSCLC patients in the MHS and general population are diagnosed with stage IV NSCLC and the percentage is increasing. Compared to the general population, NSCLC patients in the MHS have a higher percentage of stage I, a lower percentage of stage IV, and of unknown stage cancer. Universal care along with more rigorous staging across the MHS may play a role in these findings.

Phase I dose escalation study of E7080, a novel anti-angiogenic multikinase inhibitor, in Japanese patients with advanced solid tumors

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 14099-14099
Author(s):  
K. Yamada ◽  
Y. Fujiwara ◽  
N. Yamamoto ◽  
Y. Yamada ◽  
S. Suzuki ◽  
...  
Keyword(s):  
Growth Factor ◽  
Solid Tumors ◽  
Japanese Patients ◽  
Maximum Tolerated Dose ◽  
Circulating Endothelial Cells ◽  
Severe Toxicity ◽  
Advanced Solid Tumors ◽  
Dose Escalation Study ◽  
Multikinase Inhibitor ◽  
Angiogenic Proteins

14099 Background: E7080 selectively inhibits receptor phosphorylation of vascular endothelial growth factor (VEGF), platelet- derived growth factor (PDGF), fibroblast growth factor (FGF) and suppresses tumor angiogenesis and growth in preclinical studies. Methods: E7080 was orally administered to Japanese patients with advanced solid tumors twice daily by a 2 week-on 1 week-off schedule. The primary objectives were to determine the maximum tolerated dose (MTD), dose-limiting toxicity (DLT) and the recommended dose for further study. The secondary objectives were to evaluate pharmacokinetics (PK), pharmacogenomics, and efficacy. Results: Twelve patients have been enrolled into cohorts of 1, 2, 4 or 8 mg/day. Major toxicities were hypertension and hyperlipidemia. Thus far, no DLTs or severe toxicities were reported. PK analysis in cohorts of 1, 2 and 4 mg/day showed the dose-proportional increase of Cmax and AUC. Three patients in cohorts of 1 and 2 mg/day experienced long stable disease (SD) for 18 weeks or longer. One patient with colorectal cancer in 4 mg/day cohort showed significant tumor shrinkage of multiple pulmonary metastasis. Biomarkers such as plasma angiogenic proteins and cytokines, circulating endothelial cells and circulating endothelial progenitor cells are exploratively evaluated. Conclusions: E7080 is well tolerated at doses up to 8 mg/day by a 2 week-on 1 week-off schedule. Some patients experienced clinical benefit without severe toxicity. MTD has not been reached and enrollment is ongoing. No significant financial relationships to disclose.

Single nucleotide polymorphisms (SNPs) of the platinum pharmacogenetic and VEGF pathways: Association with survival of platinum-treated stage IV non-small cell lung cancer (NSCLC) patients.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 7586-7586
Author(s):  
Sinead Cuffe ◽  
Xiaoping Qiu ◽  
Abul Kalam Azad ◽  
Xin Qiu ◽  
Kevin Boyd ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Clinical Outcome ◽  
Systemic Therapy ◽  
Proportional Hazards ◽  
Stage Iv ◽  
Significant Snps ◽  
Cox Proportional Hazards ◽  
Nucleotide Polymorphisms ◽  
Vegf Pathway ◽  
Nsclc Patients

7586 Background: Two potentially important host pathways in lung cancer systemic therapy are: (i) the pharmacogenetic pathway of platinum agents (DNA repair, metabolism, and multidrug resistance genes); and (ii) the vascular endothelial growth factor (VEGF) pathway. We investigated the relationship between SNPs in these two pathways and clinical outcome in platinum-treated NSCLC patients. Methods: 188 platinum-treated Stage IV NSCLC patients underwent SNP genotyping for the platinum-related (48 SNPs in 7 genes) and VEGF (64 SNPs in 3 genes) pathways. SNPs were selected from the literature and through tagging. Association of SNPs and overall (OS) and progression free survival (PFS) were assessed using multivariate Cox proportional hazards models. Results: 72% were Caucasian; 73%, adenocarcinoma; 92%, ECOG PS 0-1; median age, 60 years; 54% received > one line of systemic therapy; 10% received anti-VEGF therapy/placebo; Median OS, 1.3 yrs; median follow up, 2.2 yrs. The top significant SNPs in the platinum-related pathway were in ABCC2 (rs8187710 and rs2756109, r2=0.68). The G variants of the top SNP, ABCC2 rs8187710 (4554G>A), were associated with worse OS (adjusted hazard ratio [aHR], 2.62; 95%CI: 1.5-4.5; p=0.0005) and PFS (aHR, 1.97; 95%CI: 1.2-3.4; p=0.01). Functionally, 4554G>A impairs ATP-ase activity and is associated with higher cellular accumulation of ABCC2 substrates [PMID: 22027652]; furthermore, ABCC2 expression is associated with cisplatin resistance and clinical outcome in other cancers [PMID: 17145840]. Within the VEGF pathway, the top significant SNPs were in the same haplotype block of VEGFR1/FLT1 (rs1324057, rs7324547, r2=1.0): for rs1324057, the aHR for OS was 1.59 (95%CI 1.2-2.1); p=0.001; and the aHR for PFS, 1.48 (95%CI 1.1-1.9); p=0.004. VEGFR1/FLT1 rs7324547 has been associated with esophageal cancer risk [PMID: 21751195], but has not been assessed in lung cancer. Conclusions: SNPS of the VEGFR1 and ABCC2 genes are strongly associated with OS and PFS in this cohort of platinum-treated advanced NSCLC patients. Future studies should assess whether these are predictive or prognostic markers.

National trends in admissions for potentially preventable conditions among patients with metastatic solid tumors, 2004-2014.

2018 ◽  
Vol 36 (30_suppl) ◽  
pp. 1-1
Author(s):  
Robert Michael Daly ◽  
Marwan S. Abougergi
Keyword(s):  
Solid Tumors ◽  
Stage Iv ◽  
Chi Square ◽  
Preventable Hospitalizations ◽  
Department Of Health ◽  
Hospitalization Costs ◽  
High Prevalence ◽  
Utilization Patterns ◽  
Nationally Representative ◽  
National Trends

1 Background: The Centers for Medicare and Medicaid Services (CMS) has identified 10 conditions for hospitalization among patients receiving chemotherapy that are potentially preventable through appropriately managed outpatient care. CMS plans to measure hospitals’ performance based on frequency of admission for: anemia, dehydration, diarrhea, emesis, nausea, neutropenia, fever, pain, pneumonia, and sepsis. Our objective was to measure hospital utilization patterns for these conditions. Methods: Nationally representative data from the 2004 and 2014 National Inpatient Sample were analyzed. Adults with stage IV solid tumors admitted with a principal diagnosis of one of the ten conditions were identified using ICD-9 codes provided by CMS. The primary outcome was number of admissions. Secondary outcomes were total hospitalization costs, length of stay (LOS), and in-hospital mortality rate. Proportions and count data were compared using chi-square and binomial test, respectively. Results: Between 2004 and 2014, potentially preventable hospitalizations increased from 64,053 to 85,740 (p < 0.01). The most frequent reason for admission was pneumonia (32%) in 2004 and sepsis (41%) in 2014. Table 1 provides the results for the year 2014 by condition. Hospitalizations for sepsis had the longest mean LOS (p < 0.01), highest mean total costs (p < 0.01) and most frequently resulted in death (p < 0.01). Conclusions: The Department of Health and Human Services states, “Improving patients’ quality of life by keeping patients out of the hospital is a main goal of cancer care.” Despite supportive care advances, the increased frequency of hospitalization demonstrates a need for continued symptom management innovation. Infectious symptoms should be a focus of these technologies given their high prevalence, mortality and resource utilization. [Table: see text]

scholarly journals The Role of Matrix Metalloproteinase9 (MMP9) in Endometriosis

2017 ◽  
pp. 203
Author(s):  
Amalia Amalia ◽  
Nusratuddin Abdullah ◽  
Umar Malinta
Keyword(s):  
Stage Iv ◽  
Stage I ◽  
Stage Iii ◽  
Chi Square ◽  
Cross Sectional ◽  
Significance Level ◽  
Chi Square Test ◽  
Cross Sectional Design ◽  
Metalloproteinase 9

Objective: To investigate the role of MMP-9 expression in endometriosis. Methods: The study was conducted from October 2015 to March 2016, an observational study with cross-sectional design. Samples are all endometriosis patients who underwent laparoscopic surgery in Dr. Wahidin Sudirohusodo Hospital and several other hospitals in Makassar. Samples were stored and fixed in the Grand Medika Histopathology Laboratory Makassar for examination the expression of MMP-9 using immunohistochemical methods. Conducted an analysis of 50 samples, of which 11 samples of stage II, 21 stage III samples, and 18 samples of stage IV. The data obtained and analyzed statistically using Mann Whitney and Chi Square test with a significance level of p <0.05. Results: The results reported rankings mean the expression of MMP-9 in stage I-II = 16.68, stage III-IV 27.99 (p = 0.013). There were differences in the expression of MMP-9 based on the stage. Stage I-II endometriosis had a more positive 2 expression of MMP-9 (45.5%), stage III-IV endometriosis have more positive 3 expression of MMP-9 (59.0%). The results of chi square test (p = 0.043). Conclusion: Higher expression of MMP-9 is significantly associated with higher degree of endometriosis. Keywords: matrix metalloproteinase-9, stages of endometriosis

The effect of tivantinib on QTc interval in subjects with advanced solid tumors and healthy subjects.

2014 ◽  
Vol 32 (15_suppl) ◽  
pp. e13528-e13528
Author(s):  
Masaya Tachibana ◽  
Kyriakos P. Papadopoulos ◽  
Lon S. Smith ◽  
Danielle Mutz ◽  
Alain C. Mita ◽  
...  
Keyword(s):  
Solid Tumors ◽  
Healthy Subjects ◽  
Qtc Interval ◽  
Advanced Solid Tumors

scholarly journals Thromboembolism in Patients with Advanced Solid Tumors Treated with Immunotherapy Compared with Platinum-Based Chemotherapy

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 1057-1057
Author(s):  
Satish Maharaj ◽  
Ruobing Xue ◽  
Anuja Abhyankar ◽  
Simone M Chang ◽  
Rebecca A. Redman ◽  
...  
Keyword(s):  
Solid Tumors ◽  
Real World ◽  
Cumulative Incidence ◽  
Stage Iv ◽  
Stage Iii ◽  
Advanced Solid Tumors ◽  
Durable Response ◽  
Vein Thrombosis ◽  
Platinum Based Chemotherapy

Abstract Background: Venous and arterial thromboembolism (VTE/ATE) in patients with cancer are a significant cause of morbidity and mortality. Platinum-based chemotherapy (Platinum) has been associated with increased risk of VTE and ATE. In the last decade immunotherapy (IO) has emerged as first line treatment for many patients, alone or in combination with Platinum. Immune checkpoint inhibition can lead to a systemic proinflammatory state with some suggesting an associated procoagulant effect. A systematic review of studies on IO in advanced cancer reported incidence of 2.7% VTE and 1.1% ATE (n=20,273, Solinas et al 2020), concluding ATE/VTE is relatively rare with IO. However, emerging real world data suggest a higher incidence of thrombosis than initially reported, and how VTE/ATE incidence compares with IO as compared with Platinum remains unknown. Methods: We conducted a retrospective cohort study of consecutive patients with advanced solid tumors including non-small cell lung cancer (NSCLC, unresectable Stage III or Stage IV), melanoma (Stage III or Stage IV) and gastrointestinal cancers (Stage IV) during the period 2014-2020 at the Brown Cancer Center. Patients with thrombophilia, anticoagulation use, &gt;1 malignancy, and use of regimens without IO/Platinum were excluded. Treatments included IO, Platinum (cisplatin, carboplatin, oxaliplatin) or combined IO-Platinum. VTE was defined as deep vein thrombosis, pulmonary embolism or visceral vein thrombosis. ATE was defined as any arterial thromboembolic event including arterial stroke, myocardial infarction, peripheral arterial thrombosis and visceral arterial thromboses. The primary outcomes of the study were cumulative incidence rates of VTE and ATE with events recorded in time from diagnosis. Cumulative incidence analyses were performed to compare rates of VTE and ATE for the different modalities of treatment (IO, IO-Platinum, Platinum). Results: A total of 357 patients were included. Clinical characteristics are presented in Table 1 - just over half were male, median age 59 yrs and predominant history of smoking. NSCLC was most represented (41%) followed by GI cancer (34%) and melanoma (25%). Treatment modalities were fairly distributed : IO (34%), IO-Platinum (30%) and Platinum (36%). Over a median follow up of 2.5 yrs, VTE occurred in 80 patients (22%), most commonly PE followed by DVT and VVT (Table 2). At median follow up, the cumulative incidence of VTE with IO was 15.1% [95% CI (9.3-24.6)] vs. IO-Platinum at 23.2% [95% CI (15.1-35.7)] and Platinum at 29.2% [95% CI (21.7-39.4)]. ATE occurred in 25 patients overall (7%) (Table 2). At median follow up, cumulative incidence of ATE with IO was 3.3% [95% CI (1.3-8.7)] vs. IO-Platinum at 7.0% [95% CI (2.5-19.4)] and Platinum at 9.9% [95% CI (5.6-17.6)]. Cumulative incidence frequencies for VTE/ATE are presented graphically according to each treatment modality (Figure). Conclusion: In this cohort of patients, increased incidence of VTE/ATE over time was seen following immunotherapy alone or combined with platinum-based chemotherapy. Immunotherapy can induce a durable response with unprecedented survival benefits and patients with advanced solid tumors are at risk for increasingly longer periods. The reasons behind increased real world incidence relative to historical adverse event reporting are likely multifactorial and further research in larger cohorts is needed. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

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